H3-4

H3.4 histone, cluster member, the group of H3 histones

Basic information

Region (hg38): 1:228424845-228425360

Previous symbols: [ "H3FT", "HIST3H3" ]

Links

ENSG00000168148 ∙ NCBI:8290 ∙ OMIM:602820 ∙ HGNC:4778 ∙ Uniprot:Q16695 ∙ 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 H3-4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the H3-4 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		1
missense			28			28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	28	1	0

Variants in H3-4

This is a list of pathogenic ClinVar variants found in the H3-4 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-228424923-G-A		not specified	Uncertain significance (Apr 06, 2023)
1-228424929-C-T		not specified	Uncertain significance (Jan 14, 2025)
1-228424960-A-G			Likely benign (Sep 01, 2022)
1-228424977-G-A		not specified	Uncertain significance (Aug 23, 2021)
1-228425019-C-T		not specified	Uncertain significance (Dec 10, 2024)
1-228425037-A-T		not specified	Uncertain significance (Jun 24, 2022)
1-228425094-C-T		not specified	Uncertain significance (Nov 26, 2024)
1-228425097-G-C		not specified	Uncertain significance (Dec 05, 2024)
1-228425102-A-T		not specified	Uncertain significance (Apr 12, 2022)
1-228425109-G-C		not specified	Uncertain significance (Jan 17, 2024)
1-228425111-A-G		not specified	Uncertain significance (Jan 09, 2024)
1-228425112-T-C		not specified	Likely benign (Feb 10, 2025)
1-228425136-G-C		not specified	Uncertain significance (May 10, 2024)
1-228425165-C-T		not specified	Uncertain significance (May 09, 2023)
1-228425168-C-T		not specified	Uncertain significance (Mar 20, 2024)
1-228425169-G-T		not specified	Uncertain significance (Aug 16, 2022)
1-228425183-G-A		not specified	Uncertain significance (Jan 21, 2025)
1-228425195-G-C		not specified	Uncertain significance (Dec 28, 2023)
1-228425201-T-C		not specified	Uncertain significance (May 03, 2023)
1-228425205-G-A		not specified	Uncertain significance (Oct 08, 2024)
1-228425208-G-A		not specified	Uncertain significance (Mar 07, 2025)
1-228425212-C-G		not specified	Uncertain significance (Dec 25, 2024)
1-228425219-A-G		not specified	Uncertain significance (Mar 15, 2024)
1-228425223-C-T		not specified	Uncertain significance (Oct 16, 2024)
1-228425231-G-T		not specified	Uncertain significance (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
H3-4	protein_coding	protein_coding	ENST00000366696	1	481

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000165	0.144	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.00	163	105	1.55	0.00000968	857
Missense in Polyphen		55	31.401	1.7515		303
Synonymous	-4.13	80	44.8	1.79	0.00000383	305
Loss of Function	-1.08	6	3.75	1.60	2.49e-7	36

LoF frequencies by population

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

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);Transcriptional misregulation in cancer - Homo sapiens (human);Alcoholism - Homo sapiens (human);Follicle Stimulating Hormone (FSH) signaling pathway;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Signaling by WNT;Signal Transduction;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;Homology Directed Repair;Reproduction;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Meiotic synapsis;Meiosis;Packaging Of Telomere Ends;Telomere Maintenance;Chromosome Maintenance;EGFR1;Condensation of Prophase Chromosomes;Mitotic Prophase;IL4;M Phase;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;Processing of DNA double-strand break ends;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.643
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.41

Haploinsufficiency Scores

• pHI: 0.602
• hipred: Y
• hipred_score: 0.595
• ghis: 0.454

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.601

Gene Damage Prediction

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

Gene ontology

• Biological process: double-strand break repair via nonhomologous end joining;nucleosome assembly;telomere capping;negative regulation of protein oligomerization;protein heterotetramerization
• Cellular component: nuclear chromosome, telomeric region;nucleosome;nuclear nucleosome;nucleus;nucleoplasm;extracellular exosome
• Molecular function: protein binding;nucleosomal DNA binding;protein heterodimerization activity