CNTN1
protein-codingcontactin 1, the group of I-set domain containing|Contactins
Gene summary
The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~380.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012929
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0012929
Submitter: Orphanet
Inheritance Pattern: Unknown
Disease ID:MONDO:0005090
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0012929
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CNTN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001843.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 179 | 3 | 186 | ||
| missense | 265 | 21 | 2 | 288 | ||
| nonsense | 7 | 1 | 8 | |||
| start loss | 0 | |||||
| frameshift | 9 | 1 | 10 | |||
| splice donor/acceptor (+/-2bp) | 5 | 3 | 8 | |||
| Total | 16 | 7 | 272 | 200 | 5 | 500 |
Highest pathogenic variant AF is 0.000006269742
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001834.2 | 23 | MANE Select | |
| Ensembl | ENSP00000447006.1 | 23 | MANE Select | |
| RefSeq | NP_001242992.1 | 15 | Standard | |
| RefSeq | NP_001242993.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cntn1b | Danio rerio | Structure: swimming behavior Quality: process quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Developmental Biology
- Signal Transduction
- Signaling by NOTCH1
- Signaling by NOTCH2
Biological Process
- cell adhesion
- Notch signaling pathway
- positive regulation of gene expression
- positive regulation of sodium ion transport
- positive regulation of neuron projection development
Molecular Function
- protein binding
- carbohydrate binding
Cellular Component
- membrane
- myelin sheath
- membrane raft
- extracellular exosome
- anchored component of postsynaptic membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000551295
- Coding exons
- 23
- Length
- 379977
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 36
- Defined
- 125747
- p
- 0.000151
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.05 | 418 | 553 | 0.755 | 0.0000283 | 6667 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.00075 | 0.00069 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.356
Intolerance Scores
- LoFtool
- 0.351
- RVIS EVS
- -1.06
- RVIS percentile EVS
- 7.48
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.821
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |