Download Supplementary Table 1 Entrez Gene (http://www.ncbi.nlm.nih.gov

Supplementary Table 1
Entrez Gene (http://www.ncbi.nlm.nih.gov/gene) descriptions of the 168 genes. When Entrez
Gene descriptions were not available, GeneCards (http://www.genecards.org) descriptions
were used (this is noted in the table)
ACBD6
acyl-CoA binding domain
containing 6
ACSL4
acyl-CoA synthetase longchain family member 4
ADK
adenosine kinase
ADRA2B
adrenoceptor alpha 2B
GeneCards Summary: ACBD6 (acyl-CoA
binding domain containing 6) is a protein-coding
gene. GO annotations related to this gene include
lipid binding and fatty-acyl-CoA binding. An
important paralog of this gene is OSTF1.
The protein encoded by this gene is an isozyme
of the long-chain fatty-acid-coenzyme A ligase
family. Although differing in substrate
specificity, subcellular localization, and tissue
distribution, all isozymes of this family convert
free long-chain fatty acids into fatty acyl-CoA
esters, and thereby play a key role in lipid
biosynthesis and fatty acid degradation. This
isozyme preferentially utilizes arachidonate as
substrate. The absence of this enzyme may
contribute to the mental retardation or Alport
syndrome. Alternative splicing of this gene
generates 2 transcript variants. (provided by
RefSeq, Jul 2008)
This gene an enzyme which catalyzes the transfer
of the gamma-phosphate from ATP to adenosine,
thereby serving as a regulator of concentrations
of both extracellular adenosine and intracellular
adenine nucleotides. Adenosine has widespread
effects on the cardiovascular, nervous,
respiratory, and immune systems and inhibitors
of the enzyme could play an important
pharmacological role in increasing intravascular
adenosine concentrations and acting as antiinflammatory agents. Multiple transcript variants
encoding different isoforms have been found for
this gene. (provided by RefSeq, Jan 2011)
Alpha-2-adrenergic receptors are members of the
G protein-coupled receptor superfamily. They
include 3 highly homologous subtypes: alpha2A,
alpha2B, and alpha2C. These receptors have a
critical role in regulating neurotransmitter release
from sympathetic nerves and from adrenergic
neurons in the central nervous system. This
intronless gene encodes the alpha2B subtype,
which was observed to associate with eIF-2B, a
guanine nucleotide exchange protein that
functions in regulation of translation. A
polymorphic variant of the alpha2B subtype,
which lacks 3 glutamic acids from a glutamic
acid repeat element, was identified to have
decreased G protein-coupled receptor kinasemediated phosphorylation and desensitization;
AFF2
AF4/FMR2 family,
member 2
ALG6
alpha-1,3glucosyltransferase
AP1S2
adaptor-related protein
complex 1, sigma 2 subunit
AP4B1
adaptor-related protein
complex 4, beta 1 subunit
AP4E1
adaptor-related protein
complex 4, epsilon 1
subunit
this polymorphic form is also associated with
reduced basal metabolic rate in obese subjects
and may therefore contribute to the pathogenesis
of obesity. (provided by RefSeq, Aug 2011)
This gene encodes a putative transcriptional
activator that is a member of the AF4\FMR2
gene family. This gene is associated with the
folate-sensitive fragile X E locus on chromosome
X. A repeat polymorphism in the fragile X E
locus results in silencing of this gene causing
Fragile X E syndrome. Fragile X E syndrome is a
form of nonsyndromic X-linked mental
retardation. Alternate splicing results in multiple
transcript variants.(provided by RefSeq, Dec
2009)
This gene encodes a member of the ALG6/ALG8
glucosyltransferase family. The encoded protein
catalyzes the addition of the first glucose residue
to the growing lipid-linked oligosaccharide
precursor of N-linked glycosylation. Mutations in
this gene are associated with congenital disorders
of glycosylation type Ic. (provided by RefSeq,
Jul 2008)
Adaptor protein complex 1 is found at the
cytoplasmic face of coated vesicles located at the
Golgi complex, where it mediates both the
recruitment of clathrin to the membrane and the
recognition of sorting signals within the cytosolic
tails of transmembrane receptors. This complex
is a heterotetramer composed of two large, one
medium, and one small adaptin subunit. The
protein encoded by this gene serves as the small
subunit of this complex and is a member of the
adaptin protein family. Transcript variants
encoding different isoforms have been found for
this gene. (provided by RefSeq, Jan 2013)
This gene encodes a subunit of a heterotetrameric
adapter-like complex 4 that is involved in
targeting proteins from the trans-Golgi network
to the endosomal-lysosomal system. Mutations in
this gene are associated with cerebral palsy
spastic quadriplegic type 5 (CPSQ5) disorder.
Alternatively spliced transcript variants encoding
different isoforms have been found for this gene.
(provided by RefSeq, Dec 2011)
This gene encodes a member of the adaptor
complexes large subunit protein family. These
proteins are components of the heterotetrameric
adaptor protein complexes, which play important
roles in the secretory and endocytic pathways by
mediating vesicle formation and sorting of
integral membrane proteins. The encoded protein
is a large subunit of adaptor protein complex-4,
which is associated with both clathrin- and
nonclathrin-coated vesicles. Disruption of this
gene may be associated with cerebral palsy.
AP4M1
adaptor-related protein
complex 4, mu 1 subunit
AP4S1
adaptor-related protein
complex 4, sigma 1 subunit
ARHGEF6
Rac/Cdc42 guanine
nucleotide exchange factor
(GEF) 6
ARHGEF9
Cdc42 guanine nucleotide
exchange factor (GEF) 9
ARID1B
AT rich interactive domain
1B (SWI1-like)
Alternatively spliced transcript variants encoding
multiple isoforms have been observed for this
gene. (provided by RefSeq, Nov 2011)
This gene encodes a subunit of the
heterotetrameric AP-4 complex. The encoded
protein belongs to the adaptor complexes
medium subunits family. This AP-4 complex is
involved in the recognition and sorting of cargo
proteins with tyrosine-based motifs from the
trans-golgi network to the endosomal-lysosomal
system. (provided by RefSeq, Jul 2008)
This gene encodes a member of the adaptor
complexes small subunit protein family. These
proteins are components of the heterotetrameric
adaptor protein complexes, which play important
roles in the secretory and endocytic pathways by
mediating vesicle formation and sorting of
integral membrane proteins. The encoded protein
is the small subunit of adaptor protein complex-4,
which is associated with both clathrin- and
nonclathrin-coated vesicles. Mutations in this
gene are associated with spastic quadriplegic
cerebral palsy-6. Alternatively spliced transcript
variants encoding multiple isoforms have been
observed for this gene, and a pseudogene of this
gene is located on the long arm of chromosome
6. (provided by RefSeq, Dec 2011)
Rho GTPases play a fundamental role in
numerous cellular processes that are initiated by
extracellular stimuli that work through G protein
coupled receptors. The encoded protein belongs
to a family of cytoplasmic proteins that activate
the Ras-like family of Rho proteins by
exchanging bound GDP for GTP. It may form a
complex with G proteins and stimulate Rhodependent signals. This protein is activated by
PI3-kinase. Mutations in this gene can cause Xchromosomal non-specific mental retardation.
(provided by RefSeq, Jul 2008)
The protein encoded by this gene is a Rho-like
GTPase that switches between the active (GTPbound) state and inactive (GDP-bound) state to
regulate CDC42 and other genes. Defects in this
gene are a cause of startle disease with epilepsy
(STHEE), also known as hyperekplexia with
epilepsy. Three transcript variants encoding
different isoforms have been found for this
gene.(provided by RefSeq, Mar 2010)
This locus encodes an AT-rich DNA interacting
domain-containing protein. The encoded protein
is a component of the SWI/SNF chromatin
remodeling complex and may play a role in cellcycle activation. The protein encoded by this
locus is similar to AT-rich interactive domaincontaining protein 1A. These two proteins
function as alternative, mutually exclusive
ARID5A
ARX
ASCL1
ASPM
ATRX
ARID-subunits of the SWI/SNF complex. The
associated complexes play opposing roles.
Alternatively spliced transcript variants encoding
different isoforms have been described. (provided
by RefSeq, Feb 2012)
AT rich interactive domain Members of the ARID protein family, including
5A (MRF1-like)
ARID5A, have diverse functions but all appear to
play important roles in development, tissuespecific gene expression, and regulation of cell
growth (Patsialou et al., 2005 (PubMed
15640446)).(supplied by OMIM, Mar 2008)
aristaless related homeobox This gene is a homeobox-containing gene
expressed during development. The expressed
protein contains two conserved domains, a Cpeptide (or aristaless domain) and the prd-like
class homeobox domain. It is a member of the
group-II aristaless-related protein family whose
members are expressed primarily in the central
and/or peripheral nervous system. This gene is
thought to be involved in CNS development.
Mutations in this gene cause X-linked mental
retardation and epilepsy. (provided by RefSeq,
Jul 2008)
achaete-scute complex
This gene encodes a member of the basic helixhomolog 1 (Drosophila)
loop-helix (BHLH) family of transcription
factors. The protein activates transcription by
binding to the E box (5'-CANNTG-3').
Dimerization with other BHLH proteins is
required for efficient DNA binding. This protein
plays a role in the neuronal commitment and
differentiation and in the generation of olfactory
and autonomic neurons. Mutations in this gene
may contribute to the congenital central
hypoventilation syndrome (CCHS) phenotype in
rare cases. (provided by RefSeq, Jul 2008)
asp (abnormal spindle)
This gene is the human ortholog of the
homolog, microcephaly
Drosophila melanogaster 'abnormal spindle' gene
associated (Drosophila)
(asp), which is essential for normal mitotic
spindle function in embryonic neuroblasts.
Studies in mouse also suggest a role of this gene
in mitotic spindle regulation, with a preferential
role in regulating neurogenesis. Mutations in this
gene are associated with microcephaly primary
type 5. Multiple transcript variants encoding
different isoforms have been found for this
gene.(provided by RefSeq, May 2011)
alpha thalassemia/mental
The protein encoded by this gene contains an
retardation syndrome XATPase/helicase domain, and thus it belongs to
linked
the SWI/SNF family of chromatin remodeling
proteins. This protein is found to undergo cell
cycle-dependent phosphorylation, which
regulates its nuclear matrix and chromatin
association, and suggests its involvement in the
gene regulation at interphase and chromosomal
segregation in mitosis. Mutations in this gene are
associated with an X-linked mental retardation
AUTS2
autism susceptibility
candidate 2
BCOR
BCL6 corepressor
BRWD3
bromodomain and WD
repeat domain containing 3
C12orf57
chromosome 12 open
reading frame 57
C9orf86, current
symbol: RABL6
RAB, member RAS
oncogene family-like 6
(XLMR) syndrome most often accompanied by
alpha-thalassemia (ATRX) syndrome. These
mutations have been shown to cause diverse
changes in the pattern of DNA methylation,
which may provide a link between chromatin
remodeling, DNA methylation, and gene
expression in developmental processes. Multiple
alternatively spliced transcript variants encoding
distinct isoforms have been reported. (provided
by RefSeq, Aug 2013)
GeneCards Summary: AUTS2 (autism
susceptibility candidate 2) is a protein-coding
gene. Diseases associated with AUTS2 include
supravalvular aortic stenosis, and smallpox. GO
annotations related to this gene include
molecular_function. An important paralog of this
gene is FBRS.
The protein encoded by this gene was identified
as an interacting corepressor of BCL6, a
POZ/zinc finger transcription repressor that is
required for germinal center formation and may
influence apoptosis. This protein selectively
interacts with the POZ domain of BCL6, but not
with eight other POZ proteins. Specific class I
and II histone deacetylases (HDACs) have been
shown to interact with this protein, which
suggests a possible link between the two classes
of HDACs. Several transcript variants encoding
different isoforms have been found for this gene.
A pseudogene of this gene is found on
chromosome Y.(provided by RefSeq, Jun 2010)
The protein encoded by this gene contains a
bromodomain and several WD repeats. It is
thought to have a chromatin-modifying function,
and may thus play a role in transcription.
Mutations in this gene cause mental retardation
X-linked type 93, which is also referred to as
mental retardation X-linked with macrocephaly.
This gene is also associated with translocations in
patients with B-cell chronic lymphocytic
leukemia. (provided by RefSeq, May 2010)
GeneCards Summary: C12orf57 (chromosome 12
open reading frame 57) is a protein-coding gene.
Diseases associated with C12orf57 include
temtamy syndrome, and alzheimer's disease.
This gene encodes a member of the Ras
superfamily of small GTPases. The encoded
protein binds to both GTP and GDP and may
play a role in cell growth and survival.
Overexpression of this gene may play a role in
breast cancer tumorigenesis, and pseudogenes of
this gene are located on the long arm of
chromosome 2 and the short arm of chromosome
18. Alternatively spliced transcript variants
encoding multiple isoforms have been observed
for this gene. (provided by RefSeq, Dec 2011)
CACNA1F
calcium channel, voltagedependent, L type, alpha
1F subunit
CACNA1G
calcium channel, voltagedependent, T type, alpha
1G subunit
CACNG2
calcium channel, voltagedependent, gamma subunit
2
CASK
calcium/calmodulindependent serine protein
kinase (MAGUK family)
CC2D1A
coiled-coil and C2 domain
containing 1A
This gene encodes a multipass transmembrane
protein that functions as an alpha-1 subunit of the
voltage-dependent calcium channel, which
mediates the influx of calcium ions into the cell.
The encoded protein forms a complex of alpha-1,
alpha-2/delta, beta, and gamma subunits in a
1:1:1:1 ratio. Mutations in this gene can cause Xlinked eye disorders, including congenital
stationary night blindness type 2A, cone-rod
dystropy, and Aland Island eye disease.
Alternatively spliced transcript variants encoding
multiple isoforms have been observed. (provided
by RefSeq, Aug 2013)
Voltage-sensitive calcium channels mediate the
entry of calcium ions into excitable cells, and are
also involved in a variety of calcium-dependent
processes, including muscle contraction,
hormone or neurotransmitter release, gene
expression, cell motility, cell division, and cell
death. This gene encodes a T-type, low-voltage
activated calcium channel. The T-type channels
generate currents that are both transient, owing to
fast inactivation, and tiny, owing to small
conductance. T-type channels are thought to be
involved in pacemaker activity, low-threshold
calcium spikes, neuronal oscillations and
resonance, and rebound burst firing. Many
alternatively spliced transcript variants encoding
different isoforms have been described for this
gene. (provided by RefSeq, Sep 2011)
The protein encoded by this gene is a type I
transmembrane AMPA receptor regulatory
protein (TARP). TARPs regulate both trafficking
and channel gating of the AMPA receptors. This
gene is part of a functionally diverse eightmember protein subfamily of the PMP22/EMP/MP20 family. This gene is a
susceptibility locus for schizophrenia. (provided
by RefSeq, Dec 2010)
This gene encodes a calcium/calmodulindependent serine protein kinase. The encoded
protein is a MAGUK (membrane-associated
guanylate kinase) protein family member. These
proteins are scaffold proteins and the encoded
protein is located at synapses in the brain.
Mutations in this gene are associated with FG
syndrome 4, mental retardation and microcephaly
with pontine and cerebellar hypoplasia, and a
form of X-linked mental retardation. Multiple
transcript variants encoding different isoforms
have been found for this gene.(provided by
RefSeq, Mar 2010)
This gene encodes a transcriptional repressor that
binds to a conserved 14-bp 5'-repressor element
and regulates expression of the 5hydroxytryptamine (serotonin) receptor 1A gene
CCNA2
cyclin A2
CDK16
cyclin-dependent kinase 16
CDK5RAP2
CDK5 regulatory subunit
associated protein 2
CDKN2AIP
CDKN2A interacting
protein
CENPJ
centromere protein J
in neuronal cells. The DNA binding and
transcriptional repressor activities of the protein
are inhibited by calcium. A mutation in this gene
results in nonsyndromic mental retardation3.(provided by RefSeq, Oct 2009)
The protein encoded by this gene belongs to the
highly conserved cyclin family, whose members
are characterized by a dramatic periodicity in
protein abundance through the cell cycle. Cyclins
function as regulators of CDK kinases. Different
cyclins exhibit distinct expression and
degradation patterns which contribute to the
temporal coordination of each mitotic event. In
contrast to cyclin A1, which is present only in
germ cells, this cyclin is expressed in all tissues
tested. This cyclin binds and activates CDC2 or
CDK2 kinases, and thus promotes both cell cycle
G1/S and G2/M transitions. (provided by RefSeq,
Jul 2008)
The protein encoded by this gene belongs to the
cdc2/cdkx subfamily of the ser/thr family of
protein kinases. It may play a role in signal
transduction cascades in terminally differentiated
cells; in exocytosis; and in transport of secretory
cargo from the endoplasmic reticulum. This gene
is thought to escape X inactivation. Alternative
splicing results in multiple transcript variants
encoding different isoforms. (provided by
RefSeq, Dec 2009)
This gene encodes a regulator of CDK5 (cyclindependent kinase 5) activity. The protein
encoded by this gene is localized to the
centrosome and Golgi complex, interacts with
CDK5R1 and pericentrin (PCNT), plays a role in
centriole engagement and microtubule
nucleation, and has been linked to primary
microcephaly and Alzheimer's disease.
Alternative splicing results in multiple transcript
variants. (provided by RefSeq, Jan 2013)
GeneCards Summary: CDKN2AIP (CDKN2A
interacting protein) is a protein-coding gene. GO
annotations related to this gene include doublestranded RNA binding and p53 binding. An
important paralog of this gene is CDKN2AIPNL.
This gene encodes a protein that belongs to the
centromere protein family. During cell division,
this protein plays a structural role in the
maintenance of centrosome integrity and normal
spindle morphology, and it is involved in
microtubule disassembly at the centrosome. This
protein can function as a transcriptional
coactivator in the Stat5 signaling pathway, and
also as a coactivator of NF-kappaB-mediated
transcription, likely via its interaction with the
coactivator p300/CREB-binding protein.
Mutations in this gene are associated with
CLCN4
CNKSR1
CNKSR2
CRBN
CSTF2
primary autosomal recessive microcephaly, a
disorder characterized by severely reduced brain
size and mental retardation. Alternatively spliced
transcript variants have been found for this gene.
(provided by RefSeq, Apr 2012)
chloride channel, voltageThe CLCN family of voltage-dependent chloride
sensitive 4
channel genes comprises nine members (CLCN17, Ka and Kb) which demonstrate quite diverse
functional characteristics while sharing
significant sequence homology. Chloride channel
4 has an evolutionary conserved CpG island and
is conserved in both mouse and hamster. This
gene is mapped in close proximity to APXL
(Apical protein Xenopus laevis-like) and OA1
(Ocular albinism type I), which are both located
on the human X chromosome at band p22.3. The
physiological role of chloride channel 4 remains
unknown but may contribute to the pathogenesis
of neuronal disorders. Alternate splicing results
in two transcript variants that encode different
proteins. (provided by RefSeq, Mar 2012)
connector enhancer of
This gene is a necessary element in receptor
kinase suppressor of Ras 1 tyrosine kinase pathways, possibly as a tyrosine
phosphorylation target. It is involved in
regulation of RAF in the MAPK pathway and
may also play a role in a MAPK-independent
pathway. (provided by RefSeq, Jul 2008)
connector enhancer of
This gene encodes a multidomain protein that
kinase suppressor of Ras 2 functions as a scaffold protein to mediate the
mitogen-activated protein kinase pathways
downstream from Ras. This gene product is
induced by vitamin D and inhibits apoptosis in
certain cancer cells. It may also play a role in
ternary complex assembly of synaptic proteins at
the postsynaptic membrane and coupling of
signal transduction to membrane/cytoskeletal
remodeling. Multiple transcript variants encoding
different isoforms have been found for this gene.
(provided by RefSeq, Dec 2009)
cereblon
This gene encodes a protein related to the Lon
protease protein family. In rodents and other
mammals this gene product is found in the
cytoplasm localized with a calcium channel
membrane protein, and is thought to play a role
in brain development. Mutations in this gene are
associated with autosomal recessive
nonsyndromic mental retardation. Multiple
transcript variants encoding different isoforms
have been found for this gene. (provided by
RefSeq, Mar 2010)
cleavage stimulation factor, This gene encodes a nuclear protein with an
3' pre-RNA, subunit 2,
RRM (RNA recognition motif) domain. The
64kDa
protein is a member of the cleavage stimulation
factor (CSTF) complex that is involved in the 3'
end cleavage and polyadenylation of premRNAs. Specifically, this protein binds GU-rich
CUL4B
cullin 4B
DCX
doublecortin
DLG1
discs, large homolog 1
(Drosophila)
DLG3
discs, large homolog 3
(Drosophila)
elements within the 3'-untranslated region of
mRNAs. (provided by RefSeq, Jul 2008)
This gene is a member of the cullin family. The
encoded protein forms a complex that functions
as an E3 ubiquitin ligase and catalyzes the
polyubiquitination of specific protein substrates
in the cell. The protein interacts with a ring finger
protein, and is required for the proteolysis of
several regulators of DNA replication including
chromatin licensing and DNA replication factor 1
and cyclin E. Multiple transcript variants
encoding different isoforms have been found for
this gene. (provided by RefSeq, Jul 2008)
This gene encodes a member of the doublecortin
family. The protein encoded by this gene is a
cytoplasmic protein and contains two
doublecortin domains, which bind microtubules.
In the developing cortex, cortical neurons must
migrate over long distances to reach the site of
their final differentiation. The encoded protein
appears to direct neuronal migration by
regulating the organization and stability of
microtubules. In addition, the encoded protein
interacts with LIS1, the regulatory gamma
subunit of platelet activating factor
acetylhydrolase, and this interaction is important
to proper microtubule function in the developing
cortex. Mutations in this gene cause abnormal
migration of neurons during development and
disrupt the layering of the cortex, leading to
epilepsy, mental retardation, subcortical band
heterotopia ('double cortex' syndrome) in females
and lissencephaly ('smooth brain' syndrome) in
males. Multiple transcript variants encoding
different isoforms have been found for this gene.
(provided by RefSeq, Sep 2010)
This gene encodes a multi-domain scaffolding
protein that is required for normal development.
This protein may have a role in septate junction
formation, signal transduction, cell proliferation,
synaptogenesis and lymphocyte activation.
Several alternatively spliced transcript variants
encoding different isoforms have been described
for this gene, but the full-length nature of some
of the variants is not known. (provided by
RefSeq, Feb 2011)
This gene encodes a member of the membraneassociated guanylate kinase protein family. The
encoded protein may play a role in clustering of
NMDA receptors at excitatory synapses. It may
also negatively regulate cell proliferation through
interaction with the C-terminal region of the
adenomatosis polyposis coli tumor suppressor
protein. Mutations in this gene have been
associated with X-linked mental retardation.
Alternatively spliced transcript variants have
DYRK1A
dual-specificity tyrosine(Y)-phosphorylation
regulated kinase 1A
EEF1B2
eukaryotic translation
elongation factor 1 beta 2
EHMT1
euchromatic histone-lysine
N-methyltransferase 1
EIF2AK3
eukaryotic translation
initiation factor 2-alpha
kinase 3
EIF2S3
eukaryotic translation
initiation factor 2, subunit
3 gamma, 52kDa
been described. (provided by RefSeq, Oct 2009)
This gene encodes a member of the Dualspecificity tyrosine phosphorylation-regulated
kinase (DYRK) family. This member contains a
nuclear targeting signal sequence, a protein
kinase domain, a leucine zipper motif, and a
highly conservative 13-consecutive-histidine
repeat. It catalyzes its autophosphorylation on
serine/threonine and tyrosine residues. It may
play a significant role in a signaling pathway
regulating cell proliferation and may be involved
in brain development. This gene is a homolog of
Drosophila mnb (minibrain) gene and rat Dyrk
gene. It is localized in the Down syndrome
critical region of chromosome 21, and is
considered to be a strong candidate gene for
learning defects associated with Down syndrome.
Alternative splicing of this gene generates several
transcript variants differing from each other
either in the 5' UTR or in the 3' coding region.
These variants encode at least five different
isoforms. (provided by RefSeq, Jul 2008)
This gene encodes a translation elongation factor.
The protein is a guanine nucleotide exchange
factor involved in the transfer of aminoacylated
tRNAs to the ribosome. Alternative splicing
results in three transcript variants which differ
only in the 5' UTR. (provided by RefSeq, Jul
2008)
The protein encoded by this gene is a histone
methyltransferase that is part of the E2F6
complex, which represses transcription. The
encoded protein methylates the Lys-9 position of
histone H3, which tags it for transcriptional
repression. This protein may be involved in the
silencing of MYC- and E2F-responsive genes
and therefore could play a role in the G0/G1 cell
cycle transition. Defects in this gene are a cause
of chromosome 9q subtelomeric deletion
syndrome (9q-syndrome). Two transcript variants
encoding different isoforms have been found for
this gene. (provided by RefSeq, Mar 2009)
The protein encoded by this gene phosphorylates
the alpha subunit of eukaryotic translationinitiation factor 2 (EIF2), leading to its
inactivation, and thus to a rapid reduction of
translational initiation and repression of global
protein synthesis. It is a type I membrane protein
located in the endoplasmic reticulum (ER), where
it is induced by ER stress caused by malfolded
proteins. Mutations in this gene are associated
with Wolcott-Rallison syndrome. (provided by
RefSeq, Jan 2010)
The protein encoded by this gene is the largest
subunit of a heterotrimeric GTP-binding protein
involved in the recruitment of methionyl-tRNA(i)
ELP2
elongator acetyltransferase
complex subunit 2
ENTPD1
ectonucleoside
triphosphate
diphosphohydrolase 1
EPB41L1
erythrocyte membrane
protein band 4.1-like 1
ERLIN2
ER lipid raft associated 2
FASN
fatty acid synthase
FGD1
FYVE, RhoGEF and PH
domain containing 1
to the 40 S ribosomal subunit. (provided by
RefSeq, Jan 2010)
GeneCards Summary: ELP2 (elongator
acetyltransferase complex subunit 2) is a proteincoding gene. Diseases associated with ELP2
include acute disseminated encephalomyelitis,
and spinal stenosis. GO annotations related to
this gene include DNA binding.
GeneCards Summary: ENTPD1 (ectonucleoside
triphosphate diphosphohydrolase 1) is a proteincoding gene. Diseases associated with ENTPD1
include radiation proctitis, and proctitis, and
among its related super-pathways are Purine
metabolism and UTP and CTP
dephosphorylation I. GO annotations related to
this gene include hydrolase activity and ATP
binding. An important paralog of this gene is
ENTPD7.
Erythrocyte membrane protein band 4.1 (EPB41)
is a multifunctional protein that mediates
interactions between the erythrocyte cytoskeleton
and the overlying plasma membrane. The protein
encoded by this gene is a neuronally-enriched
protein that is structurally similar to EPB41. The
encoded protein binds and stabilizes D2 and D3
dopamine receptors at the neuronal plasma
membrane. Multiple transcript variants encoding
different isoforms have been found for this gene.
(provided by RefSeq, Apr 2012)
This gene encodes a member of the SPFH
domain-containing family of lipid raft-associated
proteins. The encoded protein is localized to lipid
rafts of the endoplasmic reticulum and plays a
critical role in inositol 1,4,5-trisphosphate (IP3)
signaling by mediating ER-associated
degradation of activated IP3 receptors. Mutations
in this gene are a cause of spastic paraplegia-18
(SPG18). Alternatively spliced transcript variants
encoding multiple isoforms have been observed
for this gene. (provided by RefSeq, Feb 2012)
The enzyme encoded by this gene is a
multifunctional protein. Its main function is to
catalyze the synthesis of palmitate from acetylCoA and malonyl-CoA, in the presence of
NADPH, into long-chain saturated fatty acids. In
some cancer cell lines, this protein has been
found to be fused with estrogen receptor-alpha
(ER-alpha), in which the N-terminus of FAS is
fused in-frame with the C-terminus of ER-alpha.
(provided by RefSeq, Jul 2008)
This gene encodes a protein that contains Dbl
(DH) and pleckstrin (PH) homology domains and
is similar to the Rho family of small GTPbinding proteins. The encoded protein
specifically binds to the Rho family GTPase
Cdc42Hs and can stimulate the GDP-GTP
FMR1
fragile X mental
retardation 1
FOXG1
forkhead box G1
FOXP2
forkhead box P2
FRMPD4
FERM and PDZ domain
containing 4
exchange of the isoprenylated form of Cdc42Hs.
It also stimulates the mitogen activated protein
kinase cascade leading to c-Jun kinase
SAPK/JNK1 activation. Defects in this gene are
the cause of faciogenital dysplasia and X-linked
mental retardation, syndromatic 16.(provided by
RefSeq, Mar 2011)
The protein encoded by this gene binds RNA and
is associated with polysomes. The encoded
protein may be involved in mRNA trafficking
from the nucleus to the cytoplasm. A
trinucleotide repeat (CGG) in the 5' UTR is
normally found at 6-53 copies, but an expansion
to 55-230 repeats is the cause of fragile X
syndrome. Expansion of the trinucleotide repeat
may also cause one form of premature ovarian
failure (POF1). Multiple alternatively spliced
transcript variants that encode different protein
isoforms and which are located in different
cellular locations have been described for this
gene. (provided by RefSeq, May 2010)
This locus encodes a member of the forked-head
transcription factor family. The encoded protein,
which functions as a repressor, may play a role in
brain development. Mutations at this locus have
been associated with Rett syndrome. (provided
by RefSeq, Feb 2012)
This gene encodes a member of the
forkhead/winged-helix (FOX) family of
transcription factors. It is expressed in fetal and
adult brain as well as in several other organs such
as the lung and gut. The protein product contains
a FOX DNA-binding domain and a large
polyglutamine tract and is an evolutionarily
conserved transcription factor, which may bind
directly to approximately 300 to 400 gene
promoters in the human genome to regulate the
expression of a variety of genes. This gene is
required for proper development of speech and
language regions of the brain during
embryogenesis, and may be involved in a variety
of biological pathways and cascades that may
ultimately influence language development.
Mutations in this gene cause speech-language
disorder 1 (SPCH1), also known as autosomal
dominant speech and language disorder with
orofacial dyspraxia. Multiple alternative
transcripts encoding different isoforms have been
identified in this gene.(provided by RefSeq, Feb
2010)
This gene encodes a multi-domain (WW, PDZ,
FERM) containing protein. Through its
interaction with other proteins (such as PSD-95),
it functions as a positive regulator of dendritic
spine morphogenesis and density, and is required
for the maintenance of excitatory synaptic
GDI1
GDP dissociation inhibitor
1
GFAP
glial fibrillary acidic
protein
GPC3
glypican 3
GRIA3
glutamate receptor,
ionotropic, AMPA 3
transmission. (provided by RefSeq, Jan 2010)
GDP dissociation inhibitors are proteins that
regulate the GDP-GTP exchange reaction of
members of the rab family, small GTP-binding
proteins of the ras superfamily, that are involved
in vesicular trafficking of molecules between
cellular organelles. GDIs slow the rate of
dissociation of GDP from rab proteins and
release GDP from membrane-bound rabs. GDI1
is expressed primarily in neural and sensory
tissues. Mutations in GDI1 have been linked to
X-linked nonspecific mental retardation.
(provided by RefSeq, Jul 2008)
This gene encodes one of the major intermediate
filament proteins of mature astrocytes. It is used
as a marker to distinguish astrocytes from other
glial cells during development. Mutations in this
gene cause Alexander disease, a rare disorder of
astrocytes in the central nervous system.
Alternative splicing results in multiple transcript
variants encoding distinct isoforms. (provided by
RefSeq, Oct 2008)
Cell surface heparan sulfate proteoglycans are
composed of a membrane-associated protein core
substituted with a variable number of heparan
sulfate chains. Members of the glypican-related
integral membrane proteoglycan family (GRIPS)
contain a core protein anchored to the
cytoplasmic membrane via a glycosyl
phosphatidylinositol linkage. These proteins may
play a role in the control of cell division and
growth regulation. The protein encoded by this
gene can bind to and inhibit the dipeptidyl
peptidase activity of CD26, and it can induce
apoptosis in certain cell types. Deletion
mutations in this gene are associated with
Simpson-Golabi-Behmel syndrome, also known
as Simpson dysmorphia syndrome. Alternative
splicing results in multiple transcript variants.
(provided by RefSeq, Sep 2009)
Glutamate receptors are the predominant
excitatory neurotransmitter receptors in the
mammalian brain and are activated in a variety of
normal neurophysiologic processes. These
receptors are heteromeric protein complexes
composed of multiple subunits, arranged to form
ligand-gated ion channels. The classification of
glutamate receptors is based on their activation
by different pharmacologic agonists. The subunit
encoded by this gene belongs to a family of
AMPA (alpha-amino-3-hydroxy-5-methyl-4isoxazole propionate)-sensitive glutamate
receptors, and is subject to RNA editing (AGA>GGA; R->G). Alternative splicing at this locus
results in different isoforms, which may vary in
their signal transduction properties. (provided by
GRID1
glutamate receptor,
ionotropic, delta 1
GRIK2
glutamate receptor,
ionotropic, kainate 2
GRIN1
glutamate receptor,
ionotropic, N-methyl Daspartate 1
GRIN2A
glutamate receptor,
ionotropic, N-methyl Daspartate 2A
GRIN2B
glutamate receptor,
ionotropic, N-methyl Daspartate 2B
RefSeq, Jul 2008)
This gene encodes a subunit of glutamate
receptor channels. These channels mediate most
of the fast excitatory synaptic transmission in the
central nervous system and play key roles in
synaptic plasticity.(provided by RefSeq, Jan
2009)
Glutamate receptors are the predominant
excitatory neurotransmitter receptors in the
mammalian brain and are activated in a variety of
normal neurophysiologic processes. This gene
product belongs to the kainate family of
glutamate receptors, which are composed of four
subunits and function as ligand-activated ion
channels. The subunit encoded by this gene is
subject to RNA editing at multiple sites within
the first and second transmembrane domains,
which is thought to alter the structure and
function of the receptor complex. Alternatively
spliced transcript variants encoding different
isoforms have also been described for this gene.
Mutations in this gene have been associated with
autosomal recessive mental retardation.
(provided by RefSeq, Jul 2008)
The protein encoded by this gene is a critical
subunit of N-methyl-D-aspartate receptors,
members of the glutamate receptor channel
superfamily which are heteromeric protein
complexes with multiple subunits arranged to
form a ligand-gated ion channel. These subunits
play a key role in the plasticity of synapses,
which is believed to underlie memory and
learning. Cell-specific factors are thought to
control expression of different isoforms, possibly
contributing to the functional diversity of the
subunits. Alternatively spliced transcript variants
have been described. (provided by RefSeq, Jul
2008)
N-methyl-D-aspartate (NMDA) receptors are a
class of ionotropic glutamate-gated ion channels.
These receptors have been shown to be involved
in long-term potentiation, an activity-dependent
increase in the efficiency of synaptic
transmission thought to underlie certain kinds of
memory and learning. NMDA receptor channels
are heteromers composed of the key receptor
subunit NMDAR1 (GRIN1) and 1 or more of the
4 NMDAR2 subunits: NMDAR2A (GRIN2A),
NMDAR2B (GRIN2B), NMDAR2C (GRIN2C)
and NMDAR2D (GRIN2D). Alternatively
spliced transcript variants encoding different
isoforms have been found for this gene.
(provided by RefSeq, Aug 2008)
N-methyl-D-aspartate (NMDA) receptors are a
class of ionotropic glutamate receptors. NMDA
receptor channel has been shown to be involved
GRIP1
glutamate receptor
interacting protein 1
HCFC1
host cell factor C1 (VP16accessory protein)
HDAC4
histone deacetylase 4
HFE2
hemochromatosis type 2
(juvenile)
in long-term potentiation, an activity-dependent
increase in the efficiency of synaptic
transmission thought to underlie certain kinds of
memory and learning. NMDA receptor channels
are heteromers composed of three different
subunits: NR1 (GRIN1), NR2 (GRIN2A,
GRIN2B, GRIN2C, or GRIN2D) and NR3
(GRIN3A or GRIN3B). The NR2 subunit acts as
the agonist binding site for glutamate. This
receptor is the predominant excitatory
neurotransmitter receptor in the mammalian
brain. (provided by RefSeq, Jul 2008)
This gene encodes a member of the glutamate
receptor interacting protein family. The encoded
scaffold protein binds to and mediates the
trafficking and membrane organization of a
number of transmembrane proteins. Alternatively
spliced transcript variants encoding different
isoforms have been described. (provided by
RefSeq, May 2010)
This gene is a member of the host cell factor
family and encodes a protein with five Kelch
repeats, a fibronectin-like motif, and six HCF
repeats, each of which contains a highly specific
cleavage signal. This nuclear coactivator is
proteolytically cleaved at one of the six possible
sites, resulting in the creation of an N-terminal
chain and the corresponding C-terminal chain.
The final form of this protein consists of
noncovalently bound N- and C-terminal chains.
The protein is involved in control of the cell
cycle and transcriptional regulation during herpes
simplex virus infection. Alternatively spliced
variants which encode different protein isoforms
have been described; however, not all variants
have been fully characterized. (provided by
RefSeq, Jul 2008)
Histones play a critical role in transcriptional
regulation, cell cycle progression, and
developmental events. Histone
acetylation/deacetylation alters chromosome
structure and affects transcription factor access to
DNA. The protein encoded by this gene belongs
to class II of the histone deacetylase/acuc/apha
family. It possesses histone deacetylase activity
and represses transcription when tethered to a
promoter. This protein does not bind DNA
directly, but through transcription factors MEF2C
and MEF2D. It seems to interact in a
multiprotein complex with RbAp48 and HDAC3.
(provided by RefSeq, Jul 2008)
The product of this gene is involved in iron
metabolism. It may be a component of the
signaling pathway which activates hepcidin or it
may act as a modulator of hepcidin expression. It
could also represent the cellular receptor for
HIST1H4B
histone cluster 1, H4b
HIST3H3
histone cluster 3, H3
INPP4A
inositol polyphosphate-4phosphatase, type I,
107kDa
IQSEC2
IQ motif and Sec7 domain
2
hepcidin. Alternatively spliced transcript variants
encoding different isoforms have been identified
for this gene. Defects in this gene are the cause of
hemochromatosis type 2A, also called juvenile
hemochromatosis (JH). JH is an early-onset
autosomal recessive disorder due to severe iron
overload resulting in hypogonadotrophic
hypogonadism, hepatic fibrosis or cirrhosis and
cardiomyopathy, occurring typically before age
of 30. (provided by RefSeq, Jul 2008)
Histones are basic nuclear proteins that are
responsible for the nucleosome structure of the
chromosomal fiber in eukaryotes. Two molecules
of each of the four core histones (H2A, H2B, H3,
and H4) form an octamer, around which
approximately 146 bp of DNA is wrapped in
repeating units, called nucleosomes. The linker
histone, H1, interacts with linker DNA between
nucleosomes and functions in the compaction of
chromatin into higher order structures. This gene
is intronless and encodes a member of the histone
H4 family. Transcripts from this gene lack polyA
tails but instead contain a palindromic
termination element. This gene is found in the
large histone gene cluster on chromosome 6.
(provided by RefSeq, Jul 2008)
Histones are basic nuclear proteins that are
responsible for the nucleosome structure of the
chromosomal fiber in eukaryotes. Nucleosomes
consist of approximately 146 bp of DNA
wrapped around a histone octamer composed of
pairs of each of the four core histones (H2A,
H2B, H3, and H4). The chromatin fiber is further
compacted through the interaction of a linker
histone, H1, with the DNA between the
nucleosomes to form higher order chromatin
structures. This gene is intronless and encodes a
member of the histone H3 family. Transcripts
from this gene lack polyA tails; instead, they
contain a palindromic termination element. This
gene is located separately from the other H3
genes that are in the histone gene cluster on
chromosome 6p22-p21.3. (provided by RefSeq,
Jul 2008)
This gene encodes an Mg++ independent enzyme
that hydrolyzes the 4-position phosphate from the
inositol ring of phosphatidylinositol 3,4bisphosphate, inositol 1,3,4-trisphosphate, and
inositol 3,4-bisphosphate. Multiple transcript
variants encoding distinct isoforms have been
described. (provided by RefSeq, Aug 2008)
This gene encodes a guanine nucleotide exchange
factor for the ARF family of small GTP-binding
proteins. The encoded protein is a component of
the postsynaptic density at excitatory synapses,
and may play a critical role in cytoskeletal and
KCNJ10
potassium inwardlyrectifying channel,
subfamily J, member 10
KDM5A
lysine (K)-specific
demethylase 5A
KDM5C
lysine (K)-specific
demethylase 5C
KDM6B
lysine (K)-specific
demethylase 6B
KIF1A
kinesin family member 1A
synaptic organization through the activation of
selected ARF substrates including ARF1 and
ARF6. Mutations in this gene have been
implicated in nonsyndromic X-linked mental
retardation. Alternatively spliced transcript
variants encoding multiple isoforms have been
observed for this gene. (provided by RefSeq, Aug
2011)
This gene encodes a member of the inward
rectifier-type potassium channel family,
characterized by having a greater tendency to
allow potassium to flow into, rather than out of, a
cell. The encoded protein may form a
heterodimer with another potassium channel
protein and may be responsible for the potassium
buffering action of glial cells in the brain.
Mutations in this gene have been associated with
seizure susceptibility of common idiopathic
generalized epilepsy syndromes. (provided by
RefSeq, Jul 2008)
This gene encodes a member of the Jumonji, ATrich interactive domain 1 (JARID1) histone
demethylase protein family. The encoded protein
plays a role in gene regulation through the
histone code by specifically demethylating lysine
4 of histone H3. The encoded protein interacts
with many other proteins, including
retinoblastoma protein, and is implicated in the
transcriptional regulation of Hox genes and
cytokines. This gene may play a role in tumor
progression. (provided by RefSeq, Aug 2013)
This gene is a member of the SMCY homolog
family and encodes a protein with one ARID
domain, one JmjC domain, one JmjN domain and
two PHD-type zinc fingers. The DNA-binding
motifs suggest this protein is involved in the
regulation of transcription and chromatin
remodeling. Mutations in this gene have been
associated with X-linked mental retardation.
Alternative splicing results in multiple transcript
variants. (provided by RefSeq, Apr 2009)
KDM6B (lysine (K)-specific demethylase 6B) is
a protein-coding gene. Diseases associated with
KDM6B include wiskott-aldrich syndrome, and
hodgkin's lymphoma. GO annotations related to
this gene include oxidoreductase activity, acting
on single donors with incorporation of molecular
oxygen, incorporation of two atoms of oxygen
and sequence-specific DNA binding. An
important paralog of this gene is UTY.
The protein encoded by this gene is a member of
the kinesin family and functions as an
anterograde motor protein that transports
membranous organelles along axonal
microtubules. Mutations at this locus have been
associated with spastic paraplegia-30 and
LARP7
La ribonucleoprotein
domain family, member 7
LAS1L
LAS1-like (S. cerevisiae)
LMAN2L
lectin, mannose-binding 2like
MAN1B1
mannosidase, alpha, class
1B, member 1
MAOA
monoamine oxidase A
MAPK10
mitogen-activated protein
kinase 10
hereditary sensory neuropathy IIC. Alternatively
spliced transcript variants encoding distinct
isoforms have been described. (provided by
RefSeq, Apr 2012)
This gene encodes a protein which is found in the
7SK snRNP (small nuclear ribonucleoprotein).
This snRNP complex inhibits a cyclin-dependent
kinase, positive transcription elongation factor b,
which is required for paused RNA polymerase II
at a promoter to begin transcription elongation. A
pseudogene of this gene is located on
chromosome 3. Alternative splicing results in
multiple transcript variants. (provided by RefSeq,
May 2012)
GeneCards Summary: LAS1L (LAS1-like (S.
cerevisiae)) is a protein-coding gene. Diseases
associated with LAS1L include pancreatic
cancer, and pancreatitis.
GeneCards Summary: LMAN2L (lectin,
mannose-binding 2-like) is a protein-coding
gene, and is affiliated with the lncRNA class.
Diseases associated with LMAN2L include
detrusor sphincter dyssynergia, and bipolar
disorder. GO annotations related to this gene
include mannose binding and metal ion binding.
An important paralog of this gene is LMAN1.
This gene encodes an enzyme belonging to the
glycosyl hydrolase 47 family. This enzyme
functions in N-glycan biosynthesis, and is a class
I alpha-1,2-mannosidase that specifically
converts Man9GlcNAc to Man8GlcNAc isomer
B. It is required for N-glycan trimming to Man56GlcNAc2 in the endoplasmic-reticulumassociated degradation pathway. Mutations in
this gene cause autosomal-recessive intellectual
disability. Alternative splicing results in multiple
transcript variants. A related pseudogene has
been identified on chromosome 11. (provided by
RefSeq, Dec 2011)
This gene is one of two neighboring gene family
members that encode mitochondrial enzymes
which catalyze the oxidative deamination of
amines, such as dopamine, norepinephrine, and
serotonin. Mutation of this gene results in
Brunner syndrome. This gene has also been
associated with a variety of other psychiatric
disorders, including antisocial behavior.
Alternatively spliced transcript variants encoding
multiple isoforms have been observed. (provided
by RefSeq, Jul 2012)
The protein encoded by this gene is a member of
the MAP kinase family. MAP kinases act as an
integration point for multiple biochemical
signals, and are involved in a wide variety of
cellular processes such as proliferation,
differentiation, transcription regulation and
MBD5
methyl-CpG binding
domain protein 5
MBTPS2
membrane-bound
transcription factor
peptidase, site 2
MCPH1
microcephalin 1
MECP2
methyl CpG binding
protein 2 (Rett syndrome)
development. This protein is a neuronal-specific
form of c-Jun N-terminal kinases (JNKs).
Through its phosphorylation and nuclear
localization, this kinase plays regulatory roles in
the signaling pathways during neuronal
apoptosis. Beta-arrestin 2, a receptor-regulated
MAP kinase scaffold protein, is found to interact
with, and stimulate the phosphorylation of this
kinase by MAP kinase kinase 4 (MKK4). Cyclindependent kianse 5 can phosphorylate, and
inhibit the activity of this kinase, which may be
important in preventing neuronal apoptosis. Four
alternatively spliced transcript variants encoding
distinct isoforms have been reported. (provided
by RefSeq, Jul 2008)
This gene encodes a member of the methyl-CpGbinding domain (MBD) family. The MBD
consists of about 70 residues and is the minimal
region required for a methyl-CpG-binding
protein binding specifically to methylated DNA.
In addition to the MBD domain, this protein
contains a PWWP domain (Pro-Trp-Trp-Pro
motif), which consists of 100-150 amino acids
and is found in numerous proteins that are
involved in cell division, growth and
differentiation. Mutations in this gene cause
mental retardation autosomal dominant type 1.
Haploinsufficiency of this gene is associated with
a syndrome involving microcephaly, intellectual
disabilities, severe speech impairment, and
seizures. Alternatively spliced transcript variants
have been found, but their full-length nature is
not determined. (provided by RefSeq, Mar 2010)
This gene encodes a intramembrane zinc
metalloprotease, which is essential in
development. This protease functions in the
signal protein activation involved in sterol
control of transcription and the ER stress
response. Mutations in this gene have been
associated with ichthyosis follicularis with
atrichia and photophobia (IFAP syndrome); IFAP
syndrome has been quantitatively linked to a
reduction in cholesterol homeostasis and ER
stress response.(provided by RefSeq, Aug 2009)
This gene encodes a DNA damage response
protein. The encoded protein may play a role in
G2/M checkpoint arrest via maintenance of
inhibitory phosphorylation of cyclin-dependent
kinase 1. Mutations in this gene have been
associated with primary autosomal recessive
microcephaly 1 and premature chromosome
condensation syndrome. Alternatively spliced
transcript variants have been described. (provided
by RefSeq, Feb 2010)
DNA methylation is the major modification of
eukaryotic genomes and plays an essential role in
MED13L
mediator complex subunit
13-like
MEF2C
myocyte enhancer factor
2C
NCK2
NCK adaptor protein 2
NDST1
N-deacetylase/Nsulfotransferase (heparan
glucosaminyl) 1
mammalian development. Human proteins
MECP2, MBD1, MBD2, MBD3, and MBD4
comprise a family of nuclear proteins related by
the presence in each of a methyl-CpG binding
domain (MBD). Each of these proteins, with the
exception of MBD3, is capable of binding
specifically to methylated DNA. MECP2, MBD1
and MBD2 can also repress transcription from
methylated gene promoters. In contrast to other
MBD family members, MECP2 is X-linked and
subject to X inactivation. MECP2 is dispensible
in stem cells, but is essential for embryonic
development. MECP2 gene mutations are the
cause of most cases of Rett syndrome, a
progressive neurologic developmental disorder
and one of the most common causes of mental
retardation in females. (provided by RefSeq, Jul
2009)
The protein encoded by this gene is a subunit of
the Mediator complex, a large complex of
proteins that functions as a transcriptional
coactivator for most RNA polymerase IItranscribed genes. The encoded protein is
involved in early development of the heart and
brain. Defects in this gene are a cause of
transposition of the great arteries, dextro-looped
(DTGA).(provided by RefSeq, Jul 2010)
This locus encodes a member of the MADS box
transcription enhancer factor 2 (MEF2) family of
proteins, which play a role in myogenesis. The
encoded protein, MEF2 polypeptide C, has both
trans-activating and DNA binding activities. This
protein may play a role in maintaining the
differentiated state of muscle cells. Mutations
and deletions at this locus have been associated
with severe mental retardation, stereotypic
movements, epilepsy, and cerebral malformation.
Alternatively spliced transcript variants have
been described. (provided by RefSeq, Jul 2010)
This gene encodes a member of the NCK family
of adaptor proteins. The protein contains three
SH3 domains and one SH2 domain. The protein
has no known catalytic function but has been
shown to bind and recruit various proteins
involved in the regulation of receptor protein
tyrosine kinases. It is through these regulatory
activities that this protein is believed to be
involved in cytoskeletal reorganization. Alternate
transcriptional splice variants, encoding different
isoforms, have been characterized. (provided by
RefSeq, Jul 2008)
NDST1 (N-deacetylase/N-sulfotransferase
(heparan glucosaminyl) 1) is a protein-coding
gene. Diseases associated with NDST1 include
treacher collins syndrome, and goldenhar
syndrome, and among its related super-pathways
NLGN4X
neuroligin 4, X-linked
NSDHL
NAD(P) dependent steroid
dehydrogenase-like
NSUN2
NOP2/Sun RNA
methyltransferase family,
member 2
OPHN1
oligophrenin 1
PAFAH1B1
platelet-activating factor
acetylhydrolase 1b,
regulatory subunit 1
(45kDa)
are Glycosaminoglycan biosynthesis - heparan
sulfate / heparin and Metabolic pathways. GO
annotations related to this gene include [heparan
sulfate]-glucosamine N-sulfotransferase activity
and deacetylase activity. An important paralog of
this gene is HS3ST2.
This gene encodes a member of the type-B
carboxylesterase/lipase protein family. The
encoded protein belongs to a family of neuronal
cell surface proteins. Members of this family may
act as splice site-specific ligands for betaneurexins and may be involved in the formation
and remodeling of central nervous system
synapses. The encoded protein interacts with
discs large homolog 4 (DLG4). Mutations in this
gene have been associated with autism and
Asperger syndrome. Alternative splicing results
in multiple transcript variants. (provided by
RefSeq, Aug 2013)
The protein encoded by this gene is localized in
the endoplasmic reticulum and is involved in
cholesterol biosynthesis. Mutations in this gene
are associated with CHILD syndrome, which is a
X-linked dominant disorder of lipid metabolism
with disturbed cholesterol biosynthesis, and
typically lethal in males. Alternatively spliced
transcript variants with differing 5' UTR have
been found for this gene. (provided by RefSeq,
Jul 2008)
This gene encodes a methyltransferase that
catalyzes the methylation of cytosine to 5methylcytosine (m5C) at position 34 of introncontaining tRNA(Leu)(CAA) precursors. This
modification is necessary to stabilize the
anticodon-codon pairing and correctly translate
the mRNA. Alternatively spliced transcript
variants encoding different isoforms have been
noted for this gene.(provided by RefSeq, Mar
2011)
This gene encodes a Rho-GTPase-activating
protein that promotes GTP hydrolysis of Rho
subfamily members. Rho proteins are important
mediators of intracellular signal transduction,
which affects cell migration and cell
morphogenesis. Mutations in this gene are
responsible for OPHN1-related X-linked mental
retardation with cerebellar hypoplasia and
distinctive facial dysmorhphism. (provided by
RefSeq, Jul 2008)
This locus was identified as encoding a gene that
when mutated or lost caused the lissencephaly
associated with Miller-Dieker lissencephaly
syndrome. This gene encodes the non-catalytic
alpha subunit of the intracellular Ib isoform of
platelet-activating factor acteylhydrolase, a
heterotrimeric enzyme that specifically catalyzes
PAK3
p21 protein (Cdc42/Rac)activated kinase 3
PARP1
poly (ADP-ribose)
polymerase 1
PECR
peroxisomal trans-2-enoylCoA reductase
PHF6
PHD finger protein 6
the removal of the acetyl group at the SN-2
position of platelet-activating factor (identified as
1-O-alkyl-2-acetyl-sn-glyceryl-3phosphorylcholine). Two other isoforms of
intracellular platelet-activating factor
acetylhydrolase exist: one composed of multiple
subunits, the other, a single subunit. In addition, a
single-subunit isoform of this enzyme is found in
serum. (provided by RefSeq, Apr 2009)
PAK proteins are critical effectors that link Rho
GTPases to cytoskeleton reorganization and
nuclear signaling. PAK proteins, a family of
serine/threonine p21-activating kinases, serve as
targets for the small GTP binding proteins Cdc42
and RAC and have been implicated in a wide
range of biological activities. The protein
encoded by this gene forms an activated complex
with GTP-bound RAS-like (P21), CDC2 and
RAC1 proteins which then catalyzes a variety of
targets. This protein may be necessary for
dendritic development and for the rapid
cytoskeletal reorganization in dendritic spines
associated with synaptic plasticity. Defects in this
gene are the cause of non-syndromic mental
retardation X-linked type 30 (MRX30), also
called X-linked mental retardation type 47
(MRX47). Alternatively spliced transcript
variants encoding different isoforms have been
identified. (provided by RefSeq, Jul 2008)
This gene encodes a chromatin-associated
enzyme, poly(ADP-ribosyl)transferase, which
modifies various nuclear proteins by poly(ADPribosyl)ation. The modification is dependent on
DNA and is involved in the regulation of various
important cellular processes such as
differentiation, proliferation, and tumor
transformation and also in the regulation of the
molecular events involved in the recovery of cell
from DNA damage. In addition, this enzyme may
be the site of mutation in Fanconi anemia, and
may participate in the pathophysiology of type I
diabetes. (provided by RefSeq, Jul 2008)
PECR (peroxisomal trans-2-enoyl-CoA
reductase) is a protein-coding gene. Diseases
associated with PECR include alcoholism, and
hirschsprung's disease, and among its related
super-pathways are Fatty acid elongation and
Fatty Acid Beta Oxidation. GO annotations
related to this gene include 2,4-dienoyl-CoA
reductase (NADPH) activity and nucleotide
binding. An important paralog of this gene is
HPGD.
This gene is a member of the plant homeodomain
(PHD)-like finger (PHF) family. It encodes a
protein with two PHD-type zinc finger domains,
indicating a potential role in transcriptional
PHF8
PHD finger protein 8
POLR3B
polymerase (RNA) III
(DNA directed)
polypeptide B
PQBP1
polyglutamine binding
protein 1
PRMT10
protein arginine
methyltransferase 10
(putative)
PRSS12
protease, serine, 12
(neurotrypsin, motopsin)
regulation, that localizes to the nucleolus.
Mutations affecting the coding region of this
gene or the splicing of the transcript have been
associated with Borjeson-Forssman-Lehmann
syndrome (BFLS), a disorder characterized by
mental retardation, epilepsy, hypogonadism,
hypometabolism, obesity, swelling of
subcutaneous tissue of the face, narrow palpebral
fissures, and large ears. Alternate splicing results
in multiple transcript variants, encoding different
isoforms. (provided by RefSeq, Jun 2010)
The protein encoded by this gene is a histone
lysine demethylase that preferentially acts on
histones in the monomethyl or dimethyl states.
The encoded protein requires Fe(2+) ion, 2oxoglutarate, and oxygen for its catalytic activity.
Defects in this gene are a cause of mental
retardation syndromic X-linked Siderius type
(MRXSSD). Four transcript variants encoding
different isoforms have been found for this gene.
(provided by RefSeq, May 2010)
This gene encodes the second largest subunit of
RNA polymerase III, the polymerase responsible
for synthesizing transfer and small ribosomal
RNAs in eukaryotes. The largest subunit and the
encoded protein form the catalytic center of RNA
polymerase III. Mutations in this gene are a cause
of hypomyelinating leukodystrophy.
Alternatively spliced transcript variants encoding
multiple isoforms have been observed for this
gene. (provided by RefSeq, Dec 2011)
This gene encodes a nuclear polyglutaminebinding protein that is involved with transcription
activation. The encoded protein contains a WW
domain. Mutations in this gene have been found
in patients with Renpenning syndrome 1 and
other syndromes with X-linked mental
retardation. Multiple alternatively spliced
transcript variants that encode different protein
isoforms have been described for this
gene.(provided by RefSeq, Nov 2009)
GeneCards Summary: PRMT10 (protein
arginine methyltransferase 10 (putative)) is a
protein-coding gene. Diseases associated with
PRMT10 include hypertrichosis, and spina
bifida. GO annotations related to this gene
include protein methyltransferase activity. An
important paralog of this gene is PRMT7.
This gene encodes a member of the trypsin
family of serine proteases. Studies in mouse
suggest that the encoded enzyme may be
involved in structural reorganizations associated
with learning and memory. The enzyme is also
expressed in Leydig cells in the testis, but its
function in this tissue is unknown. Defects in this
gene are a cause of mental retardation autosomal
PTCH2
patched 2
PTCHD1
patched domain containing
1
RAI1
retinoic acid induced 1
RALGDS
ral guanine nucleotide
dissociation stimulator
RGS7
regulator of G-protein
signaling 7
RLIM
ring finger protein, LIM
domain interacting
recessive type 1 (MRT1). (provided by RefSeq,
Jul 2010)
This gene encodes a transmembrane receptor of
the patched gene family. The encoded protein
may function as a tumor suppressor in the
hedgehog signaling pathway. Alterations in this
gene have been associated with nevoid basal cell
carcinoma syndrome, basal cell carcinoma,
medulloblastoma, and susceptibility to congenital
macrostomia. Alternatively spliced transcript
variants have been described.(provided by
RefSeq, Oct 2009)
This gene encodes a membrane protein with a
patched domain. The encoded protein is similar
to Drosophila proteins which act as receptors for
the morphogen sonic hedgehog. Deletions in this
gene, which is located on the X chromosome, are
associated with intellectual disability and autism
(PMID: 21091464, PMID: 20844286). (provided
by RefSeq, Aug 2011)
This gene is located within the Smith-Magenis
syndrome region on chromosome 17. It is highly
similar to its mouse counterpart and is expressed
at high levels mainly in neuronal tissues. The
protein encoded by this gene includes a
polymorphic polyglutamine tract in the Nterminal domain. Expression of the mouse
counterpart in neurons is induced by retinoic
acid. This gene is associated with both the
severity of the phenotype and the response to
medication in schizophrenic patients. (provided
by RefSeq, Jul 2008)
Guanine nucleotide dissociation stimulators
(GDSs, or exchange factors), such as RALGDS,
are effectors of Ras-related GTPases (see MIM
190020) that participate in signaling for a variety
of cellular processes.(supplied by OMIM, Nov
2010)
GeneCards Summary: RGS7 (regulator of Gprotein signaling 7) is a protein-coding gene.
Diseases associated with RGS7 include
agoraphobia, and panic disorder, and among its
related super-pathways are G-AlphaQ Signaling
and Myometrial Relaxation and Contraction
Pathways. GO annotations related to this gene
include G-protein beta-subunit binding and signal
transducer activity. An important paralog of this
gene is RGS14.
The protein encoded by this gene is a RING-H2
zinc finger protein. It has been shown to be an E3
ubiquitin protein ligase that targets LIM domain
binding 1 (LDB1/CLIM), and causes
proteasome-dependent degradation of LDB1.
This protein and LDB1 are co-repressors of
LHX1/LIM-1, a homeodomain transcription
factor. Multiple alternatively spliced variants,
RPL10
ribosomal protein L10
SARS
seryl-tRNA synthetase
SCAPER
S-phase cyclin Aassociated protein in the
ER
SETBP1
SET binding protein 1
encoding the same protein, have been identified.
(provided by RefSeq, Feb 2009)
Ribosomes, the organelles that catalyze protein
synthesis, consist of a small 40S subunit and a
large 60S subunit. Together these subunits are
composed of four RNA species and
approximately 80 structurally distinct proteins.
This gene encodes a ribosomal protein that is a
component of the 60S subunit. The protein
belongs to the L10E family of ribosomal
proteins. It is located in the cytoplasm. In vitro
studies have shown that the chicken protein can
bind to c-Jun and can repress c-Jun-mediated
transcriptional activation, but these activities
have not been demonstrated in vivo. This gene
was initially identified as a candidate for a Wilms
tumor suppressor gene, but later studies
determined that this gene is not involved in the
suppression of Wilms tumor. This gene has been
referred to as 'laminin receptor homolog' because
a chimeric transcript consisting of sequence from
this gene and sequence from the laminin receptor
gene was isolated; however, it is not believed that
this gene encodes a laminin receptor. Alternative
splicing results in multiple transcript variants.
This gene also uses multiple polyA signals, with
the 3'-most polyA signal overlapping the
deoxyribonuclease I-like 1 gene on the opposite
strand. This gene is co-transcribed with the small
nucleolar RNA gene U70, which is located in its
fifth intron. As is typical for genes encoding
ribosomal proteins, there are multiple processed
pseudogenes of this gene dispersed through the
genome. (provided by RefSeq, Feb 2012)
This gene belongs to the class II amino-acyl
tRNA family. The encoded enzyme catalyzes the
transfer of L-serine to tRNA (Ser) and is related
to bacterial and yeast counterparts. Multiple
alternatively spliced transcript variants have been
described but the biological validity of all
variants is unknown. (provided by RefSeq, Jul
2010)
GeneCards Summary: SCAPER (S-phase cyclin
A-associated protein in the ER) is a proteincoding gene. Diseases associated with SCAPER
include composite lymphoma, and fanconi's
anemia. GO annotations related to this gene
include zinc ion binding.
This gene encodes a protein which contains a
several motifs including a ski homology region
and a SET-binding region in addition to three
nuclear localization signals. The encoded protein
has been shown to bind the SET nuclear
oncogene which is involved in DNA replication.
Mutations in this gene are associated with
Schinzel-Giedion midface retraction syndrome.
SHANK2
SH3 and multiple ankyrin
repeat domains 2
SHANK3
SH3 and multiple ankyrin
repeat domains 3
SIM1
single-minded homolog 1
(Drosophila)
Multiple transcript variants encoding different
isoforms have been found for this gene.
(provided by RefSeq, Aug 2011)
This gene encodes a protein that is a member of
the Shank family of synaptic proteins that may
function as molecular scaffolds in the
postsynaptic density (PSD). Shank proteins
contain multiple domains for protein-protein
interaction, including ankyrin repeats, an SH3
domain, a PSD-95/Dlg/ZO-1 domain, a sterile
alpha motif domain, and a proline-rich region.
This particular family member contains a PDZ
domain, a consensus sequence for cortactin SH3
domain-binding peptides and a sterile alpha
motif. The alternative splicing demonstrated in
Shank genes has been suggested as a mechanism
for regulating the molecular structure of Shank
and the spectrum of Shank-interacting proteins in
the PSDs of adult and developing brain. Two
alternative splice variants, encoding distinct
isoforms, are reported. Additional splice variants
exist but their full-length nature has not been
determined. (provided by RefSeq, Jul 2008)
This gene is a member of the Shank gene family.
Shank proteins are multidomain scaffold proteins
of the postsynaptic density that connect
neurotransmitter receptors, ion channels, and
other membrane proteins to the actin
cytoskeleton and G-protein-coupled signaling
pathways. Shank proteins also play a role in
synapse formation and dendritic spine
maturation. Mutations in this gene are a cause of
autism spectrum disorder (ASD), which is
characterized by impairments in social
interaction and communication, and restricted
behavioral patterns and interests. Mutations in
this gene also cause schizophrenia type 15, and
are a major causative factor in the neurological
symptoms of 22q13.3 deletion syndrome, which
is also known as Phelan-McDermid syndrome.
Additional isoforms have been described for this
gene but they have not yet been experimentally
verified. (provided by RefSeq, Mar 2012)
SIM1 and SIM2 genes are Drosophila singleminded (sim) gene homologs. SIM1 transcript
was detected only in fetal kidney out of various
adult and fetal tissues tested. Since the sim gene
plays an important role in Drosophila
development and has peak levels of expression
during the period of neurogenesis,it was
proposed that the human SIM gene is a candidate
for involvement in certain dysmorphic features
(particularly the facial and skull characteristics),
abnormalities of brain development, and/or
mental retardation of Down syndrome. (provided
by RefSeq, Jul 2008)
SLC16A2
SLC2A1
SLC31A1
SLC6A8
SLC9A6
SNAP25
solute carrier family 16,
member 2 (thyroid
hormone transporter)
This gene encodes an integral membrane protein
that functions as a transporter of thyroid
hormone. The encoded protein facilitates the
cellular importation of thyroxine (T4),
triiodothyronine (T3), reverse triiodothyronine
(rT3) and diidothyronine (T2). This gene is
expressed in many tissues and likely plays an
important role in the development of the central
nervous system. Loss of function mutations in
this gene are associated with psychomotor
retardation in males while females exhibit no
neurological defects and more moderate thyroiddeficient phenotypes. This gene is subject to Xchromosome inactivation. Mutations in this gene
are the cause of Allan-Herndon-Dudley
syndrome. (provided by RefSeq, Mar 2012)
solute carrier family 2
This gene encodes a major glucose transporter in
(facilitated glucose
the mammalian blood-brain barrier. The encoded
transporter), member 1
protein is found primarily in the cell membrane
and on the cell surface, where it can also function
as a receptor for human T-cell leukemia virus
(HTLV) I and II. Mutations in this gene have
been found in a family with paroxysmal exertioninduced dyskinesia. (provided by RefSeq, Apr
2013)
solute carrier family 31
The protein encoded by this gene is a high(copper transporter),
affinity copper transporter found in the cell
member 1
membrane. The encoded protein functions as a
homotrimer to effect the uptake of dietary
copper. (provided by RefSeq, Aug 2011)
solute carrier family 6
The protein encoded by this gene is a plasma
(neurotransmitter
membrane protein whose function is to transport
transporter), member 8
creatine into and out of cells. Defects in this gene
can result in X-linked creatine deficiency
syndrome. Multiple transcript variants encoding
different isoforms have been found for this gene.
(provided by RefSeq, Dec 2008)
solute carrier family 9,
This gene encodes a sodium-hydrogen exchanger
subfamily A (NHE6, cation that is amember of the solute carrier family 9.
proton antiporter 6),
The encoded protein localizes to early and
member 6
recycling endosomes and may be involved in
regulating endosomal pH and volume. Defects in
this gene are associated with X-linked syndromic
mental retardation, Christianson type. Alternate
splicing results in multiple transcript
variants.(provided by RefSeq, Apr 2010)
synaptosomal-associated
Synaptic vesicle membrane docking and fusion is
protein, 25kDa
mediated by SNAREs (soluble Nethylmaleimide-sensitive factor attachment
protein receptors) located on the vesicle
membrane (v-SNAREs) and the target membrane
(t-SNAREs). The assembled v-SNARE/t-SNARE
complex consists of a bundle of four helices, one
of which is supplied by v-SNARE and the other
three by t-SNARE. For t-SNAREs on the plasma
membrane, the protein syntaxin supplies one
SNAP29
synaptosomal-associated
protein, 29kDa
SNRPN
small nuclear
ribonucleoprotein
polypeptide N
SOX3
SRY (sex determining
region Y)-box 3
helix and the protein encoded by this gene
contributes the other two. Therefore, this gene
product is a presynaptic plasma membrane
protein involved in the regulation of
neurotransmitter release. Two alternative
transcript variants encoding different protein
isoforms have been described for this gene.
(provided by RefSeq, Jul 2008)
This gene, a member of the SNAP25 gene
family, encodes a protein involved in multiple
membrane trafficking steps. Two other members
of this gene family, SNAP23 and SNAP25,
encode proteins that bind a syntaxin protein and
mediate synaptic vesicle membrane docking and
fusion to the plasma membrane. The protein
encoded by this gene binds tightly to multiple
syntaxins and is localized to intracellular
membrane structures rather than to the plasma
membrane. While the protein is mostly
membrane-bound, a significant fraction of it is
found free in the cytoplasm. Use of multiple
polyadenylation sites has been noted for this
gene. (provided by RefSeq, Jul 2008)
The protein encoded by this gene is one
polypeptide of a small nuclear ribonucleoprotein
complex and belongs to the snRNP SMB/SMN
family. The protein plays a role in pre-mRNA
processing, possibly tissue-specific alternative
splicing events. Although individual snRNPs are
believed to recognize specific nucleic acid
sequences through RNA-RNA base pairing, the
specific role of this family member is unknown.
The protein arises from a bicistronic transcript
that also encodes a protein identified as the
SNRPN upstream reading frame (SNURF).
Multiple transcription initiation sites have been
identified and extensive alternative splicing
occurs in the 5' untranslated region. Additional
splice variants have been described but sequences
for the complete transcripts have not been
determined. The 5' UTR of this gene has been
identified as an imprinting center. Alternative
splicing or deletion caused by a translocation
event in this paternally-expressed region is
responsible for Angelman syndrome or PraderWilli syndrome due to parental imprint switch
failure. (provided by RefSeq, Jul 2008)
This gene encodes a member of the SOX (SRYrelated HMG-box) family of transcription factors
involved in the regulation of embryonic
development and in the determination of the cell
fate. The encoded protein may act as a
transcriptional regulator after forming a protein
complex with other proteins. Mutations in this
gene have been associated with X-linked mental
retardation with growth hormone deficiency.
ST3GAL3
ST3 beta-galactoside
alpha-2,3-sialyltransferase
3
STIL
SCL/TAL1 interrupting
locus
STXBP1
syntaxin binding protein 1
SYN1
synapsin I
(provided by RefSeq, Jul 2008)
The protein encoded by this gene is a type II
membrane protein that catalyzes the transfer of
sialic acid from CMP-sialic acid to galactosecontaining substrates. The encoded protein is
normally found in the Golgi apparatus but can be
proteolytically processed to a soluble form. This
protein is a member of glycosyltransferase family
29. Mutations in this gene have been associated
with autosomal recessive nonsymdromic mental
retardation-12 (MRT12). Multiple transcript
variants encoding several different isoforms have
been found for this gene. (provided by RefSeq,
Jul 2012)
This gene encodes a cytoplasmic protein
implicated in regulation of the mitotic spindle
checkpoint, a regulatory pathway that monitors
chromosome segregation during cell division to
ensure the proper distribution of chromosomes to
daughter cells. The protein is phosphorylated in
mitosis and in response to activation of the
spindle checkpoint, and disappears when cells
transition to G1 phase. It interacts with a mitotic
regulator, and its expression is required to
efficiently activate the spindle checkpoint. It is
proposed to regulate Cdc2 kinase activity during
spindle checkpoint arrest. Chromosomal
deletions that fuse this gene and the adjacent
locus commonly occur in T cell leukemias, and
are thought to arise through illegitimate V-(D)-J
recombination events. Multiple transcript
variants encoding different isoforms have been
found for this gene. (provided by RefSeq, Jul
2008)
This gene encodes a syntaxin-binding protein.
The encoded protein appears to play a role in
release of neurotransmitters via regulation of
syntaxin, a transmembrane attachment protein
receptor. Mutations in this gene have been
associated with infantile epileptic
encephalopathy-4. Alternatively spliced
transcript variants have been described. (provided
by RefSeq, Feb 2010)
This gene is a member of the synapsin gene
family. Synapsins encode neuronal
phosphoproteins which associate with the
cytoplasmic surface of synaptic vesicles. Family
members are characterized by common protein
domains, and they are implicated in
synaptogenesis and the modulation of
neurotransmitter release, suggesting a potential
role in several neuropsychiatric diseases. This
member of the synapsin family plays a role in
regulation of axonogenesis and synaptogenesis.
The protein encoded serves as a substrate for
several different protein kinases and
SYNGAP1
synaptic Ras GTPase
activating protein 1
SYP
synaptophysin
TAF2
TAF2 RNA polymerase II,
TATA box binding protein
(TBP)-associated factor,
150kDa
TCF4
transcription factor 4
phosphorylation may function in the regulation of
this protein in the nerve terminal. Mutations in
this gene may be associated with X-linked
disorders with primary neuronal degeneration
such as Rett syndrome. Alternatively spliced
transcript variants encoding different isoforms
have been identified. (provided by RefSeq, Jul
2008)
The protein encoded by this gene is a major
component of the postsynaptic density (PSD), a
group of proteins found associated with NMDA
receptors at synapses. The encoded protein is
phosphorylated by calmodulin-dependent protein
kinase II and dephosphorylated by NMDA
receptor activation. Defects in this gene are a
cause of mental retardation autosomal dominant
type 5 (MRD5). (provided by RefSeq, Dec 2009)
This gene encodes an integral membrane protein
of small synaptic vesicles in brain and endocrine
cells. The protein also binds cholesterol and is
thought to direct targeting of vesicle-associated
membrane protein 2 (synaptobrevin) to
intracellular compartments. Mutations in this
gene are associated with X-linked mental
retardation (XLMR). (provided by RefSeq, Aug
2011)
Initiation of transcription by RNA polymerase II
requires the activities of more than 70
polypeptides. The protein that coordinates these
activities is transcription factor IID (TFIID),
which binds to the core promoter to position the
polymerase properly, serves as the scaffold for
assembly of the remainder of the transcription
complex, and acts as a channel for regulatory
signals. TFIID is composed of the TATA-binding
protein (TBP) and a group of evolutionarily
conserved proteins known as TBP-associated
factors or TAFs. TAFs may participate in basal
transcription, serve as coactivators, function in
promoter recognition or modify general
transcription factors (GTFs) to facilitate complex
assembly and transcription initiation. This gene
encodes one of the larger subunits of TFIID that
is stably associated with the TFIID complex. It
contributes to interactions at and downstream of
the transcription initiation site, interactions that
help determine transcription complex response to
activators. (provided by RefSeq, Jul 2008)
This gene encodes transcription factor 4, a basic
helix-loop-helix transcription factor. The
encoded protein recognizes an Ephrussi-box ('Ebox') binding site ('CANNTG') - a motif first
identified in immunoglobulin enhancers. This
gene is broadly expressed, and may play an
important role in nervous system development.
Defects in this gene are a cause of Pitt-Hopkins
TMEM135
transmembrane protein 135
TRAPPC9
trafficking protein particle
complex 9
TRMT1
tRNA methyltransferase 1
homolog (S. cerevisiae)
TSPAN7
tetraspanin 7
TUBA1A
tubulin, alpha 1a
syndrome. Multiple alternatively spliced
transcript variants that encode different proteins
have been described. (provided by RefSeq, Aug
2011)
GeneCards Summary: TMEM135
(transmembrane protein 135) is a protein-coding
gene, and is affiliated with the lncRNA class.
This gene encodes a protein that likely plays a
role in NF-kappa-B signaling. Mutations in this
gene have been associated with autosomalrecessive mental retardation. Alternatively
spliced transcript variants have been
described.(provided by RefSeq, Feb 2010)
GeneCards Summary: TRMT1 (tRNA
methyltransferase 1 homolog (S. cerevisiae)) is a
protein-coding gene. GO annotations related to
this gene include RNA binding and tRNA
(guanine-N2-)-methyltransferase activity. An
important paralog of this gene is TRMT1L.
The protein encoded by this gene is a member of
the transmembrane 4 superfamily, also known as
the tetraspanin family. Most of these members
are cell-surface proteins that are characterized by
the presence of four hydrophobic domains. The
proteins mediate signal transduction events that
play a role in the regulation of cell development,
activation, growth and motility. This encoded
protein is a cell surface glycoprotein and may
have a role in the control of neurite outgrowth. It
is known to complex with integrins. This gene is
associated with X-linked mental retardation and
neuropsychiatric diseases such as Huntington's
chorea, fragile X syndrome and myotonic
dystrophy. (provided by RefSeq, Jul 2008)
Microtubules of the eukaryotic cytoskeleton
perform essential and diverse functions and are
composed of a heterodimer of alpha and beta
tubulins. The genes encoding these microtubule
constituents belong to the tubulin superfamily,
which is composed of six distinct families. Genes
from the alpha, beta and gamma tubulin families
are found in all eukaryotes. The alpha and beta
tubulins represent the major components of
microtubules, while gamma tubulin plays a
critical role in the nucleation of microtubule
assembly. There are multiple alpha and beta
tubulin genes, which are highly conserved among
species. This gene encodes alpha tubulin and is
highly similar to the mouse and rat Tuba1 genes.
Northern blotting studies have shown that the
gene expression is predominantly found in
morphologically differentiated neurologic cells.
This gene is one of three alpha-tubulin genes in a
cluster on chromosome 12q. Mutations in this
gene cause lissencephaly type 3 (LIS3) - a
neurological condition characterized by
TUBA8
tubulin, alpha 8
TUSC3
tumor suppressor candidate
3
UBE2A
ubiquitin-conjugating
enzyme E2A
UBE3A
ubiquitin protein ligase
E3A
UBR7
ubiquitin protein ligase E3
microcephaly, mental retardation, and early-onset
epilepsy and caused by defective neuronal
migration. Alternative splicing results in multiple
transcript variants encoding distinct isoforms.
(provided by RefSeq, Jul 2012)
This gene encodes a member of the alpha tubulin
protein family. Alpha tubulins are one of two
core protein families (alpha and beta tubulins)
that heterodimerize and assemble to form
microtubules. Mutations in this gene are
associated with polymicrogyria and optic nerve
hypoplasia. Alternate splicing results in multiple
transcript variants. (provided by RefSeq, Jul
2010)
This gene is a candidate tumor suppressor gene.
It is located within a homozygously deleted
region of a metastatic prostate cancer. The gene
is expressed in most nonlymphoid human tissues
including prostate, lung, liver, and colon.
Expression was also detected in many epithelial
tumor cell lines. Two transcript variants encoding
distinct isoforms have been identified for this
gene. (provided by RefSeq, Jul 2008)
The modification of proteins with ubiquitin is an
important cellular mechanism for targeting
abnormal or short-lived proteins for degradation.
Ubiquitination involves at least three classes of
enzymes: ubiquitin-activating enzymes,
ubiquitin-conjugating enzymes, and ubiquitinprotein ligases. This gene encodes a member of
the E2 ubiquitin-conjugating enzyme family.
This enzyme is required for post-replicative DNA
damage repair, and may play a role in
transcriptional regulation. Mutations in this gene
are associated with mental retardation.
Alternative splicing results in multiple transcript
variants. (provided by RefSeq, Aug 2013)
This gene encodes an E3 ubiquitin-protein ligase,
part of the ubiquitin protein degradation system.
This imprinted gene is maternally expressed in
brain and biallelically expressed in other tissues.
Maternally inherited deletion of this gene causes
Angelman Syndrome, characterized by severe
motor and intellectual retardation, ataxia,
hypotonia, epilepsy, absence of speech, and
characteristic facies. The protein also interacts
with the E6 protein of human papillomavirus
types 16 and 18, resulting in ubiquitination and
proteolysis of tumor protein p53. Alternative
splicing of this gene results in three transcript
variants encoding three isoforms with different
N-termini. Additional transcript variants have
been described, but their full length nature has
not been determined. (provided by RefSeq, Jul
2008)
GeneCards Summary: UBR7 (ubiquitin protein
component n-recognin 7
(putative)
UPF3B
WDR45L
WDR62
WHSC1
ligase E3 component n-recognin 7 (putative)) is a
protein-coding gene, and is affiliated with the
lncRNA class. GO annotations related to this
gene include ubiquitin-protein ligase activity and
molecular_function. An important paralog of this
gene is ENSG00000259066.
UPF3 regulator of
This gene encodes a protein that is part of a postnonsense transcripts
splicing multiprotein complex involved in both
homolog B (yeast)
mRNA nuclear export and mRNA surveillance.
The encoded protein is one of two functional
homologs to yeast Upf3p. mRNA surveillance
detects exported mRNAs with truncated open
reading frames and initiates nonsense-mediated
mRNA decay (NMD). When translation ends
upstream from the last exon-exon junction, this
triggers NMD to degrade mRNAs containing
premature stop codons. This protein binds to the
mRNA and remains bound after nuclear export,
acting as a nucleocytoplasmic shuttling protein. It
forms with Y14 a complex that binds specifically
20 nt upstream of exon-exon junctions. This gene
is located on the long arm of chromosome X.
Two splice variants encoding different isoforms
have been found for this gene. (provided by
RefSeq, Jul 2008)
WD repeat domain 45B
This gene encodes a member of the WIPI or
SVP1 family of WD40 repeat-containing
proteins. The protein contains seven WD40
repeats that are thought to fold into a betapropeller structure that mediates protein-protein
interactions, and a conserved motif for
interaction with phospholipids. The human
genome contains several pseudogenes of this
gene. (provided by RefSeq, Jul 2008)
WD repeat domain 62
This gene is proposed to play a role in cerebral
cortical development. Mutations in this gene
have been associated with microencephaly,
cortical malformations, and mental retardation.
Alternative splicing results in multiple transcript
variants. (provided by RefSeq, Jan 2011)
Wolf-Hirschhorn syndrome This gene encodes a protein that contains four
candidate 1
domains present in other developmental proteins:
a PWWP domain, an HMG box, a SET domain,
and a PHD-type zinc finger. It is expressed
ubiquitously in early development. WolfHirschhorn syndrome (WHS) is a malformation
syndrome associated with a hemizygous deletion
of the distal short arm of chromosome 4. This
gene maps to the 165 kb WHS critical region and
has also been involved in the chromosomal
translocation t(4;14)(p16.3;q32.3) in multiple
myelomas. Alternative splicing of this gene
results in multiple transcript variants encoding
different isoforms. Some transcript variants are
nonsense-mediated mRNA (NMD) decay
candidates, hence not represented as reference
WHSC2
YWHAE
ZBTB40
ZCCHC12
ZCCHC8
ZDHHC9
sequences. (provided by RefSeq, Jul 2008)
negative elongation factor
This gene is expressed ubiquitously with higher
complex member A
levels in fetal than in adult tissues. It encodes a
protein sharing 93% sequence identity with the
mouse protein. Wolf-Hirschhorn syndrome
(WHS) is a malformation syndrome associated
with a hemizygous deletion of the distal short
arm of chromosome 4. This gene is mapped to
the 165 kb WHS critical region, and may play a
role in the phenotype of the WHS or Pitt-RogersDanks syndrome. The encoded protein is found
to be capable of reacting with HLA-A2-restricted
and tumor-specific cytotoxic T lymphocytes,
suggesting a target for use in specific
immunotherapy for a large number of cancer
patients. This protein has also been shown to be a
member of the NELF (negative elongation factor)
protein complex that participates in the regulation
of RNA polymerase II transcription elongation.
(provided by RefSeq, Jul 2008)
tyrosine 3This gene product belongs to the 14-3-3 family of
monooxygenase/tryptophan proteins which mediate signal transduction by
5-monooxygenase
binding to phosphoserine-containing proteins.
activation protein, epsilon
This highly conserved protein family is found in
polypeptide
both plants and mammals, and this protein is
100% identical to the mouse ortholog. It interacts
with CDC25 phosphatases, RAF1 and IRS1
proteins, suggesting its role in diverse
biochemical activities related to signal
transduction, such as cell division and regulation
of insulin sensitivity. It has also been implicated
in the pathogenesis of small cell lung cancer.
Two transcript variants, one protein-coding and
the other non-protein-coding, have been found
for this gene. (provided by RefSeq, Aug 2008)
zinc finger and BTB
GeneCards Summary: ZBTB40 (zinc finger and
domain containing 40
BTB domain containing 40) is a protein-coding
gene. GO annotations related to this gene include
DNA binding and molecular_function. An
important paralog of this gene is ZNF317.
zinc finger, CCHC domain GeneCards Summary: ZCCHC12 (zinc finger,
containing 12
CCHC domain containing 12) is a protein-coding
gene. Diseases associated with ZCCHC12
include intellectual disability, and mental
retardation. GO annotations related to this gene
include zinc ion binding and nucleic acid
binding. An important paralog of this gene is
PNMA6A.
zinc finger, CCHC domain GeneCards Summary: ZCCHC8 (zinc finger,
containing 8
CCHC domain containing 8) is a protein-coding
gene. GO annotations related to this gene include
zinc ion binding and nucleic acid binding.
zinc finger, DHHC-type
This gene encodes an integral membrane protein
containing 9
that is a member of the zinc finger DHHC
domain-containing protein family. The encoded
protein forms a complex with golgin subfamily A
ZNF526
zinc finger protein 526
ZNF621
zinc finger protein 621
ZNF711
zinc finger protein 711
member 7 and functions as a
palmitoyltransferase. This protein specifically
palmitoylates HRAS and NRAS. Mutations in
this gene are associated with X-linked mental
retardation. Alternate splicing results in multiple
transcript variants that encode the same
protein.(provided by RefSeq, May 2010)
GeneCards Summary: ZNF526 (zinc finger
protein 526) is a protein-coding gene. GO
annotations related to this gene include DNA
binding and zinc ion binding. An important
paralog of this gene is ZNF574.
GeneCards Summary: ZNF621 (zinc finger
protein 621) is a protein-coding gene. Among its
related super-pathways are Gene Expression. GO
annotations related to this gene include DNA
binding and zinc ion binding. An important
paralog of this gene is ZNF19.
This gene encodes a zinc finger protein of
unknown function. It bears similarity to a zinc
finger protein which acts as a transcriptional
activator. This gene lies in a region of the X
chromosome which has been associated with
mental retardation. (provided by RefSeq, Jul
2008)
Supplementary Figure 1. Age at time of intelligence assessment, averaged over
measurement occasions within participant, for participants whose data were used in
the polygenic risk score prediction. N=2,111 (i.e., data on age in 14 out of the total
2125 participants are missing).