GeneBe

HDAC6

protein-coding

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

Gene summary

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It contains an internal duplication of two catalytic domains which appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006044.4

Inheritance

XL

ClinVar variants

P:2U:203B:59

Top phenotype

Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:48,801,377-48,824,982

External References & Databases

Ensembl (ENSG00000094631)NCBI Gene (10013)OMIM (300272)HGNC:14064GenCCUniProt (Q9UBN7)AlphaFoldClinVar (HDAC6)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~23.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

X-linked dominant chondrodysplasia, Chassaing-Lacombe typeSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010463

Submitter: Orphanet

X-linked dominant chondrodysplasia, Chassaing-Lacombe typeMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010463

Submitter: Genomics England PanelApp

X-linked dominant chondrodysplasia, Chassaing-Lacombe typeLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010463

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmiaXL

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 16001442; 20181727Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HDAC6 variants in ClinVar

7 Conditions Cataloged
not specifiedTotal: 114
not providedTotal: 54
HDAC6-related disorderTotal: 14
X-linked dominant chondrodysplasia, Chassaing-Lacombe typeTotal: 13
AutismTotal: 1
Abnormality of neuronal migrationTotal: 1
Usher syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006044.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
19
clinvar
23
clinvar
7
clinvar
 49
missense
1
clinvar
145
clinvar
29
clinvar
 175
nonsense
13
clinvar
 13
start loss
1
clinvar
 1
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
25
clinvar
 25
Total11203527264
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 119 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006044.4RefSeqNP_006035.228MANE Select
ENST00000334136.11EnsemblENSP00000334061.528MANE Select
NM_001321225.2RefSeqNP_001308154.129Standard
NM_001321226.2RefSeqNP_001308155.128Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
hdac6Danio rerio

Structure: dorsal longitudinal anastomotic vessel

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Viral carcinogenesis - Homo sapiens (human)
  • Alcoholism - Homo sapiens (human)
  • Human papillomavirus infection - Homo sapiens (human)
  • Cell Cycle
  • Neural Crest Differentiation

Biological Process

  • protein polyubiquitination
  • protein deacetylation
  • protein quality control for misfolded or incompletely synthesized proteins
  • intracellular protein transport
  • autophagy

Molecular Function

  • RNA polymerase II proximal promoter sequence-specific DNA binding
  • actin binding
  • histone deacetylase activity
  • protein binding
  • beta-catenin binding

Cellular Component

  • histone deacetylase complex
  • nucleus
  • nucleoplasm
  • cytoplasm
  • multivesicular body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000334136
Coding exons
28
Length
23609
Individuals with no LoFs
121641
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
121642
p
0.00000411
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.292854900.5820.00003987776
Missense (PolyPhen)54189.440.285052999
Synonymous0.3371881940.9690.00001572546
Loss of Function5.95041.20.000.00000274719

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000130.0000091rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.189

Intolerance Scores

LoFtool
0.0346
RVIS EVS
0.07
RVIS percentile EVS
59.11

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.604

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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