H3C2 Gene

Name H3 clustered histone 2
Description Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H3 family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]
Summary
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Several studies have established that point‐mutations altering key lysine residues—for example, the recurrent K27M and G34 alterations found in pediatric high‐grade gliomas and diffuse intrinsic pontine gliomas—profoundly disrupt normal epigenetic patterns by impairing the function of the polycomb repressive complex 2 and hence globally reducing H3K27 trimethylation while permitting focal retention at selected genomic loci."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In other tumor types such as chondroblastoma, distinct H3.3 mutations demonstrate that even subtle differences among H3 variant residues can drive tissue‐specific oncogenic programs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Equally important, the replication-independent deposition of variants like H3.3 is mediated by dedicated histone chaperones (for example, DAXX and ATRX), ensuring the maintenance of active chromatin regions and genomic stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, chromatin “reader” proteins—such as ZMYND11—specifically recognize modifications (e.g. H3.3K36me3) on these variants to modulate transcription elongation and contribute to tumor suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In aggregate, these findings underscore that H3 variants (including products of HIST1H3C and related genes) are not merely structural nucleosomal components but serve as dynamic regulators of gene expression, cell differentiation, and oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dong-Anh Khuong-Quang, Pawel Buczkowicz, Patricia Rakopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-012-0998-0"}], "href": "https://doi.org/10.1007/s00401-012-0998-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22661320"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22661320"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sriram Venneti, Mihir T Garimella, Lisa M Sullivan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of histone 3 lysine 27 trimethylation (H3K27me3) and enhancer of Zest 2 (EZH2) in pediatric glial and glioneuronal tumors shows decreased H3K27me3 in H3F3A K27M mutant glioblastomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bpa.12042"}], "href": "https://doi.org/10.1111/bpa.12042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23414300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23414300"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sriram Venneti, Mariarita Santi, Michelle Madden Felicella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A sensitive and specific histopathologic prognostic marker for H3F3A K27M mutant pediatric glioblastomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-014-1338-3"}], "href": "https://doi.org/10.1007/s00401-014-1338-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25200322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25200322"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Dong Fang, Haiyun Gan, Liang Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.36696"}], "href": "https://doi.org/10.7554/eLife.36696"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29932419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29932419"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sam Behjati, Patrick S Tarpey, Nadège Presneau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2814"}], "href": "https://doi.org/10.1038/ng.2814"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24162739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24162739"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Pascal Drané, Khalid Ouararhni, Arnaud Depaux, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.566910"}], "href": "https://doi.org/10.1101/gad.566910"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20504901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20504901"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hong Wen, Yuanyuan Li, Yuanxin Xi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZMYND11 links histone H3.3K36me3 to transcription elongation and tumour suppression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature13045"}], "href": "https://doi.org/10.1038/nature13045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24590075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24590075"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Pawel Buczkowicz, Christine Hoeman, Patricia Rakopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2936"}], "href": "https://doi.org/10.1038/ng.2936"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24705254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24705254"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "David Castel, Cathy Philippe, Raphaël Calmon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-015-1478-0"}], "href": "https://doi.org/10.1007/s00401-015-1478-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26399631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26399631"}]}]}]}
NCBI Gene ID 8358
API
Download Associations
Predicted Functions View H3C2's ARCHS4 Predicted Functions.
Co-expressed Genes View H3C2's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View H3C2's ARCHS4 Predicted Functions.

Functional Associations

H3C2 has 569 functional associations with biological entities spanning 4 categories (disease, phenotype or trait, functional term, phrase or reference, cell line, cell type or tissue, gene, protein or microRNA) extracted from 8 datasets.

Click the + buttons to view associations for H3C2 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of H3C2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of H3C2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with H3C2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of H3C2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of H3C2 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of H3C2 gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of H3C2 gene from the Rummagene Transcription Factor Associations 2026 dataset.
WikiPathways Pathways 2024 pathways involving H3C2 protein from the WikiPathways Pathways 2024 dataset.