DOT1L
Overview
DOT1L encodes a histone methyltransferase responsible for H3K79 methylation, a mark associated with active transcription and DNA damage response. DOT1L lacks a SET domain and is the only known non-SET-domain histone methyltransferase. A germline missense variant (p.Pro1146Leu) was identified in a CDH1-negative HDGC family, implicating altered H3K79 methylation in familial gastric cancer susceptibility.
Alterations observed in the corpus
- Germline missense p.Pro1146Leu identified in a CDH1-negative HDGC family; histone methyltransferase implicated in H3K79 methylation changes in familial gastric tumors PMID:24816255
- Novel significantly mutated gene (SMG) in 3% of lung ADCs in a pan-lung TCGA cohort, enriched for truncating mutations; H3K79 methyltransferase PMID:27158780
Cancer types (linked)
- STAD: Germline DOT1L variant identified in HDGC-like family; epigenetic mechanism proposed for gastric cancer predisposition PMID:24816255
Co-occurrence and mutual exclusivity
No data in current corpus.
Therapeutic relevance
Not a direct therapeutic target in current corpus. DOT1L inhibitors (e.g., pinometostat) are under investigation in other contexts (MLL-rearranged leukemias).
Open questions
No conflicts in current corpus.
Sources
This page was processed by entity-page-writer on 2026-05-11. - PMID:27158780
This page was processed by wiki-cli on 2026-05-14.