RASA4
protein-codingRAS p21 protein activator 4, the group of C2 and RasGAP domain containing
Gene summary
This gene encodes a member of the GAP1 family of GTPase-activating proteins that suppresses the Ras/mitogen-activated protein kinase pathway in response to Ca(2+). Stimuli that increase intracellular Ca(2+) levels result in the translocation of this protein to the plasma membrane, where it activates Ras GTPase activity. Consequently, Ras is converted from the active GTP-bound state to the inactive GDP-bound state and no longer activates downstream pathways that regulate gene expression, cell growth, and differentiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~37.1 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 RASA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006989.6. 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 | ||||
| missense | 4 | 4 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 4 | 1 | 0 | 5 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008920.5 | 21 | MANE Select | |
| Ensembl | ENSP00000262940.8 | 21 | MANE Select | |
| RefSeq | NP_001073346.2 | 20 | Standard | |
| Ensembl | ENSP00000412876.2 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ras signaling pathway - Homo sapiens (human)
- Ras Signaling
- Regulation of Ras family activation
- Signal Transduction
- Regulation of RAS by GAPs
Biological Process
- MAPK cascade
- negative regulation of GTPase activity
- positive regulation of GTPase activity
- negative regulation of Ras protein signal transduction
- cellular response to calcium ion
Molecular Function
- GTPase activator activity
- phospholipid binding
- metal ion binding
Cellular Component
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262940
- Coding exons
- 21
- Length
- 37112
- Individuals with no LoFs
- 119649
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 3
- Defined
- 119653
- p
- 0.0000167
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.836 | 42 | 60.3 | 0.697 | 0.00000329 | 5086 |
| Missense (PolyPhen) | 18 | 23.464 | 0.76714 | 1886 | ||
| Synonymous | 0.412 | 27 | 29.9 | 0.904 | 0.00000176 | 1622 |
| Loss of Function | 1.31 | 2 | 5.23 | 0.383 | 2.21e-7 | 458 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000066 | 0.000030 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.00011 | 0.00010 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ca(2+)-dependent Ras GTPase-activating protein, that switches off the Ras-MAPK pathway following a stimulus that elevates intracellular calcium. Functions as an adaptor for Cdc42 and Rac1 during FcR-mediated phagocytosis. {ECO:0000269|PubMed:11448776}.;
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.134
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |