PARVB
protein-codingparvin beta, the group of Parvins
Gene summary
This gene encodes a member of the parvin family of actin-binding proteins, which play a role in cytoskeleton organization and cell adhesion. These proteins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. This family member binds to alphaPIX and alpha-actinin, and it can inhibit the activity of integrin-linked kinase. This protein also functions in tumor suppression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~173.7 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 PARVB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013327.5. 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 | 1 | 3 | 4 | |||
| missense | 67 | 2 | 1 | 70 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 69 | 3 | 4 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_037459.2 | 13 | MANE Select | |
| Ensembl | ENSP00000342492.6 | 13 | MANE Select | |
| RefSeq | NP_001003828.1 | 14 | Standard | |
| RefSeq | NP_001230314.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| parvb | Danio rerio | Structure: trunk musculature Quality: retracted abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Focal adhesion - Homo sapiens (human)
- Focal Adhesion
- Integrin-linked kinase signaling
- Regulation of cytoskeletal remodeling and cell spreading by IPP complex components
- Cell-extracellular matrix interactions
Biological Process
- establishment or maintenance of cell polarity
- cell projection assembly
- lamellipodium assembly
- actin cytoskeleton reorganization
- substrate adhesion-dependent cell spreading
Molecular Function
- actin binding
- protein binding
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
- focal adhesion
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000406477
- Coding exons
- 14
- Length
- 173739
- Individuals with no LoFs
- 125656
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 92
- Defined
- 125748
- p
- 0.000366
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0967 | 233 | 237 | 0.982 | 0.0000141 | 2581 |
| Missense (PolyPhen) | 66 | 69.781 | 0.94581 | 776 | ||
| Synonymous | 0.416 | 92 | 97.2 | 0.946 | 0.00000595 | 779 |
| Loss of Function | 0.508 | 21 | 23.7 | 0.887 | 0.00000109 | 277 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00049 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0010 | 0.0010 | notable |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00029 | 0.00028 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adapter protein that plays a role in integrin signaling via ILK and in activation of the GTPases CDC42 and RAC1 by guanine exchange factors, such as ARHGEF6. Is involved in the reorganization of the actin cytoskeleton and formation of lamellipodia. Plays a role in cell adhesion, cell spreading, establishment or maintenance of cell polarity, and cell migration. {ECO:0000269|PubMed:11402068, ECO:0000269|PubMed:15005707, ECO:0000269|PubMed:15159419, ECO:0000269|PubMed:15284246, ECO:0000269|PubMed:18325335}.;
Recessive Scores
- pRec
- 0.206
Intolerance Scores
- LoFtool
- 0.782
- RVIS EVS
- 0.4
- RVIS percentile EVS
- 76.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.666
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |