# Histone H3.3 (H3-3A)

Source: https://onco.cc/targets/h3-3a/  
OnCo record `h3-3a` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

H3.3 is one of the histone proteins DNA wraps around; a single change at position 27 (K27M) locks brain-stem and midline gliomas in an immature state and defines the diagnosis.

## Summary

H3-3A (formerly H3F3A) encodes the replication-independent histone variant H3.3. The K27M substitution, and the rarer G34R/V, are the defining alterations of diffuse midline glioma, H3 K27-altered in the WHO 2021 classification, most often in the pons (DIPG), thalamus and spinal cord of children. The same mutation is found in H3-3B (H3F3B) and HIST1H3B. Dordaviprone, approved in 2025, is the first drug whose label names the H3 K27M mutation; the readout page carries the label wording and the testing route.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: H3F3A; H3.3 histone A; histone H3.3
- Tags: biomarker-parent
- Symbol: H3-3A
- Class: other
- Biology: K27M inhibits the PRC2 methyltransferase EZH2, collapsing global H3K27 trimethylation and blocking differentiation; the mutant histone is detected by a mutation-specific antibody or by sequencing.
- Where found: Diffuse midline glioma including DIPG (H3 K27M); Paediatric high-grade glioma (H3 G34)

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/H3F3A
- HGNC HGNC:4764: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4764
- UniProt P84243: https://www.uniprot.org/uniprotkb/P84243/entry

## Connected records

- biomarkers: [H3 K27M mutation](https://onco.cc/biomarkers/h3-k27m/)
- cancers: [Diffuse midline glioma, H3 K27-altered (including DIPG)](https://onco.cc/cancers/dipg-dmg/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/)
- drugs: [Dordaviprone](https://onco.cc/drugs/dordaviprone/)
- terms: [H3 K27M (diffuse midline glioma)](https://onco.cc/terms/h3k27m/)
- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)

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JSON: https://onco.cc/api/v1/entities/h3-3a.json