CNTNAP1

contactin associated protein 1, the group of Contactin associated protein family

Basic information

Region (hg38): 17:42682531-42699993

Previous symbols: [ "NRXN4" ]

Links

ENSG00000108797

∙ NCBI:8506 ∙ OMIM:602346 ∙ HGNC:8011 ∙ Uniprot:P78357 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

lethal congenital contracture syndrome 7 (Strong), mode of inheritance: AR
hypomyelination neuropathy-arthrogryposis syndrome (Supportive), mode of inheritance: AR
lethal congenital contracture syndrome 7 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lethal congenital contracture syndrome 7; Neuropathy, congenital hypomyelinating, 3	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	24319099; 27782105; 27668699; 28374019; 29511323

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNTNAP1 gene.

not provided (13 variants)
Lethal congenital contracture syndrome 7 (4 variants)
Neuropathy, congenital hypomyelinating, 3 (3 variants)
Arthrogryposis, distal, type 1A (1 variants)
Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNTNAP1 gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

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			3 clinvar	100 clinvar	7 clinvar	110
missense		5 clinvar	206 clinvar	4 clinvar	1 clinvar	216
nonsense	8 clinvar	3 clinvar	2 clinvar			13
start loss						0
frameshift	5 clinvar	1 clinvar	1 clinvar			7
splice donor/acceptor (+/-2bp)	3 clinvar	3 clinvar	2 clinvar			8
Total	16	12	214	104	8

Highest pathogenic variant AF is 0.0000459843

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNTNAP1	protein_coding	protein_coding	ENST00000264638	24	17202

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000344	1.00	125674	0	74	125748	0.000294

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.22	630	902	0.698	0.0000606	8937
Missense in Polyphen		180	302.03	0.59596		3099
Synonymous	1.38	334	368	0.909	0.0000245	2873
Loss of Function	5.79	24	79.9	0.300	0.00000527	726

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000758	0.000758
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.000217	0.000217
Finnish	0.000508	0.000508
European (Non-Finnish)	0.000265	0.000264
Middle Eastern	0.000217	0.000217
South Asian	0.000234	0.000229
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Required, with CNTNAP2, 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 paranodal region of the axo-glial junction. In association with contactin involved in the signaling between axons and myelinating glial cells. {ECO:0000269|PubMed:24319099, ECO:0000269|PubMed:27818385, ECO:0000269|PubMed:28374019}.;
Disease: DISEASE: Note=Defects in CNTNAP1 are associated with congenital hypomyelinating neuropathy (CHN). Patients show polyhydramnios and reduced fetal movements, they were hypotonic and required ventilatory support at birth. But no arthrogryposis is noted. Patients die often early in the neonatal period. {ECO:0000269|PubMed:27668699, ECO:0000269|PubMed:27818385, ECO:0000269|PubMed:28374019}.;
Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Developmental Biology;Neurofascin interactions;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

pRec: 0.108

Intolerance Scores

loftool: 0.278
rvis_EVS: -2.3
rvis_percentile_EVS: 1.21

Haploinsufficiency Scores

pHI: 0.251
hipred: Y
hipred_score: 0.706
ghis: 0.626

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.811

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cntnap1
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); vision/eye phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; 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); muscle phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: protein localization to paranode region of axon;cytoskeleton organization;cell adhesion;signal transduction;positive regulation of signal transduction;neuronal action potential propagation;central nervous system myelination;myelination in peripheral nervous system;paranodal junction assembly;neuron projection morphogenesis;neuromuscular process controlling posture;neuromuscular process controlling balance;protein localization to juxtaparanode region of axon
Cellular component: integral component of plasma membrane;voltage-gated potassium channel complex;integral component of membrane;paranodal junction;paranode region of axon;myelin sheath;presynaptic active zone membrane
Molecular function: SH3/SH2 adaptor activity;protein binding;SH3 domain binding;signaling receptor activity