H3-3A Gene (H3.3 Histone A)
A replication-independent histone variant involved in chromatin structure, gene regulation, and oncogenesis.
Gene Information Card
| Symbol | H3-3A |
|---|---|
| Full Name | H3.3 histone A |
| Gene Type | protein-coding |
| Chromosomal Location | 1q42.12 |
| NCBI Gene ID | 3020 ncbi.nlm.nih.gov/gene/3020 |
| Ensembl ID | ENSG00000163041 |
| UniProt ID | P84243 |
| OMIM ID | 601128 |
| HGNC ID | 4764 |
| Aliases | H3.3A, H3F3A, H3-3A |
Description
H3-3A encodes replication-independent histone H3.3, a variant of the canonical histone H3 that replaces H3 in nucleosomes of transcriptionally active chromatin. H3.3 is deposited throughout the cell cycle and is enriched at promoters, enhancers, and telomeres. Mutations in H3-3A are oncogenic drivers in pediatric glioblastoma and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioblastoma, pediatric | G34R/V mutation alters histone methylation landscape, driving oncogenesis | PMID: 22286216, COSMIC |
| Giant cell tumor of bone | H3-3A G34W mutation is a hallmark of this tumor type | PMID: 24705251, COSMIC |
| Chondroblastoma | H3-3A K36M mutation is a defining feature | PMID: 24705251, COSMIC |
| Diffuse intrinsic pontine glioma (DIPG) | K27M mutation in H3-3A leads to global hypomethylation and oncogenic gene expression | PMID: 22286216, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 31.2 | High |
| Testis | 28.5 | High |
| Heart | 24.1 | Medium |
| Liver | 18.7 | Medium |
| Kidney | 22.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 35.0 | High expression |
| K562 | 29.8 | High expression |
| A549 | 26.4 | Medium expression |
| HEK293 | 32.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.103G>A (p.Gly35Arg) | Missense | Rare in general population, recurrent in glioblastoma | Alters histone H3.3 function |
| c.103G>T (p.Gly35Trp) | Missense | Recurrent in giant cell tumor of bone | Oncogenic driver |
| c.110A>T (p.Lys36Met) | Missense | Recurrent in chondroblastoma | Oncogenic driver |
| c.83A>T (p.Lys27Met) | Missense | Recurrent in DIPG | Oncogenic driver |
Mutation functional classification
Loss of Function (LOF)
Not typically observed; mutations are gain-of-function or dominant-negative.
Gain of Function (GOF)
G34R/V, K27M, K36M mutations alter histone post-translational modifications, leading to aberrant gene expression.
Dominant Negative (DN)
K27M mutation acts in a dominant-negative manner to inhibit PRC2 activity, reducing H3K27me3.
View complete mutation data：
Gene Ontology (GO)
| • nucleosome assembly (GO:0006334) | • chromatin organization (GO:0006325) |
| • DNA binding (GO:0003677) | • protein heterodimerization activity (GO:0046982) |
Pathways
• Chromatin organization (Reactome: R-HSA-4839726)
• Packaging Of Telomere Ends (Reactome: R-HSA-171306)
Protein Summary
Histone H3.3 is a 136-amino acid protein that differs from canonical H3 by only 5 residues. It is encoded by two genes (H3-3A and H3-3B) and is incorporated into nucleosomes in a replication-independent manner. H3.3 is essential for maintaining chromatin structure in transcriptionally active regions and at telomeres. Mutations in the histone tail (e.g., K27M, G34R/V, K36M) are oncogenic and disrupt normal epigenetic regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| H3-3A Knockout HEK293 Cell Line | EDJ-KQ50337 | Human | 3020 | Details Get a Quote |
| H3-3A Knockout HeLa Cell Line | EDJ-KQ53485 | Human | 3020 | Details Get a Quote |
| H3-3A Knockout A-549 Cell Line | EDJ-KQ61957 | Human | 3020 | Details Get a Quote |
| H3-3A Knockout HCT 116 Cell Line | EDJ-KQ70438 | Human | 3020 | Details Get a Quote |
