CNTN4

Summary

CNTN4 (contactin 4, HGNC:2174) is a protein-coding gene on chromosome 3p26.3-p26.2, encoding Contactin-4 (Q8IWV2). Contactins mediate cell surface interactions during nervous system development.

This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 152330 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Disputed, ClinGen) — +1 more curated relationship
• GWAS associations: 50
• Clinical variants (ClinVar): 510 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_175607

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2174
Approved symbol	CNTN4
Name	contactin 4
Location	3p26.3-p26.2
Locus type	gene with protein product
Status	Approved
Aliases	BIG-2
Ensembl gene	ENSG00000144619
Ensembl biotype	protein_coding
OMIM	607280
Entrez	152330

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000397459, ENST00000397461, ENST00000418658, ENST00000422330, ENST00000427331, ENST00000427741, ENST00000430505, ENST00000434053, ENST00000438282, ENST00000455083, ENST00000473058, ENST00000473173, ENST00000473845, ENST00000475817, ENST00000480113, ENST00000484686, ENST00000490876, ENST00000968521, ENST00000968522

RefSeq mRNA: 5 — MANE Select: NM_175607 NM_001206955, NM_001206956, NM_001350095, NM_175607, NM_175613

CCDS: CCDS2558, CCDS43041

Canonical transcript exons

ENST00000418658 — 25 exons

Exon	Start	End
ENSE00001528800	2339178	2339233
ENSE00001626659	2100558	2100639
ENSE00001742756	2098866	2098978
ENSE00003474195	2900685	2900821
ENSE00003490499	3037179	3037328
ENSE00003502342	3042310	3042422
ENSE00003529385	3030855	3030975
ENSE00003530275	2819486	2819581
ENSE00003544489	2902876	2903005
ENSE00003544849	3038933	3039003
ENSE00003553752	3053807	3053975
ENSE00003595035	2736215	2736341
ENSE00003595816	3042977	3043163
ENSE00003620663	2571416	2571558
ENSE00003649288	2883145	2883247
ENSE00003655493	2988345	2988472
ENSE00003663088	2887040	2887224
ENSE00003666648	3040037	3040271
ENSE00003677554	3034632	3034790
ENSE00003681466	3026102	3026277
ENSE00003683442	2866752	2866949
ENSE00003694230	2925629	2925779
ENSE00003694585	3043592	3043704
ENSE00003790030	2745522	2745697
ENSE00003842464	3056120	3057959

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 96.87.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5669 / max 233.5652, expressed in 384 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35007	0.6382	267
35006	0.6042	242
35004	0.3913	196
35003	0.2133	143
35014	0.1330	56
35005	0.0956	53
35002	0.0878	56
34998	0.0795	37
35013	0.0786	49
35000	0.0563	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.87	gold quality
buccal mucosa cell	CL:0002336	93.50	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.81	gold quality
epithelial cell of pancreas	CL:0000083	90.65	gold quality
saphenous vein	UBERON:0007318	90.26	gold quality
thoracic aorta	UBERON:0001515	89.81	gold quality
ascending aorta	UBERON:0001496	89.72	gold quality
descending thoracic aorta	UBERON:0002345	89.48	gold quality
aorta	UBERON:0000947	89.32	gold quality
popliteal artery	UBERON:0002250	88.96	gold quality
tibial artery	UBERON:0007610	88.94	gold quality
endothelial cell	CL:0000115	88.90	gold quality
right coronary artery	UBERON:0001625	88.19	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.15	gold quality
sural nerve	UBERON:0015488	85.90	gold quality
calcaneal tendon	UBERON:0003701	84.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.72	gold quality
tibial nerve	UBERON:0001323	84.06	gold quality
colonic epithelium	UBERON:0000397	83.37	gold quality
islet of Langerhans	UBERON:0000006	83.26	gold quality
left coronary artery	UBERON:0001626	83.25	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.23	silver quality
coronary artery	UBERON:0001621	83.14	gold quality
dorsal root ganglion	UBERON:0000044	82.47	gold quality
superior frontal gyrus	UBERON:0002661	82.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.25	gold quality
cerebellar cortex	UBERON:0002129	82.13	gold quality
prefrontal cortex	UBERON:0000451	82.12	gold quality
cerebellar hemisphere	UBERON:0002245	82.10	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	82.07
E-HCAD-25	yes	43.31
E-CURD-119	yes	23.84
E-MTAB-9388	yes	11.10
E-GEOD-83139	yes	8.08
E-ANND-3	yes	7.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

177 targeting CNTN4, 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-656-3P	100.00	72.15	2788
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 16)

• Our results demonstrate the association of CNTN4 disruption with the 3p deletion syndrome phenotype and strongly suggest a causal relationship (PMID:15106122)
• The contactin 4 gene (CNTN4) is associated with cerebellar degeneration in spinocerebellar ataxia type 16. Additional studies are necessary to prove 4,256C–>T to be a causative mutation. (PMID:17030759)
• pathological examinations and molecular biological examinations are needed to confirm that this mutation is a true cause of SCA16 (PMID:17915252)
• This report suggests that mutations affecting CNTN4 function may be relevant to Autism spectrum disorder pathogenesis. (PMID:18349135)
• results do not support the candidacy of CHL1, CNTN6, and CNTN4 as tumor suppressor genes in the 3p26-pter region in ovarian cancer (PMID:19509545)
• Using array comparative genome hybridization (CGH), we identified a maternally inherited approximately 535 kb deletion at 3p26.3 encompassing the 5’ end of the contactin 4 gene (CNTN4) in a patient with autism. (PMID:21308999)
• these results suggest that rare copy number variations in CNTN4 may also influence autism susceptibility in Asian populations. (PMID:22750301)
• We identified CNTN4 as a novel candidate gene for POAG. (PMID:24764060)
• data reveal critical and novel roles for CNTN4/amyloid precursor protein in promoting target-specific axon arborization (PMID:25959733)
• By combining methylation and SNP data, CNTN4 was identified as a risk factor for regular alcohol use. (PMID:26146898)
• SNPs in ITPR1 and CNTN4 are involved in the regulation of serum uric acid concentrations in Mexican Americans (PMID:27039371)
• Association between contactin 4 (CNTN4) and antisaccade and P300 in schizophrenia. (PMID:27995817)
• SNPs within the CNTN4 gene are associated with increased risk of oral cancer. (PMID:28595731)
• High CNTN4 expression is associated with Pheochromocytomas and Paragangliomas. (PMID:28938490)
• PPARGC1B and CNTN4 genotypes are associated with elevated thromboxane A2 formation and with an excess of cardiovascular events. Aspirin appears to blunt these associations. (PMID:29258006)
• CNTN4 modulates neural elongation through interplay with APP. (PMID:38745463)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cntn3b	ENSDARG00000053454
danio_rerio		ENSDARG00000104277
mus_musculus	Cntn4	ENSMUSG00000064293
rattus_norvegicus	Cntn4	ENSRNOG00000005652

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), IGSF9 (ENSG00000085552), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), IGDCC4 (ENSG00000103742), CNTN3 (ENSG00000113805), IGSF21 (ENSG00000117154), CNTN6 (ENSG00000134115), CHL1 (ENSG00000134121), PTPRQ (ENSG00000139304), BOC (ENSG00000144857), SDK1 (ENSG00000146555), HMCN2 (ENSG00000148357), NCAM1 (ENSG00000149294), CNTN5 (ENSG00000149972), IGSF10 (ENSG00000152580), ROBO4 (ENSG00000154133), ROBO3 (ENSG00000154134), NCAM2 (ENSG00000154654), VCAM1 (ENSG00000162692), NFASC (ENSG00000163531), PRTG (ENSG00000166450), ROBO1 (ENSG00000169855), DSCAM (ENSG00000171587), IGDCC3 (ENSG00000174498), VSIG10 (ENSG00000176834), DSCAML1 (ENSG00000177103), CNTN2 (ENSG00000184144), ROBO2 (ENSG00000185008), VSIG10L (ENSG00000186806), DCC (ENSG00000187323), L1CAM (ENSG00000198910)

Protein

Protein identifiers

Contactin-4 — Q8IWV2 (reviewed: Q8IWV2)

Alternative names: Brain-derived immunoglobulin superfamily protein 2

All UniProt accessions (6): Q8IWV2, C9JGK9, C9JIY1, C9JMQ2, F8WD58, H0Y8U1

UniProt curated annotations — full annotation on UniProt →

Function. Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity. May be involved in synaptogenesis.

Subunit / interactions. Interacts with PTPRG.

Subcellular location. Cell membrane. Secreted.

Tissue specificity. Mainly expressed in brain. Highly expressed in cerebellum and weakly expressed in corpus callosum, caudate nucleus, amygdala and spinal cord. Also expressed in testis, pancreas, thyroid, uterus, small intestine and kidney. Not expressed in skeletal muscle. Isoform 2 is weakly expressed in cerebral cortex.

Disease relevance. A chromosomal aberration involving CNTN4 has been found in a boy with characteristic physical features of 3p deletion syndrome (3PDS). Translocation t(3;10)(p26;q26). 3PDS is a rare contiguous gene disorder involving the loss of the telomeric portion of the short arm of chromosome 3 and characterized by developmental delay, growth retardation, and dysmorphic features.

Induction. By retinoic acid, suggesting that it may act in response to differentiating agents.

Similarity. Belongs to the immunoglobulin superfamily. Contactin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8IWV2-1	1	yes
Q8IWV2-2	2, CNTN4A
Q8IWV2-3	3
Q8IWV2-4	4

RefSeq proteins (5): NP_001193884, NP_001193885, NP_001337024, NP_783200, NP_783302 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR033007	CNTN4_Ig6	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF00041, PF07679, PF13927

UniProt features (42 total): glycosylation site 13, domain 10, disulfide bond 6, splice variant 3, region of interest 2, compositionally biased region 2, sequence variant 2, signal peptide 1, chain 1, lipid moiety-binding region 1, propeptide 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWV2-F1	86.72	0.59

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): 1000

Disulfide bonds (6): 50–100, 144–194, 247–295, 337–384, 429–477, 519–576

Glycosylation sites (13): 65, 90, 191, 370, 375, 466, 705, 764, 858, 893, 911, 929, 954

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 199 (showing top): GOBP_NEURON_RECOGNITION, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, NKX25_02, TATTATA_MIR374, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, CAATGCA_MIR33, GOBP_NEURON_CELL_CELL_ADHESION, GOBP_SYNAPTIC_SIGNALING

GO Biological Process (13): homophilic cell-cell adhesion (GO:0007156), neuron cell-cell adhesion (GO:0007158), nervous system development (GO:0007399), axonogenesis (GO:0007409), axon guidance (GO:0007411), axonal fasciculation (GO:0007413), brain development (GO:0007420), neuron projection development (GO:0031175), negative regulation of neuron differentiation (GO:0045665), regulation of synaptic plasticity (GO:0048167), synapse organization (GO:0050808), dendrite self-avoidance (GO:0070593), cell adhesion (GO:0007155)

GO Molecular Function (2): cell-cell adhesion mediator activity (GO:0098632), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), plasma membrane (GO:0005886), axon (GO:0030424), synapse (GO:0045202), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	3
cellular anatomical structure	3
axon development	2
neuron recognition	2
membrane	2
system development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axonogenesis	1
neuron projection guidance	1
neuron projection fasciculation	1
central nervous system development	1
animal organ development	1
head development	1
neuron development	1
plasma membrane bounded cell projection organization	1
neuron differentiation	1
negative regulation of cell differentiation	1
regulation of neuron differentiation	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
cell junction organization	1
cellular process	1
cell adhesion mediator activity	1
binding	1
cell periphery	1
neuron projection	1
cell junction	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNTN4	APP	P05067	848
CNTN4	NLGN1	Q8N2Q7	836
CNTN4	PTPRG	P23470	811
CNTN4	SUMF1	Q8NBK3	783
CNTN4	NRXN1	Q9ULB1	772
CNTN4	NLGN4X	Q8N0W4	767
CNTN4	ASTN2	O75129	763
CNTN4	CNTNAP2	Q9UHC6	757
CNTN4	CDH9	Q9ULB4	732
CNTN4	NLGN3	Q9NZ94	715
CNTN4	CDH10	Q9Y6N8	707
CNTN4	FBXO40	Q9UH90	682
CNTN4	ITPR1	Q14643	681
CNTN4	SEMA5A	Q13591	655
CNTN4	COP1	Q8NHY2	644

IntAct

8 interactions, top by confidence:

A	B	Type	Score
APP	CNTN4	psi-mi:“MI:0407”(direct interaction)	0.440
APLP1	CNTN4	psi-mi:“MI:0407”(direct interaction)	0.440
App	CNTN4	psi-mi:“MI:0407”(direct interaction)	0.440
HAPLN1	CNTN4	psi-mi:“MI:0915”(physical association)	0.400
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
BTG3	CNTN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): CNTN4 (Two-hybrid), CNTN4 (Affinity Capture-MS), EEA1 (Cross-Linking-MS (XL-MS)), CNTN4 (Affinity Capture-MS), CNTN4 (Two-hybrid), CNTN4 (Two-hybrid), CNTN4 (Affinity Capture-Luminescence)

ESM2 similar proteins: B0KW95, B2KI42, B4USZ0, O00222, O18926, O55075, O60245, O94779, P10288, P15116, P19022, P19534, P24503, P33145, P33150, P35400, P39038, P47743, P55283, P55290, P58365, P68500, P70579, P97527, Q07409, Q0E9H9, Q0ZM14, Q14831, Q3B7N0, Q5H8C1, Q5R5W6, Q5R9X1, Q5RDQ8, Q62682, Q62845, Q63149, Q68ED2, Q69Z26, Q8IWV2, Q90275

Diamond homologs: A0N0X6, A2AJ76, A2CG49, A4IGL7, A4IIW9, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28, B4P5Q9, B4QC63, G5EBF1, O75325, O95428, P0C6S8, P11627, P12960, P22063, P28685, P32004, P97924, Q02246, Q07409, Q09024, Q12860, Q290N5, Q32Q07, Q3UQ28, Q3URE9, Q3V1M1, Q5R482, Q61330, Q61809, Q62682, Q62845, Q63198, Q66HV9, Q69Z26, Q6AWJ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	332
Likely benign	43
Benign	108

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
562684	GRCh37/hg19 3p26.3(chr3:61891-2447256)x1	Pathogenic
814393	GRCh37/hg19 3p26.3(chr3:298102-2679515)x1	Pathogenic
394476	GRCh37/hg19 3p26.3-26.2(chr3:2756990-2818938)x3	Likely pathogenic

SpliceAI

5387 predictions. Top by Δscore:

Variant	Effect	Δscore
3:2098979:G:GG	donor_gain	1.0000
3:2098979:GTAA:G	donor_loss	1.0000
3:2155439:GGA:G	donor_gain	1.0000
3:2226300:T:TA	donor_gain	1.0000
3:2226301:A:AA	donor_gain	1.0000
3:2319596:G:GG	donor_gain	1.0000
3:2339172:TTCTA:T	acceptor_loss	1.0000
3:2339173:TCTA:T	acceptor_loss	1.0000
3:2339174:CTAG:C	acceptor_loss	1.0000
3:2339175:TAGG:T	acceptor_loss	1.0000
3:2339176:A:G	acceptor_loss	1.0000
3:2339177:G:T	acceptor_loss	1.0000
3:2339230:AAAGG:A	donor_loss	1.0000
3:2339232:AGG:A	donor_loss	1.0000
3:2339233:GGTA:G	donor_loss	1.0000
3:2339234:GTAA:G	donor_loss	1.0000
3:2339235:T:A	donor_loss	1.0000
3:2475272:G:GT	donor_gain	1.0000
3:2571411:CACA:C	acceptor_loss	1.0000
3:2571412:ACAG:A	acceptor_loss	1.0000
3:2571413:CA:C	acceptor_loss	1.0000
3:2571414:A:AG	acceptor_gain	1.0000
3:2571414:AG:A	acceptor_loss	1.0000
3:2571415:G:A	acceptor_loss	1.0000
3:2571415:G:GG	acceptor_gain	1.0000
3:2098976:GAG:G	donor_gain	0.9900
3:2098980:T:A	donor_loss	0.9900
3:2100555:AAGT:A	acceptor_gain	0.9900
3:2100555:AAGTG:A	acceptor_gain	0.9900
3:2100556:A:G	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003393 (3:2857522 G>A), RS1000005216 (3:2311070 G>C), RS1000005420 (3:2468646 T>G), RS1000007511 (3:2824527 A>G), RS1000008221 (3:2662557 G>A), RS1000011645 (3:2268579 G>A,T), RS1000011772 (3:2464679 G>A), RS1000013721 (3:2130605 T>C), RS1000014091 (3:2606590 C>A,G), RS1000014272 (3:2626460 G>A), RS1000014731 (3:2529764 C>G,T), RS1000016531 (3:2997532 A>C,G), RS1000019452 (3:2688785 A>G), RS1000024446 (3:2163919 C>T), RS1000028367 (3:2339670 A>G)

Disease associations

OMIM: gene MIM:607280 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
autism spectrum disorder	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Disputed	AD

Mondo (3): autism spectrum disorder (MONDO:0005258), lip and oral cavity carcinoma (MONDO:0023644), autism (MONDO:0005260)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

HPO	Term
HP:0000717	Autism

GWAS associations

50 associations (top):

Study	Trait	p-value
GCST000094_3	Blood pressure	4.000000e-06
GCST000406_1	Amyotrophic lateral sclerosis	7.000000e-06
GCST000436_4	Acenocoumarol maintenance dosage	8.000000e-07
GCST000898_4	Total ventricular volume	3.000000e-06
GCST001428_1	Intelligence	9.000000e-07
GCST001428_9	Intelligence	1.000000e-07
GCST001889_7	Brain connectivity	2.000000e-09
GCST002311_2	Serum uric acid levels	7.000000e-07
GCST002358_12	Pit-and-Fissure caries	9.000000e-06
GCST002539_45	Schizophrenia	3.000000e-11
GCST002587_5	Blood pressure (smoking interaction)	5.000000e-07
GCST002875_80	Diisocyanate-induced asthma	4.000000e-07
GCST002985_6	Middle childhood and early adolescence aggressive behavior	8.000000e-06
GCST003050_27	Schizophrenia	3.000000e-06
GCST003264_769	Post bronchodilator FEV1/FVC ratio	3.000000e-07
GCST003518_97	Daytime sleep phenotypes	8.000000e-06
GCST003542_188	Night sleep phenotypes	4.000000e-06
GCST004105_1	Body mass index (change over time) in chronic obstructive pulmonary disease	4.000000e-08
GCST004521_277	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004618_57	White blood cell count (basophil)	5.000000e-09
GCST004631_18	Basophil percentage of white cells	5.000000e-13
GCST004634_17	Basophil percentage of granulocytes	5.000000e-11
GCST004946_92	Schizophrenia	7.000000e-11
GCST005042_6	Restless legs syndrome	2.000000e-13
GCST005359_9	Disease progression in age-related macular degeneration	4.000000e-06
GCST006208_1	Thiopurine-induced pancreatitis in inflammatory bowel disease	2.000000e-07
GCST006285_1	Response to aripiprazole in schizophrenia	3.000000e-08
GCST006585_1703	Blood protein levels	1.000000e-10
GCST006803_29	Schizophrenia	2.000000e-12
GCST007201_130	Schizophrenia	1.000000e-10

EFO canonical traits (28, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004337	intelligence
EFO:0004761	uric acid measurement
EFO:0006335	systolic blood pressure
EFO:0006526	pack-years measurement
EFO:0006995	response to diisocyanate
EFO:0004713	FEV/FVC ratio
EFO:0007828	daytime rest measurement
EFO:0005937	longitudinal BMI measurement
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0008336	disease progression measurement
EFO:0008328	chronotype measurement
EFO:0009958	response to bisphosphonate
EFO:0009960	atypical femoral fracture
EFO:0004784	self reported educational attainment
EFO:0010158	sugar consumption measurement
EFO:0008354	cognitive function measurement
EFO:0009768	glutamine measurement
EFO:0010341	cholesteryl ester 16:0 measurement
EFO:0009766	asparagine measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0007874	gut microbiome measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

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)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17194378	CNTN4		0.00	0

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression, affects cotreatment	3
Aflatoxin B1	increases methylation, decreases methylation	3
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Nickel	decreases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation, increases methylation	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	affects methylation	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
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Cadmium	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Malathion	increases expression	1
Methapyrilene	affects methylation	1
Phthalic Acids	affects methylation	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in 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
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
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
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder