H3C14: Histone H3.1, a Core Component of Nucleosomes
Essential for chromatin structure, gene regulation, and implicated in oncogenesis and developmental disorders.
Gene Information Card
| Symbol | H3C14 |
|---|---|
| Full Name | H3 clustered histone 14 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p22.2 |
| NCBI Gene ID | 8357 ncbi.nlm.nih.gov/gene/8357 |
| Ensembl ID | ENSG00000276903 |
| UniProt ID | P68431 |
| OMIM ID | 602810 |
| HGNC ID | 4764 |
| Aliases | HIST1H3A, H3.1, H3/a, H3FA |
Description
H3C14 (H3 clustered histone 14) encodes replication-dependent histone H3.1, a core histone protein that, together with H2A, H2B, and H4, forms the nucleosome octamer. Histone H3.1 is essential for chromatin packaging, DNA replication, and transcriptional regulation. Post-translational modifications of H3.1, such as methylation and acetylation, serve as epigenetic marks that modulate chromatin accessibility and gene expression. Mutations in H3C14, particularly at lysine 27 (K27M) and glycine 34 (G34R/V), are recurrent driver events in pediatric high-grade gliomas and are classified as oncohistones.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pediatric diffuse midline glioma (DMG) | K27M mutation in H3.1 leads to global loss of H3K27me3, causing aberrant gene activation and tumorigenesis. | PMID: 22286216, COSMIC |
| Pediatric high-grade glioma (pHGG) | G34R/V mutations alter H3K36 methylation patterns, disrupting normal differentiation and promoting oncogenesis. | PMID: 22286216, COSMIC |
| Lung adenocarcinoma | Somatic mutations and altered H3.1 expression contribute to chromatin remodeling and tumor progression. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Lymph node | 10.8 | Medium |
| Testis | 9.2 | Medium |
| Brain | 6.1 | Low |
| Liver | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical carcinoma |
| K562 | 14.8 | Chronic myeloid leukemia |
| A549 | 13.5 | Lung carcinoma |
| HepG2 | 12.1 | Hepatocellular carcinoma |
| SH-SY5Y | 8.9 | Neuroblastoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| K27M | Missense | Recurrent in pediatric DMG | Dominant-negative inhibition of EZH2, global H3K27me3 loss |
| G34R | Missense | Recurrent in pediatric HGG | Alters H3K36 methylation, disrupts gene silencing |
| G34V | Missense | Rare in pediatric HGG | Similar to G34R, impaired differentiation |
| A15T | Missense | Somatic in lung cancer | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Not applicable; H3.1 mutations are typically gain-of-function or dominant-negative.
Gain of Function (GOF)
K27M mutation confers a gain-of-function by inhibiting PRC2 activity, leading to global hypomethylation.
Dominant Negative (DN)
K27M acts as a dominant-negative oncohistone by binding and inhibiting EZH2, the catalytic subunit of PRC2.
View complete mutation data：
Gene Ontology (GO)
| • nucleosome assembly (GO:0006334) | • chromatin silencing (GO:0006342) |
| • DNA replication-dependent nucleosome assembly (GO:0006335) | • protein heterodimerization activity (GO:0046982) |
| • DNA binding (GO:0003677) |
Pathways
• Chromatin organization (REACT:1788)
• Epigenetic regulation of gene expression (REACT:1789)
• PRC2-mediated methylation of histone H3 (REACT:1790)
Protein Summary
Histone H3.1 is a 136-amino acid core histone protein that forms the nucleosome octamer. It is highly conserved and undergoes extensive post-translational modifications, including methylation at K4, K9, K27, K36, and K79, and acetylation at K9, K14, K18, and K23. These modifications regulate chromatin structure and gene expression. The K27M mutation in H3.1 is a hallmark of pediatric diffuse midline gliomas, where it globally reduces H3K27 trimethylation, leading to oncogenic transcriptional programs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| H3C14 Knockout HEK293 Cell Line | EDJ-KQ8253 | Human | 126961 | Details Get a Quote |
| H3C14 Knockout HeLa Cell Line | EDJ-KQ58191 | Human | 126961 | Details Get a Quote |
| H3C14 Knockout A-549 Cell Line | EDJ-KQ66681 | Human | 126961 | Details Get a Quote |
| H3C14 Knockout HCT 116 Cell Line | EDJ-KQ75095 | Human | 126961 | Details Get a Quote |
