CNTNAP2

contactin associated protein 2, the group of Contactin associated protein family

Basic information

Region (hg38): 7:146116002-148420998

Links

ENSG00000174469 ∙ NCBI:26047 ∙ OMIM:604569 ∙ HGNC:13830 ∙ Uniprot:Q9UHC6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cortical dysplasia-focal epilepsy syndrome (Definitive), mode of inheritance: AR
• cortical dysplasia-focal epilepsy syndrome (Definitive), mode of inheritance: AR
• cortical dysplasia-focal epilepsy syndrome (Moderate), mode of inheritance: AR
• cortical dysplasia-focal epilepsy syndrome (Supportive), mode of inheritance: AR
• cortical dysplasia-focal epilepsy syndrome (Strong), mode of inheritance: AR
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AR
• complex neurodevelopmental disorder (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pitt-Hopkins like syndrome 1	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; Neurologic	16571880; 19896112; 19582487

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNTNAP2 gene.

• Cortical dysplasia-focal epilepsy syndrome (40 variants)
• not provided (11 variants)
• Inborn genetic diseases (5 variants)
• Pitt-Hopkins-like syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNTNAP2 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			9	316	5	330
missense			731	8	1	740
nonsense	25	9				34
start loss			1			1
frameshift	23	10	5			38
inframe indel		1	7			8
splice donor/acceptor (+/-2bp)	2	11	1			14
splice region		1	29	42	5	77
non coding			92	200	101	393
Total	50	31	846	524	107

Highest pathogenic variant AF is 0.000105

Variants in CNTNAP2

This is a list of pathogenic ClinVar variants found in the CNTNAP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-146116214-TGGCGGC-T			Benign (Aug 10, 2019)
7-146116423-G-T		Pitt-Hopkins-like syndrome • Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Jun 14, 2016)
7-146116438-C-T		Pitt-Hopkins-like syndrome • Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Jun 14, 2016)
7-146116483-C-T		Cortical dysplasia-focal epilepsy syndrome • Pitt-Hopkins-like syndrome	Uncertain significance (Jun 14, 2016)
7-146116535-AT-A		Cortical dysplasia-focal epilepsy syndrome • Pitt-Hopkins-like syndrome	Conflicting classifications of pathogenicity (Aug 20, 2019)
7-146116535-A-AT		Cortical dysplasia-focal epilepsy syndrome • Pitt-Hopkins-like syndrome	Uncertain significance (Jun 14, 2016)
7-146116548-A-T		Cortical dysplasia-focal epilepsy syndrome • Pitt-Hopkins-like syndrome	Uncertain significance (Jun 14, 2016)
7-146116659-A-G		Cortical dysplasia-focal epilepsy syndrome • Pitt-Hopkins-like syndrome	Uncertain significance (Jun 14, 2016)
7-146116709-C-G		Pitt-Hopkins-like syndrome • Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Jun 14, 2016)
7-146116731-G-A		Pitt-Hopkins-like syndrome • Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Jun 14, 2016)
7-146116732-G-C		Pitt-Hopkins-like syndrome • Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Jun 14, 2016)
7-146116742-G-A		Pitt-Hopkins-like syndrome • Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Jun 14, 2016)
7-146116762-G-A		Pitt-Hopkins-like syndrome • Cortical dysplasia-focal epilepsy syndrome	Benign (Jun 14, 2018)
7-146116816-G-A		Cortical dysplasia-focal epilepsy syndrome • Pitt-Hopkins-like syndrome	Uncertain significance (Jun 14, 2016)
7-146116828-T-G		not specified • Cortical dysplasia-focal epilepsy syndrome • Pitt-Hopkins-like syndrome	Conflicting classifications of pathogenicity (Jan 13, 2018)
7-146116831-A-T		not specified	Likely benign (Oct 17, 2012)
7-146116841-C-A		Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Jan 13, 2018)
7-146116842-G-T		not specified	Likely benign (May 25, 2016)
7-146116845-C-T		not specified • Cortical dysplasia-focal epilepsy syndrome	Conflicting classifications of pathogenicity (Apr 27, 2017)
7-146116859-C-G		Pitt-Hopkins-like syndrome • Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Jun 14, 2016)
7-146116878-T-TGCAG		Cortical dysplasia-focal epilepsy syndrome	Likely pathogenic (-)
7-146116881-A-G		Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Apr 19, 2019)
7-146116885-G-C		not specified • Cortical dysplasia-focal epilepsy syndrome	Likely benign (Aug 16, 2023)
7-146116885-G-T		Cortical dysplasia-focal epilepsy syndrome	Likely benign (Sep 22, 2023)
7-146116889-C-A		Cortical dysplasia-focal epilepsy syndrome	Uncertain significance (Apr 23, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNTNAP2	protein_coding	protein_coding	ENST00000361727	24	2304638

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.87e-9	1.00	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.291	772	750	1.03	0.0000442	8794
Missense in Polyphen		168	192.1	0.87457		2320
Synonymous	-1.60	332	297	1.12	0.0000198	2495
Loss of Function	4.61	27	68.0	0.397	0.00000329	788

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000388	0.000387
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000203	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required, with CNTNAP1, for radial and longitudinal organization of myelinated axons. Plays a role in the formation of functional distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers. Demarcates the juxtaparanodal region of the axo-glial junction. {ECO:0000250|UniProtKB:Q9CPW0}.
• Disease: DISEASE: Note=A chromosomal aberration involving CNTNAP2 is found in a patient with autism spectrum disorder. Paracentric inversion 46,XY,inv(7)(q11.22;q35). The inversion breakpoints disrupt the genes AUTS2 and CNTNAP2.; DISEASE: Pitt-Hopkins-like syndrome 1 (PTHSL1) [MIM:610042]: A syndrome characterized by severe mental retardation and variable additional symptoms, such as impaired speech development, seizures, autistic behavior, breathing anomalies and a broad mouth, resembling Pitt-Hopkins syndrome. In contrast to patients with Pitt-Hopkins syndrome, PTHSL1 patients present with normal or only mildly to moderately delayed motor milestones. {ECO:0000269|PubMed:16571880, ECO:0000269|PubMed:19896112}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.186
• rvis_EVS: -2.25
• rvis_percentile_EVS: 1.3

Haploinsufficiency Scores

• pHI: 0.591
• hipred: Y
• hipred_score: 0.525
• ghis: 0.602

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.876

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cntnap2
• Phenotype: cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); taste/olfaction 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: cell adhesion;brain development;learning;neuron recognition;transmission of nerve impulse;striatum development;limbic system development;thalamus development;cerebral cortex development;adult behavior;neuron projection development;social behavior;vocal learning;clustering of voltage-gated potassium channels;neuron projection morphogenesis;superior temporal gyrus development;protein localization to juxtaparanode region of axon;vocalization behavior
• Cellular component: early endosome;Golgi apparatus;voltage-gated potassium channel complex;cell surface;membrane;integral component of membrane;axon;dendrite;axolemma;paranodal junction;neuronal cell body;perikaryon;juxtaparanode region of axon
• Molecular function: protein binding;enzyme binding