RASA3
protein-codingRAS p21 protein activator 3, the group of C2 and RasGAP domain containing|Pleckstrin homology domain containing
Gene summary
This gene encodes a protein that binds inositol 1,3,4,5-tetrakisphosphate and stimulates the GTPase activity of Ras p21. This protein functions as a negative regulator of the Ras signalling pathway. It is localized to the cell membrane via a pleckstrin homology (PH) domain in the C-terminal region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~154.8 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 RASA3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007368.4. 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 | 5 | 3 | 9 | ||
| missense | 1 | 128 | 4 | 133 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 1 | 1 | 135 | 9 | 3 | 149 |
Highest pathogenic variant AF is 0.000022581211
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_031394.2 | 24 | MANE Select | |
| Ensembl | ENSP00000335029.7 | 24 | MANE Select | |
| RefSeq | NP_001307750.1 | 13 | Standard | |
| RefSeq | NP_001307751.1 | 23 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rasa3 | Danio rerio | Structure: thrombocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ras signaling pathway - Homo sapiens (human)
- MAPK Cascade
- Ras Signaling
- Signal Transduction
- Regulation of RAS by GAPs
Biological Process
- MAPK cascade
- signal transduction
- positive regulation of GTPase activity
- negative regulation of Ras protein signal transduction
- release of sequestered calcium ion into cytosol
Molecular Function
- GTPase activator activity
- calcium-release channel activity
- metal ion binding
Cellular Component
- cytosol
- intrinsic component of the cytoplasmic side of the plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334062
- Coding exons
- 24
- Length
- 150893
- Individuals with no LoFs
- 125699
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 49
- Defined
- 125748
- p
- 0.000195
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.68 | 416 | 524 | 0.793 | 0.0000342 | 5510 |
| Missense (PolyPhen) | 192 | 254.78 | 0.7536 | 2597 | ||
| Synonymous | -2.01 | 270 | 231 | 1.17 | 0.0000175 | 1524 |
| Loss of Function | 3.16 | 24 | 47.5 | 0.505 | 0.00000228 | 564 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00019 | 0.00019 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4) with high affinity. Might be a specific IP4 receptor.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.191
- RVIS EVS
- -1.66
- RVIS percentile EVS
- 2.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.888
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |