KAT6A (MYST histone acetyltransferase (monocytic leukemia) 3

2005-12-01   Jean-Loup Huret  , Sylvie Senon  

Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
KAT6A
LOCATION
8p11.21
LOCUSID
7994
ALIAS
ARTHS,MOZ,MRD32,MYST-3,MYST3,RUNXBP2,ZC2HC6A,ZNF220
FUSION GENES
Show Gene Fusions

DNA/RNA

Description

The gene spans121 kb on minus strand; 17 exons;

Transcription

7.85 kb

Proteins

Atlas Image

Description

2004 amino acids; 225 kDa; composed from N-term of: a NEMM domain (N-term region of ENOK, MOZ or MORF) including a H15 (linker H1 and H5 like) nuclear localization domain, 2 PHD (plant homeodomain, also known as LAP (leukemia associated protein)) Zn fingers (C4HC3), a C2HC Zn finger, essential part of the histone acyl transferase domain (HAT MOZ-SAS), an acidic (Glu-Asp) domain, localisation of breakpoints in the inv(8) and in the t(8;22) in 1118, and a Ser-(Pro-Glu)-Met rich domain, localisation of the t(8;16) breakpoint in 1547.

Localisation

Nucleus

Function

Lysine acetyltransferase activity (histone acyl transferase); MYST3 (MOZ) and MYST4 (MORF) possess both transcription activation and transcription repression domains; transcriptional regulators; interact with RUNX1 and RUNX2; Moz, the zebrafish ortholog of MYST3, was also found to regulate Hox expression; Moz behaves like a trithorax group factor.

Homology

with MYST4 (MORF) (monocytic leukemia zinc finger protein-related factor), a transcription regulator with positive and negative domains and activities.

Implicated in

Entity name
t(2;8)(p23;p11) in therapy related myelodysplastic syndrome --> KAT6A / ?
Disease
Only 1 case to date, a boy aged 6 years.
Entity name
inv(8)(p11q13) in acute myelomonocytic or monocytic leukaemia (M4 or M5 AML) --> KAT6A / NCOA2
Disease
Erythrophagocytosis; very rare: less than 10 cases; young age, and female sex.
Prognosis
likely to be poor
Hybrid gene
5 MYST3 - 3 NCOA2
Fusion protein
The fusion product retains the zinc fingers, the the histone acetyl transferase (HAT) domain of MYST3 and the HAT domains and CREBBP interacting domain of NCOA2.
Entity name
t(8;16)(p11;p13) in acute myelomonocytic or monocytic leukaemia (M4 or M5 AML) and therapy related AML (t-AML) --> KAT6A / CREBBP
Disease
Erythrophagocytosis; rare: less than 1% of AML; found in children and young adults of both sex.
Prognosis
poor
Hybrid gene
5 MYST3 - 3 CREBBP
Fusion protein
The fusion product retains the zinc fingers, the HAT domain of MYST3 and most of CREBBP, including the CREBBP interacting domain and the HAT domain; the fusion protein may repress RUNX1-dependant gene expression.
Entity name
t(8;22) (p11; q13) in acute myelomonocytic or monocytic leukaemia (M4 or M5 AML) --> MYST3 / EP300
Disease
Erythrophagocytosis; very rare: less than 5 cases.
Prognosis
likely to be poor
Oncogenesis
EP300 is very similar to CRBBP (see above), the breakpoints on these 2 genes are on homologous regions; the breakpoint on MYST3 is more proximal in the t(8;22).

Breakpoints

Atlas Image

Article Bibliography

Pubmed IDLast YearTitleAuthors
93765941997Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement.Aguiar RC et al
87828171996The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein.Borrow J et al
31849871988The 8p11 anomaly in "monoblastic" leukaemia.Brizard A et al
95583661998A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia.Carapeti M et al
126191662003Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11).Imamura T et al
34726401987Three cases of translocation (8;16)(p11;p13) observed in acute myelomonocytic leukemia: a new specific subgroup?Laï JL et al
151286732004moz regulates Hox expression and pharyngeal segmental identity in zebrafish.Miller CT et al
149607132004The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases.Yang XJ et al

Other Information

Locus ID:

NCBI: 7994
MIM: 601408
HGNC: 13013
Ensembl: ENSG00000083168

Variants:

dbSNP: 7994
ClinVar: 7994
TCGA: ENSG00000083168
COSMIC: KAT6A

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000083168ENST00000265713Q92794
ENSG00000083168ENST00000396930Q92794
ENSG00000083168ENST00000406337A0A3F2YNX6
ENSG00000083168ENST00000426524C9JJY6
ENSG00000083168ENST00000485568A5PLL3
ENSG00000083168ENST00000647746A0A3B3ISZ3
ENSG00000083168ENST00000648335A0A3B3IS53
ENSG00000083168ENST00000649817A0A3B3ITI3
ENSG00000083168ENST00000649827A0A3B3ISU5

Expression (GTEx)

0
5
10
15
20
25
30
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
HATs acetylate histonesREACTOMER-HSA-3214847
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Activity through AcetylationREACTOMER-HSA-6804758

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
365372162023The histone acetyltransferase KAT6A is recruited to unmethylated CpG islands via a DNA binding winged helix domain.3
367549592023MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain.6
378617172023KAT6A mutations in Arboleda-Tham syndrome drive epigenetic regulation of posterior HOXC cluster.0
365372162023The histone acetyltransferase KAT6A is recruited to unmethylated CpG islands via a DNA binding winged helix domain.3
367549592023MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain.6
378617172023KAT6A mutations in Arboleda-Tham syndrome drive epigenetic regulation of posterior HOXC cluster.0
347489932022Epilepsy in KAT6A syndrome: Description of two individuals and revision of the literature.3
348530792022KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs.25
353322662022Matrix stiffness-induced upregulation of histone acetyltransferase KAT6A promotes hepatocellular carcinoma progression through regulating SOX2 expression.8
358922682022Speech and language development and genotype-phenotype correlation in 49 individuals with KAT6A syndrome.6
359764742022miR-339-3p inhibits cell growth and epithelial-mesenchymal transition in nasopharyngeal carcinoma by modulating the KAT6A/TRIM24 axis.0
364561392022The Expression of Histone Acetyltransferase KAT6A in Non-small Cell Lung Cancer.1
347489932022Epilepsy in KAT6A syndrome: Description of two individuals and revision of the literature.3
348530792022KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs.25
353322662022Matrix stiffness-induced upregulation of histone acetyltransferase KAT6A promotes hepatocellular carcinoma progression through regulating SOX2 expression.8

Citation

Jean-Loup Huret ; Sylvie Senon

KAT6A (MYST histone acetyltransferase (monocytic leukemia) 3

Atlas Genet Cytogenet Oncol Haematol. 2005-12-01

Online version: http://atlasgeneticsoncology.org/gene/25/kat6a-(myst-histone-acetyltransferase-(monocytic-leukemia)-3