CAVIN4
protein-codingcaveolae associated protein 4, the group of Cavins
Gene summary
This gene encodes a protein containing two coiled-coil regions. The encoded protein promotes Rho/ROCK (Rho-kinase) signaling in cardiac muscles cells, and may facilitate myofibrillar organization. [provided by RefSeq, Jun 2013]
- MURC
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.3 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 CAVIN4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001018116.2. 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 | 15 | 15 | ||||
| missense | 74 | 7 | 3 | 84 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 78 | 22 | 3 | 103 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001018126.1 | 2 | MANE Select | |
| Ensembl | ENSP00000418668.1 | 2 | MANE Select | |
| Ensembl | ENSP00000627053.1 | 2 | Standard | |
| Ensembl | ENSP00000813364.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cavin4b | Danio rerio | Structure: skeletal muscle cell Quality: irregularly shaped abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- muscle organ development
- regulation of gene expression
- cell differentiation
- regulation of Rho protein signal transduction
- positive regulation of transcription by RNA polymerase II
Molecular Function
- protein binding
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
- caveola
- Z disc
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000307584
- Coding exons
- 2
- Length
- 9828
- Individuals with no LoFs
- 125660
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 87
- Defined
- 125747
- p
- 0.000346
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.632 | 225 | 200 | 1.13 | 0.0000107 | 2416 |
| Missense (PolyPhen) | 87 | 75.34 | 1.1548 | 919 | ||
| Synonymous | 0.123 | 78 | 79.4 | 0.982 | 0.00000464 | 688 |
| Loss of Function | 0.930 | 8 | 11.4 | 0.703 | 6.53e-7 | 149 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00070 | 0.00067 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00053 | 0.00049 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00030 | 0.00029 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0.0011 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Modulates the morphology of formed caveolae in cardiomyocytes, but is not required for caveolar formation. Facilitates the recruitment of MAPK1/3 to caveolae within cardiomyocytes and regulates alpha-1 adrenergic receptor-induced hypertrophic responses in cardiomyocytes through MAPK1/3 activation. Contributes to proper membrane localization and stabilization of caveolin-3 (CAV3) in cardiomyocytes (By similarity). Induces RHOA activation and activates NPPA transcription and myofibrillar organization through the Rho/ROCK signaling pathway (PubMed:18332105). {ECO:0000250|UniProtKB:A2AMM0, ECO:0000269|PubMed:18332105}.;
Intolerance Scores
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 32.06
Essentials
- Essential (gene trap)
- N