CNTN1

Summary

CNTN1 (contactin 1, HGNC:2171) is a protein-coding gene on chromosome 12q12, encoding Contactin-1 (Q12860). Contactins mediate cell surface interactions during nervous system development.

The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1272 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Compton-North congenital myopathy (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 737 total — 18 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001843

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2171
Approved symbol	CNTN1
Name	contactin 1
Location	12q12
Locus type	gene with protein product
Status	Approved
Aliases	F3, GP135
Ensembl gene	ENSG00000018236
Ensembl biotype	protein_coding
OMIM	600016
Entrez	1272

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000347616, ENST00000348761, ENST00000547702, ENST00000547849, ENST00000548005, ENST00000548481, ENST00000550305, ENST00000551295, ENST00000551424, ENST00000552248, ENST00000552913, ENST00000901030, ENST00000901031, ENST00000901032, ENST00000959376

RefSeq mRNA: 4 — MANE Select: NM_001843 NM_001256063, NM_001256064, NM_001843, NM_175038

CCDS: CCDS58225, CCDS8737, CCDS8738

Canonical transcript exons

ENST00000551295 — 24 exons

Exon	Start	End
ENSE00000735999	40910073	40910105
ENSE00000736000	40918639	40918771
ENSE00000736002	40922256	40922428
ENSE00000736004	40924557	40924652
ENSE00000736006	40929796	40930002
ENSE00000736011	40933461	40933560
ENSE00000736014	40933697	40933878
ENSE00000736016	40936781	40936905
ENSE00000736018	40937570	40937687
ENSE00000736020	40939335	40939485
ENSE00000736022	40943597	40943724
ENSE00000736024	40943995	40944170
ENSE00000736030	40993120	40993269
ENSE00000736040	41027857	41027969
ENSE00000736042	41029063	41029219
ENSE00000887898	40959114	40959234
ENSE00000887899	40980909	40981067
ENSE00002331215	41069959	41072415
ENSE00002334214	40692439	40692592
ENSE00002387517	40908357	40908493
ENSE00003459380	41014228	41014298
ENSE00003519988	41016682	41016916
ENSE00003554425	41020337	41020440
ENSE00003566832	41025150	41025336

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 98.63.

FANTOM5 (CAGE): breadth broad, TPM avg 11.9599 / max 1133.9355, expressed in 465 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125060	8.3905	440
125077	0.8216	99
125062	0.4879	126
125078	0.4543	82
125063	0.2723	71
125071	0.2691	104
125068	0.2503	75
125061	0.1624	89
125073	0.1572	67
125072	0.1509	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.63	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.92	gold quality
endothelial cell	CL:0000115	96.98	gold quality
superior frontal gyrus	UBERON:0002661	96.89	gold quality
postcentral gyrus	UBERON:0002581	96.58	gold quality
entorhinal cortex	UBERON:0002728	96.43	gold quality
prefrontal cortex	UBERON:0000451	96.17	gold quality
cerebellar cortex	UBERON:0002129	95.91	gold quality
primary visual cortex	UBERON:0002436	95.91	gold quality
amygdala	UBERON:0001876	95.89	gold quality
cerebellar hemisphere	UBERON:0002245	95.87	gold quality
temporal lobe	UBERON:0001871	95.83	gold quality
parietal lobe	UBERON:0001872	95.65	gold quality
islet of Langerhans	UBERON:0000006	95.46	gold quality
cerebellum	UBERON:0002037	95.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.32	gold quality
Ammon’s horn	UBERON:0001954	95.25	gold quality
frontal cortex	UBERON:0001870	94.92	gold quality
substantia nigra pars compacta	UBERON:0001965	94.86	gold quality
cerebral cortex	UBERON:0000956	94.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.65	gold quality
neocortex	UBERON:0001950	94.63	gold quality
occipital lobe	UBERON:0002021	94.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.38	gold quality
cingulate cortex	UBERON:0003027	94.32	gold quality
paraflocculus	UBERON:0005351	94.17	gold quality
anterior cingulate cortex	UBERON:0009835	94.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.07	gold quality
pons	UBERON:0000988	93.96	gold quality
right frontal lobe	UBERON:0002810	93.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	622.59
E-MTAB-5061	yes	28.88
E-GEOD-84465	yes	23.83
E-GEOD-81547	yes	21.22
E-HCAD-25	yes	15.55
E-GEOD-83139	yes	9.77
E-ANND-3	yes	6.20
E-ENAD-27	no	7.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

204 targeting CNTN1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
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-4533	100.00	69.48	2758
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
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-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 32)

• F3 acts as a functional ligand for Notch during oligodendrocyte maturation. (PMID:14567914)
• The repulsive properties of contactin may be a key factor in glioma disaggregation, and may contribute to the diffuse infiltration pattern characteristic of glioma cells in human brain. (PMID:16078236)
• Mutations in CNTN1, a neural adhesion molecule and neuromuscular junction protein, cause a familial form of lethal congenital myopathy. (PMID:19026398)
• VEGF-C mediated biological function through transcription of CNTN-1, which is implicated in tumor invasion and metastasis. (PMID:21482472)
• Data revealed that knockdown of VEGFR-3 with the shRNA lentiviral vector resulted in down-regulation of the downstream neural cell adhesion molecule contactin-1 (CNTN-1). (PMID:21805024)
• report the cocrystal structure of the carbonic anhydrase-like domain of PTPRZ bound to tandem Ig repeats of CNTN1 and binding assays to show that PTPRZ binds specifically to CNTN1 expressed at the surface of oligodendrocyte precursor cells (PMID:21969550)
• a completely novel function for F3/Contactin - modulator of neurogenesis (PMID:22360968)
• A high expression of CNTN1 was markedly associated with the regional lymph node metastasis of patients with oral squamous cell carcinoma. (PMID:22580838)
• The expression of CNTN-1 is upregulated in esophageal squamous cell carcinoma tissue and is related to stage and lymphatic invasion. Thus, it may be involved in the pathogenesis & progression of esophageal squamous cell carcinoma. (PMID:22581910)
• activation of AKT plays a role in contactin-1-mediated downregulation of E-cadherin. (PMID:23724143)
• anti-CNTN1 IgG4 antibodies are associated with subacute onset of chronic inflammatory demyelinating polyneuropathy symptoms, sensory ataxia, and good response to corticosteroids. (PMID:25808373)
• under hypoxia conditions, elevated HIF-1alpha seems to up-regulate contactin-1 expression and by this activate RhoA and facilitate migration of cancer cells. (PMID:25916117)
• CNTN-1 is closely related with multidrug resistance of lung adenocarcinoma. (PMID:25960233)
• Structurally, CASPR2 is highly glycosylated and has an overall compact architecture. CASPR2 associates with micromolar affinity with CNTN1 but, under the same conditions, it does not interact with any of the other members of the contactin family. (PMID:26721881)
• CNTN1 is a new gene which can be regulated by RET/PTC3 (Ret proto-oncogene and Ret-activating protein ELE1) rearrangement gene and the protein level of CNTN1 is increasing in thyroid cancer. (PMID:26722434)
• CNTN1 promotes prostate cancer progression. (PMID:26795349)
• Proteolipid protein 1 and contactin 1 gene variation modulates interhemispheric integration (PMID:27864734)
• CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the Epithelial-Mesenchymal Transition process by activating the PI3K/Akt signaling pathway. (PMID:28934754)
• CNTN1 promotes growth, metastasis and invasion of Hs578T breast cancer cell line. (PMID:29673312)
• Findings suggest that PLP1 and CNTN1 gene variations modulate specific aspects of callosal microstructure that are in line with their gene function. (PMID:30094605)
• Contactin-1 Is Reduced in Cerebrospinal Fluid of Parkinson’s Disease Patients and Is Present within Lewy Bodies. (PMID:32806791)
• Upregulated CNTN1 is associated with lymph node metastasis and poor prognosis of colorectal cancer. (PMID:33104020)
• Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel Towards Prostate Cancer Relapse. (PMID:33578925)
• Serum Contactin-1 in CIDP: A Cross-Sectional Study. (PMID:34285092)
• Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy. (PMID:34600965)
• Characteristics of Anti-Contactin1 Antibody-Associated Autoimmune Nodopathies With Concomitant Membranous Nephropathy. (PMID:34675937)
• MicroRNA-200c-targeted contactin 1 facilitates the replication of influenza A virus by accelerating the degradation of MAVS. (PMID:35171955)
• Neurofilament-light and contactin-1 association with long-term brain atrophy in natalizumab-treated relapsing-remitting multiple sclerosis. (PMID:36062492)
• Neuroaxonal and Glial Markers in Patients of the Same Age With Multiple Sclerosis. (PMID:36543540)
• The molecular mechanism of gamma-aminobutyric acid against AD: the role of CEBPalpha/circAPLP2/miR-671-5p in regulating CNTN1/2 expression. (PMID:36734072)
• Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis. (PMID:36893151)
• Key Molecules in Bladder Cancer Affect Patient Prognosis and Immunotherapy Efficacy: Further Exploration for CNTN1 and EMP1. (PMID:37437228)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cntn1b	ENSDARG00000045685
danio_rerio	cntn1a	ENSDARG00000087843
mus_musculus	Cntn1	ENSMUSG00000055022
rattus_norvegicus	Cntn1	ENSRNOG00000004438

Paralogs (36): 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), 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-1 — Q12860 (reviewed: Q12860)

Alternative names: Glycoprotein gp135, Neural cell surface protein F3

All UniProt accessions (6): Q12860, F8VQW3, F8VUI8, F8VUI9, F8VX96, H0YIJ1

UniProt curated annotations — full annotation on UniProt →

Function. Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between axons and myelinating glial cells via its association with CNTNAP1. Participates in oligodendrocytes generation by acting as a ligand of NOTCH1. Its association with NOTCH1 promotes NOTCH1 activation through the released notch intracellular domain (NICD) and subsequent translocation to the nucleus. Interaction with TNR induces a repulsion of neurons and an inhibition of neurite outgrowth.

Subunit / interactions. Monomer. Interacts with CNTNAP1 in cis form. Binds to the carbonic-anhydrase like domain of PTPRZ1. Interacts with NOTCH1 and TNR. Detected in a complex with NRCAM and PTPRB. Interacts with TASOR.

Subcellular location. Cell membrane Cell membrane.

Tissue specificity. Strongly expressed in brain and in neuroblastoma and retinoblastoma cell lines. Lower levels of expression in lung, pancreas, kidney and skeletal muscle.

Disease relevance. Congenital myopathy 12 (CMYO12) [MIM:612540] A lethal, autosomal recessive, congenital myopathy characterized by fetal akinesia, neonatal hypotonia, severe muscle weakness, loss of beta2-syntrophin and alpha-dystrobrevin from the muscle sarcolemma and disruption of sarcomeres with disorganization of the Z band. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the immunoglobulin superfamily. Contactin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q12860-1	1	yes
Q12860-2	2
Q12860-3	3

RefSeq proteins (4): NP_001242992, NP_001242993, NP_001834, NP_778203 (=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
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036992	Contactin-1_Ig1	Domain
IPR047100	Contactin-1_Ig-like_3	Domain
IPR047101	Contactin-1_Ig6	Domain
IPR047102	Contactin-1_2_Ig1	Domain

Pfam: PF00041, PF00047, PF07679, PF13927

UniProt features (72 total): strand 25, domain 10, glycosylation site 9, disulfide bond 6, sequence conflict 5, helix 4, splice variant 3, sequence variant 3, turn 2, signal peptide 1, chain 1, region of interest 1, lipid moiety-binding region 1, propeptide 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3S97	X-RAY DIFFRACTION	2.3
2EE2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12860-F1	87.29	0.62

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): 993

Disulfide bonds (6): 65–114, 158–211, 263–310, 352–391, 436–484, 526–583

Glycosylation sites (9): 208, 258, 338, 457, 473, 494, 521, 591, 933

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2122948	Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-2979096	NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-373760	L1CAM interactions
R-HSA-447043	Neurofascin interactions

MSigDB gene sets: 772 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, MORF_RAGE, GOBP_HINDBRAIN_DEVELOPMENT, REACTOME_SIGNALING_BY_NOTCH, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_PROTEIN_ACTIVATION_CASCADE, GOBP_METENCEPHALON_DEVELOPMENT, ZHAN_MULTIPLE_MYELOMA_PR_DN, GOBP_BEHAVIOR, GOBP_REGULATION_OF_WOUND_HEALING

GO Biological Process (14): cell adhesion (GO:0007155), Notch signaling pathway (GO:0007219), axon guidance (GO:0007411), brain development (GO:0007420), locomotory behavior (GO:0007626), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), positive regulation of sodium ion transport (GO:0010765), positive regulation of neuron projection development (GO:0010976), cerebellum development (GO:0021549), central nervous system myelin formation (GO:0032289), cell-cell adhesion (GO:0098609), neuron projection development (GO:0031175), myelination (GO:0042552)

GO Molecular Function (3): carbohydrate binding (GO:0030246), cell-cell adhesion mediator activity (GO:0098632), protein binding (GO:0005515)

GO Cellular Component (9): plasma membrane (GO:0005886), membrane (GO:0016020), axon (GO:0030424), presynaptic membrane (GO:0042734), postsynaptic membrane (GO:0045211), extracellular exosome (GO:0070062), side of membrane (GO:0098552), glutamatergic synapse (GO:0098978), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by NOTCH1	1
Signaling by NOTCH2	1
Axon guidance	1
L1CAM interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
membrane	2
cellular anatomical structure	2
synaptic membrane	2
cellular process	1
cell surface receptor signaling pathway	1
axonogenesis	1
neuron projection guidance	1
central nervous system development	1
animal organ development	1
head development	1
behavior	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of sodium ion transport	1
sodium ion transport	1
positive regulation of monoatomic ion transport	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
metencephalon development	1
anatomical structure development	1
central nervous system myelination	1
myelin assembly	1
cell adhesion	1
neuron development	1
plasma membrane bounded cell projection organization	1
axon ensheathment	1
cell-cell adhesion	1
cell adhesion mediator activity	1
cell periphery	1
neuron projection	1
presynapse	1
postsynapse	1
extracellular vesicle	1
leaflet of membrane bilayer	1
synapse	1
cell junction	1

Protein interactions and networks

STRING

2540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNTN1	CNTNAP1	P78357	997
CNTN1	NFASC	O94856	915
CNTN1	PTPRZ1	P23471	752
CNTN1	PTPRB	P23467	707
CNTN1	FLOT1	O75955	698
CNTN1	SNTB2	Q13425	680
CNTN1	GLDN	Q6ZMI3	669
CNTN1	GNPAT	O15228	649
CNTN1	TJP1	Q07157	642
CNTN1	PODXL	O00592	620
CNTN1	CRB3	Q9BUF7	595
CNTN1	HAPLN2	Q9GZV7	584
CNTN1	PRNP	P04156	557
CNTN1	APP	P05067	554
CNTN1	MBP	P02686	554

IntAct

81 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
MCAM	CNTN1	psi-mi:“MI:0914”(association)	0.750
CNTN1	MCAM	psi-mi:“MI:0915”(physical association)	0.750
MCAM	CNTN1	psi-mi:“MI:0407”(direct interaction)	0.750
CNTN1	NRCAM	psi-mi:“MI:0915”(physical association)	0.700
CNTN1	NRCAM	psi-mi:“MI:0407”(direct interaction)	0.700
NRCAM	CNTN1	psi-mi:“MI:0407”(direct interaction)	0.700
NRCAM	CNTN1	psi-mi:“MI:0403”(colocalization)	0.700
PTPRZ1	CNTN1	psi-mi:“MI:0915”(physical association)	0.610
PTPRZ1	CNTN1	psi-mi:“MI:0407”(direct interaction)	0.610
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
HOXB5	VPS37C	psi-mi:“MI:0914”(association)	0.530
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CCNL2	ZBTB43	psi-mi:“MI:0914”(association)	0.530
RYK	PCDH7	psi-mi:“MI:0914”(association)	0.530
CNTNAP2	CNTN1	psi-mi:“MI:0915”(physical association)	0.460
CNTN1	CNTNAP2	psi-mi:“MI:0403”(colocalization)	0.460
CNTN1	CNTNAP2	psi-mi:“MI:0915”(physical association)	0.460
CNTNAP2	CNTN1	psi-mi:“MI:0403”(colocalization)	0.460
CNTN1	CNTN1	psi-mi:“MI:0407”(direct interaction)	0.440
CNTN1	Ptprz1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (96): CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A6I8TCE0, B0X4T2, F1NY98, O00533, O35158, O55005, O60469, O89026, O97394, P12960, P14781, P16092, P17790, P18460, P18461, P21802, P21803, P28685, P29074, P35331, P35832, P57097, P70232, P97686, Q12860, Q12866, Q28106, Q32MD9, Q3UH53, Q4KMG0, Q60805, Q61851, Q63198, Q7Z5N4, Q7ZXX1, Q810U4, Q8AV58, Q8AXZ4, Q8JG38, Q8VHZ8

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

2 interactions.

A	Effect	B	Mechanism
CNTNAP1	“up-regulates activity”	CNTN1	relocalization
CNTNAP2	“up-regulates activity”	CNTN1	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
axonogenesis	6	11.6×	3e-03
central nervous system development	7	9.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	6
Uncertain significance	289
Likely benign	324
Benign	70

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
1432053	NM_001843.4(CNTN1):c.62del (p.Glu21fs)	Pathogenic
1445514	NM_001843.4(CNTN1):c.1615del (p.Val539fs)	Pathogenic
1455215	NM_001843.4(CNTN1):c.2632_2636del (p.Phe878fs)	Pathogenic
2071790	NM_001843.4(CNTN1):c.2273_2274del (p.Thr758fs)	Pathogenic
2082836	NM_001843.4(CNTN1):c.1470_1471del (p.Gly491fs)	Pathogenic
2126618	NM_001843.4(CNTN1):c.268C>T (p.Arg90Ter)	Pathogenic
2910519	NM_001843.4(CNTN1):c.1711C>T (p.Arg571Ter)	Pathogenic
2995467	NM_001843.4(CNTN1):c.482dup (p.Tyr162fs)	Pathogenic
2997007	NM_001843.4(CNTN1):c.739C>T (p.Gln247Ter)	Pathogenic
3069138	CNTN1, EX2-15DEL and EX18-19DEL	Pathogenic
3662140	NM_001843.4(CNTN1):c.1362G>A (p.Trp454Ter)	Pathogenic
3716597	NM_001843.4(CNTN1):c.2512G>T (p.Glu838Ter)	Pathogenic
469421	NM_001843.4(CNTN1):c.2795C>A (p.Ser932Ter)	Pathogenic
537192	NM_001843.4(CNTN1):c.2923G>T (p.Glu975Ter)	Pathogenic
568623	NM_001843.4(CNTN1):c.215dup (p.Val74fs)	Pathogenic
651866	NM_001843.4(CNTN1):c.2506del (p.Lys835_Ile836insTer)	Pathogenic
655024	NM_001843.4(CNTN1):c.1074del (p.Ile359fs)	Pathogenic
9539	NM_001843.4(CNTN1):c.871dup (p.Ser291fs)	Pathogenic
1348320	NM_001843.4(CNTN1):c.2597_2710+7delinsTT	Likely pathogenic
2875068	NM_001843.4(CNTN1):c.94+2T>C	Likely pathogenic
2886308	NM_001843.4(CNTN1):c.704-1G>A	Likely pathogenic
3722051	NM_001843.4(CNTN1):c.2711-1G>A	Likely pathogenic
469412	NM_001843.4(CNTN1):c.1683+1G>A	Likely pathogenic
620468	NM_001843.4(CNTN1):c.202C>T (p.Arg68Ter)	Likely pathogenic

SpliceAI

6145 predictions. Top by Δscore:

Variant	Effect	Δscore
12:40879329:T:G	donor_gain	1.0000
12:40908349:T:A	acceptor_gain	1.0000
12:40908352:TGCA:T	acceptor_loss	1.0000
12:40908355:A:AC	acceptor_loss	1.0000
12:40908355:A:AG	acceptor_gain	1.0000
12:40908356:G:GG	acceptor_gain	1.0000
12:40908356:GGT:G	acceptor_gain	1.0000
12:40908490:GCAG:G	donor_gain	1.0000
12:40908493:GG:G	donor_loss	1.0000
12:40908494:GTAAG:G	donor_loss	1.0000
12:40908495:T:G	donor_loss	1.0000
12:40918716:G:GT	donor_gain	1.0000
12:40918720:G:GT	donor_gain	1.0000
12:40918721:A:T	donor_gain	1.0000
12:40918765:TTTAC:T	donor_gain	1.0000
12:40918772:G:GG	donor_gain	1.0000
12:40922252:ATAG:A	acceptor_loss	1.0000
12:40922253:T:G	acceptor_gain	1.0000
12:40922253:TA:T	acceptor_loss	1.0000
12:40922254:A:AG	acceptor_gain	1.0000
12:40922254:AGAT:A	acceptor_gain	1.0000
12:40922254:AGATG:A	acceptor_gain	1.0000
12:40922255:G:GT	acceptor_gain	1.0000
12:40922255:GAT:G	acceptor_gain	1.0000
12:40922255:GATG:G	acceptor_gain	1.0000
12:40922255:GATGG:G	acceptor_gain	1.0000
12:40922424:TGGAT:T	donor_gain	1.0000
12:40922425:GGAT:G	donor_gain	1.0000
12:40922425:GGATG:G	donor_gain	1.0000
12:40922426:GAT:G	donor_gain	1.0000

AlphaMissense

6689 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:40922259:G:C	W77C	1.000
12:40922259:G:T	W77C	1.000
12:40933716:T:A	W275R	1.000
12:40933716:T:C	W275R	1.000
12:40933718:G:C	W275C	1.000
12:40933718:G:T	W275C	1.000
12:40937644:C:A	N395K	1.000
12:40937644:C:G	N395K	1.000
12:40918739:T:G	C65W	0.999
12:40922257:T:A	W77R	0.999
12:40922257:T:C	W77R	0.999
12:40922258:G:C	W77S	0.999
12:40922321:T:C	L98P	0.999
12:40922362:T:G	Y112D	0.999
12:40922368:T:A	C114S	0.999
12:40922368:T:C	C114R	0.999
12:40922369:G:C	C114S	0.999
12:40922370:T:G	C114W	0.999
12:40922382:T:A	N118K	0.999
12:40922382:T:G	N118K	0.999
12:40929813:T:A	W172R	0.999
12:40929813:T:C	W172R	0.999
12:40929815:G:C	W172C	0.999
12:40929815:G:T	W172C	0.999
12:40929886:T:C	L196P	0.999
12:40929930:T:C	C211R	0.999
12:40929932:C:G	C211W	0.999
12:40933544:T:C	C263R	0.999
12:40933717:G:C	W275S	0.999
12:40933777:T:C	L295P	0.999

dbSNP variants (sampled 300 via entrez): RS1000015029 (12:41071298 C>A,T), RS1000018242 (12:40855466 T>G), RS1000020438 (12:40814341 G>A), RS1000022380 (12:40888963 G>A), RS1000040311 (12:40821069 T>G), RS1000041060 (12:40720143 G>A), RS1000049288 (12:40983070 C>T), RS1000058545 (12:40692000 T>G), RS1000062021 (12:40841429 T>G), RS1000062163 (12:40992886 C>G), RS1000064787 (12:40765378 C>A), RS1000073158 (12:40705028 C>T), RS1000075710 (12:40849436 T>C), RS1000095474 (12:40765696 C>G), RS1000104747 (12:41023396 A>G)

Disease associations

OMIM: gene MIM:600016 | disease phenotypes: MIM:612540

GenCC curated gene-disease

Disease	Classification	Inheritance
Compton-North congenital myopathy	Strong	Autosomal recessive
schizophrenia	No Known Disease Relationship	Unknown

Mondo (2): Compton-North congenital myopathy (MONDO:0012929), schizophrenia (MONDO:0005090)

Orphanet (1): Congenital lethal myopathy, Compton-North type (Orphanet:210163)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000268	Dolichocephaly
HP:0000300	Oval face
HP:0000316	Hypertelorism
HP:0001166	Arachnodactyly
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001284	Areflexia
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001518	Small for gestational age
HP:0001522	Death in infancy
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001622	Premature birth
HP:0001989	Fetal akinesia sequence
HP:0002033	Poor suck
HP:0002304	Akinesia
HP:0002705	High, narrow palate
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004415	Pulmonary artery stenosis
HP:0009473	Joint contracture of the hand
HP:0010557	Overlapping fingers
HP:0011968	Feeding difficulties
HP:0012385	Camptodactyly
HP:0030799	Scaphocephaly
HP:0033333	Jaw contracture

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000189_25	Protein quantitative trait loci	1.000000e-10
GCST002119_28	Metabolite levels (X-11787)	4.000000e-06
GCST002515_3	Pneumoconiosis in silica exposure	5.000000e-06
GCST002593_16	Dementia and core Alzheimer’s disease neuropathologic changes	5.000000e-06
GCST002759_22	Motion sickness	8.000000e-10
GCST003074_16	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	9.000000e-08
GCST005951_72	Body mass index	1.000000e-10
GCST005951_73	Body mass index	4.000000e-10
GCST006585_1816	Blood protein levels	1.000000e-11
GCST007355_4	Antidepressant treatment resistance (> 2 drugs prescribed)	5.000000e-07
GCST009325_75	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	6.000000e-14

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0005276	hydroxy-leucine measurement
EFO:0006801	Alzheimer’s disease neuropathologic change
EFO:0006928	motion sickness
EFO:0007707	cerebral amyloid deposition measurement
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567261	Myopathy, Congenital, Compton-North (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067142 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.42	Kd	37.92	nM	CHEMBL5653589
7.07	ED50	84.65	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148102: Binding affinity to human CNTN1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0379	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects reaction, increases expression, affects cotreatment, affects expression	9
sodium arsenite	increases expression	3
alpha-cobratoxin	decreases reaction, increases expression, decreases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Mecamylamine	decreases expression, decreases reaction, increases expression	2
Nickel	decreases expression	2
Nicotine	increases expression, decreases expression, decreases reaction	2
Tretinoin	decreases expression, increases expression	2
Tubocurarine	decreases expression, decreases reaction, increases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
trichostatin A	increases expression	1
diethyl maleate	increases expression	1
arsenite	decreases expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tobacco tar	decreases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
deguelin	decreases expression	1
2-palmitoylglycerol	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651144	Binding	Binding affinity to human CNTN1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety