CNTN3

Summary

CNTN3 (contactin 3, HGNC:2173) is a protein-coding gene on chromosome 3p12.3, encoding Contactin-3 (Q9P232). Contactins mediate cell surface interactions during nervous system development.

Predicted to be involved in cell adhesion. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in neuron projection.

Source: NCBI Gene 5067 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 180 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_020872

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2173
Approved symbol	CNTN3
Name	contactin 3
Location	3p12.3
Locus type	gene with protein product
Status	Approved
Aliases	BIG-1
Ensembl gene	ENSG00000113805
Ensembl biotype	protein_coding
OMIM	601325
Entrez	5067

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000263665, ENST00000477856, ENST00000906976, ENST00000962149, ENST00000962150

RefSeq mRNA: 2 — MANE Select: NM_020872 NM_001393376, NM_020872

CCDS: CCDS33790

Canonical transcript exons

ENST00000263665 — 23 exons

Exon	Start	End
ENSE00000773971	74267266	74267378
ENSE00000773972	74285305	74285491
ENSE00000773973	74295121	74295236
ENSE00000773974	74297957	74298191
ENSE00000773977	74301398	74301547
ENSE00000773978	74301647	74301805
ENSE00000773979	74302690	74302807
ENSE00000773980	74334735	74334910
ENSE00000773981	74336531	74336658
ENSE00000773982	74361890	74362040
ENSE00000966963	74365566	74365702
ENSE00001142855	74364467	74364596
ENSE00001204236	74369189	74369373
ENSE00001244155	74299868	74299938
ENSE00001244222	74371196	74371399
ENSE00001244229	74262568	74264501
ENSE00001244237	74424845	74424940
ENSE00001430676	74486456	74486631
ENSE00001498193	74499659	74499785
ENSE00001498194	74521058	74521192
ENSE00001680603	74369889	74369991
ENSE00003551851	74266481	74266649
ENSE00003935039	74614391	74614659

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 95.92.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	95.92	gold quality
endothelial cell	CL:0000115	95.69	gold quality
right uterine tube	UBERON:0001302	91.99	gold quality
seminal vesicle	UBERON:0000998	91.85	gold quality
caput epididymis	UBERON:0004358	91.78	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.50	gold quality
bronchial epithelial cell	CL:0002328	91.34	gold quality
middle temporal gyrus	UBERON:0002771	90.07	gold quality
superior frontal gyrus	UBERON:0002661	90.03	gold quality
bronchus	UBERON:0002185	89.63	gold quality
pigmented layer of retina	UBERON:0001782	88.45	gold quality
epithelial cell of pancreas	CL:0000083	88.35	silver quality
postcentral gyrus	UBERON:0002581	87.92	gold quality
entorhinal cortex	UBERON:0002728	87.61	gold quality
primary visual cortex	UBERON:0002436	87.40	gold quality
parietal lobe	UBERON:0001872	86.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.91	gold quality
occipital lobe	UBERON:0002021	84.80	gold quality
right frontal lobe	UBERON:0002810	84.13	gold quality
germinal epithelium of ovary	UBERON:0001304	84.07	gold quality
cerebral cortex	UBERON:0000956	83.77	gold quality
ascending aorta	UBERON:0001496	83.65	gold quality
frontal cortex	UBERON:0001870	83.55	gold quality
thoracic aorta	UBERON:0001515	83.45	gold quality
neocortex	UBERON:0001950	83.22	gold quality
temporal lobe	UBERON:0001871	83.19	gold quality
oviduct epithelium	UBERON:0004804	83.07	gold quality
ventricular zone	UBERON:0003053	82.84	gold quality
cardiac muscle of right atrium	UBERON:0003379	82.51	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

176 targeting CNTN3, 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-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230

Literature-anchored findings (GeneRIF, showing 3)

• BIG1 and BIG2 have roles in endomembrane organization (PMID:20360857)
• SLC1A1, SLC16A9, and CNTN3 Are Potential Biomarkers for the Occurrence of Colorectal Cancer. (PMID:32566650)
• Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period. (PMID:35030990)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cntn3	ENSMUSG00000030075
rattus_norvegicus	Cntn3	ENSRNOG00000006144

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), IGSF9 (ENSG00000085552), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), IGDCC4 (ENSG00000103742), IGSF21 (ENSG00000117154), CNTN6 (ENSG00000134115), CHL1 (ENSG00000134121), PTPRQ (ENSG00000139304), CNTN4 (ENSG00000144619), 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-3 — Q9P232 (reviewed: Q9P232)

Alternative names: Brain-derived immunoglobulin superfamily protein 1, Plasmacytoma-associated neuronal glycoprotein

All UniProt accessions (1): Q9P232

UniProt curated annotations — full annotation on UniProt →

Function. Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity.

Subunit / interactions. Interacts with PTPRG.

Subcellular location. Cell membrane.

Tissue specificity. In brain, it is expressed in frontal lobe, occipital lobe, cerebellum and amygdala.

Similarity. Belongs to the immunoglobulin superfamily. Contactin family.

RefSeq proteins (2): NP_001380305, NP_065923* (*=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
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF00041, PF07679, PF13927

UniProt features (40 total): glycosylation site 11, domain 10, disulfide bond 6, strand 6, sequence variant 2, signal peptide 1, chain 1, region of interest 1, lipid moiety-binding region 1, propeptide 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1WJ3	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P232-F1	86.80	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): 1002

Disulfide bonds (6): 50–100, 144–196, 249–297, 339–386, 431–479, 521–577

Glycosylation sites (11): 65, 193, 375, 468, 489, 765, 860, 895, 913, 931, 956

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: 116 (showing top): CHANDRAN_METASTASIS_DN, MODULE_206, GOCC_NEURON_PROJECTION, TGCCTTA_MIR124A, LEE_CALORIE_RESTRICTION_NEOCORTEX_DN, chr3p12, GOCC_SIDE_OF_MEMBRANE, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, CHICAS_RB1_TARGETS_GROWING, CHICAS_RB1_TARGETS_CONFLUENT, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN, BRIDEAU_IMPRINTED_GENES, REACTOME_POST_TRANSLATIONAL_MODIFICATION_SYNTHESIS_OF_GPI_ANCHORED_PROTEINS, GSE13522_WT_VS_IFNG_KO_SKIN_UP, SMCHD1_TARGET_GENES

GO Biological Process (1): cell adhesion (GO:0007155)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), neuron projection (GO:0043005), 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
cellular anatomical structure	3
membrane	2
cellular process	1
binding	1
cell periphery	1
plasma membrane bounded cell projection	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNTN3	PTPRG	P23470	772
CNTN3	NTNG1	Q9Y2I2	445
CNTN3	SUSD1	Q6UWL2	429
CNTN3	FLRT1	Q9NZU1	421
CNTN3	LTAP1	Q9BWL3	415
CNTN3	IFRD2	Q12894	413
CNTN3	SEMA6D	Q8NFY4	413
CNTN3	MEGF11	A6BM72	408
CNTN3	DMRT3	Q9NQL9	406
CNTN3	WNT7A	O00755	406
CNTN3	EGF	P01133	394
CNTN3	OSBPL9	Q96SU4	389
CNTN3	PDZRN3	Q9UPQ7	386
CNTN3	JAG1	P78504	383
CNTN3	INPP5J	Q15735	383

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CNTN3	APP	psi-mi:“MI:0407”(direct interaction)	0.440
CNTN3	APLP1	psi-mi:“MI:0407”(direct interaction)	0.440
App	CNTN3	psi-mi:“MI:0407”(direct interaction)	0.440
Dlg4	CNTN3	psi-mi:“MI:0407”(direct interaction)	0.440

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	127
Likely benign	19
Benign	12

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
57773	GRCh38/hg38 3p13-12.3(chr3:70296167-74865078)x1	Pathogenic
1676304	GRCh37/hg19 3p13-q12.1(chr3:72488757-99614758)x3	Likely pathogenic

SpliceAI

5377 predictions. Top by Δscore:

Variant	Effect	Δscore
3:74266477:TTACT:T	donor_loss	1.0000
3:74266478:TA:T	donor_loss	1.0000
3:74266479:A:AC	donor_gain	1.0000
3:74266479:AC:A	donor_loss	1.0000
3:74266480:C:CC	donor_gain	1.0000
3:74266480:CT:C	donor_gain	1.0000
3:74266480:CTG:C	donor_gain	1.0000
3:74266480:CTGG:C	donor_gain	1.0000
3:74267264:A:AC	donor_gain	1.0000
3:74267265:C:CC	donor_gain	1.0000
3:74267380:T:C	acceptor_gain	1.0000
3:74267380:T:TC	acceptor_gain	1.0000
3:74285303:A:AC	donor_gain	1.0000
3:74285303:ACG:A	donor_gain	1.0000
3:74285304:C:CC	donor_gain	1.0000
3:74285304:CGC:C	donor_gain	1.0000
3:74285304:CGCG:C	donor_gain	1.0000
3:74298188:CTGG:C	acceptor_gain	1.0000
3:74298192:C:CC	acceptor_gain	1.0000
3:74299866:A:AC	donor_gain	1.0000
3:74299866:ACAT:A	donor_gain	1.0000
3:74299866:ACATC:A	donor_gain	1.0000
3:74299867:C:CC	donor_gain	1.0000
3:74299867:CAT:C	donor_gain	1.0000
3:74299867:CATC:C	donor_gain	1.0000
3:74299867:CATCC:C	donor_gain	1.0000
3:74299878:A:AC	donor_gain	1.0000
3:74299939:C:CC	acceptor_gain	1.0000
3:74299949:C:CT	acceptor_gain	1.0000
3:74299950:A:T	acceptor_gain	1.0000

AlphaMissense

6705 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:74267314:C:A	W923C	1.000
3:74267314:C:G	W923C	1.000
3:74369352:C:A	W261C	1.000
3:74369352:C:G	W261C	1.000
3:74369354:A:G	W261R	1.000
3:74369354:A:T	W261R	1.000
3:74486628:C:A	W62C	1.000
3:74486628:C:G	W62C	1.000
3:74267316:A:G	W923R	0.999
3:74267316:A:T	W923R	0.999
3:74285373:A:T	V879D	0.999
3:74295169:C:A	W823C	0.999
3:74295169:C:G	W823C	0.999
3:74295171:A:G	W823R	0.999
3:74295171:A:T	W823R	0.999
3:74299873:A:G	W721R	0.999
3:74299873:A:T	W721R	0.999
3:74301472:C:G	R674P	0.999
3:74301475:A:G	F673S	0.999
3:74301663:C:A	W643C	0.999
3:74301663:C:G	W643C	0.999
3:74301665:A:G	W643R	0.999
3:74301665:A:T	W643R	0.999
3:74301738:C:A	W618C	0.999
3:74301738:C:G	W618C	0.999
3:74301740:A:G	W618R	0.999
3:74301740:A:T	W618R	0.999
3:74334800:A:G	W535R	0.999
3:74334800:A:T	W535R	0.999
3:74336574:G:C	N483K	0.999

dbSNP variants (sampled 300 via entrez): RS1000011596 (3:74399501 C>G,T), RS1000024734 (3:74319860 G>C,T), RS1000040259 (3:74279574 T>A,C), RS1000040391 (3:74521612 TAAAG>T), RS1000044460 (3:74507921 C>T), RS1000049758 (3:74279951 T>C), RS1000053197 (3:74322032 A>G,T), RS1000060397 (3:74571754 A>G), RS1000062305 (3:74447928 T>C), RS1000065888 (3:74598318 C>T), RS1000081062 (3:74444217 C>A), RS1000081337 (3:74550056 T>C), RS1000082245 (3:74362218 A>C,G), RS1000089456 (3:74322219 G>C), RS1000098077 (3:74378480 C>T)

Disease associations

OMIM: gene MIM:601325 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002927_16	Mercury levels	6.000000e-07
GCST002936_24	Cadmium levels	9.000000e-07
GCST004523_6	Resting metabolic rate	6.000000e-06
GCST005788_27	Heart rate response to recovery post exercise	1.000000e-09
GCST005847_5	Heart rate response to recovery post exercise (20 sec)	8.000000e-09
GCST005850_3	Heart rate response to recovery post exercise (30 sec)	1.000000e-09
GCST006221_2	White matter growth	3.000000e-06
GCST006624_80	Systolic blood pressure	1.000000e-09
GCST007335_9	Age at first sexual intercourse	5.000000e-08
GCST009391_1183	Metabolite levels	9.000000e-06
GCST90013421_27	Left-handedness	3.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0008004	resting metabolic rate measurement
EFO:0009185	heart rate response to recovery post exercise
EFO:0009335	white matter growth measurement
EFO:0006335	systolic blood pressure
EFO:0009749	age at first sexual intercourse measurement
EFO:0010454	adenosine monophosphate measurement
EFO:0009902	handedness

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
rs502114	CNTN3		0.00	0

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	4
methylmercuric chloride	affects cotreatment, decreases expression	3
belinostat	decreases expression, affects cotreatment	2
Aflatoxin B1	decreases methylation, increases expression	2
trichostatin A	increases expression	1
diallyl trisulfide	increases expression	1
dichloroacetonitrile	affects response to substance	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Poly(amidoamine)	increases expression	1
bisphenol S	decreases methylation	1
incobotulinumtoxinA	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Clorgyline	increases expression	1
Copper	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Progesterone	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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