RASA1

Overview

RASA1 encodes RAS p21 protein activator 1, a GTPase-activating protein (GAP) that negatively regulates RAS signaling by accelerating GTP hydrolysis. Inactivating mutations in RASA1 relieve this brake on RAS activity, contributing to oncogenic signaling in a variety of tumors.

Alterations observed in the corpus

  • Recurrently mutated (loss-of-function) in gastric cancer as a negative regulator of RAS; identified as a significantly mutated gene in the TCGA gastric cancer cohort. PMID:25079317
  • Two nonsense mutations (C372, R679) identified as shared trunk events between primary and matched liver metastasis in patient 14, mutually exclusive with RAS mutations in colorectal carcinoma; not on original MSK-IMPACT panel design but added in subsequent version PMID:25164765
  • RASA1 mutated in 12.8% of aggressive cSCC (5/39 patients); 66% truncating mutations; nominated as a novel candidate tumor suppressor (RAS GTPase activating protein family) PMID:25303977
  • Non-passenger mutation in breast adenoid cystic carcinoma (AdCC); rarely mutated in basal-like breast cancers. PMID:26095796
  • Novel significantly mutated gene (SMG) in lung SqCC enriched for frameshift mutations (p < 0.001 for RASA1 frameshift enrichment) in the 1,144-tumor NSCLC landscape study; also significantly enriched in oncogene-negative lung ADC (q < 0.1), nominating RASA1 (p120GAP, a RAS-GAP) as a candidate driver in RTK/Ras/Raf pathway-negative lung ADC. Raised the overall proportion of lung ADCs with a candidate driver to 76%. PMID:27158780
  • E208Vfs*16 frameshift mutation in 1/19 (5%) of 1p/19q-codeleted anaplastic oligodendroglioma PMID:28472509
  • Newly nominated CCA driver; inactivating mutations in 4.1% (10 frame-shift, 4 nonsense) plus focal copy-number losses, both correlated with reduced expression; shRNA knockdown in CCA cell lines (M213, HUCCT1) enhanced migration and invasion in Transwell assays, supporting tumor-suppressor function PMID:28667006

Cancer types (linked)

  • Gastric cancer (STAD/GS subtype): RASA1 inactivating mutations contribute to RAS pathway dysregulation. PMID:25079317

Co-occurrence and mutual exclusivity

  • Co-occurs with other RAS pathway alterations in gastric cancer; functional context overlaps with KRAS and NF1 alterations. PMID:25079317

Therapeutic relevance

  • Loss of RASA1 may sensitize tumors to RAS pathway inhibitors; therapeutic implications not directly assessed in the citing study. PMID:25079317

Open questions

  • Frequency, mutation spectrum, and subtype distribution of RASA1 mutations across the full TCGA gastric cohort remain to be characterized in detail.

Sources

This page was processed by entity-page-writer on 2026-05-15.