ZMYM3

Overview

ZMYM3 (Zinc Finger MYM-Type Containing 3) is an X-linked chromatin regulator involved in H3K4me3 histone modification. ZMYM3 physically interacts with KDM6A (UTX) and KDM1A (LSD1) as part of a histone demethylase regulatory complex. In medulloblastoma, ZMYM3 mutations are enriched in the subgroup-4 molecular subtype, predominantly in males, consistent with its X-linked location and the known prevalence of subgroup-4 in male patients.

Alterations observed in the corpus

  • Frameshift, nonsense, and missense mutations in ZMYM3 identified in medulloblastoma WGS (PCGP cohort, 37 tumors); alterations cluster in subgroup-4 tumors from male patients; co-mutated with KDM6A and KDM1A in H3K4me3 regulatory complex PMID:22722829
  • Identified as a significantly mutated gene in CLL WES of 160 tumors; ZMYM3 encodes a zinc finger MYM-type protein involved in chromatin regulation PMID:23415222
  • ZMYM3 mutated in 3/112 Ewing sarcoma cases (two L82fs frameshift indels and one 17-kb intragenic deletion) PMID:25223734
  • Significantly mutated in 2% of primary prostate cancer (PRAD); novel in prostate cancer context PMID:26544944
  • Recurrent histone-methylation-modifier mutation especially enriched in medulloblastoma methylation subtype VIII; recurrently altered across subgroups in the 491-sample ICGC cohort PMID:28726821
  • Confirmed as an established prostate cancer driver in the SU2C/PCF 1,013-sample cohort; metastasis-vs-primary enrichment quantified PMID:29610475

Cancer types (linked)

  • Medulloblastoma (MBL): ZMYM3 mutations in subgroup-4 (male patients); anti-correlated with EZH2 copy-number gain, consistent with opposing roles in H3K4me3/H3K27me3 balance PMID:22722829

Co-occurrence and mutual exclusivity

  • Co-mutated with KDM6A and KDM1A in subgroup-3/4 medulloblastoma, all targeting H3K4me3 regulation PMID:22722829
  • Anti-correlated with EZH2 copy-number gain (which maintains H3K27me3) in medulloblastoma subgroups PMID:22722829

Therapeutic relevance

  • No direct targeted therapies identified for ZMYM3-mutant tumors in the corpus. Subgroup-4 medulloblastoma has intermediate prognosis; ZMYM3/KDM6A pathway disruption may indicate dependency on residual H3K4me3 regulation.

Open questions

  • Whether ZMYM3 mutations cooperate with KDM6A loss to fully inactivate the H3K4me3 regulatory complex, or whether they target distinct aspects of chromatin regulation, is not resolved in the corpus.
  • The male predominance of ZMYM3 mutations (consistent with X-linked escape) warrants further investigation of sex-specific medulloblastoma biology.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:23415222

This page was processed by crosslinker on 2026-05-14. - PMID:25223734

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by crosslinker on 2026-05-14. - PMID:28726821

This page was processed by wiki-cli on 2026-05-15. - PMID:29610475

This page was processed by wiki-cli on 2026-05-15.