PVR
protein-codingPVR cell adhesion molecule, the group of V-set domain containing|CD molecules|C2-set domain containing|Nectins and nectin-like molecules
Gene summary
The protein encoded by this gene is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]
- PVS
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PVR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006505.5. 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 | 4 | 2 | 8 | ||
| missense | 64 | 6 | 2 | 72 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 66 | 10 | 4 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006496.4 | 8 | MANE Select | |
| Ensembl | ENSP00000402060.2 | 8 | MANE Select | |
| RefSeq | NP_001129240.1 | 8 | Standard | |
| RefSeq | NP_001129241.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Immune System
- Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
- Adaptive Immune System
- Beta3 integrin cell surface interactions
Biological Process
- positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
- homophilic cell adhesion via plasma membrane adhesion molecules
- heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
- adherens junction organization
- susceptibility to natural killer cell mediated cytotoxicity
Molecular Function
- virus receptor activity
- protein binding
- signaling receptor activity
- protein homodimerization activity
- cell adhesion molecule binding
Cellular Component
- extracellular space
- cytoplasm
- plasma membrane
- cell-cell adherens junction
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000425690
- Coding exons
- 8
- Length
- 19753
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125747
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.999 | 209 | 254 | 0.823 | 0.0000159 | 2641 |
| Missense (PolyPhen) | 54 | 73.871 | 0.731 | 810 | ||
| Synonymous | 1.90 | 87 | 113 | 0.772 | 0.00000768 | 890 |
| Loss of Function | 0.573 | 16 | 18.7 | 0.857 | 9.77e-7 | 196 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00055 | 0.00054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates NK cell adhesion and triggers NK cell effector functions. Binds two different NK cell receptors: CD96 and CD226. These interactions accumulates at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytoxicity of activated NK cells. May also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Plays a role in mediating tumor cell invasion and migration. {ECO:0000269|PubMed:15471548, ECO:0000269|PubMed:15607800}.; FUNCTION: (Microbial infection) Acts as a receptor for Pseudorabies virus. {ECO:0000269|PubMed:9616127}.;
Recessive Scores
- pRec
- 0.154
Intolerance Scores
- LoFtool
- 0.311
- RVIS EVS
- 0.8
- RVIS percentile EVS
- 87.59
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.706
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |