PLXNA2

Summary

PLXNA2 (plexin A2, HGNC:9100) is a protein-coding gene on chromosome 1q32.2, encoding Plexin-A2 (O75051). Coreceptor for SEMA3A and SEMA6A.

This gene encodes a member of the plexin-A family of semaphorin co-receptors. Semaphorins are a large family of secreted or membrane-bound proteins that mediate repulsive effects on axon pathfinding during nervous system development. A subset of semaphorins are recognized by plexin-A/neuropilin transmembrane receptor complexes, triggering a cellular signal transduction cascade that leads to axon repulsion. This plexin-A family member is thought to transduce signals from semaphorin-3A and -3C.

Source: NCBI Gene 5362 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 1,035 total — 2 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_025179

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9100
Approved symbol	PLXNA2
Name	plexin A2
Location	1q32.2
Locus type	gene with protein product
Status	Approved
Aliases	OCT, FLJ11751, FLJ30634, KIAA0463
Ensembl gene	ENSG00000076356
Ensembl biotype	protein_coding
OMIM	601054
Entrez	5362

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding_CDS_not_defined, 4 protein_coding

ENST00000367033, ENST00000460870, ENST00000463510, ENST00000480053, ENST00000483048, ENST00000486969, ENST00000866340, ENST00000866341, ENST00000866342

RefSeq mRNA: 1 — MANE Select: NM_025179 NM_025179

CCDS: CCDS31013

Canonical transcript exons

ENST00000367033 — 32 exons

Exon	Start	End
ENSE00000810254	208210280	208210462
ENSE00000960304	208142329	208142463
ENSE00000960306	208103147	208103247
ENSE00000960307	208098846	208098969
ENSE00000960309	208096730	208096883
ENSE00000960310	208096029	208096125
ENSE00000960312	208084380	208084580
ENSE00001010244	208044508	208044742
ENSE00001010248	208033319	208033509
ENSE00001010254	208051256	208051423
ENSE00001010257	208043061	208043203
ENSE00001010260	208038825	208038984
ENSE00001010262	208045878	208046117
ENSE00001010265	208051009	208051102
ENSE00001010267	208054421	208054538
ENSE00001010268	208052327	208052463
ENSE00001010274	208045067	208045210
ENSE00001010278	208034493	208034592
ENSE00001071271	208079260	208079450
ENSE00001071275	208060686	208060837
ENSE00001071284	208082412	208082508
ENSE00001443297	208022242	208027338
ENSE00001443300	208216735	208218002
ENSE00001443301	208243643	208244384
ENSE00001751444	208038371	208038474
ENSE00002331630	208039992	208040058
ENSE00002359964	208028830	208029042
ENSE00002366986	208092786	208092900
ENSE00002407343	208042098	208042366
ENSE00002407628	208031590	208031759
ENSE00003478263	208039621	208039767
ENSE00003615724	208028009	208028159

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.3722 / max 108.2498, expressed in 1262 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17211	2.5969	893
17213	1.6416	726
17212	0.4952	250
17210	0.4585	214
17209	0.1703	74
201933	0.0054	1
17198	0.0044	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.47	gold quality
cortical plate	UBERON:0005343	96.69	gold quality
body of pancreas	UBERON:0001150	95.97	gold quality
right lung	UBERON:0002167	93.98	gold quality
embryo	UBERON:0000922	93.53	gold quality
upper lobe of left lung	UBERON:0008952	92.72	gold quality
upper lobe of lung	UBERON:0008948	92.43	gold quality
left ovary	UBERON:0002119	91.45	gold quality
lower esophagus mucosa	UBERON:0035834	91.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.96	gold quality
right ovary	UBERON:0002118	90.87	gold quality
cerebellar hemisphere	UBERON:0002245	90.62	gold quality
cerebellar cortex	UBERON:0002129	90.51	gold quality
esophagus mucosa	UBERON:0002469	90.37	gold quality
pancreas	UBERON:0001264	90.26	gold quality
cerebellum	UBERON:0002037	90.03	gold quality
postcentral gyrus	UBERON:0002581	89.60	gold quality
left coronary artery	UBERON:0001626	89.08	gold quality
right coronary artery	UBERON:0001625	88.92	gold quality
paraflocculus	UBERON:0005351	88.89	gold quality
coronary artery	UBERON:0001621	88.79	gold quality
apex of heart	UBERON:0002098	88.63	gold quality
sural nerve	UBERON:0015488	88.56	gold quality
esophagus	UBERON:0001043	88.54	gold quality
parietal lobe	UBERON:0001872	88.37	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.27	gold quality
right frontal lobe	UBERON:0002810	88.23	gold quality
lung	UBERON:0002048	88.14	gold quality
popliteal artery	UBERON:0002250	87.83	gold quality
tibial artery	UBERON:0007610	87.80	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	1067.31
E-MTAB-7008	yes	104.45
E-HCAD-5	yes	14.14
E-ANND-3	yes	13.26
E-MTAB-9388	yes	8.35
E-GEOD-93593	yes	7.16
E-GEOD-137537	yes	5.14
E-GEOD-99795	no	29.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA6, GLI1, IRF6, JDP2

miRNA regulators (miRDB)

306 targeting PLXNA2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776

Literature-anchored findings (GeneRIF, showing 17)

• An association is identified between variants in the PLXNA2 gene and schizophrenia in two collections of schizophrenia cases and controls. High-density SNP mapping showed that the region of association spans approximately 60 kb of the PLXNA2 gene. (PMID:16402134)
• results suggest that PLXNA2 may not play a major role in the development of schizophrenia in our Japanese sample (PMID:17346868)
• PLXNA2 confers a varying genetic risk for schizophrenia among different populations. (PMID:18065206)
• Analysis of 3 SNPs at the PLXN A2 locus; we failed to replicate previously reported association of this locus and schizophrenia. (PMID:18096369)
• Data show that the expression of Sema3A receptors (neuropilin-1 (NRP-1), NRP-2, plexin A1, plexin A2, and plexin A3) significantly increased during M-CSF-mediated differentiation of monocytes into macrophages. (PMID:19480842)
• mutations in GATA6 are genetic causes of congenital heart diseases involving outflow tract defects, as a result of the disruption of the direct regulation of semaphorin 3C-plexin A2 signaling (PMID:19666519)
• in vitro analysis of PLXNA2 revealed that the gene has higher expression in more aggressive breast cancer cell types. (PMID:21925246)
• PLXNA2 polymorphisms show association with ankylosing spondylitis. (PMID:22011406)
• results of our study reveal that PlxnA2 has a pro-osteogenic function by modulating BMP2 signaling (PMID:22095611)
• PLXNA2 has been identified as a new rare copy number variations gene for tetralogy of Fallot. (PMID:22912587)
• PLXNA2 upregulation contributes to TMPRSS2:ERG-mediated enhancements of PC3c cell migration and invasion. (PMID:23708657)
• although plexin-A4 overexpression restored Sema3A signaling in plexin-A1-silenced cells, it failed to restore Sema3B signaling in plexin-A2-silenced cells. (PMID:25335892)
• Data indicate that plexin A1-4 (PLXNA1-4) mediation of neuroanatomical traits can be detected using in vivo neuroimaging techniques. (PMID:25518740)
• Data suggest that Fyn tyrosine kinase (Fyn)-dependent phosphorylation at two critical tyrosines is a key feature of vertebrate plexin A1 (PlxnA1) and plexin A2 (PlxnA2) signal transduction. (PMID:29091353)
• PLXNA2 and LRRC40 as candidate genes in autism spectrum disorder. (PMID:33749153)
• PLXNA2 as a candidate gene in patients with intellectual disability. (PMID:34327814)
• Plexin-A2 enables the proliferation and the development of tumors from glioblastoma derived cells. (PMID:36658114)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plxna2	ENSDARG00000060372
mus_musculus	Plxna2	ENSMUSG00000026640
rattus_norvegicus	Plxna2	ENSRNOG00000007324

Paralogs (8): PLXND1 (ENSG00000004399), PLXNA1 (ENSG00000114554), PLXNA3 (ENSG00000130827), PLXNC1 (ENSG00000136040), PLXNB1 (ENSG00000164050), PLXNB2 (ENSG00000196576), PLXNB3 (ENSG00000198753), PLXNA4 (ENSG00000221866)

Protein

Protein identifiers

Plexin-A2 — O75051 (reviewed: O75051)

Alternative names: Semaphorin receptor OCT

All UniProt accessions (1): O75051

UniProt curated annotations — full annotation on UniProt →

Function. Coreceptor for SEMA3A and SEMA6A. Necessary for signaling by SEMA6A and class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.

Subunit / interactions. Homodimer. The PLXNA2 homodimer interacts with a SEMA6A homodimer, giving rise to a heterotetramer. Interacts directly with NRP1 and NRP2. Interacts with RND1.

Subcellular location. Cell membrane.

Tissue specificity. Detected in fetal brain.

Similarity. Belongs to the plexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75051-1	1	yes
O75051-2	2

RefSeq proteins (1): NP_079455* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR002165	Plexin_repeat	Repeat
IPR002909	IPT_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR013548	Plexin_cytoplasmic_RasGAP_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR031148	Plexin	Family
IPR036352	Semap_dom_sf	Homologous_superfamily
IPR041019	TIG1_plexin	Domain
IPR041362	TIG2_plexin	Domain
IPR042826	Plexin-A2_sema	Domain
IPR046800	Plexin_RBD	Domain

Pfam: PF01403, PF01437, PF01833, PF08337, PF17960, PF18020, PF20170, PF24479

UniProt features (54 total): disulfide bond 10, glycosylation site 7, sequence variant 6, sequence conflict 6, strand 6, domain 5, splice variant 3, helix 3, topological domain 2, signal peptide 1, chain 1, coiled-coil region 1, modified residue 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3Q3J	X-RAY DIFFRACTION	1.97

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75051-F1	84.81	0.50

Functional residue map

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

Post-translational modifications (1): 1612

Disulfide bonds (10): 94–103, 129–137, 284–405, 300–356, 374–393, 511–528, 517–559, 520–537, 531–543, 594–613

Glycosylation sites (7): 76, 91, 327, 598, 696, 756, 1205

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-399954	Sema3A PAK dependent Axon repulsion
R-HSA-399955	SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
R-HSA-399956	CRMPs in Sema3A signaling
R-HSA-416700	Other semaphorin interactions

MSigDB gene sets: 280 (showing top): GOBP_HINDBRAIN_DEVELOPMENT, RRAGTTGT_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, REACTOME_OTHER_SEMAPHORIN_INTERACTIONS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_NEURAL_TUBE_DEVELOPMENT, CHX10_01, NKX61_01, BILD_HRAS_ONCOGENIC_SIGNATURE, MODULE_66

GO Biological Process (14): somitogenesis (GO:0001756), synapse assembly (GO:0007416), neural tube development (GO:0021915), cerebellar granule cell precursor tangential migration (GO:0021935), regulation of cell migration (GO:0030334), centrosome localization (GO:0051642), pharyngeal system development (GO:0060037), limb bud formation (GO:0060174), semaphorin-plexin signaling pathway (GO:0071526), cell surface receptor signaling pathway (GO:0007166), nervous system development (GO:0007399), anatomical structure morphogenesis (GO:0009653), tube development (GO:0035295), animal organ development (GO:0048513)

GO Molecular Function (4): semaphorin receptor activity (GO:0017154), identical protein binding (GO:0042802), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (3): semaphorin receptor complex (GO:0002116), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Semaphorin interactions	4

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chordate embryonic development	3
anatomical structure development	3
anatomical structure formation involved in morphogenesis	2
nervous system development	2
system development	2
anterior/posterior pattern specification	1
segmentation	1
somite development	1
cell junction assembly	1
synapse organization	1
tube development	1
epithelium development	1
hindbrain tangential cell migration	1
cell migration	1
regulation of cell motility	1
microtubule organizing center localization	1
limb morphogenesis	1
cell surface receptor signaling pathway	1
signal transduction	1
developmental process	1
multicellular organism development	1
transmembrane signaling receptor activity	1
semaphorin-plexin signaling pathway	1
protein binding	1
signaling receptor activity	1
binding	1
signaling receptor complex	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLXNA2	SEMA3A	Q14563	998
PLXNA2	NRP1	O14786	992
PLXNA2	SEMA6A	Q9H2E6	985
PLXNA2	SEMA6B	Q9H3T3	965
PLXNA2	SEMA3C	Q99985	954
PLXNA2	NRP2	O60462	899
PLXNA2	SEMA4D	Q92854	882
PLXNA2	SEMA6D	Q8NFY4	820
PLXNA2	SEMA3B	Q13214	815
PLXNA2	SEMA6C	Q9H3T2	762
PLXNA2	SEMA3E	O15041	755
PLXNA2	MICAL1	Q8TDZ2	755
PLXNA2	DPYSL2	Q16555	665
PLXNA2	SEMA3F	Q13275	626
PLXNA2	EVL	Q9UI08	616

IntAct

104 interactions, top by confidence:

A	B	Type	Score
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
KIR3DL2	METTL15	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
SPINK4	PLXNA2	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
GPHA2	PLXNA2	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
CD1E	SUSD5	psi-mi:“MI:0914”(association)	0.530
GALNT6	NDUFS4	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
LACRT	PLXNA2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
BTNL3	FAM171A2	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530
CCL22	PLXNA2	psi-mi:“MI:0914”(association)	0.530
ADAM21	PLXNA2	psi-mi:“MI:0914”(association)	0.530

BioGRID (122): PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), XAB2 (Co-fractionation), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS)

ESM2 similar proteins: A0A5B9, A6NDV4, A6QLK4, B1AWJ5, E9PTA2, O75051, O94759, P01850, P01851, P01852, P01857, P01859, P01860, P01861, P01869, P01870, P01906, P01909, P03987, P06333, P0DSE2, P0DTU4, P11364, P15151, P15981, P20759, P20762, P32506, P54900, Q1WIM1, Q1WIM3, Q3TMX7, Q6P767, Q6ZRP7, Q7TQ33, Q812F8, Q8N126, Q8NFZ8, Q8R143, Q8R464

Diamond homologs: B0S5N4, B2RXS4, D3ZLH5, D3ZPX4, O15031, O43157, O60486, O75051, P51805, P70206, P70207, P70208, Q3UH93, Q6BEA0, Q80UG2, Q8CJH3, Q9HCM2, Q9NTN9, Q9QY40, Q9QZC2, Q9UIW2, Q9ULL4, Q9V4A7, Q9WUH7, Q9Y4D7, Q09YN5, Q80ZA4, Q60519, Q9P283, O42236, Q13591, Q9C0C4, Q62190, Q626H5, Q9H2E6, O95754, Q64151, Q9Z123, Q9Z143, Q90665

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SEMA3B	“up-regulates activity”	PLXNA2	binding
SEMA3A	up-regulates	PLXNA2	binding
GATA6	“up-regulates quantity by expression”	PLXNA2	“transcriptional regulation”
SEMA3C	“up-regulates activity”	PLXNA2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

1035 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	556
Likely benign	377
Benign	60

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3911834	NM_025179.4(PLXNA2):c.3640-1G>A	Likely pathogenic
431732	NM_025179.4(PLXNA2):c.2206G>A (p.Gly736Ser)	Likely pathogenic

SpliceAI

5238 predictions. Top by Δscore:

Variant	Effect	Δscore
1:208028010:T:TA	donor_gain	1.0000
1:208028016:CTATA:C	donor_gain	1.0000
1:208028058:AG:A	donor_gain	1.0000
1:208028059:G:C	donor_gain	1.0000
1:208028826:TGAC:T	donor_loss	1.0000
1:208028827:GACCT:G	donor_loss	1.0000
1:208028828:A:AC	donor_gain	1.0000
1:208028829:C:CC	donor_gain	1.0000
1:208028829:CCT:C	donor_gain	1.0000
1:208028831:TCTCC:T	donor_gain	1.0000
1:208028841:G:C	donor_gain	1.0000
1:208029038:GGAGG:G	acceptor_gain	1.0000
1:208029039:GAGG:G	acceptor_gain	1.0000
1:208029040:AGG:A	acceptor_gain	1.0000
1:208029041:GG:G	acceptor_gain	1.0000
1:208029042:GC:G	acceptor_loss	1.0000
1:208029043:C:CA	acceptor_loss	1.0000
1:208029043:C:CC	acceptor_gain	1.0000
1:208029044:T:G	acceptor_loss	1.0000
1:208029045:G:C	acceptor_gain	1.0000
1:208033314:GTTA:G	donor_loss	1.0000
1:208033315:TTA:T	donor_loss	1.0000
1:208033316:TA:T	donor_loss	1.0000
1:208033317:ACC:A	donor_loss	1.0000
1:208033318:CCTT:C	donor_loss	1.0000
1:208038365:TCTCA:T	donor_loss	1.0000
1:208038366:CTCAC:C	donor_loss	1.0000
1:208038367:TCACC:T	donor_loss	1.0000
1:208038370:C:CT	donor_loss	1.0000
1:208038471:CACT:C	acceptor_gain	1.0000

AlphaMissense

12441 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:208028100:A:G	L1833P	1.000
1:208028866:G:T	A1801D	1.000
1:208028870:A:C	Y1800D	1.000
1:208028872:A:G	L1799P	1.000
1:208028872:A:T	L1799H	1.000
1:208028875:A:C	L1798R	1.000
1:208028875:A:G	L1798P	1.000
1:208028875:A:T	L1798Q	1.000
1:208028877:C:A	K1797N	1.000
1:208028877:C:G	K1797N	1.000
1:208028879:T:C	K1797E	1.000
1:208028922:A:C	C1782W	1.000
1:208028923:C:T	C1782Y	1.000
1:208028924:A:G	C1782R	1.000
1:208028927:A:G	S1781P	1.000
1:208028929:T:A	D1780V	1.000
1:208028929:T:C	D1780G	1.000
1:208028929:T:G	D1780A	1.000
1:208028930:C:G	D1780H	1.000
1:208028932:A:T	M1779K	1.000
1:208028940:C:A	Q1776H	1.000
1:208028940:C:G	Q1776H	1.000
1:208028944:G:T	A1775D	1.000
1:208028945:C:G	A1775P	1.000
1:208028956:A:G	L1771P	1.000
1:208028958:G:C	C1770W	1.000
1:208028960:A:G	C1770R	1.000
1:208028997:G:C	F1757L	1.000
1:208028997:G:T	F1757L	1.000
1:208028999:A:G	F1757L	1.000

dbSNP variants (sampled 300 via entrez): RS1000003404 (1:208233328 G>A,T), RS1000034035 (1:208048308 G>C), RS1000035462 (1:208082761 C>T), RS1000042537 (1:208025784 G>A), RS1000059364 (1:208032629 G>A), RS1000070246 (1:208178041 A>C), RS1000074355 (1:208049491 C>A), RS1000106535 (1:208208458 C>A), RS1000113676 (1:208088517 T>C), RS1000121125 (1:208186310 T>A,C), RS1000133877 (1:208222136 C>T), RS1000151587 (1:208168664 G>A), RS1000160036 (1:208097335 T>C), RS1000174448 (1:208199663 C>G), RS1000180036 (1:208106619 A>T)

Disease associations

OMIM: gene MIM:601054 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (2): autism (MONDO:0005260), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000717	Autism

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000960_10	Cardiac hypertrophy	6.000000e-06
GCST002932_23	Manganese levels	1.000000e-06
GCST004747_8	Lung cancer in never smokers	6.000000e-06
GCST004750_94	Squamous cell lung carcinoma	2.000000e-06
GCST005024_46	Pursuit maintenance gain	1.000000e-06
GCST007323_80	Risk-taking tendency (4-domain principal component model)	2.000000e-10
GCST007325_221	General risk tolerance (MTAG)	3.000000e-09
GCST007327_92	Smoking status (ever vs never smokers)	9.000000e-10
GCST008476_10	Emphysema annual change measurement in smokers (percent low attenuation area)	6.000000e-06
GCST008476_28	Emphysema annual change measurement in smokers (percent low attenuation area)	6.000000e-06
GCST008522_90	Bitter alcoholic beverage consumption	7.000000e-06
GCST008788_14	Adolescent idiopathic scoliosis	4.000000e-08
GCST008789_12	Adolescent idiopathic scoliosis	4.000000e-08
GCST010002_375	Refractive error	2.000000e-54

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0002503	cardiac hypertrophy
EFO:0008433	pursuit maintenance gain measurement
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0007626	emphysema imaging measurement
EFO:0010092	bitter alcoholic beverage consumption measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	8
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	5
bisphenol A	increases expression, affects cotreatment, decreases methylation	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases expression	3
Cyclosporine	decreases expression, decreases methylation, increases expression	3
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Doxorubicin	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, increases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
methylparaben	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone	affects response to substance	1

Clinical trials (associated diseases)

302 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
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms