ARHGAP35

Overview

ARHGAP35 (Rho GTPase Activating Protein 35, also known as p190-A) encodes a GTPase-activating protein that stimulates the GTPase activity of Rho family proteins. In lung cancer, ARHGAP35 loss-of-function mutations contribute to Ras/Rho pathway activation and are catalogued as part of an expanded druggable pool in lung adenocarcinoma. Its inactivation raises the proportion of lung ADCs with a detectable Ras/Raf/RTK pathway driver event.

Alterations observed in the corpus

  • Loss-of-function mutations in lung ADC (TCGA pan-lung WES); contributes to the Ras/Rho pathway driver landscape; inclusion of ARHGAP35 as a Ras pathway member raises proportion of lung ADCs with a candidate driver to 76% (85% in expert-reviewed subset) PMID:27158780
  • Possible biallelic events (missense + LoF) in endometrial polyps; recurrently mutated alongside PIEZO2 in a WGS cohort of 23 polyps PMID:28445112

Cancer types (linked)

  • LUAD (lung adenocarcinoma): Loss-of-function mutations identified by pan-lung WES; part of the expanded Ras/Raf/RTK pathway driver catalogue PMID:27158780

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • Mutations in ARHGAP35 activate Rho signaling, potentially sensitizing tumors to downstream Ras/Rho pathway inhibitors; currently an indirect therapeutic hypothesis PMID:27158780

Open questions

  • Clinical significance of ARHGAP35 loss-of-function specifically in lung ADC has not been individually validated; grouped with other Ras-pathway members PMID:27158780

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:28445112

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