HDAC5

histone deacetylase 5, the group of Histone deacetylases, class IIA

Basic information

Region (hg38): 17:44076745-44123702

Links

ENSG00000108840 ∙ NCBI:10014 ∙ OMIM:605315 ∙ HGNC:14068 ∙ Uniprot:Q9UQL6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HDAC5 gene.

• Inborn genetic diseases (42 variants)
• not provided (15 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HDAC5 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				3	1	4
missense			41	2	4	47
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	3	4
non coding			1		1	2
Total	0	0	42	5	6

Variants in HDAC5

This is a list of pathogenic ClinVar variants found in the HDAC5 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-44078383-G-A		not specified	Uncertain significance (Apr 20, 2023)
17-44078405-C-T		not specified	Uncertain significance (Apr 22, 2022)
17-44078413-G-A		not specified	Uncertain significance (Aug 26, 2022)
17-44078506-C-T		not specified	Uncertain significance (Jul 26, 2022)
17-44078524-G-A			Benign (Jul 07, 2018)
17-44078543-C-T		not specified	Uncertain significance (Nov 29, 2021)
17-44078546-C-T		not specified	Uncertain significance (Jan 03, 2024)
17-44078621-G-A		not specified	Uncertain significance (Oct 06, 2022)
17-44078636-C-T		not specified	Uncertain significance (Oct 12, 2022)
17-44078674-G-A			Benign (Jun 08, 2018)
17-44078849-G-C		not specified	Uncertain significance (Oct 12, 2021)
17-44079173-C-T		not specified	Uncertain significance (Dec 20, 2023)
17-44080213-C-A		not specified	Uncertain significance (Apr 17, 2023)
17-44080441-C-A		not specified	Uncertain significance (Jul 11, 2023)
17-44080836-G-T			Benign (Jul 17, 2018)
17-44080837-G-A		not specified	Uncertain significance (Sep 14, 2023)
17-44080885-A-G			Benign (Jul 13, 2018)
17-44082617-A-T		not specified	Uncertain significance (Dec 20, 2023)
17-44083552-T-C		not specified	Uncertain significance (Dec 17, 2023)
17-44083611-A-C		not specified	Uncertain significance (May 09, 2023)
17-44083613-T-C		not specified	Uncertain significance (Jul 06, 2021)
17-44083621-T-C		not specified	Uncertain significance (Jul 11, 2023)
17-44083637-C-T		not specified	Uncertain significance (Jul 20, 2021)
17-44083837-T-G		not specified	Uncertain significance (Dec 20, 2023)
17-44084566-T-C		not specified	Uncertain significance (Jul 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HDAC5	protein_coding	protein_coding	ENST00000225983	26	46957

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.06e-7	125720	0	27	125747	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.32	402	638	0.630	0.0000389	7215
Missense in Polyphen		183	330.45	0.5538		3757
Synonymous	0.176	276	280	0.987	0.0000185	2316
Loss of Function	6.49	3	54.9	0.0547	0.00000258	639

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000187	0.000186
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000117	0.000114
Middle Eastern	0.000163	0.000163
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000269|PubMed:24413532}.
• Pathway: Apelin signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Alcoholism - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Cell Cycle;MicroRNAs in cardiomyocyte hypertrophy;Cell Differentiation - Index expanded;Cell Differentiation - Index;Neural Crest Differentiation;Cardiac Hypertrophic Response;Initiation of transcription and translation elongation at the HIV-1 LTR;VEGFA-VEGFR2 Signaling Pathway;Ethanol effects on histone modifications;Disease;Signal Transduction;regulation of pgc-1a;nfat and hypertrophy of the heart ;mets affect on macrophage differentiation;Signaling by NOTCH1;Signaling by NOTCH;TGF-beta super family signaling pathway canonical;control of skeletal myogenesis by hdac and calcium/calmodulin-dependent kinase (camk);Signaling events mediated by HDAC Class II;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Intracellular signaling by second messengers;Diseases of signal transduction;NOTCH1 Intracellular Domain Regulates Transcription (Consensus)

Recessive Scores

• pRec: 0.287

Intolerance Scores

• loftool: 0.426
• rvis_EVS: -1.28
• rvis_percentile_EVS: 5.17

Haploinsufficiency Scores

• pHI: 0.426
• hipred: Y
• hipred_score: 0.831
• ghis: 0.544

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hdac5
• Phenotype: renal/urinary 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); muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin organization;chromatin remodeling;chromatin silencing;protein deacetylation;inflammatory response;regulation of myotube differentiation;negative regulation of myotube differentiation;response to activity;histone deacetylation;neuron differentiation;B cell differentiation;cellular response to insulin stimulus;regulation of gene expression, epigenetic;B cell activation;response to cocaine;regulation of protein binding;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of DNA-binding transcription factor activity;histone H3 deacetylation;cellular response to lipopolysaccharide;negative regulation of cell migration involved in sprouting angiogenesis;regulation of histone H3-K9 acetylation
• Cellular component: histone deacetylase complex;nucleus;nucleoplasm;cytoplasm;Golgi apparatus;cytosol;nuclear speck
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II transcription factor binding;chromatin binding;histone deacetylase activity;protein kinase C binding;protein binding;transcription factor binding;NAD-dependent histone deacetylase activity (H3-K14 specific);protein deacetylase activity;histone deacetylase binding;transcription regulatory region DNA binding;metal ion binding;repressing transcription factor binding