H3-3B Gene (Histone H3.3B)
Replacement histone variant involved in chromatin structure and gene regulation
Gene Information Card
| Symbol | H3-3B |
|---|---|
| Full Name | H3.3 histone B |
| Gene Type | protein-coding |
| Chromosomal Location | 17q25.1 |
| NCBI Gene ID | 3021 ncbi.nlm.nih.gov/gene/3021 |
| Ensembl ID | ENSG00000132475 |
| UniProt ID | P84243 |
| OMIM ID | 601058 |
| HGNC ID | 4764 |
| Aliases | H3F3B, H3.3B, H3 histone family 3B |
Description
H3-3B (H3F3B) encodes a replication-independent histone H3 variant, H3.3, which replaces canonical H3 in non-dividing cells and is enriched at active chromatin regions, promoters, and telomeres. H3.3 is deposited by specific chaperones (e.g., HIRA, ATRX/DAXX) and plays critical roles in chromatin remodeling, transcriptional regulation, and genome stability. Mutations in H3-3B are oncogenic drivers in certain bone tumors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Giant cell tumor of bone | Recurrent H3-3B p.Gly34Trp mutation alters histone post-translational modifications, leading to aberrant gene expression and tumorigenesis | COSMIC, ClinVar |
| Chondroblastoma | Recurrent H3-3B p.Gly34Leu mutation disrupts histone methylation patterns, promoting tumor formation | COSMIC, ClinVar |
| Pediatric high-grade glioma | H3-3B p.Lys27Met mutation (H3.3K27M) impairs polycomb repression, driving gliomagenesis | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 48.2 | High |
| Brain | 35.1 | Medium |
| Heart | 28.7 | Medium |
| Liver | 22.4 | Medium |
| Lung | 18.9 | Medium |
| Kidney | 16.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 42.5 | High expression |
| HeLa | 38.1 | High expression |
| K562 | 30.2 | Medium expression |
| MCF7 | 25.6 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gly34Trp (G34W) | Missense | >90% in giant cell tumor of bone | Alters H3.3 post-translational modifications, drives oncogenesis |
| p.Gly34Leu (G34L) | Missense | >90% in chondroblastoma | Disrupts histone methylation, promotes tumorigenesis |
| p.Lys27Met (K27M) | Missense | ~30% in pediatric high-grade glioma | Reduces H3K27me3, impairs polycomb repression |
Mutation functional classification
Loss of Function (LOF)
Not typically observed; H3-3B mutations are gain-of-function or dominant-negative.
Gain of Function (GOF)
p.Gly34Trp and p.Gly34Leu alter histone modification landscapes, promoting oncogenic transcription.
Dominant Negative (DN)
p.Lys27Met acts as a dominant-negative inhibitor of polycomb repressive complex 2 (PRC2), reducing global H3K27me3.
View complete mutation data：
Gene Ontology (GO)
| • nucleosome (GO:0000786) | • DNA binding (GO:0003677) |
| • nucleosome assembly (GO:0006334) | • protein binding (GO:0005515) |
| • protein heterodimerization activity (GO:0046982) |
Pathways
• Chromatin organization (Reactome R-HSA-4839726)
• Packaging of telomere ends (Reactome R-HSA-171306)
• PRC2 methylates histones and DNA (Reactome R-HSA-212300)
Protein Summary
Histone H3.3 is a variant of histone H3 that is incorporated into chromatin independently of DNA replication. It is encoded by two genes, H3-3A and H3-3B. H3.3 differs from canonical H3 by only a few amino acids but is enriched at active genes, regulatory elements, and telomeres. It is deposited by the HIRA complex at active regions and by the ATRX/DAXX complex at heterochromatic regions including telomeres. Mutations in H3-3B are recurrent in bone tumors and pediatric gliomas, altering the epigenetic landscape and driving tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| H3-3B Knockout HEK293 Cell Line | EDJ-KQ3030 | Human | 3021 | Details Get a Quote |
| H3-3B Knockout A-549 Cell Line | EDJ-KQ24254 | Human | 3021 | Details Get a Quote |
| H3-3B Knockout HCT 116 Cell Line | EDJ-KQ24255 | Human | 3021 | Details Get a Quote |
| H3-3B Knockout HeLa Cell Line | EDJ-KQ24256 | Human | 3021 | Details Get a Quote |
