CNTN1

contactin 1, the group of I-set domain containing|Contactins

Basic information

Region (hg38): 12:40692438-41072415

Links

ENSG00000018236 ∙ NCBI:1272 ∙ OMIM:600016 ∙ HGNC:2171 ∙ Uniprot:Q12860 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
• Compton-North congenital myopathy (Moderate), mode of inheritance: AR
• Compton-North congenital myopathy (Supportive), mode of inheritance: AR
• Compton-North congenital myopathy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital myopathy 12	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	12899872; 19026398

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNTN1 gene.

• Compton-North congenital myopathy (451 variants)
• not provided (133 variants)
• not specified (39 variants)
• Inborn genetic diseases (27 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNTN1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	119	7	130
missense			209	13	3	225
nonsense	3	1				4
start loss						0
frameshift	8					8
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2	2			4
splice region			15	29	1	45
non coding				90	59	149
Total	11	3	216	222	69

Variants in CNTN1

This is a list of pathogenic ClinVar variants found in the CNTN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-40692480-C-A			Benign (Jun 29, 2020)
12-40692833-A-G			Benign (Jul 03, 2018)
12-40908032-T-G			Likely benign (Jun 19, 2018)
12-40908306-C-G			Benign (Aug 06, 2019)
12-40908421-A-G		not specified	Benign (Aug 08, 2016)
12-40908452-T-A		Compton-North congenital myopathy	Uncertain significance (May 03, 2022)
12-40908453-C-T		Compton-North congenital myopathy	Likely benign (Dec 31, 2022)
12-40908459-T-A		Compton-North congenital myopathy	Uncertain significance (Dec 06, 2022)
12-40908472-T-A		Compton-North congenital myopathy	Uncertain significance (Aug 09, 2020)
12-40908474-T-C		Compton-North congenital myopathy	Likely benign (Dec 25, 2020)
12-40908475-A-G		Compton-North congenital myopathy	Uncertain significance (Nov 08, 2022)
12-40908481-A-C		Compton-North congenital myopathy	Uncertain significance (Oct 03, 2023)
12-40908486-T-C		Compton-North congenital myopathy	Benign (Dec 11, 2023)
12-40908488-T-C		Compton-North congenital myopathy	Likely benign (Mar 08, 2023)
12-40908498-G-A		Compton-North congenital myopathy	Uncertain significance (Apr 04, 2018)
12-40908504-T-G		Compton-North congenital myopathy	Likely benign (Aug 17, 2022)
12-40908509-T-C		Compton-North congenital myopathy	Likely benign (Oct 12, 2021)
12-40908549-G-A			Likely benign (Jul 27, 2018)
12-40908567-G-A			Likely benign (Oct 09, 2018)
12-40908572-A-C			Likely benign (Jun 19, 2018)
12-40908622-A-G			Benign (Jun 19, 2018)
12-40909884-C-T			Likely benign (Jul 27, 2018)
12-40910023-A-C			Benign (Jun 14, 2018)
12-40910058-T-C		Compton-North congenital myopathy	Likely benign (Oct 30, 2023)
12-40910072-GA-G		Compton-North congenital myopathy	Pathogenic (Apr 04, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNTN1	protein_coding	protein_coding	ENST00000551295	23	379977

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.151	0.849	125709	2	36	125747	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.05	418	553	0.755	0.0000283	6667
Missense in Polyphen		139	238.08	0.58384		2914
Synonymous	-0.371	202	195	1.03	0.0000107	1936
Loss of Function	5.40	14	58.7	0.239	0.00000339	672

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000795	0.0000791
Middle Eastern	0.0000544	0.0000544
South Asian	0.000751	0.000686
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). {ECO:0000250}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Developmental Biology;Signal Transduction;Signaling by NOTCH1;Signaling by NOTCH2;Signaling by NOTCH;Neurofascin interactions;NOTCH2 Activation and Transmission of Signal to the Nucleus;L1CAM interactions;Notch signaling pathway;Axon guidance;Activated NOTCH1 Transmits Signal to the Nucleus (Consensus)

Recessive Scores

• pRec: 0.356

Intolerance Scores

• loftool: 0.351
• rvis_EVS: -1.06
• rvis_percentile_EVS: 7.48

Haploinsufficiency Scores

• pHI: 0.271
• hipred: Y
• hipred_score: 0.809
• ghis: 0.618

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.821

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cntn1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: cntn1b
• Affected structure: swimming behavior
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: cell adhesion;Notch signaling pathway;positive regulation of gene expression;positive regulation of sodium ion transport;positive regulation of neuron projection development;cerebellum development;neuron projection development;positive regulation of peptidyl-tyrosine phosphorylation
• Cellular component: membrane;myelin sheath;membrane raft;extracellular exosome;anchored component of postsynaptic membrane;anchored component of presynaptic membrane
• Molecular function: protein binding;carbohydrate binding