HDAC6

histone deacetylase 6, the group of Histone deacetylases, class IIB|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): X:48801376-48824982

Links

ENSG00000094631 ∙ NCBI:10013 ∙ OMIM:300272 ∙ HGNC:14064 ∙ Uniprot:Q9UBN7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked dominant chondrodysplasia, Chassaing-Lacombe type (Moderate), mode of inheritance: XL
• X-linked dominant chondrodysplasia, Chassaing-Lacombe type (Supportive), mode of inheritance: XL
• X-linked dominant chondrodysplasia, Chassaing-Lacombe type (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	16001442; 20181727

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HDAC6 gene.

• not provided (46 variants)
• Inborn genetic diseases (21 variants)
• X-linked dominant chondrodysplasia, Chassaing-Lacombe type (6 variants)
• Usher syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HDAC6 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	7	23
missense		1	20	13		34
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				1	2	3
Total	0	1	21	30	9

Variants in HDAC6

This is a list of pathogenic ClinVar variants found in the HDAC6 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-48802684-TCCTCAACTATGA-T			Uncertain significance (Nov 01, 2023)
X-48802739-G-A		not specified	Uncertain significance (Feb 28, 2023)
X-48802743-G-C		not specified	Uncertain significance (Aug 13, 2021)
X-48802784-C-G			Likely benign (Nov 01, 2022)
X-48802894-C-T			Likely benign (Mar 01, 2022)
X-48802925-G-A		not specified	Uncertain significance (Jan 18, 2023)
X-48802953-T-C		not specified	Uncertain significance (Feb 03, 2022)
X-48802995-G-C			Likely benign (-)
X-48803118-T-C			Benign (Dec 31, 2019)
X-48805444-G-A			Likely benign (Feb 01, 2023)
X-48805510-C-T			Likely benign (Dec 31, 2019)
X-48805635-G-A		not specified	Uncertain significance (Jan 10, 2023)
X-48805666-T-C		HDAC6-related disorder	Benign (Jul 06, 2020)
X-48806405-A-C			Likely benign (Feb 01, 2024)
X-48806443-C-T		X-linked dominant chondrodysplasia, Chassaing-Lacombe type	Benign/Likely benign (Mar 02, 2022)
X-48806644-T-A			Benign (Dec 31, 2019)
X-48806665-G-A			Likely benign (Sep 01, 2017)
X-48806714-T-G		HDAC6-related disorder	Likely benign (Jul 20, 2020)
X-48808081-G-C		not specified	Uncertain significance (Feb 15, 2024)
X-48808146-C-A			Likely benign (Apr 04, 2018)
X-48808283-C-T		not specified	Uncertain significance (Jan 25, 2024)
X-48808285-C-T			Likely benign (Jan 05, 2018)
X-48814437-C-CA		HDAC6-related disorder	Likely benign (May 25, 2022)
X-48814509-G-T			Uncertain significance (-)
X-48814749-G-A		HDAC6-related disorder	Likely benign (Apr 17, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HDAC6	protein_coding	protein_coding	ENST00000334136	28	23609

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.68e-7	121641	0	1	121642	0.00000411

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.29	285	490	0.582	0.0000398	7776
Missense in Polyphen		54	189.44	0.28505		2999
Synonymous	0.337	188	194	0.969	0.0000157	2546
Loss of Function	5.95	0	41.2	0.00	0.00000274	719

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)	0.0000126	0.00000914
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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 (By similarity). Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000250, ECO:0000269|PubMed:12024216, ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:24413532}.
• Disease: DISEASE: Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia (CDP-PBHM) [MIM:300863]: A disease characterized by chondrodysplasia, severe platyspondyly, hydrocephaly, and facial features with microphthalmia. Bone abnormalities include a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. Affected females show a milder phenotype with small stature, sometimes associated with body asymmetry and mild mental retardation. {ECO:0000269|PubMed:20181727}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Viral carcinogenesis - Homo sapiens (human);Alcoholism - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Cell Cycle;Neural Crest Differentiation;Ectoderm Differentiation;Ethanol effects on histone modifications;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Disease;Signal Transduction;Gene expression (Transcription);HSF1 activation;sumoylation by ranbp2 regulates transcriptional repression;Generic Transcription Pathway;Cellular responses to stress;RNA Polymerase II Transcription;Signaling by NOTCH1;Signaling by NOTCH;TGF-beta super family signaling pathway canonical;Cellular responses to external stimuli;Signaling events mediated by HDAC Class II;Cellular response to heat stress;TNFalpha;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;Diseases of signal transduction;NOTCH1 Intracellular Domain Regulates Transcription;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.189

Intolerance Scores

• loftool: 0.0346
• rvis_EVS: 0.07
• rvis_percentile_EVS: 59.11

Haploinsufficiency Scores

• pHI: 0.146
• hipred: Y
• hipred_score: 0.761
• ghis: 0.552

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.604

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hdac6
• Phenotype: hematopoietic system phenotype; 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton 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

Zebrafish Information Network

• Gene name: hdac6
• Affected structure: dorsal longitudinal anastomotic vessel
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: protein polyubiquitination;protein deacetylation;protein quality control for misfolded or incompletely synthesized proteins;intracellular protein transport;autophagy;negative regulation of microtubule depolymerization;response to toxic substance;positive regulation of signal transduction;response to organic substance;regulation of signaling receptor activity;regulation of autophagy;positive regulation of epithelial cell migration;negative regulation of hydrogen peroxide metabolic process;positive regulation of receptor biosynthetic process;regulation of macroautophagy;histone deacetylation;regulation of protein stability;lysosome localization;positive regulation of protein oligomerization;protein-containing complex disassembly;positive regulation of peptidyl-serine phosphorylation;peptidyl-lysine deacetylation;cellular response to topologically incorrect protein;regulation of gene expression, epigenetic;ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway;negative regulation of protein complex disassembly;regulation of fat cell differentiation;negative regulation of proteolysis;negative regulation of transcription, DNA-templated;collateral sprouting;negative regulation of oxidoreductase activity;mitochondrion localization;response to misfolded protein;cilium assembly;regulation of microtubule-based movement;regulation of androgen receptor signaling pathway;dendritic spine morphogenesis;parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization;regulation of establishment of protein localization;cellular response to hydrogen peroxide;aggresome assembly;polyubiquitinated misfolded protein transport;Hsp90 deacetylation;response to growth factor;histone H3 deacetylation;cellular response to misfolded protein;positive regulation of chaperone-mediated protein complex assembly;tubulin deacetylation;positive regulation of hydrogen peroxide-mediated programmed cell death;regulation of autophagy of mitochondrion
• Cellular component: histone deacetylase complex;nucleus;nucleoplasm;cytoplasm;multivesicular body;cytosol;microtubule;microtubule associated complex;cytoplasmic microtubule;caveola;inclusion body;aggresome;dynein complex;axon;dendrite;cell leading edge;perikaryon;perinuclear region of cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;actin binding;histone deacetylase activity;protein binding;beta-catenin binding;microtubule binding;zinc ion binding;enzyme binding;polyubiquitin modification-dependent protein binding;ubiquitin protein ligase binding;NAD-dependent histone deacetylase activity (H3-K14 specific);histone deacetylase binding;tubulin deacetylase activity;alpha-tubulin binding;ubiquitin binding;tau protein binding;beta-tubulin binding;misfolded protein binding;Hsp90 protein binding;dynein complex binding