H2BC4

H2B clustered histone 4, the group of H2B histones

Basic information

Region (hg38): 6:26114872-26123926

Previous symbols: [ "H2BFL", "HIST1H2BC" ]

Links

ENSG00000180596 ∙ NCBI:8347 ∙ OMIM:602847 ∙ HGNC:4757 ∙ Uniprot:P62807 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the H2BC4 gene.

• Hereditary hemochromatosis (149 variants)
• Hemochromatosis type 1 (65 variants)
• not provided (61 variants)
• Inborn genetic diseases (32 variants)
• not specified (14 variants)
• 6 conditions (12 variants)
• Tessadori-van Haaften neurodevelopmental syndrome 1 (3 variants)
• Cardiomyopathy (2 variants)
• Bronze diabetes (2 variants)
• HFE POLYMORPHISM (2 variants)
• Cutaneous photosensitivity;Porphyrinuria (1 variants)
• Abnormality of iron homeostasis (1 variants)
• HFE-related condition (1 variants)
• 7 conditions (1 variants)
• Alzheimer disease type 1 (1 variants)
• Hereditary cancer-predisposing syndrome (1 variants)
• Cystic fibrosis (1 variants)
• Variegate porphyria (1 variants)
• HFE-related disorder (1 variants)
• Juvenile hemochromatosis (1 variants)
• HIST1H4C-associated disorder (1 variants)
• HFE INTRONIC POLYMORPHISM (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the H2BC4 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						0
missense			1			1
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region	1		1			2
non coding	18	13	101	101	13	246
Total	18	13	102	101	13

Highest pathogenic variant AF is 0.0000329

Variants in H2BC4

This is a list of pathogenic ClinVar variants found in the H2BC4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-26123550-C-A		not specified	Uncertain significance (Dec 21, 2023)
6-26123711-G-A		not specified	Uncertain significance (Aug 02, 2022)
6-26123817-G-A		not specified	Uncertain significance (May 27, 2022)
6-26123826-C-T		not specified	Uncertain significance (Jun 11, 2021)
6-26123892-C-T		not specified	Uncertain significance (Sep 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
H2BC4	protein_coding	protein_coding	ENST00000314332	1	9054

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00382	0.422	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.357	62	70.4	0.880	0.00000336	811
Missense in Polyphen		14	19.426	0.72067		259
Synonymous	-7.82	83	29.2	2.84	0.00000150	264
Loss of Function	-0.502	3	2.20	1.37	9.31e-8	35

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000791	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• 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.
• Pathway: Systemic lupus erythematosus - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Alcoholism - Homo sapiens (human);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);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;DNA Repair;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);Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;Generic Transcription Pathway;Oxidative Stress Induced Senescence;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Homology Directed Repair;Cellular responses to stress;Post-translational protein modification;HDACs deacetylate histones;Metabolism of proteins;Reproduction;RNA Polymerase I Promoter Clearance;RNA Polymerase I Promoter Opening;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Chromatin modifying enzymes;G2/M Checkpoints;Cell Cycle Checkpoints;RNA Polymerase I Transcription;Amyloid fiber formation;RNA Polymerase I Chain Elongation;Meiotic recombination;Meiotic synapsis;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;Packaging Of Telomere Ends;Telomere Maintenance;Chromosome Maintenance;Ub-specific processing proteases;Condensation of Prophase Chromosomes;Deubiquitination;Signaling by Nuclear Receptors;Chromatin organization;Mitotic Prophase;M Phase;Protein ubiquitination;Estrogen-dependent gene expression;Transcriptional regulation by small RNAs;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Cell Cycle, Mitotic;ESR-mediated signaling;Transcriptional regulation by RUNX1;E3 ubiquitin ligases ubiquitinate target proteins;Processing of DNA double-strand break ends;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: 0.392
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

• pHI: 0.564
• hipred: N
• hipred_score: 0.393
• ghis: 0.603

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hist1h2bg

Gene ontology

• Biological process: innate immune response in mucosa;nucleosome assembly;protein ubiquitination;antibacterial humoral response;defense response to Gram-positive bacterium;antimicrobial humoral immune response mediated by antimicrobial peptide
• Cellular component: nucleosome;extracellular space;nucleus;nucleoplasm;cytosol;extracellular exosome
• Molecular function: DNA binding;protein binding;identical protein binding;protein heterodimerization activity