RRAS2: A RAS-Related GTPase with Emerging Roles in Development and Cancer
Comprehensive gene card, expression, mutations, and disease associations for RRAS2 (TC21).
Gene Information Card
| Symbol | RRAS2 |
|---|---|
| Full Name | RAS related 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.2 |
| NCBI Gene ID | 22800 ncbi.nlm.nih.gov/gene/22800 |
| Ensembl ID | ENSG00000133818 |
| UniProt ID | P62070 |
| OMIM ID | 600098 |
| HGNC ID | 10471 |
| Aliases | TC21 |
Description
RRAS2 (RAS related 2), also known as TC21, encodes a member of the RAS subfamily of small GTPases. It functions as a molecular switch in signal transduction pathways, regulating cell proliferation, differentiation, and survival. Activating mutations and overexpression of RRAS2 have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia | Gain-of-function mutations in RRAS2 lead to hyperactivation of the RAS-MAPK pathway | ClinVar, OMIM |
| Breast cancer | Overexpression and activating mutations promote oncogenic signaling | COSMIC, NCBI |
| Ovarian cancer | Recurrent mutations (e.g., Q72L) drive tumorigenesis | COSMIC |
| Lung adenocarcinoma | Somatic mutations and copy number gains contribute to malignancy | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Low |
| Heart | 6.5 | Low |
| Kidney | 12.3 | Medium |
| Liver | 9.1 | Low |
| Lung | 15.7 | Medium |
| Ovary | 18.4 | Medium |
| Pancreas | 7.8 | Low |
| Spleen | 11.2 | Medium |
| Testis | 22.1 | High |
| Thyroid | 14.6 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 20.5 | Embryonic kidney cells; high expression |
| HeLa | 18.3 | Cervical cancer cells; medium-high |
| A549 | 22.7 | Lung adenocarcinoma; high expression |
| MCF7 | 15.9 | Breast cancer; medium expression |
| K562 | 12.1 | Leukemia; medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Q72L | Missense | ~2% in COSMIC | Gain-of-function; constitutive activation |
| G23V | Missense | ~1% in COSMIC | Gain-of-function; impaired GTP hydrolysis |
| A146T | Missense | ~0.5% in COSMIC | Gain-of-function; altered nucleotide exchange |
| E81K | Missense | Rare | Putative gain-of-function; observed in Noonan syndrome |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in major databases.
Gain of Function (GOF)
Common mutations (e.g., Q72L, G23V) increase GTP-bound active state, driving oncogenic signaling.
Dominant Negative (DN)
No dominant-negative mutations described for RRAS2 in current literature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RAS signaling pathway (Reactome: R-HSA-5673001)
• MAPK cascade (Reactome: R-HSA-5673000)
• Signaling by Rho GTPases (Reactome: R-HSA-194315)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
Protein Summary
RRAS2 (TC21) is a 204-amino-acid small GTPase that cycles between inactive GDP-bound and active GTP-bound states. It localizes to the plasma membrane via C-terminal prenylation and mediates signals from receptor tyrosine kinases to downstream effectors such as RAF and PI3K. Activating mutations impair intrinsic GTP hydrolysis, leading to persistent signaling and oncogenic transformation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RRAS2 Knockout HEK293 Cell Line | EDJ-KQ755 | Human | 22800 | Details Get a Quote |
| RRAS2 Knockout HeLa Cell Line | EDJ-KQ18253 | Human | 22800 | Details Get a Quote |
| RRAS2 Knockout A-549 Cell Line | EDJ-KQ19417 | Human | 22800 | Details Get a Quote |
| RRAS2 Knockout HCT 116 Cell Line | EDJ-KQ19418 | Human | 22800 | Details Get a Quote |
