PARVA
protein-codingparvin alpha, the group of Parvins
Gene summary
This gene encodes a member of the parvin family of actin-binding proteins. Parvins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. The encoded protein is part of the integrin-linked kinase signaling complex and plays a role in cell adhesion, motility and survival. [provided by RefSeq, Dec 2010]
- MXRA2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~157.8 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 PARVA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018222.5. 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 | 1 | 2 | |||
| missense | 45 | 45 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 50 | 1 | 0 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060692.3 | 13 | MANE Select | |
| Ensembl | ENSP00000334008.9 | 13 | MANE Select | |
| Ensembl | ENSP00000435860.1 | 8 | Standard | |
| Ensembl | ENSP00000573639.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| parvaa | Danio rerio | Structure: caudal fin lower lobe Quality: rough abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Focal adhesion - Homo sapiens (human)
- Primary Focal Segmental Glomerulosclerosis FSGS
- Focal Adhesion
- Integrin-linked kinase signaling
- Localization of the PINCH-ILK-PARVIN complex to focal adhesions
Biological Process
- sprouting angiogenesis
- outflow tract septum morphogenesis
- establishment or maintenance of cell polarity
- regulation of cell shape
- cell projection assembly
Molecular Function
- actin binding
- protein binding
- cadherin binding
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
- focal adhesion
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334956
- Coding exons
- 13
- Length
- 153617
- Individuals with no LoFs
- 125025
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125038
- p
- 0.0000520
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.998 | 176 | 217 | 0.809 | 0.0000117 | 2635 |
| Missense (PolyPhen) | 44 | 68.511 | 0.64223 | 851 | ||
| Synonymous | -0.718 | 98 | 89.4 | 1.10 | 0.00000473 | 829 |
| Loss of Function | 3.43 | 5 | 22.6 | 0.221 | 0.00000118 | 261 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.000060 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000082 | 0.000079 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in sarcomere organization and in smooth muscle cell contraction. Required for normal development of the embryonic cardiovascular system, and for normal septation of the heart outflow tract. Plays a role in sprouting angiogenesis and is required for normal adhesion of vascular smooth muscle cells to endothelial cells during blood vessel development (By similarity). Plays a role in the reorganization of the actin cytoskeleton, formation of lamellipodia and ciliogenesis. Plays a role in the establishement of cell polarity, cell adhesion, cell spreading, and directed cell migration. {ECO:0000250, ECO:0000269|PubMed:11134073, ECO:0000269|PubMed:11331308, ECO:0000269|PubMed:15284246, ECO:0000269|PubMed:20393563}.;
Recessive Scores
- pRec
- 0.171
Intolerance Scores
- LoFtool
- 0.621
- RVIS EVS
- -0.41
- RVIS percentile EVS
- 26.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.640
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |