• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
HDAC8 (HGNC:13315) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
histone deacetylase 8
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
HDACL1, WTS, MRXS6
Alias symbols
RPD3, KDAC8
%HI
15.01(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.98(Read more about gnomAD pLI score)
LOEUF
0.3(Read more about gnomAD LOEUF score)
Cytoband
Xq13.1
Genomic Coordinates
GRCh37/hg19: chrX:71549366-71792693 NCBI Ensembl UCSC
GRCh38/hg38: chrX:72329516-72572843 NCBI Ensembl UCSC
MANE Select Transcript
NM_018486.3 ENST00000373573.9 (Read more about MANE Select)
Function
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:14701748, PubMed:28497810). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:14701748). Histone deacetylases act via the forma... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-6116
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
03/28/2018

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Cornelia de Lange syndrome (CdLS) Monarch
HI Evidence:
  • PUBMED: 22885700
    Deardorff MA et al identified four de novo missense mutations and one de novo nonsense HDAC8 mutations in 6 CdLS probands. None of the mutations was seen in 290 ethnically matched control chromosomes or in 629 individuals of the 1000 Genomes Project. All probands were diagnosed of CdLS, pre-screened and were negative for mutations in NIPBL, SMC1A and SMC3.
  • PUBMED: 24403048
    Kaiser FJ et al reported a cohort of 38 individuals with an emerging spectrum of features caused by HDAC8 mutations. The mutations were detected by whole-genome SNP array, and most are missense and de novo. To evaluate the effect of these mutations on protein function, they mapped mutations on crystal structure of HDAC8 and expressed each of the mutated protein in E. coli. The results showed varying loss of activity of HDAC8 protein.
  • PUBMED: 26671848
    Parenti I et al reported on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in HDAC8. They used different approaches including Sanger sequencing, a targetd NGS panel including the five known CdLS genes, and whole exome sequencing. The variants include one exchange affecting a conserved splice donor site (c.910+1G>A), one nonsense variant p.(R166*), one frame-shift deletion p.(F207Nfs*3) and seven single amino acid substitutions, namely p.(S150P), p.(C153R), p.(N156K), p.(T280I), p.(P257L), p.(C287Y), and p.(G320R).
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)