RASD2
protein-codingRASD family member 2, the group of RAS type GTPase family
Gene summary
This gene belongs to the Ras superfamily of small GTPases and is enriched in the striatum. The encoded protein functions as an E3 ligase for attachment of small ubiquitin-like modifier (SUMO). This protein also binds to mutant huntingtin (mHtt), the protein mutated in Huntington disease (HD). Sumoylation of mHTT by this protein may cause degeneration of the striatum. The protein functions as an activator of mechanistic target of rapamycin 1 (mTOR1), which in turn plays a role in myelination, axon growth and regeneration. Reduced levels of mRNA expressed by this gene were found in HD patients. [provided by RefSeq, Jan 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.2 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 RASD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014310.4. 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 | 1 | ||||
| missense | 27 | 1 | 28 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 27 | 2 | 0 | 29 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055125.2 | 2 | MANE Select | |
| Ensembl | ENSP00000216127.4 | 2 | MANE Select | |
| RefSeq | NP_001353654.1 | 2 | Standard | |
| RefSeq | NP_001363444.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- synaptic transmission, dopaminergic
- signal transduction
- locomotory behavior
- negative regulation of protein ubiquitination
- positive regulation of protein sumoylation
Molecular Function
- GTPase activity
- GTP binding
- ubiquitin conjugating enzyme binding
- G-protein beta-subunit binding
- phosphatidylinositol 3-kinase binding
Cellular Component
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216127
- Coding exons
- 2
- Length
- 13134
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125717
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.69 | 127 | 193 | 0.659 | 0.0000136 | 1761 |
| Missense (PolyPhen) | 40 | 86.779 | 0.46094 | 778 | ||
| Synonymous | -0.0621 | 84 | 83.3 | 1.01 | 0.00000676 | 519 |
| Loss of Function | 1.99 | 1 | 6.44 | 0.155 | 2.74e-7 | 82 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTPase signaling protein that binds to and hydrolyzes GTP. Regulates signaling pathways involving G-proteins-coupled receptor and heterotrimeric proteins such as GNB1, GNB2 and GNB3. May be involved in selected striatal competencies, mainly locomotor activity and motor coordination. {ECO:0000269|PubMed:11976265, ECO:0000269|PubMed:19255495}.;
Recessive Scores
- pRec
- 0.153
Intolerance Scores
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.855
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |