Biomarker: HDACs 4

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: 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 via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their preferential binding to co-chaperone STUB1 (PubMed:27708256)

UniProt ID: P56524

UniProt Link: https://www.uniprot.org/uniprotkb/P56524/entry

Biological function from UniProt: #Transcription #Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: Ubiquitous.

Subcellular UniProt: #Cytoplasm #Nucleus

Catalytic activity: H2O + N6-acetyl-L-lysyl-[histone] = acetate + L-lysyl-[histone];

Recommended name: Histone deacetylase 4

Gene name from HGNC: HDAC4 (BDMR, HA6116, HD4, HDAC-4, HDAC-A, HDACA, KIAA0288)

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

AlphaFold DB: P56524

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P56524

HPA link: https://www.proteinatlas.org/ENSG00000068024-HDAC4

Tissue specificity RNA from HPA: Tissue enhanced (skeletal muscle)

Tissue expression from HPA: Cytoplasmic expression in most tissues.

Single cell type specificity Group enriched (Oligodendrocytes, Excitatory neurons, Oligodendrocyte precursor cells, Inhibitory neurons, Early spermatids, Astrocytes, Late spermatids, Microglial cells)

Immune cell specificity: Immune cell enhanced (neutrophil, basophil)

Subcellular summary HPA Located in Nucleoplasm, Nuclear speckles, Cytosol (Single cell variability)

Cancer prognostic summary HPA Prognostic marker in pancreatic cancer (favorable) and ovarian cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000068024-HDAC4/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000068024-HDAC4/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

Disease: No disease ID

Note1: HDAC4 point mutations and chromosomal microdeletions encompassing this gene have been found in patients with brachydactyly and intellectual disability syndrome (PubMed:20691407, PubMed:24715439, PubMed:23188045). However, HDAC4 haploinsufficiency is not fully penetrant and multiple genes may contribute to manifestation of the full phenotypic spectrum (PubMed:24715439, PubMed:23188045)

OMIM: 605314

OMIM link2: https://www.omim.org/entry/605314

HGNC ID: HGNC:14063

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14063