H3C4
H3 clustered histone 4, the group of H3 histones
Basic information
Region (hg38): 6:26196783-26197286
Previous symbols: [ "H3FB", "HIST1H3D" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the H3C4 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 5 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 5 | 1 | 0 |
Variants in H3C4
This is a list of pathogenic ClinVar variants found in the H3C4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-26196862-C-A | not specified | Uncertain significance (Nov 22, 2023) | ||
| 6-26196908-C-G | not specified | Uncertain significance (Aug 09, 2021) | ||
| 6-26196937-A-G | not specified | Uncertain significance (Aug 16, 2021) | ||
| 6-26196947-C-T | not specified | Uncertain significance (Jun 17, 2024) | ||
| 6-26196961-C-T | not specified | Uncertain significance (Jan 03, 2024) | ||
| 6-26197068-C-T | Likely benign (Sep 01, 2022) | |||
| 6-26197154-T-A | not specified | Uncertain significance (Apr 13, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| H3C4 | protein_coding | protein_coding | ENST00000377831 | 1 | 2454 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00113 | 0.403 | 125722 | 0 | 26 | 125748 | 0.000103 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.384 | 75 | 85.0 | 0.883 | 0.00000393 | 857 |
| Missense in Polyphen | 25 | 31.043 | 0.80534 | 334 | ||
| Synonymous | -4.81 | 72 | 35.5 | 2.03 | 0.00000165 | 312 |
| Loss of Function | -0.261 | 4 | 3.47 | 1.15 | 1.52e-7 | 35 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000119 | 0.000119 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000527 | 0.0000527 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.000523 | 0.000523 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.;
- Disease
- DISEASE: Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:22286216}. Note=The gene represented in this entry is involved in disease pathogenesis. HIST1H3B mutations affecting residue Lys-28 involved in post-translational modifications of histone H3.1 are recurrent in malignant, aggressive gliomas including pediatric non-brain stem glioblastoma and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histone methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23603901). {ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23603901}.; DISEASE: Note=HIST1H3B or HIST1H3C mutations affecting residue Lys-37 of histone H3.1 are involved in the pathogenesis of pediatric undifferentiated soft tissue sarcomas. The mechanism through which mutations lead to tumorigenesis involves altered histones methylation with gain of global H3K27 methylation, altered Polycomb repressive complex 1 (PRC1) activity, aberrant epigenetic regulation of gene expression and impaired differentiation of mesenchimal progenitor cells. {ECO:0000269|PubMed:27174990}.;
- Pathway
- Systemic lupus erythematosus - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Alcoholism - Homo sapiens (human);Histone Modifications;B-WICH complex positively regulates rRNA expression;ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;Positive epigenetic regulation of rRNA expression;SIRT1 negatively regulates rRNA expression;Interleukin-7 signaling;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Signaling by WNT;Signal Transduction;DNA methylation;Epigenetic regulation of gene expression;Gene expression (Transcription);Signaling by Interleukins;Generic Transcription Pathway;Cytokine Signaling in Immune system;Oxidative Stress Induced Senescence;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Factors involved in megakaryocyte development and platelet production;Cellular responses to stress;HDACs deacetylate histones;Metabolism of proteins;Reproduction;HDMs demethylate histones;RNA Polymerase I Promoter Clearance;PKMTs methylate histone lysines;RNA Polymerase I Promoter Opening;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;RMTs methylate histone arginines;Chromatin modifying enzymes;Immune System;RNA Polymerase I Transcription;Amyloid fiber formation;RNA Polymerase I Chain Elongation;Meiotic recombination;Meiosis;Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3;RHO GTPases activate PKNs;HATs acetylate histones;Cellular responses to external stimuli;RHO GTPase Effectors;Signaling by Rho GTPases;Hemostasis;Condensation of Prophase Chromosomes;Signaling by Nuclear Receptors;Chromatin organization;Mitotic Prophase;M Phase;Estrogen-dependent gene expression;Transcriptional regulation by small RNAs;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Cell Cycle;Cell Cycle, Mitotic;ESR-mediated signaling;Transcriptional regulation by RUNX1;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Gene Silencing by RNA;PRC2 methylates histones and DNA
(Consensus)
Intolerance Scores
- loftool
- 0.321
- rvis_EVS
- -0.14
- rvis_percentile_EVS
- 42.88
Haploinsufficiency Scores
- pHI
- hipred
- N
- hipred_score
- 0.258
- ghis
- 0.525
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hist1h3a
- Phenotype