NECTIN4
protein-codingnectin cell adhesion molecule 4, the group of V-set domain containing|C2-set domain containing|Nectins and nectin-like molecules
Gene summary
This gene encodes a member of the nectin family. The encoded protein contains two immunoglobulin-like (Ig-like) C2-type domains and one Ig-like V-type domain. It is involved in cell adhesion through trans-homophilic and -heterophilic interactions. It is a single-pass type I membrane protein. The soluble form is produced by proteolytic cleavage at the cell surface by the metalloproteinase ADAM17/TACE. The secreted form is found in both breast tumor cell lines and breast tumor patients. Mutations in this gene are the cause of ectodermal dysplasia-syndactyly syndrome type 1, an autosomal recessive disorder. Alternatively spliced transcript variants have been found but the full-length nature of the variant has not been determined.[provided by RefSeq, Jan 2011]
- PVRL4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0024565
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013311
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0024565
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0024565
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Dental; Dermatologic; 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 NECTIN4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030916.3. 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 | 2 | 29 | 5 | 36 | ||
| missense | 4 | 1 | 26 | 2 | 3 | 36 |
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 3 | |||
| Total | 10 | 2 | 30 | 31 | 8 | 81 |
Highest pathogenic variant AF is 0.000017349494
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_112178.2 | 9 | MANE Select | |
| Ensembl | ENSP00000356991.3 | 9 | MANE Select | |
| Ensembl | ENSP00000561689.1 | 9 | Standard | |
| Ensembl | ENSP00000561689.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adherens junction - Homo sapiens (human)
- Cell-cell junction organization
- Nectin/Necl trans heterodimerization
- Adherens junctions interactions
- Cell junction organization
Biological Process
- homophilic cell adhesion via plasma membrane adhesion molecules
- heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
- adherens junction organization
- viral entry into host cell
Molecular Function
- virus receptor activity
- protein binding
- signaling receptor activity
- identical protein binding
- protein homodimerization activity
Cellular Component
- plasma membrane
- cell-cell adherens junction
- integral component of membrane
- apical junction complex
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368012
- Coding exons
- 9
- Length
- 18605
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 44
- Defined
- 125748
- p
- 0.000175
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.28 | 248 | 312 | 0.796 | 0.0000210 | 3243 |
| Missense (PolyPhen) | 56 | 99.97 | 0.56017 | 1028 | ||
| Synonymous | 0.140 | 139 | 141 | 0.985 | 0.00000996 | 1114 |
| Loss of Function | 3.73 | 4 | 23.5 | 0.170 | 0.00000130 | 239 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00058 | 0.00058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Seems to be involved in cell adhesion through trans- homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvirus entry into cells.;
- Disease
- DISEASE: Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) [MIM:613573]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDSS1 is characterized by the association of hair and teeth abnormalities with cutaneous syndactyly of the hands and/or feet. Hair morphologic abnormalities include twists at irregular intervals (pilli torti) and swelling along the shafts, particularly associated with areas of breakage. Dental findings consist of abnormally widely spaced teeth, with peg- shaped and conical crowns. Patients have normal sweating. {ECO:0000269|PubMed:20691405}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- RVIS EVS
- -0.33
- RVIS percentile EVS
- 30.7
Essentials
- Essential (gene trap)
- N