HIRA

histone cell cycle regulator, the group of WD repeat domain containing|HIRA histone chaperone complex subunits

Basic information

Region (hg38): 22:19330697-19447450

Previous symbols: [ "TUPLE1" ]

Links

ENSG00000100084 ∙ NCBI:7290 ∙ OMIM:600237 ∙ HGNC:4916 ∙ Uniprot:P54198 ∙ 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 HIRA gene.

• not provided (51 variants)
• Inborn genetic diseases (27 variants)
• HIRA-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIRA 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				16	8	24
missense			26	2	1	29
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	1	4
non coding					19	19
Total	0	0	27	18	28

Variants in HIRA

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

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

Position	Type	Phenotype	Significance	ClinVar
22-19331389-C-T			Benign (May 15, 2021)
22-19351400-C-T			Likely benign (Jun 06, 2018)
22-19353365-C-A		not specified	Uncertain significance (Feb 12, 2024)
22-19353365-C-T			Likely benign (Aug 14, 2018)
22-19353375-T-C			Likely benign (Dec 31, 2019)
22-19353376-G-A		not specified	Uncertain significance (Sep 13, 2023)
22-19353386-G-A		not specified	Uncertain significance (Nov 14, 2023)
22-19353405-G-A		HIRA-related disorder	Benign (Dec 31, 2019)
22-19353483-A-G			Benign (Dec 31, 2019)
22-19353492-G-C		not specified	Uncertain significance (Feb 13, 2024)
22-19353500-G-A		not specified	Uncertain significance (Nov 09, 2023)
22-19353502-G-A		not specified	Uncertain significance (Jul 20, 2022)
22-19353518-A-G		not specified	Uncertain significance (Aug 17, 2021)
22-19354025-C-T			Benign (Dec 31, 2019)
22-19354026-G-A		not specified	Uncertain significance (Feb 23, 2023)
22-19354106-A-C			Benign (Dec 31, 2019)
22-19355751-C-T		HIRA-related disorder	Benign (Dec 31, 2019)
22-19355775-G-A		not specified	Uncertain significance (Feb 23, 2023)
22-19355789-C-T		HIRA-related disorder	Likely benign (Sep 17, 2019)
22-19355800-C-T		not specified	Uncertain significance (Jan 30, 2024)
22-19355801-G-A			Likely benign (Jul 16, 2018)
22-19355831-C-T			Likely benign (Aug 16, 2018)
22-19355853-G-A		not specified	Uncertain significance (Apr 12, 2023)
22-19355982-C-A			Benign (May 23, 2021)
22-19356222-T-C			Likely benign (May 21, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HIRA	protein_coding	protein_coding	ENST00000263208	25	117004

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.35e-7	125742	0	5	125747	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.71	352	610	0.578	0.0000371	6603
Missense in Polyphen		86	234.29	0.36707		2454
Synonymous	-0.423	260	251	1.03	0.0000163	2058
Loss of Function	6.63	3	57.1	0.0526	0.00000303	619

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	0.0000925	0.0000924
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the periodic repression of histone gene transcription during the cell cycle. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit. {ECO:0000269|PubMed:12370293, ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15621527}.
• Pathway: Formation of Senescence-Associated Heterochromatin Foci (SAHF);DNA Damage/Telomere Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.232

Intolerance Scores

• loftool: 0.0158
• rvis_EVS: -1.37
• rvis_percentile_EVS: 4.43

Haploinsufficiency Scores

• pHI: 0.942
• hipred: Y
• hipred_score: 0.816
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• 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: Hira
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; skeleton phenotype; immune system phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype

Gene ontology

• Biological process: mitotic sister chromatid segregation;osteoblast differentiation;DNA replication-independent nucleosome assembly;transcription, DNA-templated;regulation of transcription by RNA polymerase II;gastrulation;anatomical structure morphogenesis;chromatin silencing at centromere;regulation of chromatin silencing;muscle cell differentiation
• Cellular component: HIR complex;chromosome, centromeric region;nuclear chromatin;nucleus;nucleoplasm;PML body;protein-containing complex;extracellular exosome
• Molecular function: DNA binding;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;nucleosome binding