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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.
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.
In plain words · 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.
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.
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.
No product in this corpus aims at Histone H3.3 (H3-3A) yet. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (H3 K27M mutation) absent from normal cells. HPA H3-3A: RNA low tissue specificity; blood lineage lineage enriched (granulocytes 4,496 nTPM); high antibody staining in 44 normal tissues; highest cancer staining glioma (12 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Brain and spinal cord tumours (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (glioma). (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: H3 K27M mutation label threshold; Human Protein Atlas H3-3A tissue; Open Targets ENSG00000163041 associations
First described 1981. Earliest sequence paper UniProt cites for the protein: Ohe et al, J. Biochem, 1981, "Human spleen histone H3. Isolation and amino acid sequence". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
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.
RNA: low tissue specificity, detected in all normal tissues. Blood: lineage enriched (granulocytes 4,496 nTPM).
Medium: Oral mucosa.
HPA H3-3A tissue · HPA H3-3A pathology · HPA protein class: Essential proteins
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Query for this target: (TITLE:"Histone H3.3" OR ABSTRACT:"Histone H3.3" OR TITLE:"H3-3A" OR ABSTRACT:"H3-3A" OR TITLE:"H3F3A" OR ABSTRACT:"H3F3A" OR TITLE:"H3.3 histone A" OR ABSTRACT:"H3.3 histone A" OR TITLE:"histone H3.3" OR ABSTRACT:"histone H3.3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Histone H3.3 (H3-3A), not a curated reading list.
Shares CIViC, IntOGen, Open Targets Platform and the tag biomarker-parent.
Shares CIViC and the tag biomarker-parent.
Shares CIViC and the tag biomarker-parent.
Shares CIViC, IntOGen, Open Targets Platform and the tag biomarker-parent.
Shares Dordaviprone, H3 K27M (diffuse midline glioma), Diffuse midline glioma, H3 K27-altered (including DIPG).
Shares Diffuse midline glioma, H3 K27-altered (including DIPG), CIViC, Open Targets Platform.
Shares Diffuse midline glioma, H3 K27-altered (including DIPG), CIViC, IntOGen, Open Targets Platform.
Shares Diffuse midline glioma, H3 K27-altered (including DIPG), CIViC.