H3-4
H3.4 Histone, Member of the H3 Histone Family
Gene Information Card
| Symbol | H3-4 |
|---|---|
| Full Name | H3.4 histone, member of the H3 histone family |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.2 |
| NCBI Gene ID | 113676 ncbi.nlm.nih.gov/gene/113676 |
| Ensembl ID | ENSG00000197498 |
| UniProt ID | P68431 |
| OMIM ID | 602810 |
| HGNC ID | 20501 |
| Aliases | H3.4, H3/g, H3FT, H3F1T, H3F3B |
Description
The H3-4 gene encodes histone H3.4, a core histone protein that forms the nucleosome structure by wrapping DNA. Histone H3.4 is a replication-independent histone variant expressed throughout the cell cycle and involved in chromatin remodeling, transcriptional regulation, and DNA repair. Mutations in H3-4 are associated with various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioblastoma multiforme | Somatic mutations (e.g., K27M) alter histone methylation patterns, leading to oncogenic transcriptional reprogramming | COSMIC, ClinVar |
| Diffuse intrinsic pontine glioma (DIPG) | K27M mutation in H3-4 drives aberrant PRC2 activity and H3K27me3 loss | COSMIC, ClinVar |
| Pediatric high-grade glioma | Recurrent H3.3 G34R/V mutations disrupt H3K36 methylation and gene expression | COSMIC, ClinVar |
| Chondroblastoma | H3.3 K36M mutation impairs SETD2 activity, altering H3K36me3 | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 25.6 | Medium |
| Brain | 18.3 | Medium |
| Lung | 12.1 | Low |
| Liver | 9.8 | Low |
| Heart | 15.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.5 | Cervical cancer cell line |
| K562 | 19.8 | Leukemia cell line |
| HEK293 | 17.2 | Embryonic kidney cell line |
| A549 | 14.6 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| K27M | Missense | Frequent in DIPG | Reduces H3K27me3, activates oncogenes |
| G34R | Missense | Recurrent in pediatric glioma | Alters H3K36me3, disrupts gene silencing |
| G34V | Missense | Recurrent in pediatric glioma | Similar to G34R, impairs H3K36 methylation |
| K36M | Missense | Common in chondroblastoma | Inhibits SETD2, reduces H3K36me3 |
Mutation functional classification
Loss of Function (LOF)
K27M reduces global H3K27me3, leading to loss of polycomb-mediated repression.
Gain of Function (GOF)
G34R/V may gain ability to recruit aberrant chromatin modifiers.
Dominant Negative (DN)
K27M acts dominant-negatively by inhibiting EZH2 activity on wild-type histones.
View complete mutation data：
Gene Ontology (GO)
| • nucleosome assembly (GO:0006334) | • chromatin silencing (GO:0006342) |
| • DNA repair (GO:0006281) | • protein heterodimerization activity (GO:0046982) |
| • DNA binding (GO:0003677) |
Pathways
• Chromatin organization (Reactome: R-HSA-4839726)
• Epigenetic regulation of gene expression (KEGG: hsa05202)
• Transcriptional misregulation in cancer (KEGG: hsa05202)
Protein Summary
Histone H3.4 is a 136-amino acid core histone protein that, together with H2A, H2B, and H4, forms the nucleosome octamer. It contains a histone-fold domain that mediates DNA wrapping and a flexible N-terminal tail subject to post-translational modifications (e.g., methylation, acetylation, phosphorylation) that regulate chromatin dynamics. H3.4 is encoded by the H3-4 gene and is ubiquitously expressed, with highest levels in testis and brain.
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