CNTNAP1
contactin associated protein 1, the group of Contactin associated protein family
Basic information
Region (hg38): 17:42682530-42699993
Previous symbols: [ "NRXN4" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- not provided (372 variants)
- Inborn genetic diseases (48 variants)
- Lethal congenital contracture syndrome 7 (13 variants)
- Neuropathy, congenital hypomyelinating, 3 (9 variants)
- Lethal congenital contracture syndrome 7;Neuropathy, congenital hypomyelinating, 3 (2 variants)
- not specified (2 variants)
- Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (2 variants)
- Congenital hypomyelination neuropathy with or without arthrogryposis (2 variants)
- Arthrogryposis, distal, type 1A (1 variants)
- See cases (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.
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 | 86 | 97 | ||||
| missense | 161 | 168 | ||||
| nonsense | 12 | |||||
| start loss | 0 | |||||
| frameshift | 7 | |||||
| inframe indel | 5 | |||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| splice region ? | 8 | 15 | 1 | 24 | ||
| non coding ? | 44 | 42 | 92 | |||
| Total | 15 | 10 | 179 | 132 | 51 |
Highest pathogenic variant AF is 0.0000460
Variants in CNTNAP1
This is a list of pathogenic ClinVar variants found in the CNTNAP1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| 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:
- 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