DIRAS1: A RAS-Related GTPase with Tumor Suppressive Potential
Comprehensive genomic and functional analysis of DIRAS1, a member of the RAS superfamily implicated in cancer and developmental processes.
Gene Information Card
| Symbol | DIRAS1 |
|---|---|
| Full Name | DIRAS family GTPase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 148252 ncbi.nlm.nih.gov/gene/148252 |
| Ensembl ID | ENSG00000167552 |
| UniProt ID | O95057 |
| OMIM ID | 607173 |
| HGNC ID | 29308 |
| Aliases | GBP, Di-Ras1, DiRas1, RASD1 |
Description
DIRAS1 (DIRAS family GTPase 1) is a member of the RAS superfamily of small GTPases. It functions as a molecular switch, cycling between an active GTP-bound and inactive GDP-bound state. Unlike classical RAS oncogenes, DIRAS1 exhibits tumor-suppressive properties, often downregulated or silenced in various cancers. It is involved in cell cycle regulation, apoptosis, and signal transduction pathways.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | Downregulation of DIRAS1 promotes cell proliferation and invasion; acts as a tumor suppressor. | PMID: 23455478 |
| Colorectal Cancer | Hypermethylation of DIRAS1 promoter leads to reduced expression, associated with poor prognosis. | PMID: 25656899 |
| Lung Cancer | Loss of DIRAS1 expression correlates with increased tumor growth and metastasis. | PMID: 27197187 |
| Ovarian Cancer | DIRAS1 silencing via epigenetic mechanisms contributes to oncogenesis. | PMID: 28827720 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.5 | Medium |
| Heart | 3.2 | Low |
| Lung | 2.1 | Low |
| Liver | 1.5 | Not detected |
| Kidney | 4.0 | Low |
| Testis | 12.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 6.7 | Embryonic kidney cells |
| MCF7 | 1.2 | Breast cancer cell line; low expression |
| A549 | 0.8 | Lung cancer cell line; low expression |
| HCT116 | 2.3 | Colorectal cancer cell line; reduced expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.34G>A (p.Gly12Ser) | Missense | <0.1% | Potential loss of GTPase activity |
| c.181C>T (p.Arg61Trp) | Missense | <0.1% | Unknown functional impact |
| c.256G>A (p.Glu86Lys) | Missense | <0.1% | Predicted damaging |
Mutation functional classification
Loss of Function (LOF)
Promoter hypermethylation and missense mutations in the GTP-binding domain reduce DIRAS1 activity, impairing tumor suppression.
Gain of Function (GOF)
No evidence of gain-of-function mutations in DIRAS1.
Dominant Negative (DN)
Not reported for DIRAS1.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • GTP binding |
| • GDP binding | • signal transduction |
| • cell cycle arrest | • apoptotic process |
| • negative regulation of cell proliferation | • RAS protein signal transduction |
Pathways
• RAS signaling pathway
• MAPK signaling pathway
• PI3K-Akt signaling pathway
• Apoptosis
Protein Summary
DIRAS1 encodes a 198-amino acid protein belonging to the RAS family. It contains conserved GTP-binding domains and a C-terminal CAAX motif for membrane localization. Unlike oncogenic RAS, DIRAS1 suppresses cell growth and induces apoptosis. Its expression is frequently lost in cancers due to epigenetic silencing, suggesting a role as a tumor suppressor.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DIRAS1 Knockout HEK293 Cell Line | EDJ-KQ10027 | Human | 148252 | Details Get a Quote |
| DIRAS1 Knockout A-549 Cell Line | EDJ-KQ38321 | Human | 148252 | Details Get a Quote |
| DIRAS1 Knockout HCT 116 Cell Line | EDJ-KQ38322 | Human | 148252 | Details Get a Quote |
| DIRAS1 Knockout HeLa Cell Line | EDJ-KQ58603 | Human | 148252 | Details Get a Quote |
