KDM5C

Overview

KDM5C (Lysine Demethylase 5C, also known as JARID1C) is an X-linked histone H3K4 demethylase and epigenetic regulator. It is recurrently mutated in clear cell renal cell carcinoma (ccRCC) and has been associated with differential immunotherapy and targeted therapy response patterns in TCGA-based molecular subtyping studies.

Alterations observed in the corpus

  • Recurrently mutated in clear cell renal cell carcinoma (ccRCC); mutational frequency varied across ICI and TKI score groups in a TCGA KIRC molecular subtyping study PMID:22138691
  • Among the top eight most significantly mutated genes (q<0.00001) in ccRCC; identified by TCGA comprehensive molecular characterization PMID:23792563
  • Parallel evolution of KDM5C inactivation previously demonstrated across spatially separated tumor regions in ccRCC (EV001/EV002), illustrating intratumor heterogeneity of this X-linked histone demethylase PMID:24487277
  • Frameshift in 1 UMD (unmatched molecular driver) patient in a prospective LUAD cohort (860 patients, MSK-IMPACT); patient achieved 6-month stable disease on off-label azacitidine PMID:28336552
  • KDM5C identified as a significantly mutated gene (SMG) in KIRC (kidney renal clear cell carcinoma) by MuSiC2 after long-gene filtering, but not by MutSig2CV, in the MC3 pan-cancer open-access MAF analysis (10,295 tumor samples). PMID:29596782

Cancer types (linked)

  • KIRC: Identified as a recurrently mutated gene; frequency distribution across immunotherapy (ICI) and TKI response score groups suggests potential relevance to treatment stratification PMID:22138691

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • Mutational frequency across ICI-high and TKI-high score groups suggests KDM5C status may contribute to immunotherapy vs. TKI response classification in ccRCC; specific drug targeting not reported in the corpus PMID:22138691

Open questions

  • The directional effect of KDM5C mutation on ICI vs. TKI response is not clearly characterized in the corpus.
  • Whether KDM5C mutations are enriched in specific HiTME (Histological Tumor Microenvironment) subtypes requires further investigation.

Sources

This page was processed by entity-page-writer on 2026-05-06. - PMID:23792563

This page was processed by wiki-cli on 2026-05-09. - PMID:24487277

This page was processed by wiki-cli on 2026-05-11. - PMID:28336552

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