{"entity":{"id":"h3-3a","kind":"target","name":"Histone H3.3 (H3-3A)","aka":["H3F3A","H3.3 histone A","histone H3.3"],"tldr":"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.","asOf":"2026-09-23","wikipedia":"https://en.wikipedia.org/wiki/H3F3A","links":[{"label":"HGNC HGNC:4764","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4764"},{"label":"UniProt P84243","url":"https://www.uniprot.org/uniprotkb/P84243/entry"}],"tags":["biomarker-parent"],"related":["h3-k27m"],"cancers":["dipg-dmg","paediatric-high-grade-glioma"],"sections":[],"technologies":[],"targets":[],"drugs":["dordaviprone"],"companies":[],"institutions":[],"pathways":[],"terms":["h3k27m"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"H3-3A","role":["drug-target","oncogene-driver","biomarker"],"evidenceTier":"clinical-evidence","sources":[],"specificity":"tumour-specific","distribution":"one-type","specificityNote":"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.)","specificitySources":[{"label":"H3 K27M mutation label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ad45b43e-fdef-47ad-9c34-055b41bdc576","note":"H3 K27M mutation, progressive disease after prior therapy"},{"label":"Human Protein Atlas H3-3A tissue","url":"https://www.proteinatlas.org/ENSG00000163041-H3-3A/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000163041 associations","url":"https://platform.opentargets.org/target/ENSG00000163041/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:4764","ensembl":"ENSG00000163041","uniprot":"P84243","entrez":"3020","firstDescribed":1981,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Ohe et al, J. Biochem, 1981, \"Human spleen histone H3. Isolation and amino acid sequence\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/7309716/","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.","whereFound":["Diffuse midline glioma including DIPG (H3 K27M)","Paediatric high-grade glioma (H3 G34)"],"targetClass":"other","prevalence":[]},"route":"/targets/h3-3a/","neighbours":{"biomarker":[{"id":"h3-k27m","kind":"biomarker","name":"H3 K27M mutation","route":"/biomarkers/h3-k27m/"}],"cancer":[{"id":"dipg-dmg","kind":"cancer","name":"Diffuse midline glioma, H3 K27-altered (including DIPG)","route":"/cancers/dipg-dmg/"},{"id":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline glioma)","route":"/cancers/paediatric-high-grade-glioma/"}],"drug":[{"id":"dordaviprone","kind":"drug","name":"Dordaviprone","route":"/drugs/dordaviprone/"}],"term":[{"id":"h3k27m","kind":"term","name":"H3 K27M (diffuse midline glioma)","route":"/terms/h3k27m/"}],"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}]}}