KDM5D
Overview
KDM5D (Lysine Demethylase 5D, also known as JARID1D) encodes a histone H3 lysine 4 (H3K4) trimethylation demethylase located on the Y chromosome. It is a recurrently deleted gene in cholangiocarcinoma and is catalogued among Y-chromosome-linked tumor suppressors. Loss of KDM5D alters the H3K4me3 chromatin landscape, potentially de-repressing oncogenic transcriptional programs.
Alterations observed in the corpus
- Recurrent deletion in cholangiocarcinoma (n=16 deletions by WGS), making it one of the most frequently deleted genes in the CCA cohort PMID:28667006
Cancer types (linked)
- Cholangiocarcinoma (CCA): Among the most recurrently deleted genes (n=16) by whole-genome sequencing across a multi-center CCA cohort PMID:28667006
Co-occurrence and mutual exclusivity
- Co-deleted with UTY (n=17 deletions) and CDKN2A (n=17 deletions) in the same CCA cohort, consistent with Y-chromosome arm deletion events PMID:28667006
Therapeutic relevance
- Loss of KDM5D may produce H3K4me3 landscape alterations targetable by epigenetic strategies; no clinical-grade KDM5D-directed therapy has been validated.
Open questions
- Whether KDM5D deletion co-segregates with specific CCA molecular subtypes (Clusters 1–4) and whether it is an independent driver or passenger of Y-chromosome arm loss remains to be determined.
Sources
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