NRGN

Summary

NRGN (neurogranin, HGNC:8000) is a protein-coding gene on chromosome 11q24.2, encoding Neurogranin (Q92686). Acts as a ’third messenger’ substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling.

Neurogranin (NRGN) is the human homolog of the neuron-specific rat RC3/neurogranin gene. This gene encodes a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. The NRGN gene contains four exons and three introns. The exons 1 and 2 encode the protein and exons 3 and 4 contain untranslated sequences. It is suggested that the NRGN is a direct target for thyroid hormone in human brain, and that control of expression of this gene could underlay many of the consequences of hypothyroidism on mental states during development as well as in adult subjects.

Source: NCBI Gene 4900 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_006176

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8000
Approved symbol	NRGN
Name	neurogranin
Location	11q24.2
Locus type	gene with protein product
Status	Approved
Aliases	RC3
Ensembl gene	ENSG00000154146
Ensembl biotype	protein_coding
OMIM	602350
Entrez	4900

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000284292, ENST00000412681, ENST00000893844, ENST00000943690, ENST00000943691, ENST00000943692

RefSeq mRNA: 2 — MANE Select: NM_006176 NM_001126181, NM_006176

CCDS: CCDS8451

Canonical transcript exons

ENST00000284292 — 4 exons

Exon	Start	End
ENSE00001014304	124745503	124745729
ENSE00001014306	124739942	124740099
ENSE00002182133	124746404	124747210
ENSE00002437913	124745965	124745982

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 127.6955 / max 6809.6986, expressed in 1571 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117383	113.2937	1544
117382	14.4018	1037

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	99.96	gold quality
prefrontal cortex	UBERON:0000451	99.83	gold quality
frontal pole	UBERON:0002795	99.83	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.78	gold quality
cingulate cortex	UBERON:0003027	99.74	gold quality
caudate nucleus	UBERON:0001873	99.73	gold quality
anterior cingulate cortex	UBERON:0009835	99.73	gold quality
putamen	UBERON:0001874	99.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.59	gold quality
parietal lobe	UBERON:0001872	99.57	gold quality
monocyte	CL:0000576	99.56	gold quality
orbitofrontal cortex	UBERON:0004167	99.56	gold quality
postcentral gyrus	UBERON:0002581	99.53	gold quality
amygdala	UBERON:0001876	99.49	gold quality
middle frontal gyrus	UBERON:0002702	99.45	gold quality
mononuclear cell	CL:0000842	99.42	gold quality
nucleus accumbens	UBERON:0001882	99.39	gold quality
leukocyte	CL:0000738	99.36	gold quality
superior frontal gyrus	UBERON:0002661	99.36	gold quality
frontal cortex	UBERON:0001870	99.10	gold quality
frontal lobe	UBERON:0016525	99.10	gold quality
temporal lobe	UBERON:0001871	99.08	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.05	gold quality
CA1 field of hippocampus	UBERON:0003881	99.04	gold quality
Ammon’s horn	UBERON:0001954	98.82	gold quality
granulocyte	CL:0000094	98.67	gold quality
entorhinal cortex	UBERON:0002728	98.47	gold quality
right frontal lobe	UBERON:0002810	98.44	gold quality
occipital lobe	UBERON:0002021	98.40	gold quality
lateral globus pallidus	UBERON:0002476	98.36	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	17402.54
E-MTAB-9221	yes	16859.86
E-HCAD-30	yes	4112.84
E-GEOD-150728	yes	3864.05
E-HCAD-35	yes	2732.92
E-GEOD-180759	yes	2065.78
E-CURD-55	yes	1298.86
E-HCAD-32	yes	418.58
E-HCAD-25	yes	81.57
E-HCAD-4	yes	57.81
E-HCAD-10	yes	41.63
E-CURD-112	yes	33.02
E-CURD-122	yes	24.33
E-HCAD-6	yes	20.46
E-ANND-3	yes	14.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting NRGN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-564	95.85	65.01	163
HSA-MIR-4649-5P	93.02	63.85	141
HSA-MIR-6729-5P	93.02	62.76	138
HSA-MIR-6090	91.01	62.65	222

Literature-anchored findings (GeneRIF, showing 40)

• IL-2 deprivation raises the level of RC3 and other apoptotic factors, which induce apoptosis by increasing the intracellular Ca(2+) concentration (PMID:12808095)
• Nevertheless, by gel shift assays, Sp1 and Sp3 were not found to be responsible for the protein-DNA complexes formed by the GC-rich sequence. (PMID:16677608)
• Genotype distribution showed association of the rs7113041 SNP with schizophrenia in males of Portuguese origin, which was confirmed by the analysis of the proband-parent triads. (PMID:17140601)
• Data suggest that BSX is essential for global cognitive function and that haplo-insufficiency may cause severe mental retardation, and that deletion of Neurogranin contributes to the auditory attention deficit observed in most 11q- patients. (PMID:18855024)
• Elevated cerebrospinal fluid neurogranin levels together with Alzheimer disease biomarkers may reflect synaptic degeneration. (PMID:20875798)
• No association between the schizophrenia associated NRGN variant rs12807809 and cognition could be detected in these samples. (PMID:21112188)
• our study provides strong evidence that common exonic variation does not account for the genome-wide signi fi cant association between schizophrenia and variation at NRGN (PMID:21538840)
• Hippocampal activation diminished during the acquisition of contextual fear in healthy carriers of the genome-wide-supported risk variant for schizophrenia, rs12807809 in neurogranin. (PMID:21647148)
• The influence of NRGN genotype on the neural correlates of memory encoding and retrieval is manifest in the cingulate cortex and is involved in hippocampal formation. (PMID:21799211)
• The genome-wide associated genetic risk variant in the NRGN gene may be related to a small gray matter volume in the anterior cingulate cortex in the left hemisphere in patients with schizophrenia. (PMID:22253779)
• This study demonistrated that multiple rare mutations in schizophrenia, and provides genetic clues that indicate the involvement of NRGN in this disorder. (PMID:22306195)
• This study provides further evidence of the association of the NRGN gene with schizophrenia. (PMID:22461181)
• single nucleotide polymorphism located upstream of the neurogranin (NRGN) gene has been identified as a risk variant for schizophrenia. (PMID:22856365)
• Our results support an association between the NRGN gene and schizophrenia and a hypothesis that the NRGN gene may mediate the risk associated with schizophrenia via intellectual dysfunction. (PMID:23903071)
• NRGN risk variants contribute to subtle changes in neural functioning and anatomy. (PMID:24098564)
• These findings help to clarify underlying NRGN mediated pathophysiological mechanisms involving cortical-subcortical brain networks in schizophrenia. (PMID:24386483)
• Data indicate that neurogranin makes contacts with both the N- and C-domains of calmodulin that functionally leads to altered calcium binding kinetics. (PMID:24713697)
• neurogranin binds to alpha-synuclein in the human cortex, and this interaction decreases in Parkinson’s disease along with the phosphorylation of neurogranin, a molecular process thought to be involved in learning and memory (PMID:25446004)
• This report provides evidence to support larger and controlled traumatic brain injury clinical studies for NRGN validation and prediction of outcomes. (PMID:26025774)
• Within-person levels of NGRN increased in cognitively normal participants but not in patients with later stage mild cognitive impairment or Alzhiemer’s disease; NGRN may reflect presymptomatic synaptic dysfunction or loss. (PMID:26366630)
• Cerebrospinal fluid neurogranin was increased in patients with Alzheimer’s dementia, progressive mild cognitive impairment (MCI) and stable MCI compared with controls, and in Alzheimer’s dementia and progressive MCI compared with stable MCI. (PMID:26373605)
• Neurogranin and YKL-40 are promising AD biomarkers, independent of and complementary to the established core Alzheimer’s disease (AD) biomarkers, reflecting additional pathological changes in the course of AD (PMID:26698298)
• These results confirm an increase in CSF Ng concentration in patients with AD as previously reported and show that this is specific to AD and not seen in a range of other neurodegenerative diseases. (PMID:26826204)
• Polymorphisms in NRGN are associated with schizophrenia, major depressive disorder and bipolar disorder in the Han Chinese population. (PMID:26828755)
• The results of this results showed that increased CSF neurogranin levels in Alzheimer Disease. (PMID:27018940)
• associations of neuromodulin and neurogranin to Alzheimer’s disease (PMID:27604409)
• Study observed an association of rs12807809 with schizophrenia in a South Indian population. This study contributes toward the establishment of neurogranin as a susceptibility gene for schizophrenia South Indian Population. (PMID:28389239)
• The dynamics of calmodulin interactions with neurogranin and Ca(2+) /CAMKII alpha proteins has been reported. (PMID:28449373)
• Plasma neurogranin did not correlate with stroke severity. (PMID:28854881)
• This study, cross-sectional analysis showed that high CSF Ng was significantly associated with lower memory scores in pooled participants with NC and MCI. (PMID:29429972)
• Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information (PMID:29523639)
• These data support that CSF Ng is increased specifically in Alzheimer disease, that high CSF Ng concentrations likely reflect synaptic dysfunction and that CSF Ng is associated with beta-amyloid plaque pathology. (PMID:29700597)
• In first episode psychosis patients, levels of the synaptic marker CSF neurogranin appear unaltered. (PMID:30733168)
• These findings are the first to suggest an association between rs12807809 and abnormal Papez circuit function in patients with SZ. This study also implicates NRGN variation and abnormal Papez circuit function in SZ pathophysiology. (PMID:30953482)
• NRGN, S100B and GFAP levels are significantly increased in patients with structural lesions resulting from mild traumatic brain injuries. (PMID:31234132)
• Cerebrospinal fluid levels of neurogranin in Parkinsonian disorders. (PMID:31837067)
• significant association between SNP rs12807809 and schizophrenia susceptibility in Caucasians but not Asians [meta-analysis] (PMID:31861040)
• Interrelations of Alzheimer s disease candidate biomarkers neurogranin, fatty acid-binding protein 3 and ferritin to neurodegeneration and neuroinflammation. (PMID:32894885)
• Neurogranin as a Novel Biomarker in Alzheimer’s Disease. (PMID:32926148)
• The role of synaptic biomarkers in the spectrum of neurodegenerative diseases. (PMID:33028119)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrgna	ENSDARG00000039626
danio_rerio	spa17	ENSDARG00000069361
mus_musculus	Nrgn	ENSMUSG00000053310
rattus_norvegicus	Nrgn	ENSRNOG00000010688

Protein

Protein identifiers

Neurogranin — Q92686 (reviewed: Q92686)

Alternative names: RC3

All UniProt accessions (1): Q92686

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a ’third messenger’ substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. Binds to calmodulin in the absence of calcium.

Tissue specificity. In the cerebral cortex, found in the cell bodies of neurons in layers II-VI, and in apical and basal dendrites of pyramidal neurons. Is not found in the dendrites in patients with Alzheimer disease.

Post-translational modifications. Phosphorylated at Ser-36 by PHK and PKC, phosphorylation prevents interaction with Calmodulin and interrupts several learning- and memory-associated functions.

Domain organisation. Neurogranin is intrinsically unstructured; however, upon binding with CaM, The IQ domain adopts a helical conformation.

Similarity. Belongs to the neurogranin family.

RefSeq proteins (2): NP_001119653, NP_006167* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site

Pfam: PF00612

UniProt features (11 total): modified residue 4, domain 2, chain 1, peptide 1, region of interest 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92686-F1	69.72	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 38 (crucial for interaction with calmodulin)

Post-translational modifications (4): 68, 1, 36, 68

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9620244	Long-term potentiation
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-438064	Post NMDA receptor activation events
R-HSA-442755	Activation of NMDA receptors and postsynaptic events

MSigDB gene sets: 305 (showing top): RNGTGGGC_UNKNOWN, MODY_HIPPOCAMPUS_POSTNATAL, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, LFA1_Q6, GCANCTGNY_MYOD_Q6, CMYB_01, GOBP_ASSOCIATIVE_LEARNING, MODULE_45, EFC_Q6, GOBP_FOREBRAIN_DEVELOPMENT, SREBP1_02, GOBP_CELL_CELL_SIGNALING

GO Biological Process (6): signal transduction (GO:0007165), nervous system development (GO:0007399), associative learning (GO:0008306), telencephalon development (GO:0021537), postsynaptic modulation of chemical synaptic transmission (GO:0099170), positive regulation of long-term synaptic potentiation (GO:1900273)

GO Molecular Function (4): calmodulin binding (GO:0005516), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), phosphatidic acid binding (GO:0070300), protein binding (GO:0005515)

GO Cellular Component (10): cytosol (GO:0005829), trans-Golgi network transport vesicle membrane (GO:0012510), axon (GO:0030424), mitochondrial membrane (GO:0031966), neuronal cell body (GO:0043025), dendritic spine head (GO:0044327), postsynaptic membrane (GO:0045211), glutamatergic synapse (GO:0098978), dendrite (GO:0030425), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Post NMDA receptor activation events	1
Transmission across Chemical Synapses	1
Neuronal System	1
Activation of NMDA receptors and postsynaptic events	1
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
postsynapse	2
anion binding	2
neuron projection	2
synapse	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
learning	1
forebrain development	1
anatomical structure development	1
modulation of chemical synaptic transmission	1
positive regulation of synaptic transmission	1
long-term synaptic potentiation	1
regulation of long-term synaptic potentiation	1
protein binding	1
phosphatidylinositol phosphate binding	1
phospholipid binding	1
binding	1
cytoplasm	1
trans-Golgi network transport vesicle	1
transport vesicle membrane	1
Golgi-associated vesicle membrane	1
clathrin-coated vesicle membrane	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1
somatodendritic compartment	1
cell body	1
postsynaptic density	1
dendritic spine	1
synaptic membrane	1
dendritic tree	1

Protein interactions and networks

STRING

834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRGN	CALM1	P02593	992
NRGN	CALML3	P27482	992
NRGN	CALML6	Q8TD86	992
NRGN	CALML4	Q96GE6	992
NRGN	CALML5	Q9NZT1	992
NRGN	GAP43	P17677	833
NRGN	NEFL	P07196	763
NRGN	IQCJ	Q1A5X6	750
NRGN	IQCJ-SCHIP1	B3KU38	712
NRGN	F8WDG0	F8WDG0	712
NRGN	VSNL1	P28677	697
NRGN	ZNF804A	Q7Z570	693
NRGN	SNCA	P37840	658
NRGN	CHI3L1	P30923	657
NRGN	SNAP25	P13795	610

IntAct

12 interactions, top by confidence:

A	B	Type	Score
NUDT6	DENR	psi-mi:“MI:0914”(association)	0.530
Prep	NRGN	psi-mi:“MI:0570”(protein cleavage)	0.440
GLP1R	NRGN	psi-mi:“MI:0915”(physical association)	0.440
GLP1R	NRGN	psi-mi:“MI:0403”(colocalization)	0.440
NRGN	EIF5	psi-mi:“MI:0915”(physical association)	0.370
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
KLHL20	KRBA1	psi-mi:“MI:0914”(association)	0.350
NRGN	EFCAB7	psi-mi:“MI:0914”(association)	0.350
RWDD2B	DENR	psi-mi:“MI:0914”(association)	0.350
MED9	SPAG9	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): NRGN (Affinity Capture-MS), NRGN (Affinity Capture-MS), NRGN (Affinity Capture-MS), NRGN (Affinity Capture-MS), TRIM62 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), NRGN (Affinity Capture-MS), NRGN (Affinity Capture-MS), NRGN (Affinity Capture-MS), NRGN (Affinity Capture-MS), SNCA (Affinity Capture-Western), NRGN (Affinity Capture-Western), EFCAB7 (Affinity Capture-MS), TRIM62 (Affinity Capture-MS), NRGN (Affinity Capture-MS)

ESM2 similar proteins: A1XQU7, A6QLZ1, A7ER98, A8MWX3, A9CB93, F1N8V3, F4IXN6, O24413, P02260, P14201, P20810, P20811, P35722, P41110, P54877, P55822, P56724, P60761, P84286, Q04940, Q07266, Q16643, Q32NA2, Q32PF3, Q3ZBM6, Q5FWN9, Q5RCI9, Q6PGL7, Q6ZQ03, Q717R8, Q7TP40, Q80X08, Q8I6U3, Q8N6N3, Q8R1R5, Q8SUD4, Q8TDB4, Q8WW12, Q92686, Q95208

Diamond homologs: O62770, P35722, P54866, P54877, P60761, Q04940, Q92686, P06836, P17677, P35001, Q5IS67, Q5NVP7, Q6S9D9, Q95K78, Q98987

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKCA	“up-regulates activity”	NRGN	phosphorylation
PRKCB	“up-regulates activity”	NRGN	phosphorylation
PRKCG	“up-regulates activity”	NRGN	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

10 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

782 predictions. Top by Δscore:

Variant	Effect	Δscore
11:124740095:GCACC:G	donor_gain	1.0000
11:124740098:CC:C	donor_gain	1.0000
11:124740100:G:GG	donor_gain	1.0000
11:124745646:G:GT	donor_gain	1.0000
11:124745928:T:A	acceptor_gain	1.0000
11:124745931:A:AG	acceptor_gain	1.0000
11:124745932:T:G	acceptor_gain	1.0000
11:124745942:T:TA	acceptor_gain	1.0000
11:124740096:CACC:C	donor_gain	0.9900
11:124740097:ACC:A	donor_gain	0.9900
11:124740098:CCGTA:C	donor_loss	0.9900
11:124740099:CGTA:C	donor_loss	0.9900
11:124740100:GTA:G	donor_loss	0.9900
11:124740101:T:G	donor_loss	0.9900
11:124740104:G:GG	donor_gain	0.9900
11:124745623:A:G	donor_gain	0.9900
11:124745947:C:CA	acceptor_gain	0.9900
11:124745952:T:A	acceptor_gain	0.9900
11:124745957:C:A	acceptor_gain	0.9900
11:124746402:A:AG	acceptor_gain	0.9900
11:124746403:G:GA	acceptor_gain	0.9900
11:124745111:G:GT	donor_gain	0.9800
11:124745501:A:AG	acceptor_gain	0.9800
11:124745501:A:C	acceptor_loss	0.9800
11:124745502:G:GC	acceptor_loss	0.9800
11:124745502:G:GG	acceptor_gain	0.9800
11:124745634:A:T	donor_gain	0.9800
11:124740103:A:AG	donor_gain	0.9700
11:124745502:GGA:G	acceptor_gain	0.9700
11:124745960:A:AG	acceptor_gain	0.9700

AlphaMissense

501 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:124745585:T:A	I33N	1.000
11:124745585:T:C	I33T	1.000
11:124745585:T:G	I33S	1.000
11:124745596:T:C	F37L	1.000
11:124745598:T:A	F37L	1.000
11:124745598:T:G	F37L	1.000
11:124745576:C:A	A30D	0.999
11:124745589:G:C	Q34H	0.999
11:124745589:G:T	Q34H	0.999
11:124745590:G:C	A35P	0.999
11:124745597:T:C	F37S	0.999
11:124745597:T:G	F37C	0.999
11:124745543:T:C	I19T	0.998
11:124745573:C:A	A29D	0.998
11:124745605:C:G	H40D	0.998
11:124745599:C:G	R38G	0.997
11:124745600:G:C	R38P	0.997
11:124745603:G:A	G39D	0.997
11:124745578:G:C	A31P	0.996
11:124745584:A:G	I33V	0.996
11:124745596:T:A	F37I	0.996
11:124745615:G:C	R43P	0.996
11:124745602:G:C	G39R	0.995
11:124745572:G:C	A29P	0.994
11:124745583:A:C	K32N	0.994
11:124745583:A:T	K32N	0.994
11:124745584:A:T	I33F	0.994
11:124745596:T:G	F37V	0.994
11:124745602:G:T	G39C	0.994
11:124745603:G:T	G39V	0.994

dbSNP variants (sampled 300 via entrez): RS1000310683 (11:124738880 A>G), RS1000421288 (11:124739303 C>T), RS1001544994 (11:124743282 T>C), RS1001906664 (11:124741424 G>A), RS1002143014 (11:124741813 C>G,T), RS1002474217 (11:124742060 T>C), RS1003071717 (11:124740345 C>T), RS1003540032 (11:124740022 A>G), RS1003569831 (11:124745948 G>C), RS1003641738 (11:124745557 C>A,T), RS1004035005 (11:124746689 C>A,T), RS1004515809 (11:124746343 A>C,G), RS1004542869 (11:124740360 G>A,T), RS1004890198 (11:124738140 C>T), RS1004942490 (11:124738408 T>TG)

Disease associations

OMIM: gene MIM:602350 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000435_7	Schizophrenia	2.000000e-09
GCST002539_10	Schizophrenia	3.000000e-12
GCST004521_214	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004946_129	Schizophrenia	1.000000e-12
GCST006803_11	Schizophrenia	2.000000e-15
GCST007201_126	Schizophrenia	4.000000e-13
GCST007201_156	Schizophrenia	1.000000e-11
GCST008595_109	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-10
GCST009600_127	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
sodium arsenite	affects expression, affects cotreatment, increases expression, decreases expression	4
Benzo(a)pyrene	decreases methylation, increases expression	3
Air Pollutants	decreases expression, increases abundance	2
Tretinoin	decreases expression, affects cotreatment, increases expression	2
Cadmium Chloride	increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
OTX015	increases expression	1
lasiocarpine	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
zinc chromate	decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
diallyl trisulfide	decreases expression	1
pentanal	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
pentabromodiphenyl ether	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
beta-hydroxy simvastatin acid	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.