NRXN2

Summary

NRXN2 (neurexin 2, HGNC:8009) is a protein-coding gene on chromosome 11q13.1, encoding Neurexin-2-beta (P58401). Neuronal cell surface protein that may be involved in cell recognition and cell adhesion.

This gene encodes a member of the neurexin gene family. The products of these genes function as cell adhesion molecules and receptors in the vertebrate nervous system. These genes utilize two promoters. The majority of transcripts are produced from the upstream promoter and encode alpha-neurexin isoforms while a smaller number of transcripts are produced from the downstream promoter and encode beta-neuresin isoforms. The alpha-neurexins contain epidermal growth factor-like (EGF-like) sequences and laminin G domains, and have been shown to interact with neurexophilins. The beta-neurexins lack EGF-like sequences and contain fewer laminin G domains than alpha-neurexins. Alternative splicing and the use of alternative promoters may generate thousands of transcript variants (PMID: 12036300, PMID: 11944992).

Source: NCBI Gene 9379 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, ClinGen) — +2 more curated relationships
• GWAS associations: 15
• Clinical variants (ClinVar): 344 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_015080

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8009
Approved symbol	NRXN2
Name	neurexin 2
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000110076
Ensembl biotype	protein_coding
OMIM	600566
Entrez	9379

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000265459, ENST00000301894, ENST00000377559, ENST00000409571, ENST00000417749, ENST00000423049, ENST00000437746, ENST00000442300, ENST00000464307, ENST00000466324, ENST00000467055, ENST00000486057, ENST00000487484, ENST00000496291, ENST00000688050, ENST00000688454, ENST00000689935, ENST00000693456, ENST00000704781, ENST00000704782

RefSeq mRNA: 10 — MANE Select: NM_015080 NM_001376262, NM_001376263, NM_001376265, NM_001376266, NM_001376267, NM_001400681, NM_001400682, NM_015080, NM_138732, NM_138734

CCDS: CCDS31597, CCDS8077, CCDS8078, CCDS91500

Canonical transcript exons

ENST00000265459 — 23 exons

Exon	Start	End
ENSE00000992616	64648219	64648338
ENSE00000992618	64630402	64630573
ENSE00001120034	64651255	64651636
ENSE00001120037	64667250	64667688
ENSE00001120038	64648734	64648907
ENSE00001120039	64692847	64692876
ENSE00001120040	64690405	64690476
ENSE00001120041	64660332	64660535
ENSE00001120042	64650448	64650638
ENSE00001120043	64668443	64668604
ENSE00001120046	64676993	64677037
ENSE00002461272	64626463	64626552
ENSE00003490413	64697775	64697792
ENSE00003491046	64712970	64713943
ENSE00003498235	64685646	64685947
ENSE00003512783	64652035	64652154
ENSE00003546612	64653696	64653722
ENSE00003556561	64635271	64635452
ENSE00003559211	64606174	64608082
ENSE00003657209	64660753	64661139
ENSE00003663133	64620294	64620372
ENSE00003789659	64622753	64623078
ENSE00003897231	64722971	64723197

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 99.31.

FANTOM5 (CAGE): breadth broad, TPM avg 29.9168 / max 2493.3525, expressed in 690 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120411	25.2017	473
120422	1.4945	184
120410	0.9779	231
120409	0.3929	144
120413	0.3502	123
120414	0.3342	119
120423	0.2629	101
120418	0.2446	146
120421	0.2182	91
120416	0.2069	111

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.31	gold quality
cerebellar hemisphere	UBERON:0002245	99.26	gold quality
cerebellar cortex	UBERON:0002129	99.25	gold quality
cortical plate	UBERON:0005343	98.75	gold quality
cerebellum	UBERON:0002037	98.73	gold quality
prefrontal cortex	UBERON:0000451	97.87	gold quality
right frontal lobe	UBERON:0002810	97.80	gold quality
amygdala	UBERON:0001876	96.67	gold quality
cingulate cortex	UBERON:0003027	96.64	gold quality
anterior cingulate cortex	UBERON:0009835	96.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.48	gold quality
frontal cortex	UBERON:0001870	96.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.31	gold quality
frontal lobe	UBERON:0016525	96.31	gold quality
neocortex	UBERON:0001950	96.18	gold quality
temporal lobe	UBERON:0001871	95.55	gold quality
ganglionic eminence	UBERON:0004023	95.36	gold quality
paraflocculus	UBERON:0005351	95.28	gold quality
cerebral cortex	UBERON:0000956	95.25	gold quality
cerebellar vermis	UBERON:0004720	95.10	gold quality
nucleus accumbens	UBERON:0001882	94.94	gold quality
entorhinal cortex	UBERON:0002728	94.92	gold quality
telencephalon	UBERON:0001893	94.77	gold quality
postcentral gyrus	UBERON:0002581	94.48	gold quality
parietal lobe	UBERON:0001872	94.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.25	gold quality
superior frontal gyrus	UBERON:0002661	94.16	gold quality
hypothalamus	UBERON:0001898	94.06	gold quality
caudate nucleus	UBERON:0001873	93.96	gold quality
Ammon’s horn	UBERON:0001954	93.73	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	13.87
E-GEOD-137537	yes	7.46
E-ANND-3	no	4.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting NRXN2, 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-188-3P	100.00	68.76	1240
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-7106-5P	99.53	67.47	3574

Literature-anchored findings (GeneRIF, showing 10)

• Truncating mutations in NRXN2 is associated with autism spectrum disorders and schizophrenia (PMID:21424692)
• The rare variants in NRXN2 were significantly associated with smoking status. (PMID:25450229)
• NRXN2 may play a part in early cortical synaptogenesis, but NRXNs could have diverse roles in development including axon guidance, and intercellular communication between proliferating cells and/or migrating neurons. (PMID:28013231)
• The neurexins are a family of synaptic adhesion proteins encoded by paralogous genes that play key roles in synaptic function. (PMID:29045040)
• NRXN2 gene had incomplete penetrance for autistic behavioral phenotype. (PMID:29654904)
• Mutations in NRXN1 (c.2686C>T, p.Arg896Trp) and NRXN2 (c.3176G>A, p.Arg1059Gln) were found in a patient with early-onset epileptic encephalopathy and respiratory depression. (PMID:30709877)
• Translational Inhibition of alpha-Neurexin 2. (PMID:32099033)
• A genetic interaction of NRXN2 with GABRE, SYT1 and CASK in migraine patients: a case-control study. (PMID:34126933)
• NRXN2 Possesses a Tumor Suppressor Potential via Inhibiting the Growth of Thyroid Cancer Cells. (PMID:34777568)
• Neurexin 2 p.G849D variant, implicated in Parkinson’s disease, increases reactive oxygen species, and reduces cell viability and mitochondrial membrane potential in SH-SY5Y cells. (PMID:36242655)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	NRXN2	ENSDARG00000113112
mus_musculus	Nrxn2	ENSMUSG00000033768
rattus_norvegicus	Nrxn2	ENSRNOG00000021103
drosophila_melanogaster	Nrx-1	FBGN0038975

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Neurexin-2-beta — P58401 (reviewed: P58401, Q9P2S2)

Alternative names: Neurexin II-beta

All UniProt accessions (14): P58401, Q9P2S2, A0A8I5KTJ4, A0A8I5KY42, A0A8I5QJ84, A0A8I5QJA1, A0A8I5QKZ8, A0A994J4N8, A0A994J5C3, G5E9G7, H7BZC7, H7C2R8, H7C3D6, H7C3J4

UniProt curated annotations — full annotation on UniProt →

Function. Neuronal cell surface protein that may be involved in cell recognition and cell adhesion.

Subunit / interactions. Interacts (via cytoplasmic C-terminal region) with CASK. Specific isoforms bind alpha-dystroglycan and neuroligins NLGN1, NLGN2 and NLGN3. Interacts with CBLN1, CBLN2 and, less avidly, with CBLN4. Interacts with CLSTN3.

Subcellular location. Presynaptic cell membrane.

Post-translational modifications. O-glycosylated; contains heparan sulfate. Heparan sulfate attachment is required for synapse development by mediating interactions with neuroligins.

Domain organisation. Alternative splicing in the laminin G-like domain regulates binding to alpha-dystroglycan.

Similarity. Belongs to the neurexin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P58401-1	1b	yes
Q9P2S2-1	1a
Q9P2S2-2	2a, Alpha-2B

RefSeq proteins (10): NP_001363191, NP_001363192, NP_001363194, NP_001363195, NP_001363196, NP_001387610, NP_001387611, NP_055895, NP_620060, NP_620063 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001791	Laminin_G	Domain
IPR003585	Neurexin-like	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR050372	Neurexin-related_CASP	Family
IPR000742	EGF	Domain

Pfam: PF02210

UniProt features (70 total): binding site 14, disulfide bond 12, domain 10, region of interest 9, glycosylation site 7, topological domain 4, splice variant 4, signal peptide 2, chain 2, compositionally biased region 2, transmembrane region 2, strand 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4NXR	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P58401-F1	61.68	0.28
AF-Q9P2S2-F1	75.09	0.45

Functional residue map

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

P58401 (canonical)

Ligand- & substrate-binding residues (4): 143; 160; 242; 244

Glycosylation sites (2): 190, 354

Q9P2S2

Ligand- & substrate-binding residues (10): 335; 352; 420; 779; 796; 854; 1189; 1206; 1288; 1290

Disulfide bonds (12): 206–219, 213–229, 231–241, 450–486, 657–686, 694–705, 699–714, 716–726, 1065–1093, 1100–1111, 1105–1120, 1122–1132

Glycosylation sites (5): 60, 338, 841, 1236, 1400

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins

MSigDB gene sets: 177 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GNF2_RTN1, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, GOBP_MEMBRANE_BIOGENESIS, GCANCTGNY_MYOD_Q6, GOBP_ADULT_BEHAVIOR, AREB6_01, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, chr11q13, GOBP_CELL_CELL_SIGNALING

GO Biological Process (17): neuron cell-cell adhesion (GO:0007158), signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), neurotransmitter secretion (GO:0007269), synapse assembly (GO:0007416), adult behavior (GO:0030534), social behavior (GO:0035176), vocal learning (GO:0042297), vocalization behavior (GO:0071625), postsynaptic membrane assembly (GO:0097104), gephyrin clustering involved in postsynaptic density assembly (GO:0097116), neuroligin clustering involved in postsynaptic membrane assembly (GO:0097118), postsynaptic density protein 95 clustering (GO:0097119), presynaptic modulation of chemical synaptic transmission (GO:0099171), regulation of postsynapse assembly (GO:0150052), cell adhesion (GO:0007155), learning (GO:0007612)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), metal ion binding (GO:0046872), cell adhesion molecule binding (GO:0050839), neuroligin family protein binding (GO:0097109), calcium channel regulator activity (GO:0005246)

GO Cellular Component (7): plasma membrane (GO:0005886), presynaptic membrane (GO:0042734), protein-containing complex (GO:0032991), glutamatergic synapse (GO:0098978), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein-protein interactions at synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
presynapse	3
behavior	3
cellular process	2
postsynaptic membrane organization	2
postsynapse assembly	2
cellular anatomical structure	2
cell-cell adhesion	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anterograde trans-synaptic signaling	1
neurotransmitter transport	1
chemical synaptic transmission	1
establishment of localization in cell	1
signal release from synapse	1
nervous system development	1
cell junction assembly	1
synapse organization	1
biological process involved in intraspecies interaction between organisms	1
auditory behavior	1
imitative learning	1
learned vocalization behavior or vocal learning	1
membrane assembly	1
protein localization to synapse	1
postsynaptic density assembly	1
receptor clustering	1
postsynaptic membrane assembly	1
protein localization to membrane	1
postsynaptic density organization	1
modulation of chemical synaptic transmission	1
regulation of synapse assembly	1
regulation of postsynapse organization	1
learning or memory	1
signaling receptor activity	1
cation binding	1
protein binding	1
signaling receptor binding	1
calcium channel activity	1
ion channel regulator activity	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
MAPK6	NRXN2	psi-mi:“MI:0915”(physical association)	0.370
CAVIN1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CBLN4	NRXN2	psi-mi:“MI:0914”(association)	0.350
HADHA	AP3B1	psi-mi:“MI:0914”(association)	0.350
HADHB	AGRN	psi-mi:“MI:0914”(association)	0.350
LRRTM1	AGRN	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): NLGN1 (Reconstituted Complex), NLGN2 (Reconstituted Complex), NRXN2 (Two-hybrid), NRXN2 (Affinity Capture-MS), RPL6 (Cross-Linking-MS (XL-MS)), NRXN2 (Affinity Capture-MS), SFPQ (Cross-Linking-MS (XL-MS)), NRXN2 (Affinity Capture-MS), NRXN2 (Affinity Capture-MS), NRXN2 (Affinity Capture-RNA), NRXN2 (Two-hybrid), MACF1 (Two-hybrid), NRXN2 (Two-hybrid)

ESM2 similar proteins: A1XQX1, A1XQX3, A1XQY0, A8WGA3, C6K2K4, D0PRN2, D0PRN4, D4A1J9, E9PUN2, O13097, O42596, O73612, O73874, P0DI97, P52795, P52796, P58400, P58401, P98172, Q01974, Q0PMD2, Q17QD6, Q28142, Q28143, Q460M5, Q63373, Q63376, Q6NW40, Q6PCX7, Q6PFE7, Q7TQ33, Q80TG9, Q8BNJ6, Q8BXA0, Q8C985, Q8IYR6, Q8NC67, Q91590, Q96B86, Q96NI6

Diamond homologs: A1XQX0, A1XQX1, A1XQX2, A1XQX3, A1XQX8, A1XQY0, A1XQY1, A1XQY3, A6MFK7, D0PRN2, D0PRN3, D0PRN4, E9PUN2, E9Q7X7, P00741, P0DI97, P16294, P16296, P58400, P58401, Q07310, Q28142, Q28143, Q28146, Q3KN41, Q63372, Q63373, Q63374, Q63376, Q6P9K9, Q6SA95, Q8C985, Q9CS84, Q9DDD0, Q9HDB5, Q9P2S2, Q9ULB1, Q9Y4C0, O02768, O19183

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
NLGN3	“up-regulates activity”	NRXN2	binding
NLGN4Y	“up-regulates activity”	NRXN2	binding
NLGN1	“up-regulates activity”	NRXN2	binding
NLGN4X	“up-regulates activity”	NRXN2	binding
NLGN2	“up-regulates activity”	NRXN2	binding
DGC	“up-regulates activity”	NRXN2	binding
NRXN2	“up-regulates activity”	NLGN2	binding
NRXN2	“up-regulates activity”	DAG1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	249
Likely benign	42
Benign	36

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4291708	NM_015080.4(NRXN2):c.433C>T (p.Gln145Ter)	Likely pathogenic

SpliceAI

4676 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64620289:CTCA:C	donor_loss	1.0000
11:64620290:TCA:T	donor_loss	1.0000
11:64620291:CA:C	donor_loss	1.0000
11:64620292:A:AC	donor_gain	1.0000
11:64620292:A:AT	donor_loss	1.0000
11:64620293:C:CC	donor_gain	1.0000
11:64620371:TT:T	acceptor_gain	1.0000
11:64620372:TC:T	acceptor_loss	1.0000
11:64620373:C:CA	acceptor_loss	1.0000
11:64620373:C:CC	acceptor_gain	1.0000
11:64622747:CCTCA:C	donor_loss	1.0000
11:64622748:CTCAC:C	donor_loss	1.0000
11:64622749:TCAC:T	donor_loss	1.0000
11:64622750:CAC:C	donor_loss	1.0000
11:64622751:A:C	donor_loss	1.0000
11:64623080:T:C	acceptor_gain	1.0000
11:64623084:A:T	acceptor_gain	1.0000
11:64623088:G:C	acceptor_gain	1.0000
11:64623088:G:GC	acceptor_gain	1.0000
11:64630397:CCTAC:C	donor_loss	1.0000
11:64630398:CTACC:C	donor_loss	1.0000
11:64630399:TACCT:T	donor_loss	1.0000
11:64630401:C:CG	donor_loss	1.0000
11:64630404:G:A	donor_gain	1.0000
11:64630572:TC:T	acceptor_gain	1.0000
11:64630573:CC:C	acceptor_gain	1.0000
11:64635260:AGGGT:A	donor_gain	1.0000
11:64635264:T:TA	donor_gain	1.0000
11:64635269:A:AC	donor_gain	1.0000
11:64635270:C:CC	donor_gain	1.0000

AlphaMissense

11124 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64607374:A:G	L1654P	1.000
11:64607377:A:G	L1653P	1.000
11:64607377:A:T	L1653H	1.000
11:64607380:A:T	I1652N	1.000
11:64607383:A:G	L1651P	1.000
11:64607389:C:T	C1649Y	1.000
11:64607390:A:G	C1649R	1.000
11:64607392:A:G	L1648P	1.000
11:64607392:A:T	L1648H	1.000
11:64607413:C:T	G1641D	1.000
11:64607414:C:G	G1641R	1.000
11:64620338:C:G	C1403S	1.000
11:64620339:A:G	C1403R	1.000
11:64620339:A:T	C1403S	1.000
11:64623004:C:G	G1308R	1.000
11:64623009:A:C	F1306C	1.000
11:64626476:C:A	W1278C	1.000
11:64626476:C:G	W1278C	1.000
11:64626478:A:G	W1278R	1.000
11:64626478:A:T	W1278R	1.000
11:64630443:A:G	L1239P	1.000
11:64630464:C:G	R1232P	1.000
11:64630470:A:G	F1230S	1.000
11:64635278:A:G	L1193P	1.000
11:64635284:A:G	L1191P	1.000
11:64635350:A:G	F1169S	1.000
11:64635362:A:G	L1165P	1.000
11:64635400:C:A	W1152C	1.000
11:64635400:C:G	W1152C	1.000
11:64635402:A:G	W1152R	1.000

dbSNP variants (sampled 300 via entrez): RS1000004122 (11:64657257 G>A), RS1000004882 (11:64689176 C>T), RS1000021415 (11:64701508 G>A), RS1000035191 (11:64656993 G>A), RS1000058709 (11:64708938 T>A), RS1000079469 (11:64639198 G>A,C), RS1000096114 (11:64715213 A>G), RS1000105058 (11:64683024 T>C), RS1000114984 (11:64682531 T>A,C), RS1000129357 (11:64696349 G>A), RS1000143741 (11:64624776 T>C), RS1000170951 (11:64651759 G>A,T), RS1000176162 (11:64650969 G>A), RS1000177388 (11:64695350 G>A,C), RS1000231234 (11:64645056 C>G,T)

Disease associations

OMIM: gene MIM:600566 | disease phenotypes: MIM:181500, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
autism	Limited	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	AD

Mondo (7): schizophrenia (MONDO:0005090), autism spectrum disorder (MONDO:0005258), epilepsy (MONDO:0005027), intellectual disability (MONDO:0001071), developmental and epileptic encephalopathy, 1 (MONDO:0010632), autism (MONDO:0005260), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001163_5	Urate levels	6.000000e-11
GCST001791_47	Urate levels	4.000000e-11
GCST002828_2	Urate levels in obese individuals	2.000000e-06
GCST002829_34	Urate levels in overweight individuals	9.000000e-14
GCST002829_43	Urate levels in overweight individuals	1.000000e-09
GCST002830_27	Urate levels in lean individuals	1.000000e-06
GCST003263_93	Post bronchodilator FEV1 in COPD	4.000000e-06
GCST004904_238	Body mass index	1.000000e-08
GCST005793_3	Uric acid levels	2.000000e-15
GCST005983_2	Serum uric acid levels	0.000000e+00
GCST007725_22	Serum uric acid levels	1.000000e-300
GCST008129_23	Body mass index	2.000000e-09
GCST008522_66	Bitter alcoholic beverage consumption	2.000000e-06
GCST012338_28	Gout	2.000000e-18
GCST90002388_540	Lymphocyte count	1.000000e-14

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004314	forced expiratory volume
EFO:0004340	body mass index
EFO:0004761	uric acid measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0004587	lymphocyte count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	3
belinostat	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
arsenite	decreases methylation	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
Vorinostat	decreases expression	1
Panobinostat	affects cotreatment, decreases expression	1
Aldehydes	increases expression	1
Arsenic	affects methylation	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Lead	affects expression, affects splicing	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia