KAT8

Summary

KAT8 (lysine acetyltransferase 8, HGNC:17933) is a protein-coding gene on chromosome 16p11.2, encoding Histone acetyltransferase KAT8 (Q9H7Z6). Histone acetyltransferase that catalyzes histone H4 acetylation at ‘Lys-5’- and ‘Lys-8’ (H4K5ac and H4K8ac) or ‘Lys-16’ (H4K16ac), depending on the context. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).

This gene encodes a member of the MYST histone acetylase protein family. The encoded protein has a characteristic MYST domain containing an acetyl-CoA-binding site, a chromodomain typical of proteins which bind histones, and a C2HC-type zinc finger. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 84148 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Li-Ghorbani-Weisz-Hubshman syndrome (Strong, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 170 total — 8 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 28
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_032188

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17933
Approved symbol	KAT8
Name	lysine acetyltransferase 8
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	MOF, FLJ14040, hMOF
Ensembl gene	ENSG00000103510
Ensembl biotype	protein_coding
OMIM	609912
Entrez	84148

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 retained_intron

ENST00000219797, ENST00000448516, ENST00000537402, ENST00000538768, ENST00000539683, ENST00000543774, ENST00000573144, ENST00000652764

RefSeq mRNA: 2 — MANE Select: NM_032188 NM_032188, NM_182958

CCDS: CCDS10706, CCDS45468

Canonical transcript exons

ENST00000219797 — 11 exons

Exon	Start	End
ENSE00002682252	31131195	31131359
ENSE00003505670	31127189	31127353
ENSE00003528935	31120186	31120260
ENSE00003572667	31130017	31130157
ENSE00003602168	31130746	31130900
ENSE00003620323	31130267	31130360
ENSE00003644011	31128050	31128139
ENSE00003673960	31130456	31130606
ENSE00003889346	31127035	31127088
ENSE00003889472	31120339	31120514
ENSE00003892058	31117664	31117892

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 96.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.6510 / max 758.6153, expressed in 1825 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153769	51.2839	1825
153774	0.1550	24
153771	0.1382	69
153772	0.0447	18
153773	0.0293	8

Top tissues by expression

297 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	96.93	gold quality
cerebellar cortex	UBERON:0002129	96.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.86	gold quality
right ovary	UBERON:0002118	96.71	gold quality
left ovary	UBERON:0002119	96.70	gold quality
cerebellum	UBERON:0002037	96.57	gold quality
corpus epididymis	UBERON:0004359	96.54	gold quality
cerebellar vermis	UBERON:0004720	96.29	gold quality
paraflocculus	UBERON:0005351	95.76	gold quality
left uterine tube	UBERON:0001303	95.70	gold quality
lateral globus pallidus	UBERON:0002476	95.64	gold quality
endocervix	UBERON:0000458	95.44	gold quality
apex of heart	UBERON:0002098	95.44	gold quality
body of uterus	UBERON:0009853	95.37	gold quality
tibial nerve	UBERON:0001323	95.36	gold quality
right lobe of thyroid gland	UBERON:0001119	95.29	gold quality
left lobe of thyroid gland	UBERON:0001120	95.28	gold quality
gastrocnemius	UBERON:0001388	95.17	gold quality
right lung	UBERON:0002167	95.15	gold quality
adult organism	UBERON:0007023	95.14	gold quality
monocyte	CL:0000576	95.13	gold quality
granulocyte	CL:0000094	95.10	gold quality
mononuclear cell	CL:0000842	95.10	gold quality
mucosa of stomach	UBERON:0001199	95.05	gold quality
right atrium auricular region	UBERON:0006631	95.05	gold quality
leukocyte	CL:0000738	95.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.94	gold quality
muscle of leg	UBERON:0001383	94.91	gold quality
thyroid gland	UBERON:0002046	94.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.66

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
BCL2
CD74
ERVW-4
FGFR1
KAT2B
SMARCA2

miRNA regulators (miRDB)

4 targeting KAT8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6826-3P	98.19	66.32	1153

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• These results suggest that hMOF influences the function of ATM. (PMID:15923642)
• hMOF has a role in DNA damage response during cell cycle progression. (PMID:16024812)
• A multisubunit human histone acetylase complex that contains homologs of the Drosophila MSL proteins MOF, MSL1 (hampin A), MSL2, and MSL3 was described. This complex is responsible for histone H4 lysine-16 acetylation of all cellular chromosomes. (PMID:16227571)
• hMOF is an important component of many cellular processes and plays role the in cell malignant transformation. (PMID:17694080)
• MOF is an essential factor for embryogenesis and oncogenesis (PMID:17967868)
• downregulation of hMOF protein expression was associated with lower survival rates identifying hMOF as an independent prognostic marker for clinical outcome in univariate as well as multivariate analyses (PMID:18058815)
• Data show that MOF acetylates TIP5, the largest subunit of NoRC, at a single lysine residue, K633, adjacent to the TIP5 RNA-binding domain, and that SIRT1 (removes the acetyl group from K633. (PMID:19578370)
• Although MSL-associated MOF acetylates nucleosomal histone H4 almost exclusively on lysine 16, NSL-associated MOF exhibits a relaxed specificity and also acetylates nucleosomal histone H4 on lysines 5 and 8. (PMID:20018852)
• MOF activity was associated with general chromatin upon DNA damage and colocalized with the synaptonemal complex in male meiocytes. (PMID:20479123)
• data indicate that H4K20me3 invokes gene repression by antagonizing hMOF-mediated H4K16Ac (PMID:21321083)
• hMOF is autoacetylated in vitro and in vivo, and SIRT1, the deacetylase for H4K16Ac, is responsible for deacetylating acetylated hMOF. (PMID:21502975)
• hMOF employs a novel regulatory mechanism of acetyltransferase activities (PMID:21691301)
• MYST protein acetyltransferase activity requires active site lysine autoacetylation. (PMID:22020126)
• RNAi-mediated silencing of MOF reduced both gene activation and tumor suppression by FOXP3, while both somatic mutations in clinical cancer samples and targeted mutation of FOXP3 in mouse prostate epithelial cells disrupted nuclear localization of MOF. (PMID:22152480)
• uncover novel pathways in which SIRT1 dynamically interacts with and regulates hMOF and TIP60 through deacetylation and provide additional mechanistic insights by which SIRT1 regulates DNA damage response (PMID:22586264)
• new insights into the mechanism and function of MYST HAT autoacetylation. (PMID:22918831)
• The hMOF mediated S phase entry by regulating H4K16ac in the Skp2 promoter region in NSCLC cells. (PMID:23628702)
• Our results demonstrate an important role of KAT8 in cancer (PMID:23638218)
• induction of autophagy is coupled to reduction of histone H4 lysine 16 acetylation through downregulation of the histone acetyltransferase hMOF; and this histone modification regulates the outcome of autophagy (PMID:23863932)
• MOF acetylation of DBC1 inhibits binding to SirT1 and serves as a mechanism that connects DNA damage signaling to SirT1 and cell fate determination. (PMID:24126058)
• low expression of hMOF was strongly correlated with tumor differentiation and survival of patients with gastric cancer. While in patients with renal cell carcinoma, downregulation of hMOF was connected to ccRCC and tissues with T1 tumor status. (PMID:24452485)
• review of regulation and function (PMID:24452550)
• hMOF was overexpressed in human non-small cell lung cancer and was a predictor of poor survival. (PMID:24571482)
• Functional interactions of MYST1 with androgen receptor and NF-KB are critical for prostate cancer progression. (PMID:24702180)
• MOF expression was down-regulated in failing hearts at protein and mRNA levels. (PMID:24802406)
• MOF mediates Notch signaling by manipulating Histone H4 acetylation. (PMID:24898892)
• Mutant MOF-T392A expression abrogates DSB repair in S/G2 phase cells. MOF-T392A has delayed 53BP1 dissociation and decreased DNA association. (PMID:24953651)
• The histone acetyltransferase hMOF suppresses hepatocellular carcinoma growth by targeting the expression of SIRT6. (PMID:25181338)
• Results show the expression of hMOF mRNA and protein was significantly downregulated in ovarian epithelial cancer tissues, and patients with high hMOF levels showed improved survival as compared to those with low hMOF levels. (PMID:25483274)
• Data found downregulation of hMOF in gastric cancer cells and tissues. Declined hMOF expression, but not high level of HDAC4, may account for global histone H4K16ac suggesting that loss of hMOF expression may be involved in gastric cancer progression. (PMID:25873202)
• EZH2 (enhancer of zeste homolog 2) was up-regulated in human oral tongue squamous cell carcinoma tissues and its level positively correlated with level of hMOF. (PMID:26032517)
• MOF is highly enriched in induced pluripotent stem cells (iPSCs), and MOF expression is upregulated during the reprogramming process. The ectopic expression of MOF promotes reprogramming. MOF affects Wdr5 and endogenous Oct4 expression. (PMID:26091365)
• This work identifies MOF as a key regulator of cellular stress response in glomerular podocytes. (PMID:26387537)
• Along with the PHF20/MOF complex, G9a links the crosstalk between ERalpha methylation and histone acetylation that governs the epigenetic regulation of hormonal gene expression. (PMID:26960573)
• recent results indicate MOF is an upstream regulator of the ATM (ataxia-telangiectasia mutated) protein, the loss of which is responsible for ataxia telangiectasia (AT). ATM is a key regulatory kinase that interacts with and phosphorylates multiple substrates that influence critical, cell-cycle control and DNA damage repair pathways in addition to other pathways. (PMID:27038808)
• Data describe a trans-histone modification pathway involving PKN1/histone H3 threonine 11 phosphorylation followed by WDR5/MLL histone methyltransferase and KAT8/histone acetyltransferase recruitment to effect androgen-dependent gene activation and prostate cancer cell proliferation. (PMID:27268279)
• These findings provide insight into the regulation of LSD1 and Epithelial-to-Mesenchymal Transition (EMT) and identify MOF as a critical suppressor of EMT and tumor progression. (PMID:27292636)
• these studies point to the critical and specific role of hMOF Lys-274 autoacetylation in hMOF stability and cognate substrate acetylation and argues that binding of Ac-CoA to hMOF likely drives Lys-274 autoacetylation for subsequent cognate substrate acetylation. (PMID:27382063)
• our findings reveal that TET1 forms a complex with hMOF to modulate its function and the level of H4K16Ac ultimately affect gene expression and DNA repair. (PMID:27733505)
• MOF is a dual-transcriptional regulator of nuclear and mitochondrial genomes connecting epigenetics and metabolism. (PMID:27768893)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	kat8	ENSDARG00000027187
mus_musculus	Kat8	ENSMUSG00000030801
rattus_norvegicus	Kat8	ENSRNOG00000019485
drosophila_melanogaster	mof	FBGN0014340
drosophila_melanogaster	CG1894	FBGN0039585
caenorhabditis_elegans	mys-2	WBGENE00010537

Paralogs (9): DPF1 (ENSG00000011332), RSF1 (ENSG00000048649), KAT6A (ENSG00000083168), PHF10 (ENSG00000130024), DPF2 (ENSG00000133884), KAT7 (ENSG00000136504), KAT6B (ENSG00000156650), KAT5 (ENSG00000172977), DPF3 (ENSG00000205683)

Protein

Protein identifiers

Histone acetyltransferase KAT8 — Q9H7Z6 (reviewed: Q9H7Z6)

Alternative names: Lysine acetyltransferase 8, MOZ, YBF2/SAS3, SAS2 and TIP60 protein 1, Males-absent on the first protein homolog, Protein acetyltransferase KAT8, Protein propionyltransferase KAT8

All UniProt accessions (3): Q9H7Z6, A0A494C0I2, H3BMX5

UniProt curated annotations — full annotation on UniProt →

Function. Histone acetyltransferase that catalyzes histone H4 acetylation at ‘Lys-5’- and ‘Lys-8’ (H4K5ac and H4K8ac) or ‘Lys-16’ (H4K16ac), depending on the context. Catalytic component of the MSL histone acetyltransferase complex, a multiprotein complex that mediates the majority of histone H4 acetylation at ‘Lys-16’ (H4K16ac), an epigenetic mark that prevents chromatin compaction. H4K16ac constitutes the only acetylation mark intergenerationally transmitted and regulates key biological processes, such as oogenesis, embryonic stem cell pluripotency, hematopoiesis or glucose metabolism. The MSL complex is required for chromosome stability and genome integrity by maintaining homeostatic levels of H4K16ac. The MSL complex is also involved in gene dosage by promoting up-regulation of genes expressed by the X chromosome. X up-regulation is required to compensate for autosomal biallelic expression. The MSL complex also participates in gene dosage compensation by promoting expression of Tsix non-coding RNA. As part of the NSL histone acetyltransferase complex, catalyzes histone H4 acetylation at ‘Lys-5’- and ‘Lys-8’ (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation. The NSL complex also acts as a regulator of gene expression in mitochondria: KAT8 associates with mitochondrial DNA and controls expression of respiratory genes in an acetyltransferase-dependent mechanism. Also functions as an acetyltransferase for non-histone targets, such as ALKBH5, COX17, IRF3, KDM1A/LSD1, LMNA, PAX7 or TP53/p53. Acts as an inhibitor of antiviral immunity by acetylating IRF3, preventing IRF3 recruitment to promoters. Acts as a regulator of asymmetric division in muscle stem cells by mediating acetylation of PAX7. As part of the NSL complex, acetylates TP53/p53 at ‘Lys-120’. Acts as a regulator of epithelial-to-mesenchymal transition as part of the NSL complex by mediating acetylation of KDM1A/LSD1. The NSL complex is required for nuclear architecture maintenance by mediating acetylation of LMNA. Promotes mitochondrial integrity by catalyzing acetylation of COX17. In addition to protein acetyltransferase activity, able to mediate protein propionylation.

Subunit / interactions. Component of a multisubunit histone acetyltransferase complex (MSL) at least composed of the MOF/KAT8, MSL1/hampin, MSL2L1 and MSL3L1. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MOF/KAT8, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with the chromodomain of MORF4L1/MRG15. Interacts with ATM (via its Tudor-knot domain); possibly regulating the activity of ATM. Interacts with NELFD.

Subcellular location. Nucleus. Chromosome. Mitochondrion.

Post-translational modifications. Acetylation at Lys-274 facilitates cognate substrate Lys-binding and acetylation. Although considered as an autoacetylation event, acetylation at Lys-274 probably takes place via a non-enzymatic process following acetyl-CoA-binding, which primes KAT8 for cognate protein-lysine acetylation. Deacetylated by SIRT1.

Disease relevance. Li-Ghorbani-Weisz-Hubshman syndrome (LIGOWS) [MIM:618974] An autosomal dominant disorder characterized by global developmental delay, mild to moderate intellectual disability, speech and language impairment, and variable facial dysmorphism. Some patients have seizures and autistic features. Brain imaging abnormalities are observed in some patients and include decreased white matter volume, enlarged ventricles, thin corpus callosum, and gray matter nodular heterotopia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The acetyltransferase activity is inhibited by anacardic acid derivatives.

Similarity. Belongs to the MYST (SAS/MOZ) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H7Z6-1	1	yes
Q9H7Z6-2	2

RefSeq proteins (2): NP_115564, NP_892003 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR002717	HAT_MYST-type	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR025995	Tudor-knot	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR040706	Zf-MYST	Domain
IPR050603	MYST_HAT	Family

Pfam: PF01853, PF11717, PF17772

Enzyme classification (BRENDA):

• EC 2.3.1.48 — histone acetyltransferase (BRENDA: 41 organisms, 681 substrates, 1134 inhibitors, 140 Km, 96 kcat entries)

Substrate kinetics (BRENDA)

27 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYL-COA	0.0002–0.046	51
HISTONE H3	0.007–2.09	23
HISTONE H4	—	11
HISTONE H4 PEPTIDE	0.0208–0.197	7
HISTONE	0.075–1.4	6
HISTONE H3 TAIL PEPTIDE	0.044–0.112	4
PICCOLONUA4 PEPTIDE	0.135–0.372	4
3-AZIDOPROPIONYL-COA	0.0002–0.0086	3
4-PENTYNOYL-COA	0.0009–0.0859	3
SPERMIDINE	0.18–0.27	3
5-HEXYNOYL-COA	0.0006–0.0117	2
6-HEPTYNOYL-COA	0.0003–0.0237	2
HISTONE H3-PEPTIDE	0.05–0.49	2
PROTEIN P53	1.28–4.63	2
3-AZIDOPROPANOYL-COA	0.0103	1

Catalyzed reactions (Rhea), 3 shown:

• L-lysyl-[histone] + acetyl-CoA = N(6)-acetyl-L-lysyl-[histone] + CoA + H(+) (RHEA:21992)
• L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+) (RHEA:45948)
• propanoyl-CoA + L-lysyl-[protein] = N(6)-propanoyl-L-lysyl-[protein] + CoA + H(+) (RHEA:54020)

UniProt features (90 total): binding site 22, strand 15, helix 13, sequence variant 8, mutagenesis site 7, modified residue 6, sequence conflict 4, turn 3, domain 2, region of interest 2, compositionally biased region 2, initiator methionine 1, chain 1, active site 1, splice variant 1, zinc finger region 1, short sequence motif 1

Structure

Experimental structures (PDB)

43 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9OOA	X-RAY DIFFRACTION	1.39
2PQ8	X-RAY DIFFRACTION	1.45
9OOF	X-RAY DIFFRACTION	1.68
6OIN	X-RAY DIFFRACTION	1.7
6OIO	X-RAY DIFFRACTION	1.7
6OIQ	X-RAY DIFFRACTION	1.75
6OWI	X-RAY DIFFRACTION	1.75
5WCI	X-RAY DIFFRACTION	1.78
6OIP	X-RAY DIFFRACTION	1.8
8W13	X-RAY DIFFRACTION	1.81
9OOJ	X-RAY DIFFRACTION	1.82
9OOB	X-RAY DIFFRACTION	1.83
6BA2	X-RAY DIFFRACTION	1.85
6PDG	X-RAY DIFFRACTION	1.92
2GIV	X-RAY DIFFRACTION	1.94
6BA4	X-RAY DIFFRACTION	1.95
6PDC	X-RAY DIFFRACTION	1.96
6OWH	X-RAY DIFFRACTION	2
6OIR	X-RAY DIFFRACTION	2.03
4DNC	X-RAY DIFFRACTION	2.05
9OOH	X-RAY DIFFRACTION	2.05
3QAH	X-RAY DIFFRACTION	2.1
9OOC	X-RAY DIFFRACTION	2.1
9OOE	X-RAY DIFFRACTION	2.1
6CT2	X-RAY DIFFRACTION	2.13
6PDD	X-RAY DIFFRACTION	2.15
5J8C	X-RAY DIFFRACTION	2.17
7CMR	X-RAY DIFFRACTION	2.2
9OO9	X-RAY DIFFRACTION	2.2
9OOD	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7Z6-F1	83.01	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 350 (proton donor/acceptor)

Ligand- & substrate-binding residues (22): 210; 213; 226; 230; 317; 317; 319; 319; 325; 325; 326; 327 …

Post-translational modifications (6): 2, 37, 42, 113, 274, 348

Mutagenesis-validated functional residues (7):

Position	Phenotype
143	abolished association with importin-alpha-1 (kpna2) and translocation into the nucleus.
144	abolished association with importin-alpha-1 (kpna2) and translocation into the nucleus.
145	abolished association with importin-alpha-1 (kpna2) and translocation into the nucleus.
268	does not affect non-enzymatic ‘autoacetylation’.
274	loss of acetylation, leading to abolished histone acetyltransferase activity.
316	strongly reduces histone acetyltransferase activity without abolishing non-enzymatic ‘autoacetylation’.
350	abolishes histone acetyltransferase activity without abolishing non-enzymatic ‘autoacetylation’. abolished ability to re

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-74160	Gene expression (Transcription)
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 274 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_AUTOPHAGY, JI_RESPONSE_TO_FSH_UP, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_SKELETAL_MUSCLE_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, MORF_ATRX, GOBP_OOGENESIS, GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, MORF_ESR1, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION

GO Biological Process (30): dosage compensation by inactivation of X chromosome (GO:0009048), regulation of autophagy (GO:0010506), negative regulation of epithelial to mesenchymal transition (GO:0010719), neurogenesis (GO:0022008), myeloid cell differentiation (GO:0030099), negative regulation of type I interferon production (GO:0032480), post-embryonic hemopoiesis (GO:0035166), transcription initiation-coupled chromatin remodeling (GO:0045815), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), oogenesis (GO:0048477), regulation of mRNA processing (GO:0050684), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), positive regulation of skeletal muscle satellite cell differentiation (GO:1902726), regulation of mitochondrial transcription (GO:1903108), epithelial to mesenchymal transition (GO:0001837), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), positive regulation of macromolecule biosynthetic process (GO:0010557), negative regulation of macromolecule biosynthetic process (GO:0010558), positive regulation of epithelial to mesenchymal transition (GO:0010718), skeletal muscle satellite cell differentiation (GO:0014816), hemopoiesis (GO:0030097), positive regulation of type I interferon production (GO:0032481), epigenetic regulation of gene expression (GO:0040029), regulation of cell differentiation (GO:0045595), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935), negative regulation of multicellular organismal process (GO:0051241), membraneless organelle assembly (GO:0140694)

GO Molecular Function (18): transcription coactivator activity (GO:0003713), zinc ion binding (GO:0008270), histone H4 acetyltransferase activity (GO:0010485), enzyme binding (GO:0019899), histone H4K5 acetyltransferase activity (GO:0043995), histone H4K8 acetyltransferase activity (GO:0043996), histone H4K16 acetyltransferase activity (GO:0046972), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein-lysine-acetyltransferase activity (GO:0061733), protein propionyltransferase activity (GO:0061920), promoter-specific chromatin binding (GO:1990841), histone acetyltransferase activity (GO:0004402), protein binding (GO:0005515), acetyltransferase activity (GO:0016407), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), metal ion binding (GO:0046872), DNA-binding transcription factor binding (GO:0140297)

GO Cellular Component (12): histone acetyltransferase complex (GO:0000123), kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), mitochondrion (GO:0005739), nuclear matrix (GO:0016363), NuA4 histone acetyltransferase complex (GO:0035267), NSL complex (GO:0044545), MLL1 complex (GO:0071339), MSL complex (GO:0072487), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Gene expression (Transcription)	1
Chromatin organization	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	3
histone H4 acetyltransferase activity	3
cell differentiation	2
hemopoiesis	2
transcription initiation at RNA polymerase II promoter	2
acyltransferase activity, transferring groups other than amino-acyl groups	2
intracellular membraneless organelle	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cellular anatomical structure	2
H4 histone acetyltransferase complex	2
sex-chromosome dosage compensation	1
heterochromatin formation	1
autophagy	1
regulation of catabolic process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
negative regulation of multicellular organismal process	1
nervous system development	1
negative regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
post-embryonic development	1
positive regulation of gene expression, epigenetic	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
germ cell development	1
female gamete generation	1
mRNA processing	1
regulation of mRNA metabolic process	1
positive regulation of transcription by RNA polymerase II	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
skeletal muscle satellite cell differentiation	1
positive regulation of skeletal muscle cell differentiation	1
mitochondrial transcription	1
regulation of mitochondrial gene expression	1
mesenchymal cell differentiation	1

Protein interactions and networks

STRING

2150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KAT8	KANSL1	Q7Z3B3	844
KAT8	MSL3	Q8N5Y2	839
KAT8	WDR5	P61964	833
KAT8	H4C7	Q99525	776
KAT8	KANSL3	Q9P2N6	758
KAT8	KANSL2	Q9H9L4	752
KAT8	H4C16	P02304	686
KAT8	KAT2B	Q92831	680
KAT8	MCRS1	Q96EZ8	678
KAT8	KAT2A	Q92830	677
KAT8	PHF20	Q9BVI0	676
KAT8	MSL2	Q9HCI7	644
KAT8	EP300	Q09472	614
KAT8	SIRT1	Q96EB6	593
KAT8	OGT	O15294	590

IntAct

52 interactions, top by confidence:

A	B	Type	Score
ASH2L	WDR5	psi-mi:“MI:0403”(colocalization)	0.950
RBBP5	KMT2A	psi-mi:“MI:0914”(association)	0.940
MSL3	MSL1	psi-mi:“MI:0914”(association)	0.760
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
KAT8	WDR5	psi-mi:“MI:0914”(association)	0.690
KAT8	MSL1	psi-mi:“MI:0914”(association)	0.640
KAT8	KMT2A	psi-mi:“MI:0915”(physical association)	0.590
KMT2A	KAT8	psi-mi:“MI:0407”(direct interaction)	0.590
TP53	KAT8	psi-mi:“MI:0915”(physical association)	0.560
PBK	TRIM37	psi-mi:“MI:0914”(association)	0.550
H2AX	SMARCA4	psi-mi:“MI:0914”(association)	0.540
MSL1	MSL3B	psi-mi:“MI:0914”(association)	0.530
MSL2	HBB	psi-mi:“MI:0914”(association)	0.530
PHF20	PTPN14	psi-mi:“MI:0914”(association)	0.530
DYRK1B	BMAL1	psi-mi:“MI:0914”(association)	0.530
RNF2	KAT8	psi-mi:“MI:0915”(physical association)	0.500
TP53	MEN1	psi-mi:“MI:0914”(association)	0.480
HST2	KAT8	psi-mi:“MI:0197”(deacetylation reaction)	0.440
KAT8	HHF1	psi-mi:“MI:0192”(acetylation reaction)	0.440
HHF1	KAT8	psi-mi:“MI:0192”(acetylation reaction)	0.440
Kat8	PHF20L1	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MSL3	TUBA1B	psi-mi:“MI:0914”(association)	0.350
WDR5	PHF20L1	psi-mi:“MI:0914”(association)	0.350
KAT8	HCFC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (179): HIST1H4A (Biochemical Activity), PAF1 (Reconstituted Complex), KAT8 (Affinity Capture-MS), KAT8 (Affinity Capture-MS), HNRNPA1 (Co-fractionation), KAT8 (Proximity Label-MS), KAT8 (Affinity Capture-MS), KAT8 (Affinity Capture-MS), KAT8 (Affinity Capture-MS), KAT8 (Biochemical Activity), TP53BP1 (Affinity Capture-Western), TP53BP1 (Reconstituted Complex), KAT8 (Affinity Capture-MS), KAT8 (Affinity Capture-MS), KAT8 (Affinity Capture-Western)

ESM2 similar proteins: A1YVX4, A3KMI0, B2RRD7, F1MAB7, F4I240, G5E8P1, O60341, O75164, O75912, O94953, O95696, P29375, P41229, P41230, Q23541, Q30DN6, Q38JA7, Q3UXZ9, Q5F3R2, Q5RD88, Q5VZ89, Q5XI06, Q5XUN4, Q61T02, Q62240, Q6C710, Q6IQX0, Q6P158, Q6P5D3, Q6PGC1, Q6ZQ88, Q7YTB0, Q7Z3E5, Q7Z478, Q80Y84, Q8BW72, Q8CHK4, Q8CIG3, Q8NB78, Q8VCD7

Diamond homologs: C8VBH4, K8ERR8, O02193, O94446, O95251, P0CP02, P0CP03, P34218, P40963, Q08649, Q10325, Q2UMQ5, Q4IEV4, Q4P3S3, Q4WHG1, Q5A7Q2, Q5RBG4, Q5SVQ0, Q5TKR9, Q5XI06, Q6BU95, Q6C710, Q6CKE9, Q6FPH9, Q75BY2, Q7S9B6, Q810T5, Q8BRB7, Q8BZ21, Q8CHK4, Q8LI34, Q8WML3, Q8WYB5, Q92794, Q92993, Q960X4, Q99MK2, Q9D1P2, Q9FLF7, Q9H7Z6

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
KMT2A	up-regulates	KAT8	binding
KAT8	“form complex”	“MSL acetyltransferase”	binding
KAT8	“form complex”	“NSL histone acetyltransferase”	binding
KAT8	“down-regulates quantity by destabilization”	FASN	acetylation
ATM	“up-regulates activity”	KAT8	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of WDR5-containing histone-modifying complexes	10	71.8×	2e-14
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	8	31.7×	1e-08
Formation of the beta-catenin:TCF transactivating complex	9	29.2×	3e-09
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	8	26.0×	5e-08
Regulation of PD-L1(CD274) transcription	8	23.5×	8e-08
PKMTs methylate histone lysines	5	21.7×	1e-04
Epigenetic regulation by WDR5-containing histone modifying complexes	5	20.9×	1e-04
HATs acetylate histones	9	19.3×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation-coupled chromatin remodeling	7	57.0×	7e-09
chromatin remodeling	7	10.9×	4e-04
DNA damage response	9	10.2×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

170 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	4
Uncertain significance	122
Likely benign	13
Benign	3

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1684624	NM_032188.3(KAT8):c.275A>G (p.His92Arg)	Pathogenic
1690352	NM_032188.3(KAT8):c.296G>A (p.Arg99Gln)	Pathogenic
2217472	NM_032188.3(KAT8):c.418C>T (p.Arg140Cys)	Pathogenic
3253327	NM_032188.3(KAT8):c.295C>T (p.Arg99Trp)	Pathogenic
687383	GRCh37/hg19 16p11.2(chr16:30851860-31156762)x1	Pathogenic
976461	NM_032188.3(KAT8):c.293G>A (p.Arg98Gln)	Pathogenic
976462	NM_032188.3(KAT8):c.523A>G (p.Lys175Glu)	Pathogenic
976463	NM_032188.3(KAT8):c.543G>C (p.Lys181Asn)	Pathogenic
1329928	NM_032188.3(KAT8):c.524A>C (p.Lys175Thr)	Likely pathogenic
2683826	NM_032188.3(KAT8):c.649A>C (p.Met217Leu)	Likely pathogenic
3343475	NM_032188.3(KAT8):c.322C>T (p.Arg108Trp)	Likely pathogenic
976460	NM_032188.3(KAT8):c.269A>G (p.Tyr90Cys)	Likely pathogenic

SpliceAI

1724 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31117694:G:GT	donor_gain	1.0000
16:31120184:A:AG	acceptor_gain	1.0000
16:31120185:G:GG	acceptor_gain	1.0000
16:31120257:GGCT:G	donor_gain	1.0000
16:31120258:GCTG:G	donor_gain	1.0000
16:31120545:G:GT	donor_gain	1.0000
16:31127027:T:A	acceptor_gain	1.0000
16:31127028:G:A	acceptor_gain	1.0000
16:31127030:CCCA:C	acceptor_loss	1.0000
16:31127031:CCAG:C	acceptor_loss	1.0000
16:31127032:CAGA:C	acceptor_loss	1.0000
16:31127033:A:AG	acceptor_gain	1.0000
16:31127033:A:G	acceptor_loss	1.0000
16:31127034:G:GG	acceptor_gain	1.0000
16:31127034:GA:G	acceptor_gain	1.0000
16:31127034:GAC:G	acceptor_gain	1.0000
16:31127034:GACT:G	acceptor_gain	1.0000
16:31127034:GACTT:G	acceptor_gain	1.0000
16:31127085:GGCG:G	donor_gain	1.0000
16:31127086:GCGG:G	donor_gain	1.0000
16:31127088:GGT:G	donor_loss	1.0000
16:31127089:G:GA	donor_loss	1.0000
16:31127089:G:GG	donor_gain	1.0000
16:31127090:T:A	donor_loss	1.0000
16:31127180:T:TA	acceptor_gain	1.0000
16:31127186:CA:C	acceptor_loss	1.0000
16:31127187:A:AG	acceptor_gain	1.0000
16:31127187:AGAT:A	acceptor_loss	1.0000
16:31127188:G:GA	acceptor_gain	1.0000
16:31127317:G:GG	donor_gain	1.0000

AlphaMissense

2997 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31117868:T:C	C63R	1.000
16:31117870:C:G	C63W	1.000
16:31120192:C:A	A73D	1.000
16:31120198:T:A	V75E	1.000
16:31120201:T:A	I76N	1.000
16:31120210:G:C	R79P	1.000
16:31120242:T:C	Y90H	1.000
16:31120242:T:G	Y90D	1.000
16:31120246:T:A	V91E	1.000
16:31120248:C:G	H92D	1.000
16:31120249:A:C	H92P	1.000
16:31120251:T:G	Y93D	1.000
16:31120343:C:A	N97K	1.000
16:31120343:C:G	N97K	1.000
16:31120344:C:G	R98G	1.000
16:31120344:C:T	R98W	1.000
16:31120345:G:C	R98P	1.000
16:31120345:G:T	R98L	1.000
16:31120347:C:G	R99G	1.000
16:31120347:C:T	R99W	1.000
16:31120348:G:A	R99Q	1.000
16:31120348:G:C	R99P	1.000
16:31120348:G:T	R99L	1.000
16:31120351:T:C	L100P	1.000
16:31120353:G:A	D101N	1.000
16:31120353:G:C	D101H	1.000
16:31120353:G:T	D101Y	1.000
16:31120354:A:C	D101A	1.000
16:31120354:A:G	D101G	1.000
16:31120354:A:T	D101V	1.000

dbSNP variants (sampled 300 via entrez): RS1000243212 (16:31115669 G>A), RS1000377856 (16:31121455 A>G), RS1000493949 (16:31121237 C>T), RS1000654361 (16:31116639 GGGCACGGT>G), RS1000709085 (16:31122653 G>A), RS1000721338 (16:31126542 A>C,G,T), RS1000740217 (16:31122434 A>C), RS1000984143 (16:31117000 G>T), RS1001089604 (16:31126893 T>C), RS1001117994 (16:31118114 C>G,T), RS1001193634 (16:31122022 A>T), RS1001232586 (16:31117808 C>T), RS1001362679 (16:31127696 AG>A), RS1001383400 (16:31123756 C>T), RS1001555310 (16:31129955 G>A,C)

Disease associations

OMIM: gene MIM:609912 | disease phenotypes: MIM:618974

GenCC curated gene-disease

Disease	Classification	Inheritance
Li-Ghorbani-Weisz-Hubshman syndrome	Strong	Autosomal dominant

Mondo (1): Li-Ghorbani-Weisz-Hubshman syndrome (MONDO:0033547)

Orphanet (0):

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000286	Epicanthus
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000506	Telecanthus
HP:0000540	Hypermetropia
HP:0000565	Esotropia
HP:0000582	Upslanted palpebral fissure
HP:0000601	Hypotelorism
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0001845	Overlapping toe
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002194	Delayed gross motor development
HP:0002714	Downturned corners of mouth
HP:0004209	Clinodactyly of the 5th finger
HP:0005280	Depressed nasal bridge
HP:0007018	Attention deficit hyperactivity disorder
HP:0007165	Periventricular heterotopia
HP:0008872	Feeding difficulties in infancy
HP:0010862	Delayed fine motor development
HP:0012471	Thick vermilion border

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002783_258	Body mass index	9.000000e-11
GCST002783_387	Body mass index	8.000000e-10
GCST002783_474	Body mass index	2.000000e-06
GCST004495_56	BMI (adjusted for smoking behaviour)	5.000000e-08
GCST004497_13	Body mass index (joint analysis main effects and smoking interaction)	1.000000e-07
GCST004499_83	BMI in non-smokers	2.000000e-06
GCST004902_10	Parkinson’s disease	5.000000e-12
GCST007320_70	Alzheimer’s disease or family history of Alzheimer’s disease	4.000000e-08
GCST007321_26	Family history of Alzheimer’s disease	4.000000e-06
GCST008103_175	Bipolar disorder	8.000000e-06
GCST008115_45	Bipolar I disorder	5.000000e-07
GCST010173_108	Triglyceride levels	3.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0009268	family history of Alzheimer’s disease
EFO:0009963	bipolar I disorder
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1932912 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.3.1.48 Histone acetyltransferases (HATs)

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
PF-9363	Inhibition	6.17	pIC50
MG149	Inhibition	4.33	pIC50

ChEMBL bioactivities

55 potent at pChembl≥5 of 428 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.77	Ki	17	nM	CHEMBL576321
7.00	Ki	100	nM	CHEMBL5886450
6.96	Ki	110	nM	CHEMBL5852195
6.80	Ki	160	nM	CHEMBL5812221
6.77	Ki	170	nM	CHEMBL5993180
6.66	Ki	220	nM	CHEMBL5818085
6.62	Ki	240	nM	CHEMBL5955544
6.46	Ki	350	nM	CHEMBL5853409
6.38	Ki	420	nM	CHEMBL5959733
6.33	Ki	470	nM	CHEMBL5927368
6.33	Ki	470	nM	CHEMBL5996948
6.30	Ki	500	nM	CHEMBL5723326
6.28	Ki	530	nM	CHEMBL6005841
6.27	Ki	540	nM	CHEMBL5941367
6.25	Ki	560	nM	CHEMBL5883288
6.18	Ki	660	nM	CHEMBL5857566
6.18	Ki	660	nM	CHEMBL5723326
6.16	Kd	700	nM	CHEMBL576321
6.14	Ki	730	nM	CHEMBL5723326
6.09	Ki	820	nM	CHEMBL5723326
6.08	Ki	830	nM	CHEMBL5924783
6.05	Ki	900	nM	CHEMBL5963038
6.02	Ki	960	nM	CHEMBL5993009
6.00	Ki	1010	nM	CHEMBL5998930
5.97	Ki	1070	nM	CHEMBL5847041
5.96	IC50	1100	nM	CHEMBL576321
5.96	Ki	1110	nM	CHEMBL5925551
5.84	Ki	1440	nM	CHEMBL5830107
5.82	Ki	1510	nM	CHEMBL5867166
5.80	IC50	1600	nM	CHEMBL576321
5.76	Ki	1750	nM	CHEMBL6057979
5.75	IC50	1800	nM	CHEMBL576321
5.71	Ki	1970	nM	CHEMBL5785798
5.69	Kd	2040	nM	CHEMBL5437016
5.58	Kd	2600	nM	CHEMBL576321
5.58	Ki	2600	nM	CHEMBL576321
5.54	Ki	2870	nM	CHEMBL5980695
5.49	Ki	3260	nM	CHEMBL5896279
5.49	Ki	3260	nM	CHEMBL5930092
5.49	Ki	3260	nM	CHEMBL5792825
5.49	Ki	3260	nM	CHEMBL5860247
5.49	Ki	3260	nM	CHEMBL5779221
5.49	Ki	3260	nM	CHEMBL5759534
5.49	Ki	3260	nM	CHEMBL6007870
5.48	Ki	3320	nM	CHEMBL5871508
5.44	IC50	3660	nM	CHEMBL4470091
5.35	Ki	4460	nM	CHEMBL5842425
5.31	Kd	4940	nM	CHEMBL5426408
5.30	Ki	4950	nM	CHEMBL6020167
5.22	IC50	6000	nM	CHEMBL4282866

PubChem BioAssay actives

16 with measured affinity, of 241 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-aminonaphthalen-1-ol	1507735: Inhibition of N-terminal His6-tagged KAT8 catalytic domain (125 to 458 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as inhibitor-acetylated enzyme complex using SGRGKGGKGLGKGGAKRHRK-NH2 as substrate after 5 mins in presence of Ac-CoA by fluorescence assay	ki	0.0170	uM
4-[(4Z)-5-oxo-3-phenyl-4-(1H-pyrrol-2-ylmethylidene)pyrazol-1-yl]benzoic acid	1989075: Binding affinity to N-terminal 6His tagged KAT8 (173 to 458 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as dissociation constant by SPR analysis	kd	2.0400	uM
2-fluoro-N’-naphthalen-2-ylsulfonylbenzohydrazide	2138649: Inhibition of full length recombinant human KAT8 catalytic domain using H4 peptide and [3H]-acetyl-coA as substrate incubated for 1 hr by liquid scintillation counter analysis	ic50	3.6600	uM
4-[(4Z)-3-methyl-5-oxo-4-(1H-pyrrol-2-ylmethylidene)pyrazol-1-yl]benzoic acid	1989075: Binding affinity to N-terminal 6His tagged KAT8 (173 to 458 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) assessed as dissociation constant by SPR analysis	kd	4.9400	uM
4-[(E)-2-(1,3-benzothiazol-2-yl)ethenyl]-N,N-diethylbenzenesulfonamide	1408179: Inhibition of human His-tagged MOF using histone H4 substrate by radioactive acetylation assay	ic50	6.0000	uM
N,N-diethyl-4-[(E)-2-(6-fluoro-1,3-benzothiazol-2-yl)ethenyl]benzenesulfonamide	1408178: Inhibition of human His-tagged MOF preincubated for 10 mins followed by biotin-labeled H4K16 substrate addition measured after 30 mins in presence of acetyl-CoA by alphascreen assay	ic50	6.6000	uM
8-aminoisoquinolin-5-ol	1507709: Inhibition of N-terminal His6-tagged KAT8 catalytic domain (125 to 458 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) using SGRGKGGKGLGKGGAKRHRK-NH2 as substrate after 5 mins in presence of Ac-CoA by fluorescence assay	ic50	7.6000	uM
4-[(E)-2-(5,6-dimethyl-1,3-benzothiazol-2-yl)ethenyl]-N,N-diethylbenzenesulfonamide	1408179: Inhibition of human His-tagged MOF using histone H4 substrate by radioactive acetylation assay	ic50	7.7000	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, decreases expression, decreases response to substance	3
Valproic Acid	affects expression, decreases expression	3
FR900359	affects phosphorylation	1
DC_MO1	decreases activity	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	affects response to substance	1
coumarin	increases phosphorylation	1
isobutyl alcohol	decreases expression, increases abundance, affects cotreatment	1
cylindrospermopsin	increases expression	1
monomethylarsonous acid	affects response to substance	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Caffeine	increases phosphorylation	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Quercetin	decreases phosphorylation	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Zinc	increases expression	1
Zinc Sulfate	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

71 unique, capped per target: 71 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1938115	Binding	Inhibition of human MOF expressed in Escherichia coli BL21(DE3) cells using [14C]AC-CoA and histone H4 as substrate after 5 mins by scintillation counting	6-alkylsalicylates are selective Tip60 inhibitors and target the acetyl-CoA binding site. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3L0	SEES3-1V human KAT8, clone1	Embryonic stem cell	Male
CVCL_A3L1	SEES3-1V human KAT8, clone2	Embryonic stem cell	Male
CVCL_A3L2	SEES3-1V human KAT8, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.