CNTN4

contactin 4, the group of Contactins|I-set domain containing

Basic information

Region (hg38): 3:2098813-3057959

Links

ENSG00000144619 ∙ NCBI:152330 ∙ OMIM:607280 ∙ HGNC:2174 ∙ Uniprot:Q8IWV2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Disputed Evidence), mode of inheritance: AD
• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNTN4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNTN4 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				22	11	33
missense			71	6	4	81
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				1	3	4
non coding			2	1	82	85
Total	0	0	74	29	97

Variants in CNTN4

This is a list of pathogenic ClinVar variants found in the CNTN4 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-2484388-G-A		CNTN4-associated neurodevelopmental disorder	Uncertain significance (Jul 16, 2021)
3-2492876-C-A			Benign (May 10, 2021)
3-2493088-G-A			Benign (May 10, 2021)
3-2542692-G-T			Benign (May 10, 2021)
3-2543055-A-G			Benign (May 24, 2021)
3-2571094-G-A			Benign (Jun 19, 2021)
3-2571317-A-G			Benign (Nov 10, 2018)
3-2571534-C-A		not specified	Uncertain significance (Dec 05, 2024)
3-2571536-A-G		CNTN4-related disorder	Likely benign (Jun 11, 2019)
3-2571548-G-C			Benign (Dec 31, 2019)
3-2571552-C-G		not specified	Uncertain significance (Apr 25, 2022)
3-2592603-C-T			Benign (May 11, 2021)
3-2633505-C-T		Lip and oral cavity carcinoma	association (Jan 01, 2016)
3-2642630-A-G			Benign (May 10, 2021)
3-2642673-A-G			Benign (May 10, 2021)
3-2692523-A-C			Benign (May 10, 2021)
3-2735938-A-G			Benign (Nov 10, 2018)
3-2736142-T-C			Benign (Jun 20, 2021)
3-2736243-T-A		not specified	Uncertain significance (Nov 29, 2023)
3-2736274-T-G		not specified	Uncertain significance (Sep 29, 2023)
3-2736310-G-C		not specified	Uncertain significance (Dec 12, 2022)
3-2736331-C-A		not specified	Uncertain significance (Mar 23, 2023)
3-2736334-C-A		not specified	Uncertain significance (Feb 16, 2023)
3-2736475-A-T			Benign (Jun 18, 2021)
3-2736482-G-A			Benign (Nov 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNTN4	protein_coding	protein_coding	ENST00000397461	22	959149

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000330	1.00	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.572	524	562	0.932	0.0000305	6694
Missense in Polyphen		127	181.73	0.69885		2161
Synonymous	-2.37	253	209	1.21	0.0000126	2011
Loss of Function	4.46	20	56.0	0.357	0.00000322	625

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000214	0.000210
Ashkenazi Jewish	0.000595	0.000595
East Asian	0.000273	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000176	0.000176
Middle Eastern	0.000273	0.000272
South Asian	0.000131	0.000131
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity. May be involved in synaptogenesis.
• Disease: DISEASE: Note=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. {ECO:0000269|PubMed:15106122}.
• Pathway: Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.558
• rvis_EVS: -1.48
• rvis_percentile_EVS: 3.7

Haploinsufficiency Scores

• pHI: 0.125
• hipred: Y
• hipred_score: 0.575
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.200

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cntn4
• 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)

Gene ontology

• Biological process: homophilic cell adhesion via plasma membrane adhesion molecules;neuron cell-cell adhesion;nervous system development;axonogenesis;axon guidance;axonal fasciculation;brain development;neuron projection development;negative regulation of neuron differentiation;regulation of synaptic plasticity;dendrite self-avoidance
• Cellular component: extracellular region;plasma membrane;axon;anchored component of membrane
• Molecular function: cell-cell adhesion mediator activity