HAT1

Summary

HAT1 (histone acetyltransferase 1, HGNC:4821) is a protein-coding gene on chromosome 2q31.1, encoding Histone acetyltransferase type B catalytic subunit (O14929). Histone acetyltransferase that plays a role in different biological processes including cell cycle progression, glucose metabolism, histone production or DNA damage repair.

The protein encoded by this gene is a type B histone acetyltransferase (HAT) that is involved in the rapid acetylation of newly synthesized cytoplasmic histones, which are in turn imported into the nucleus for de novo deposition onto nascent DNA chains. Histone acetylation, particularly of histone H4, plays an important role in replication-dependent chromatin assembly. Specifically, this HAT can acetylate soluble but not nucleosomal histone H4 at lysines 5 and 12, and to a lesser degree, histone H2A at lysine 5. Alternatively spliced transcript variants have been identified for this gene.

Source: NCBI Gene 8520 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 46 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003642

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4821
Approved symbol	HAT1
Name	histone acetyltransferase 1
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	KAT1
Ensembl gene	ENSG00000128708
Ensembl biotype	protein_coding
OMIM	603053
Entrez	8520

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000264108, ENST00000392584, ENST00000412731, ENST00000457761, ENST00000460481, ENST00000494601, ENST00000897838, ENST00000897839, ENST00000925994, ENST00000925995, ENST00000925996, ENST00000925997, ENST00000925998, ENST00000964804

RefSeq mRNA: 1 — MANE Select: NM_003642 NM_003642

CCDS: CCDS2245

Canonical transcript exons

ENST00000264108 — 11 exons

Exon	Start	End
ENSE00001907611	171922461	171922507
ENSE00003471171	171983185	171983686
ENSE00003503745	171966409	171966513
ENSE00003522430	171966843	171966949
ENSE00003535007	171952881	171953001
ENSE00003571110	171946708	171946783
ENSE00003606874	171925537	171925641
ENSE00003620929	171979247	171979363
ENSE00003640354	171965787	171965908
ENSE00003670011	171965338	171965517
ENSE00003689087	171976157	171976308

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 97.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.7082 / max 2171.6600, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23679	39.7322	1806
23678	6.9759	1656

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.40	gold quality
biceps brachii	UBERON:0001507	96.62	gold quality
ventricular zone	UBERON:0003053	96.62	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.35	gold quality
palpebral conjunctiva	UBERON:0001812	96.28	gold quality
amniotic fluid	UBERON:0000173	96.14	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.11	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.09	gold quality
bronchial epithelial cell	CL:0002328	96.08	gold quality
cartilage tissue	UBERON:0002418	96.06	gold quality
tendon of biceps brachii	UBERON:0008188	95.99	gold quality
trabecular bone tissue	UBERON:0002483	95.74	gold quality
eye	UBERON:0000970	95.61	gold quality
islet of Langerhans	UBERON:0000006	95.45	gold quality
vastus lateralis	UBERON:0001379	95.42	gold quality
tendon	UBERON:0000043	95.36	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.31	gold quality
epithelium of nasopharynx	UBERON:0001951	95.22	gold quality
nasopharynx	UBERON:0001728	95.20	gold quality
calcaneal tendon	UBERON:0003701	95.11	gold quality
secondary oocyte	CL:0000655	95.09	gold quality
gastrocnemius	UBERON:0001388	95.05	gold quality
quadriceps femoris	UBERON:0001377	95.03	gold quality
muscle organ	UBERON:0001630	94.80	gold quality
muscle of leg	UBERON:0001383	94.78	gold quality
parietal pleura	UBERON:0002400	94.65	gold quality
germinal epithelium of ovary	UBERON:0001304	94.42	gold quality
pericardium	UBERON:0002407	94.42	gold quality
skeletal muscle tissue	UBERON:0001134	94.30	gold quality
embryo	UBERON:0000922	94.29	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	23.11
E-GEOD-93593	yes	7.26
E-MTAB-6524	no	234.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, GATA3, KAT7, TAF1

miRNA regulators (miRDB)

46 targeting HAT1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-516A-3P	99.46	67.96	1378

Literature-anchored findings (GeneRIF, showing 27)

• the role of Hat1 in DNA damage repair is evolutionarily conserved, the ability of H3 acetylation to compensate for Hat1 deletion appears to be more variable (PMID:17052979)
• HAT gene expression is required for cisplatin resistance and Clock and Tip60 regulate not only transcription, but also DNA repair, through periodic histone acetylation (PMID:18458078)
• The expression of HAT1 and MYST1, did not differ between drug-sensitive and -resistant cells (PMID:18458078)
• HAT1 differentially impacts nucleosome assembly of H3.1-H4 and H3.3-H4. (PMID:22228774)
• Data indicate that HAT1 is required for homologous recombination in DNA repair. (PMID:23653357)
• Human histone acetyltransferase 1 (Hat1) acetylates lysine 5 of histone H2A in vivo. (PMID:24682716)
• The high-resolution crystal structure of a Hat1p/Hat2p/CoA/H4 peptide complex was solved and it was found that the H4 tail interacts with both Hat1p and Hat2p, by which substrate recruitment is facilitated. It was discovered that H3 N-terminal peptides can bind to the Hat2p WD40 domain. (PMID:24835250)
• The expression of HAT1 was higher in the primary Esophageal carcinoma tumors and adjacent tissue as compared to that of the normal esophageal tissue and HAT1 expression was directly correlated with the poor tumor differentiation (PMID:25120766)
• Signalling from Toll-like or TNF-alpha receptors triggers the calcium/calmodulin-dependent protein kinase (CaMK2) to activate histone acetyltransferase-1 (HAT1), which then acetylates the transcriptional regulator PLZF. Acetylation of PLZF promotes the assembly of a repressor complex incorporating HDAC3 and the NF-kappa B p50 subunit that limits the NF-kappa B response. (PMID:25865065)
• These data indicated that miR-486 aggravate the cholesterol accumulation in THP-1 cells by targeting HAT1. (PMID:26654953)
• Results show a novel interaction of the Lsm4 RGG domain with HAT1 and RBBP7, leading to the possibility of a posttranslational modifications network involved in mRNP regulation. (PMID:27247266)
• HAT1 was upregulated in hepatocellular carcinoma.HAT1 acts as an oncogenic protein promoting cell proliferation and inducing cisplatin resistance in hepatocellular carcinoma. (PMID:27938492)
• Nuclear HDAC2 immunopositivity was significantly higher in actinic cheilitis (AC) when compared with lip squamous cell carcinoma (LSCC). HDAC1 and HAT1 nuclear immunostaining were higher in AC, with no statistical significance. When comparing data with our previous study, we found a positive correlation between HDAC1 X DNMT1/DNMT3b, HDAC2 X DNMT3b, and HAT1 X DNMT1/DNMT3b for certain studied groups. (PMID:28107582)
• AMPK phosphorylates DNMT1, RBBP7, and HAT1 and increases interactions of DNMT1, RBBP7, and HAT1. (PMID:28143904)
• Data show that PP32 and SET/TAF-Ibeta proteins block HAT1-mediated H4 acetylation. (PMID:28977641)
• HAT1 is involved in the STAT5 binding to the Bcl2L12 promoter. HAT1 increased the expression of Bcl2L12. Bcl2L12 mediated the effects of HAT1 on suppressing NPC cell apoptosis. Absorption of the HAT1 shRNA plasmid-carrying liposomes induced NPC cell apoptosis. In conclusion, inhibition of HAT1 can induce NPC cell apoptosis via increasing Bcl2L12 expression, which can be a potential therapy for NPC treatment. (PMID:29621521)
• In this work, we assessed the relationship between single-nucleotide polymorphisms (SNPs) of KAT1, KAT2 and IDO1 gene encoding, and the risk of depression development. Our study was performed on the DNA isolated from peripheral blood of 281 depressed patients and 236 controls. We genotyped, by using TaqMan probes, four polymorphisms. (PMID:29777939)
• High HAT1 expression is associated with Pancreatic ductal adenocarcinoma. (PMID:30709380)
• these data describe a feedforward circuit whereby HAT1 captures acetyl groups on nascent histones and drives H4 production by chromatin binding to support chromatin replication and acetylation. (PMID:31278053)
• Histone acetyltransferase 1 is a succinyltransferase for histones and non-histones and promotes tumorigenesis. (PMID:33372411)
• Histone acetyltransferase 1 promotes gemcitabine resistance by regulating the PVT1/EZH2 complex in pancreatic cancer. (PMID:34564701)
• Proteomic analysis identifies novel binding partners of BAP1. (PMID:34591877)
• FOXP3/HAT1 Axis Controls Treg Infiltration in the Tumor Microenvironment by Inducing CCR4 Expression in Breast Cancer. (PMID:35222362)
• HAT1: Landscape of Biological Function and Role in Cancer. (PMID:37048148)
• Understanding HAT1: A Comprehensive Review of Noncanonical Roles and Connection with Disease. (PMID:37107673)
• HMGB1/SET/HAT1 complex-mediated SASH1 repression drives glycolysis and metastasis in lung adenocarcinoma. (PMID:37794134)
• Decreased HAT1 expression in granulosa cells disturbs oocyte meiosis during mouse ovarian aging. (PMID:37907924)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hat1	ENSDARG00000034916
mus_musculus	Hat1	ENSMUSG00000027018
rattus_norvegicus	Hat1	ENSRNOG00000001524
drosophila_melanogaster	Hat1	FBGN0037376
caenorhabditis_elegans		WBGENE00044069

Protein

Protein identifiers

Histone acetyltransferase type B catalytic subunit — O14929 (reviewed: O14929)

Alternative names: Histone acetyltransferase 1, Histone methacryltransferase HAT1

All UniProt accessions (3): O14929, F8W9G7, F8WEW1

UniProt curated annotations — full annotation on UniProt →

Function. Histone acetyltransferase that plays a role in different biological processes including cell cycle progression, glucose metabolism, histone production or DNA damage repair. Coordinates histone production and acetylation via H4 promoter binding. Acetylates histone H4 at ‘Lys-5’ (H4K5ac) and ‘Lys-12’ (H4K12ac) and, to a lesser extent, histone H2A at ‘Lys-5’ (H2AK5ac). Drives H4 production by chromatin binding to support chromatin replication and acetylation. Since transcription of H4 genes is tightly coupled to S-phase, plays an important role in S-phase entry and progression. Promotes homologous recombination in DNA repair by facilitating histone turnover and incorporation of acetylated H3.3 at sites of double-strand breaks. In addition, acetylates other substrates such as chromatin-related proteins. Also acetylates RSAD2 which mediates the interaction of ubiquitin ligase UBE4A with RSAD2 leading to RSAD2 ubiquitination and subsequent degradation. In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as 2-methylpropenoyl-CoA (methacryl-CoA), and is able to mediate histone methacrylation. (Microbial infection) Contributes to hepatitis B virus (HBV) replication by acetylating histone H4 at the sites of ‘Lys-5’ and ‘Lys-12’ on the covalently closed circular DNA (cccDNA) minichromosome leading to its accumulation within the host cell.

Subunit / interactions. Catalytic subunit of the type B histone acetyltransferase (HAT) complex, composed of RBBP7 and HAT1. Interacts with histones H4 and H2A. The interaction is dependent of the ability of RBBP7 to bind to the N-terminus of histones. Component of the histone H3.1 and H3.3 complexes.

Subcellular location. Nucleus matrix. Mitochondrion Cytoplasm. Nucleus. Nucleoplasm.

Post-translational modifications. Phosphorylated by AMPK at Ser-190; phosphorylation increases HAT1 activity.

Induction. By viruses and interferons. Up-regulated also by estrogen.

Similarity. Belongs to the HAT1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14929-1	A, a, Nuclear	yes
O14929-2	B, b

RefSeq proteins (1): NP_003633* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013523	Hist_AcTrfase_HAT1_C	Homologous_superfamily
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR017380	Hist_AcTrfase_B-typ_cat-su	Family
IPR019467	Hat1_N	Domain
IPR037113	Hat1_N_sf	Homologous_superfamily
IPR048776	HAT1_C	Domain

Pfam: PF10394, PF21183

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), 2 shown:

• L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+) (RHEA:45948)
• 2-methylpropenoyl-CoA + L-lysyl-[protein] = N(6)-methacrylyl-L-lysyl-[protein] + CoA + H(+) (RHEA:83547)

UniProt features (56 total): helix 17, strand 13, mutagenesis site 8, modified residue 5, turn 3, region of interest 2, binding site 2, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, active site 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6VO5	X-RAY DIFFRACTION	1.6
2P0W	X-RAY DIFFRACTION	1.9
9MJG	X-RAY DIFFRACTION	2.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14929-F1	93.01	0.81

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 (2): 276 (proton donor/acceptor); 199 (interaction with histone h4 n-terminus)

Ligand- & substrate-binding residues (2): 241–243; 248–254

Post-translational modifications (5): 15, 190, 343, 2, 9

Mutagenesis-validated functional residues (8):

Position	Phenotype
62	strongly reduces hat activity.
64	strongly reduces hat activity.
187	strongly reduces hat activity.
190	complete loss of activity after pulsatile shear stress.
190	no loss of activity after pulsatile shear stress.
199	strongly reduces hat activity.
276	strongly reduces hat activity.
277	strongly reduces hat activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones

MSigDB gene sets: 275 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MODULE_52, MORF_ESPL1, GNF2_CENPF, MORF_SMC1L1, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_BUB1, PAL_PRMT5_TARGETS_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MORF_RRM1, KENNY_CTNNB1_TARGETS_UP, MORF_UBE2N, MORF_RAD21, MORF_HDAC2, MODULE_16

GO Biological Process (5): nucleosome assembly (GO:0006334), internal protein amino acid acetylation (GO:0006475), subtelomeric heterochromatin formation (GO:0031509), chromosome organization (GO:0051276), chromatin organization (GO:0006325)

GO Molecular Function (9): histone acetyltransferase activity (GO:0004402), histone H4 acetyltransferase activity (GO:0010485), histone binding (GO:0042393), histone H4K12 acetyltransferase activity (GO:0043997), histone methacryltransferase activity (GO:0140218), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), protein-lysine-acetyltransferase activity (GO:0061733)

GO Cellular Component (8): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), nuclear matrix (GO:0016363), protein-containing complex (GO:0032991), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Chromatin modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
histone modifying activity	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
protein acetylation	1
chromosome, telomeric region	1
constitutive heterochromatin formation	1
organelle organization	1
cellular component organization	1
protein-lysine-acetyltransferase activity	1
histone acetyltransferase activity	1
protein binding	1
histone H4 acetyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
protein N-acetyltransferase activity	1
chromosomal region	1
chromosome	1
cytoplasm	1
cellular_component	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HAT1	RBBP7	Q16576	974
HAT1	H4C7	Q99525	877
HAT1	AASDHPPT	Q9NRN7	872
HAT1	H4C16	P02304	867
HAT1	POLDIP3	Q9BY77	780
HAT1	NASP	P49321	768
HAT1	H3C1	P02295	705
HAT1	KAT2A	Q92830	688
HAT1	RBBP4	P31149	666
HAT1	KAT2B	Q92831	665
HAT1	IPO4	Q8TEX9	627
HAT1	ELP3	Q9H9T3	594
HAT1	LSM4	Q9Y4Z0	592
HAT1	H2BC21	Q16778	561
HAT1	ASF1A	Q9Y294	557
HAT1	ASF1B	Q9NVP2	557

IntAct

152 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HAT1	RBBP4	psi-mi:“MI:0915”(physical association)	0.800
RBBP4	HAT1	psi-mi:“MI:0915”(physical association)	0.800
HAT1	RBBP4	psi-mi:“MI:0914”(association)	0.800
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
H3C1	HAT1	psi-mi:“MI:0914”(association)	0.770
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
HAT1	H4C16	psi-mi:“MI:0407”(direct interaction)	0.700
HAT1	H4C16	psi-mi:“MI:0192”(acetylation reaction)	0.700
H4C16	HAT1	psi-mi:“MI:0914”(association)	0.700
H4C16	HAT1	psi-mi:“MI:0915”(physical association)	0.700
ASF1A	HAT1	psi-mi:“MI:0914”(association)	0.640
ASF1B	HAT1	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
MEOX2	HAT1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (327): HAT1 (Two-hybrid), HAT1 (Two-hybrid), HAT1 (Two-hybrid), HAT1 (Two-hybrid), HAT1 (Two-hybrid), RBBP7 (Affinity Capture-MS), HAT1 (Affinity Capture-MS), HAT1 (Affinity Capture-RNA), C5orf51 (Co-fractionation), HAT1 (Co-fractionation), HAT1 (Co-fractionation), HAT1 (Co-fractionation), HAT1 (Co-fractionation), HAT1 (Co-fractionation), HAT1 (Co-fractionation)

ESM2 similar proteins: A0A8J1LLF7, A0A974H8H3, A0MQH0, A4FUD6, A5HK05, B3DLA6, O14929, P11029, P11497, P42694, P54198, Q13085, Q25BN1, Q28559, Q4R4U1, Q504Q3, Q5R660, Q5RCC1, Q5RDU9, Q5SWU9, Q61666, Q6DFV5, Q6IE70, Q6NYU2, Q6P1X5, Q6TUI4, Q6TV19, Q80YV4, Q8BGF7, Q8BHL5, Q8BPU7, Q8C176, Q8CIQ7, Q8IWV8, Q8IZD9, Q8R418, Q8R5L3, Q8VHE0, Q923S8, Q92556

Diamond homologs: O14929, Q2UEX1, Q4PBE6, Q4X0W8, Q5M939, Q6CC99, Q869X7, Q86J12, Q8BY71, G4N7S6, P0CO06, P0CO07, Q12341, Q4I6A4, Q5AZR6, Q7RYU8, Q59VF4, Q6BSQ1, Q6CN95, Q6FKS5, Q750F5, Q9UTM7

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PRKAA1	“up-regulates activity”	HAT1	phosphorylation
RBBP7	“up-regulates activity”	HAT1	binding
AMPK	“up-regulates activity”	HAT1	phosphorylation
HAT1	“down-regulates activity”	H4C1	acetylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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
FCERI mediated MAPK activation	5	23.1×	7e-05
PRC2 methylates histones and DNA	6	12.2×	1e-04
NuRD complex assembly	6	11.3×	2e-04
Defective pyroptosis	5	10.4×	1e-03
Regulation of PD-L1(CD274) transcription	7	10.2×	1e-04
Interaction of NuRD complexes with transcription factors	6	10.2×	3e-04
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	5	10.2×	1e-03
Oxidative Stress Induced Senescence	8	9.7×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	5	15.2×	6e-03
nucleosome assembly	8	10.9×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1405 predictions. Top by Δscore:

Variant	Effect	Δscore
2:171925532:CTTAG:C	acceptor_loss	1.0000
2:171925533:TTAGG:T	acceptor_loss	1.0000
2:171925534:TAG:T	acceptor_loss	1.0000
2:171925535:A:AG	acceptor_gain	1.0000
2:171925535:AG:A	acceptor_gain	1.0000
2:171925536:G:GG	acceptor_gain	1.0000
2:171925536:GG:G	acceptor_gain	1.0000
2:171925642:G:C	donor_loss	1.0000
2:171925643:T:G	donor_loss	1.0000
2:171946700:T:A	acceptor_gain	1.0000
2:171946706:A:AG	acceptor_gain	1.0000
2:171946707:G:GG	acceptor_gain	1.0000
2:171946707:GTTC:G	acceptor_gain	1.0000
2:171946778:GGA:G	donor_gain	1.0000
2:171946779:GA:G	donor_gain	1.0000
2:171946779:GATGA:G	donor_gain	1.0000
2:171946782:GA:G	donor_gain	1.0000
2:171946784:G:GG	donor_gain	1.0000
2:171952874:A:AG	acceptor_gain	1.0000
2:171952875:T:G	acceptor_gain	1.0000
2:171952877:TCAGT:T	acceptor_loss	1.0000
2:171952878:CA:C	acceptor_loss	1.0000
2:171952879:A:AG	acceptor_gain	1.0000
2:171952879:AGT:A	acceptor_gain	1.0000
2:171952879:AGTG:A	acceptor_loss	1.0000
2:171952880:G:GT	acceptor_gain	1.0000
2:171952880:GT:G	acceptor_gain	1.0000
2:171952880:GTG:G	acceptor_gain	1.0000
2:171952880:GTGAA:G	acceptor_gain	1.0000
2:171952998:AGAG:A	donor_loss	1.0000

AlphaMissense

2795 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:171952895:G:A	G68D	0.999
2:171965892:T:A	W199R	0.999
2:171965892:T:C	W199R	0.999
2:171952891:T:C	F67L	0.998
2:171952893:T:A	F67L	0.998
2:171952893:T:G	F67L	0.998
2:171952895:G:T	G68V	0.998
2:171965847:T:A	W184R	0.998
2:171965847:T:C	W184R	0.998
2:171976190:G:C	R286P	0.998
2:171979339:A:C	K356N	0.998
2:171979339:A:T	K356N	0.998
2:171946753:C:A	P53H	0.997
2:171952894:G:C	G68R	0.997
2:171965857:A:T	E187V	0.997
2:171966893:T:C	L256P	0.997
2:171952897:T:G	Y69D	0.996
2:171965830:T:C	L178P	0.996
2:171979278:G:C	R336P	0.996
2:171952894:G:T	G68C	0.995
2:171966512:A:C	S239R	0.995
2:171966843:T:A	S239R	0.995
2:171966843:T:G	S239R	0.995
2:171979338:A:T	K356I	0.995
2:171925633:T:C	L35P	0.994
2:171965863:C:A	A189D	0.994
2:171966455:G:C	G220R	0.994
2:171966456:G:A	G220D	0.994
2:171946708:T:A	V38D	0.993
2:171952889:C:A	A66D	0.993

dbSNP variants (sampled 300 via entrez): RS1000010416 (2:171950304 G>A), RS1000051812 (2:171957358 G>A), RS1000065141 (2:171933128 G>T), RS1000226424 (2:171945211 T>G), RS1000279688 (2:171950962 A>G), RS1000432912 (2:171951225 T>C), RS1000435184 (2:171944518 A>G), RS1000483380 (2:171929842 A>G), RS1000523387 (2:171942663 A>G), RS1000544969 (2:171955902 C>A,G,T), RS1000545261 (2:171939307 C>G,T), RS1000706789 (2:171946206 T>C), RS1000728809 (2:171937900 T>A,C), RS1000741108 (2:171962711 T>A,C), RS1000804377 (2:171973567 C>G)

Disease associations

OMIM: gene MIM:603053 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003997_44	Myopia	3.000000e-15
GCST006291_115	Spherical equivalent or myopia (age of diagnosis)	3.000000e-16
GCST008595_58	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-08
GCST010002_404	Refractive error	2.000000e-39

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4523128 (SINGLE PROTEIN), CHEMBL5465253 (PROTEIN COMPLEX), CHEMBL6066577 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 136,163 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1534	RIBOFLAVIN	4	136,163

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)

Binding affinities (BindingDB)

421 measured of 511 human assays (596 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[(1R,3S)-1-fluoro-2’,5’-dioxo-6-(1-propan-2-ylpyrazol-4-yl)spiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	0.2 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-6-(1-cyclobutylpyrazol-4-yl)-1-fluoro-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	0.2 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-(1-methylpyrazol-4-yl)-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	0.4 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-6-(1-ethylpyrazol-4-yl)-1-fluoro-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	0.4 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-2-[(1R,3S)-1-fluoro-6-[1-[1-(oxetan-3-yl)azetidin-3-yl]pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]acetamide	IC50	0.5 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-[1-[1-(oxetan-3-yl)azetidin-3-yl]pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide	IC50	0.6 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-2-[(1R,3S)-1-fluoro-6-[1-[1-(oxetan-3-yl)azetidin-3-yl]pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]acetamide	IC50	0.6 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-[1-[1-(oxetan-3-yl)azetidin-3-yl]pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide	IC50	0.9 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-2’,5’-dioxo-6-(1-propan-2-ylpyrazol-4-yl)spiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	1 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
6-(Dimethylamino)-N-((2-methylquinolin-8-yl)sulfonyl)-4-(trifluoromethyl)benzofuran-2-carboxamide	IC50	1.47 nM	US-12357603: Acyl sulfonamides for treating cancer
2-[(1R,3S)-6-[1-(2-cyanopropan-2-yl)pyrazol-4-yl]-1-fluoro-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	2 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-(3-fluoro-1-methylpyrazol-4-yl)-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	2 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-(1-methylpyrazol-4-yl)-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	2 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-6-(1-ethylpyrazol-4-yl)-1-fluoro-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	2 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
US12357603, Example 107	IC50	2.29 nM	US-12357603: Acyl sulfonamides for treating cancer
N-((5-(tert-butyl)-2-methoxyphenyl)sulfonyl)-6-(dimethylamino)benzofuran-2-carboxamide	IC50	2.63 nM	US-12357603: Acyl sulfonamides for treating cancer
N-[(5-(tert-butyl)-2-cyclobutoxyphenyl)sulfonyl]-6-(dimethylamino)benzofuran-2-carboxamide	IC50	2.67 nM	US-12357603: Acyl sulfonamides for treating cancer
2-[(1R,3S)-1,5-difluoro-6-(1-methylpyrazol-4-yl)-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	3 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
US12357603, Example 227	IC50	4 nM	US-12357603: Acyl sulfonamides for treating cancer
N-((5-(tert-butyl)-2-(cyclopropylmethoxy)phenyl)sulfonyl)-6-(dimethylamino)benzofuran-2-carboxamide	IC50	4.36 nM	US-12357603: Acyl sulfonamides for treating cancer
6-(Dimethylamino)-N-(2-ethoxy-5-sec-butyl-phenyl)sulfonyl-benzofuran-2-carboxamide (rac)	IC50	4.4 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 108	IC50	4.6 nM	US-12357603: Acyl sulfonamides for treating cancer
2-[(3S)-6-[1-(2-cyanopropan-2-yl)pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	5 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-(1-methylpyrazol-4-yl)-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]-N-[[4-(trifluoromethyl)phenyl]methyl]acetamide	IC50	5 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
6-(Dimethylamino)-N-((2-ethoxyphenyl)sulfonyl)-4-(trifluoromethyl)benzofuran-2-carboxamide	IC50	5.73 nM	US-12357603: Acyl sulfonamides for treating cancer
N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-[(3S)-6-[1-[1-(oxetan-3-yl)azetidin-3-yl]pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]acetamide	IC50	6 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
N-[(4-fluorophenyl)methyl]-2-[(3S)-6-(1-methylpyrazol-4-yl)-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	6 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-(5-fluoro-1-methylpyrazol-4-yl)-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	6 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-[1-(oxetan-3-ylmethyl)pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	6 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-[1-(oxan-4-yl)pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide	IC50	7 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-[1-(1-hydroxy-2-methylpropan-2-yl)pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	7 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
US12357603, Example 109	IC50	7.09 nM	US-12357603: Acyl sulfonamides for treating cancer
N-([1,1’-biphenyl]-2-ylsulfonyl)-6-(dimethylamino)-4-(trifluoromethyl)benzofuran-2-carboxamide	IC50	7.14 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 113	IC50	7.25 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 110	IC50	7.48 nM	US-12357603: Acyl sulfonamides for treating cancer
N-[2-(cyclopropylmethoxy)-5-isopropyl-phenyl]sulfonyl-6-(dimethylamino)benzofuran-2-carboxamide	IC50	7.91 nM	US-12357603: Acyl sulfonamides for treating cancer
N-((2-((2,2-difluorocyclopropyl)methoxy)-5-isopropylphenyl)sulfonyl)-6-(dimethylamino)benzofuran-2-carboxamide (rac)	IC50	8.47 nM	US-12357603: Acyl sulfonamides for treating cancer
3-[(2R)-2-[[(2R)-2-(4-cyanophenyl)propyl]amino]-2-phenylacetyl]-N-ethyl-1H-indole-6-carboxamide	IC50	8.76 nM	US-11414384: P300/CBP hat inhibitors
US12357603, Example 111	IC50	8.93 nM	US-12357603: Acyl sulfonamides for treating cancer
N-[(2-(Benzyloxy)-5-(tert-butyl)phenyl)sulfonyl]-6-(dimethylamino)benzofuran-2-carboxamide	IC50	8.95 nM	US-12357603: Acyl sulfonamides for treating cancer
2-[(1R,3S)-1-fluoro-6-[1-[1-(oxetan-3-yl)piperidin-4-yl]pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide	IC50	9 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-6-[1-(2-cyanopropan-2-yl)pyrazol-4-yl]-1-fluoro-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	9 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
2-[(1R,3S)-1-fluoro-6-[1-(oxetan-3-yl)pyrazol-4-yl]-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(5-fluoro-2-pyridinyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide	IC50	10 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
6-(Dimethylamino)-N-[5-isopropyl-2-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-benzofuran-2-carboxamide	IC50	11 nM	US-12357603: Acyl sulfonamides for treating cancer
2-[(1R,3S)-6-[1-[[3-(dimethylamino)oxetan-3-yl]methyl]pyrazol-4-yl]-1-fluoro-2’,5’-dioxospiro[1,2-dihydroindene-3,4’-imidazolidine]-1’-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide	IC50	11 nM	US-20250257055: TERTIARY AMIDE DERIVATIVES SUBSTITUTED WITH 4-MEMBERED RING STRUCTURE
6-(Dimethylamino)-N-(2-ethoxy-5-phenoxy-phenyl)sulfonyl-benzofuran-2-carboxamide	IC50	11.8 nM	US-12357603: Acyl sulfonamides for treating cancer
N-[(5-(tert-butyl)-2-(2,2,2-trifluoroethoxy)phenyl)sulfonyl]-6-(dimethylamino)benzofuran-2-carboxamide	IC50	11.8 nM	US-12357603: Acyl sulfonamides for treating cancer
N-(2-Benzyloxy-5-isopropyl-phenyl)sulfonyl-6-(dimethylamino)benzofuran-2-carboxamide	IC50	12.8 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 129	IC50	13.5 nM	US-12357603: Acyl sulfonamides for treating cancer
N-((5-(tert-butyl)-2-isopropoxyphenyl)sulfonyl)-6-(dimethylamino)benzofuran-2-carboxamide	IC50	15.4 nM	US-12357603: Acyl sulfonamides for treating cancer

ChEMBL bioactivities

259 potent at pChembl≥5 of 303 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.06	IC50	8.76	nM	CHEMBL5948549
8.03	IC50	9.36	nM	CHEMBL6021203
7.81	IC50	15.6	nM	CHEMBL5770805
7.77	IC50	17.1	nM	CHEMBL5810237
7.77	IC50	17	nM	CHEMBL5877627
7.75	IC50	17.7	nM	CHEMBL5836346
7.72	IC50	19	nM	CHEMBL5957574
7.68	IC50	20.7	nM	CHEMBL6041803
7.68	IC50	21.1	nM	CHEMBL5877638
7.66	IC50	21.8	nM	CHEMBL5849718
7.63	IC50	23.2	nM	CHEMBL6041468
7.58	IC50	26	nM	CHEMBL5744919
7.55	IC50	28	nM	CHEMBL5849914
7.54	IC50	28.8	nM	CHEMBL5773451
7.44	IC50	36.2	nM	CHEMBL5789949
7.41	IC50	39	nM	CHEMBL6057197
7.39	IC50	41	nM	CHEMBL4633516
7.38	IC50	41.9	nM	CHEMBL5767025
7.37	IC50	42.4	nM	CHEMBL5966598
7.36	IC50	44	nM	CHEMBL5752305
7.36	IC50	44	nM	CHEMBL5823999
7.34	IC50	46	nM	CHEMBL5936857
7.28	Kd	52.65	nM	CHEMBL5653589
7.28	ED50	52.65	nM	CHEMBL5653589
7.28	IC50	53.1	nM	CHEMBL5843631
7.27	IC50	53.8	nM	CHEMBL5961948
7.23	IC50	58.3	nM	CHEMBL5945001
7.23	IC50	59.2	nM	CHEMBL5991231
7.21	IC50	62	nM	CHEMBL5874495
7.19	IC50	64.3	nM	CHEMBL6006190
7.18	IC50	66	nM	CHEMBL5981007
7.10	IC50	80	nM	CHEMBL6041641
7.10	IC50	79.8	nM	CHEMBL5902799
7.09	IC50	82	nM	CHEMBL5752305
7.09	IC50	81.6	nM	CHEMBL5988861
7.06	IC50	87.1	nM	CHEMBL5955760
7.02	IC50	95.1	nM	CHEMBL6022136
7.01	IC50	97	nM	CHEMBL5944900
7.00	IC50	101	nM	CHEMBL5903879
6.94	IC50	116	nM	CHEMBL4639768
6.93	IC50	118	nM	CHEMBL6035457
6.91	IC50	123	nM	CHEMBL5830673
6.87	IC50	134	nM	CHEMBL6047272
6.87	IC50	136	nM	CHEMBL5996007
6.87	IC50	135	nM	CHEMBL5948672
6.85	IC50	140	nM	CHEMBL5936146
6.81	IC50	154	nM	CHEMBL5973229
6.80	IC50	160	nM	CHEMBL6042170
6.79	IC50	164	nM	CHEMBL6019817
6.78	IC50	166	nM	CHEMBL5925733

PubChem BioAssay actives

3 with measured affinity, of 78 total; 3 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-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148485: Binding affinity to human HAT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0527	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148485: Binding affinity to human HAT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1828	uM
7-chloro-8-ethyl-10-[2-(2-methylpropoxy)ethyl]benzo[g]pteridine-2,4-dione	2030513: Binding affinity to CM5 sensor chip immobilized C-terminal FLAG tagged full length human HAT1/Rbap46 assessed as dissociation constant by SPR analysis	kd	5.2000	uM

CTD chemical–gene interactions

74 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, increases expression, decreases expression, increases abundance	8
bisphenol A	decreases methylation, increases expression, affects expression, decreases expression	6
Cisplatin	decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
Arsenic	increases methylation, decreases expression, increases abundance	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
Batroxase, Bothrops atrox	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	decreases expression	1
gossypol acetic acid	decreases expression	1
1-aminomethylphosphonic acid	increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases reaction, increases expression	1
2-hydroxychavicol	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases activity	1
K 7174	decreases expression	1
pyrazolanthrone	decreases reaction, increases activity	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4325442	Binding	Inhibition of HAT1 (unknown origin)	Discovery of Highly Potent, Selective, and Orally Efficacious p300/CBP Histone Acetyltransferases Inhibitors. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8H4	Abcam HCT 116 HAT1 KO	Cancer cell line	Male
CVCL_B8WH	Abcam MCF-7 HAT1 KO	Cancer cell line	Female
CVCL_B9JE	Abcam A-549 HAT1 KO	Cancer cell line	Male
CVCL_SQ90	HAP1 HAT1 (-) 1	Cancer cell line	Male
CVCL_SQ91	HAP1 HAT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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