Biomarker: HDACs 8

Histology type: endometrial stromal tumor

Stage: low grade

Country: Korea

Region: Angyang

Followed up time :

Conclusion: HDACs 1, 4, 6, 7, and 8, that showed an especially high frequency of strong immunoreactivity, may represent potential therapeutic targets for ESS.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : strong positive(181-300 was strongly positive (3+).percentage of the total width that was stained was then multiplied to yield the total score;)

Expression elevation: A semi-quantitative scoring system was used to determine the immunostaining intensity (categorized as 0, 1, 2, or 3). The percentage of the total width that was stained was then multiplied to yield the total score; 0-20 points was considered to be negative, 21-80 was weakly positive (1+), 81-180 was moderately positive (2+), and 181-300 was strongly positive (3+).

Statictics: Median;Range

Cohort age: 46;23-64

Funtion Uniprot: 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 formation of large multiprotein complexes (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:14701748). Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin (PubMed:22885700). May play a role in smooth muscle cell contractility (PubMed:15772115). In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase by mediating decrotonylation ((2E)-butenoyl) of histones (PubMed:28497810).

UniProt ID: Q9BY41

UniProt Link: https://www.uniprot.org/uniprotkb/Q9BY41/entry

Biological function from UniProt: #Transcription #Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: Weakly expressed in most tissues. Expressed at higher level in heart, brain, kidney and pancreas and also in liver, lung, placenta, prostate and kidney.

Subcellular UniProt: #Chromosome #Cytoplasm #Nucleus

Alternative name from UniProt:

Catalytic activity: H2O + N6-acetyl-L-lysyl-[histone] = acetate + L-lysyl-[histone],H2O + N6-acetyl-L-lysyl-[protein] = acetate + L-lysyl-[protein],H2O + N6-(2E)-butenoyl-L-lysyl-[protein] = (2E)-2-butenoate + L-lysyl-[protein]

Activity regulation: Its activity is inhibited by trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), 3-(1-methyl-4-phenylacetyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide (APHA), 4-dimethylamino-N-(6-hydroxycarbamoyethyl)benzamide-N-hydroxy-7-(4-dimethylaminobenzoyl)aminoheptanamide (MS-344), 5-(4-methyl-benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide 4'-hydroxyamide (CRA-A) and butyrate.

Recommended name: Histone deacetylase 8

Gene name from HGNC: HDAC8 (HDACL1, KDAC8, MRXS6, RPD3, WTS)

HPA class: Disease related genes Enzymes FDA approved drug targets Human disease related genes

AlphaFold DB: Q9BY41

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q9BY41

HPA link: https://www.proteinatlas.org/ENSG00000147099-HDAC8

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: General nuclear expression.

Single cell type specificity Cell type enhanced (Inhibitory neurons, Excitatory neurons, Oligodendrocyte precursor cells, Oligodendrocytes, Microglial cells, Astrocytes)

Immune cell specificity: Low immune cell specificity

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000147099-HDAC8/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000147099-HDAC8/pathology/endometrial+cancer

Expression figure legend: Strong expression (3+) of histone deacetylase (HDACs) in endometrial stromal sarcoma. Images were provided by the Department of Pathology, Asan Medical Center (magnification ×200).

Expression figure link: https://ar.iiarjournals.org/content/anticanres/36/5/2527/F1.large.jpg

Survival figure legend: Disease-free survival based on the intensity of immunoreactivity (Semi-quantitative scoring system) for histone deacetylase (HDAC) 1, 4, 6, 7, and 8 in endometrial stromal sarcoma.

Survival curve link: https://ar.iiarjournals.org/content/anticanres/36/5/2527/F2.large.jpg

Phenotype ID: 300882

Disease: Cornelia de Lange syndrome 5 (CDLS5)

Note1: The disease is caused by variants affecting the gene represented in this entry

OMIM: 300269

OMIM link1: https://www.omim.org/entry/300882

OMIM link2: https://www.omim.org/entry/300269

HGNC ID: HGNC:13315

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13315