HDAC1

Summary

HDAC1 (histone deacetylase 1, HGNC:4852) is a protein-coding gene on chromosome 1p35.2-p35.1, encoding Histone deacetylase 1 (Q13547). Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family and is a component of the histone deacetylase complex. It also interacts with retinoblastoma tumor-suppressor protein and this complex is a key element in the control of cell proliferation and differentiation. Together with metastasis-associated protein-2, it deacetylates p53 and modulates its effect on cell growth and apoptosis.

Source: NCBI Gene 3065 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Disputed, ClinGen)
• Clinical variants (ClinVar): 63 total — 1 likely-pathogenic
• Druggable target: yes — 48 molecules with ChEMBL bioactivity
• Transcription factor: yes — 84 downstream targets (CollecTRI)
• MANE Select transcript: NM_004964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4852
Approved symbol	HDAC1
Name	histone deacetylase 1
Location	1p35.2-p35.1
Locus type	gene with protein product
Status	Approved
Aliases	HD1, GON-10, KDAC1
Ensembl gene	ENSG00000116478
Ensembl biotype	protein_coding
OMIM	601241
Entrez	3065

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000373548, ENST00000428704, ENST00000463172, ENST00000471488, ENST00000472928, ENST00000476391, ENST00000481281, ENST00000482310, ENST00000484305, ENST00000490081, ENST00000718279, ENST00000906551, ENST00000906552, ENST00000906553, ENST00000906554, ENST00000906555, ENST00000906556, ENST00000933659, ENST00000933660, ENST00000933661, ENST00000943499

RefSeq mRNA: 1 — MANE Select: NM_004964 NM_004964

CCDS: CCDS360

Canonical transcript exons

ENST00000373548 — 14 exons

Exon	Start	End
ENSE00001850850	32292083	32292218
ENSE00003469455	32316665	32316782
ENSE00003539653	32324479	32324553
ENSE00003547692	32331676	32331806
ENSE00003550072	32326939	32327077
ENSE00003564227	32329068	32329160
ENSE00003567410	32332701	32332749
ENSE00003578115	32330768	32330908
ENSE00003626458	32327536	32327677
ENSE00003638824	32330578	32330686
ENSE00003657444	32332090	32332242
ENSE00003691785	32331474	32331582
ENSE00003693858	32333017	32333626
ENSE00004034612	32302621	32302733

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.0677 / max 361.9177, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1979	21.8285	1808
1978	21.2187	1809
1977	1.0204	531

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic mucosa	UBERON:0000317	99.03	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.01	gold quality
mucosa of transverse colon	UBERON:0004991	98.43	gold quality
epithelium of nasopharynx	UBERON:0001951	98.42	gold quality
rectum	UBERON:0001052	98.35	gold quality
lymph node	UBERON:0000029	98.28	gold quality
esophagus squamous epithelium	UBERON:0006920	98.00	gold quality
pylorus	UBERON:0001166	97.98	gold quality
right uterine tube	UBERON:0001302	97.94	gold quality
caecum	UBERON:0001153	97.92	gold quality
transverse colon	UBERON:0001157	97.90	gold quality
gingiva	UBERON:0001828	97.90	gold quality
vermiform appendix	UBERON:0001154	97.85	gold quality
gingival epithelium	UBERON:0001949	97.85	gold quality
islet of Langerhans	UBERON:0000006	97.84	gold quality
epithelium of esophagus	UBERON:0001976	97.84	gold quality
granulocyte	CL:0000094	97.70	gold quality
pharyngeal mucosa	UBERON:0000355	97.57	gold quality
duodenum	UBERON:0002114	97.53	gold quality
oral cavity	UBERON:0000167	97.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.47	gold quality
stromal cell of endometrium	CL:0002255	97.46	gold quality
esophagus mucosa	UBERON:0002469	97.46	gold quality
squamous epithelium	UBERON:0006914	97.46	gold quality
right lobe of thyroid gland	UBERON:0001119	97.44	gold quality
thymus	UBERON:0002370	97.43	gold quality
large intestine	UBERON:0000059	97.39	gold quality
gall bladder	UBERON:0002110	97.34	gold quality
colon	UBERON:0001155	97.33	gold quality
intestine	UBERON:0000160	97.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.51

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

84 targets.

Target	Regulation
ABCB1	Repression
ADAM10	Repression
ALOX15	Unknown
APOC3	Unknown
AR	Unknown
BAMBI	Repression
BCL2A1	Activation
BIRC3	Activation
BIRC5	Unknown
BRCA2	Repression
CCND1	Activation
CCND2	Repression
CD1D	Repression
CD44	Repression
CD82	Repression
CDH1	Repression
CDK4	Activation
CDKN1A	Repression
CDKN2A	Unknown
CEBPA	Repression
CLDN7	Activation
COL1A2	Activation
CXCL8	Unknown
CYP3A4	Unknown
DEFB1	Unknown
DNMT1	Unknown
E2F1	Repression
EGFR	Repression
EGR1	Repression
EHMT2

Upstream regulators (CollecTRI, top): AR, DNMT1, EZH2, FLI1, GATA1, MTA1, NFKB1, NR4A1, PDGFB, PPARG, PYHIN1, RELA, RFX1, SATB1, YY1

miRNA regulators (miRDB)

74 targeting HDAC1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4719	99.73	72.10	3329

Literature-anchored findings (GeneRIF, showing 40)

• Expression profile of histone deacetylase 1 in gastric cancer tissues (PMID:11749695)
• role in regulation of the telomerase reverse transcriptase (hTERT) gene (PMID:11855854)
• Phosphatase inhibition leads to histone deacetylases 1 and 2 phosphorylation and disruption of corepressor interactions (PMID:11919195)
• association with proliferating cell nuclar antigen, integrating DNA replication and chromatin modification (PMID:11929879)
• Counterregulation of chromatin deacetylation and histone deacetylase occupancy at the integrated promoter of human immunodeficiency virus type 1 (HIV-1) by the HIV-1 repressor YY1 and HIV-1 activator Tat. (PMID:11940654)
• Androgen receptor, Tip60, and HDAC1 form a trimeric complex upon the endogenous AR-responsive PSA promoter, acetylation and deacetylation of the AR is an important mechanism for regulating transcriptional activity. (PMID:11994312)
• interaction with large subunit of replication factor C (PMID:12045192)
• associated with silencing DAP kinase gene expression in colorectal and gastric cancers (PMID:12087472)
• HDAC-Sin3A complex regulates LHR Gene transcription (PMID:12091390)
• interaction with mCpG-binding domain of MBD2 (PMID:12124384)
• localization in Aurora-A-positive centrosomes in M phase (PMID:12354758)
• Data show that the adenovirus protein Gam1 counteracts histone deacetylase 1 sumoylation both in vivo and in vitro. (PMID:12393750)
• The HDAC1 complex binds MDM2 in a p53-independent manner and deacetylates p53 at all known acetylated lysines in vivo. (PMID:12426395)
• Che-1 affects cell growth by interfering with the recruitment of HDAC1 by retinoblastoma protein. Che-1 overexpression activates DNA synthesis in quiescent NIH-3T3 cells through HDAC1 displacement. (PMID:12450794)
• recruited by prohibitin for transcriptional repression (PMID:12466959)
• We demonstrate that MI-ER1 repressor activity is due to interaction and recruitment of a trichostatin A-sensitive HDAC1, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1alpha and hMI-ER1beta occurs through their common ELM2 domain. (PMID:12482978)
• Here we show that HDAC1 associates with and blocks Ser133 phosphorylation of CREB during pre-stimulus and attenuation phases of the cAMP response (PMID:12567184)
• histone deacetylase 1 overexpression is associated with advanced stage esophageal squamous cell carcinoma. (PMID:12579268)
• deacetylase HDAC1 acts as an antagonist of the tumor suppressor p53 in the regulation of the cyclin-dependent kinase inhibitor p21 (PMID:12665570)
• We investigated occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between pRb2/p130 and chromatin-modifying enzymes in the regulation of ER-alpha transcription (PMID:12789259)
• p52 NF-kappaB subunit associates with histone deacetylase 1 when p53 represses cyclin D1 transcription through down regulation of Bcl-3 (PMID:12808109)
• The MLL repression domain specifically interacts with HDAC1. (PMID:12829790)
• HDAC1 is displaced from the p21WAF1/CIP1 promoter by Che-1 in human colonic carcinoma (PMID:12847090)
• IkappaBalpha regulates the transcriptional activity of homeodomain-containing proteins positively through cytoplasmic sequestration of HDAC1 and HDAC3 (PMID:12972430)
• HDAC1 represses the small GTPase RhoB expression in human nonsmall lung carcinoma cell line. (PMID:13679859)
• HDAC1 has a role in interferon-stimulated transcription and innate antiviral immunity (PMID:14645718)
• MeCP2 acts as a corepressor of PU.1 probably due to facilitating complex formation with mSin3A and HDACs. (PMID:14647463)
• HDAC1 interacts with p300 C/H3 domain. Its overexpression interferes with either activation of Gal14p300 fusion protein or p300-dependent co-activation of MyoD and p53. E1A competes with HDAC1 for C/H3 binding. (PMID:14968110)
• interaction of HPV type 31 E7 with HDACs and the integrity of the zinc finger-like motifs are essential for extending the life span of keratinocytes and for stable maintenance of viral genomes (PMID:15016876)
• HDAC1 upregulated in pre-malignant and malignant lesions, with the highest increase in expression in hormone refractory (HR) prostate cancer; in CWR22 xenograft model, androgen dependent regulation of HDAC1 demonstrated. (PMID:15042618)
• Ezh2 competes with HDAC1 in binding to pRb2/p130, disrupting their occupancy on the cyclin A promoter. (PMID:15077161)
• histone deacetylase has a role in transforming growth factor-beta signaling in breast cancer cells (PMID:15155736)
• Tax interacts directly with HDAC1 and regulates binding of the repressor to the HTLV-1 promoter (PMID:15194748)
• SENP1’s ability to enhance AR-dependent transcription is not mediated through desumoylation of AR, but rather through its ability to deconjugate histone deacetylase 1 (HDAC1), thereby reducing its deacetylase activity. (PMID:15199155)
• stabilization of NF-E4 by acetylation is PCAF-dependent; acetylation of Lys(43) also reduces the interaction between NF-E4 and HDAC1, potentially maximizing the activating ability of the factor (PMID:15273251)
• Accumulation of ICBP90 in breast-cancer cells might suppress expression of tumor suppressor genes through deacetylation of histones after recruitment of HDAC1. (PMID:15361834)
• In prostate tissues, the abundance of HDAC1 protein, which was exclusively expressed in the cell nucleus, was similar in normal and malignant epithelial cells, but was usually lower in stromal cells. (PMID:15590418)
• HDAC1 negatively regulates the cardiovascular transcription factor KLF5 through direct interaction (PMID:15668237)
• plays a critical role in repression of endothelial constitutive nitric oxide synthase gene (PMID:15722551)
• interleukin-5 transcription repression by the glucocorticoid receptor targets GATA3 signaling and involves histone deacetylase recruitment (PMID:15826950)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdac1	ENSDARG00000015427
mus_musculus	Hdac1	ENSMUSG00000028800
rattus_norvegicus	Hdac1	ENSRNOG00000009568
rattus_norvegicus	Hdac1l	ENSRNOG00000013695
caenorhabditis_elegans		WBGENE00009657
caenorhabditis_elegans		WBGENE00009663
caenorhabditis_elegans		WBGENE00219378

Paralogs (10): HDAC9 (ENSG00000048052), HDAC7 (ENSG00000061273), HDAC4 (ENSG00000068024), HDAC6 (ENSG00000094631), HDAC10 (ENSG00000100429), HDAC5 (ENSG00000108840), HDAC8 (ENSG00000147099), HDAC11 (ENSG00000163517), HDAC3 (ENSG00000171720), HDAC2 (ENSG00000196591)

Protein

Protein identifiers

Histone deacetylase 1 — Q13547 (reviewed: Q13547)

Alternative names: Protein deacetylase HDAC1, Protein deacylase HDAC1

All UniProt accessions (3): Q13547, Q5TEE2, Q6IT96

UniProt curated annotations — full annotation on UniProt →

Function. Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. As part of the SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription. Also functions as a deacetylase for non-histone targets, such as NR1D2, RELA, SP1, SP3, STAT3, ZNF76 and TSHZ3. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates ‘Lys-310’ in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation. In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase and delactylase by mediating decrotonylation ((2E)-butenoyl) and delactylation (lactoyl) of histones, respectively.

Subunit / interactions. Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7, the core complex associates with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and HDAC2. Component of the SIN3B complex, which includes SIN3B, HDAC1, PHF12 and MORF4L1. Found in a trimeric complex with APBB1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3. Forms a complex comprising APPL1, RUVBL2, APPL2, CTNNB1 and HDAC2. Component of a RCOR/GFI/KDM1A/HDAC complex. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2. The large PER complex involved in the histone deacetylation is composed of at least HDAC1, PER2, SFPQ and SIN3A. Associates with the 9-1-1 complex; interacts with HUS1. Found in a complex with DNMT3A and HDAC7. Found in a complex with YY1, SIN3A and GON4L. Identified in a histone deacetylase complex that contains DNTTIP1, HDAC1 and MIDEAS; this complex assembles into a tetramer that contains four copies of each protein chain. Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1. Interacts with GFI1; the interaction is direct. Interacts directly with GFI1B. Interacts with TSHZ3 (via N-terminus); the interaction is direct. Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with BANP. Interacts with BAZ2A/TIP5. Interacts with BCL6. Interacts with BCOR. Interacts with BHLHE40/DEC1. Interacts with BRCC3; this interaction is enhanced in the presence of PWWP2B. Interacts with BRMS1. Interacts with BRMS1L. Interacts with C10orf90/FATS (via its N-terminal); the interaction prevents binding of HDAC1 to CDKN1A/p21 and facilitates the acetylation and stabilization of CDKN1A/p21. Interacts with CBFA2T3. Interacts with CCAR2. Interacts with CDK2AP1. Interacts with CHD3. Interacts with CHD4. Interacts with CHFR. Interacts with CIART. Interacts with CDKN1A/p21. Interacts with CDK5 complexed to CDK5R1 (p25). Interacts with CRY1. Interacts with DAXX. Interacts with DDIT3/CHOP. Interacts with DDX5. Interacts with DHX36; this interaction occurs in a RNA-dependent manner. Interacts with DNMT1. Interacts with DNTTIP1. Interacts with E4F1. Interacts with EP300. Interacts with ERCC6. Interacts with GATAD2A. Interacts with HCFC1. Interacts with HDAC9. Interacts with HUS1. Interacts with INSM1. Interacts with KDM4A. Interacts with KDM5A; this interaction impairs histone deacetylation. Interacts with KDM5B. Interacts with KLF1. Interacts with MBD3L2. Interacts with MIER1. Interacts with NFE4. Interacts with NR4A2/NURR1. Interacts with NR1D2 (via C-terminus). Interacts with NRIP1. Interacts with NSD2. Interacts with PACS2. Interacts with PHB2. Interacts with PPHLN1. Interacts with PRDM6. Interacts with PRDM16. Interacts with PWWP2A in a MTA1-dependent manner. Interacts with PWWP2B. Interacts with RB1. Interacts with RERE. Interacts with SANBR (via the BTB domain). Interacts with SAMSN1. Interacts with SAP30L. Interacts with SETDB1. Interacts with SIN3A. Interacts with SMAD3. Interacts with SMAD4; positively regulated by ZBTB7A. Interacts with SMARCAD1. Interacts with SMARCA4/BRG1. Interacts with SMYD2. Interacts with SMYD4 (via MYND-type zinc finger). Interacts with SP1; the interaction deacetylates SP1 and regulates its transcriptional activity. Interacts with SP3; the interaction deacetylates SP3 and regulates its transcriptional activity. In vitro, C(18) ceramides increase this interaction and the subsequent SP3 deacetylation and SP3-mediated repression of the TERT promoter. Interacts with SPEN/MINT. Interacts with SPHK2. Interacts with SUV39H1. Interacts with TGIF. Interacts with TGIF2. Interacts with TRAF6. Interacts with TRIM28; the interaction recruits HDAC1 to E2F1 and inhibits its acetylation. Interacts with TSC22D3 isoform 1; this interaction affects HDAC1 activity on MYOG promoter and thus inhibits MYOD1 transcriptional activity. Interacts with UHRF1. Interacts with UHRF2. Interacts with ZBTB7A. Interacts with ZMYND8. Interacts with ZMYND15. Interacts with ZNF431. Interacts with ZNF516; this interaction is enhanced in the presence of PWWP2B. Interacts with ZNF541. Interacts with ZNF638. Interacts with ZNHIT1. Interacts with the non-histone region of MACROH2A1. Identified in a complex with HDAC2, KCTD19, DNTTIP1 and ZNF541. Interacts with VRK1. (Microbial infection) Interacts with SV40 large T antigen.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous, with higher levels in heart, pancreas and testis, and lower levels in kidney and brain.

Post-translational modifications. Sumoylated on Lys-444 and Lys-476; which promotes enzymatic activity. Desumoylated by SENP1. Phosphorylation on Ser-421 and Ser-423 promotes enzymatic activity and interactions with NuRD and SIN3 complexes. Phosphorylated by CDK5. Ubiquitinated by CHFR, leading to its degradation by the proteasome. Ubiquitinated by KCTD11, leading to proteasomal degradation.

Activity regulation. Inositol tetraphosphate (1D-myo-inositol 1,4,5,6-tetrakisphosphate) may act as an intermolecular glue between HDAC1 and N-Cor repressor complex components.

Similarity. Belongs to the histone deacetylase family. HD type 1 subfamily.

RefSeq proteins (1): NP_004955* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000286	HDACs	Family
IPR003084	HDAC_I/II	Family
IPR023696	Ureohydrolase_dom_sf	Homologous_superfamily
IPR023801	His_deacetylse_dom	Domain
IPR037138	His_deacetylse_dom_sf	Homologous_superfamily

Pfam: PF00850

Enzyme classification (BRENDA):

• EC 3.5.1.98 — histone deacetylase (BRENDA: 33 organisms, 161 substrates, 590 inhibitors, 88 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
FLUOR DE LYS HDAC8 SUBSTRATE	0.14–1.1	9
AC-KHK(ACETYL)K(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.273–2.403	6
FLUOR DE LYS HDAC SUBSTRATE	0.013–0.088	6
AC-FEK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0023–0.0359	5
AC-GGK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0043–0.0877	5
AC-GS(PO3)K(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0123–0.0666	5
AC-GSK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.004–0.0241	5
AC-IHK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0007–0.108	5
AC-KYK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0044–0.107	4
FLUOR DE LYS	—	4
AC-LYK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0069–0.03	3
AC-VLK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0119–0.0221	3
RHK(ACETYL)K(ACETYL)-FLUOROPHORE	0.16–1.1	3
AC-DQK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0024–0.0165	2
BENZYLOXYCARBONYL-L-LYS(ACETYL)-7-AMIDO-4-METHYL	0.078–0.099	2

Catalyzed reactions (Rhea), 4 shown:

• N(6)-acetyl-L-lysyl-[protein] + H2O = L-lysyl-[protein] + acetate (RHEA:58108)
• N(6)-acetyl-L-lysyl-[histone] + H2O = L-lysyl-[histone] + acetate (RHEA:58196)
• N(6)-(2E)-butenoyl-L-lysyl-[protein] + H2O = (2E)-2-butenoate + L-lysyl-[protein] (RHEA:69172)
• N(6)-[(S)-lactoyl]-L-lysyl-[protein] + H2O = (S)-lactate + L-lysyl-[protein] (RHEA:81387)

UniProt features (83 total): helix 16, mutagenesis site 13, strand 12, modified residue 10, cross-link 10, turn 7, binding site 6, compositionally biased region 4, region of interest 2, chain 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
7SME	X-RAY DIFFRACTION	2.64
9R4I	ELECTRON MICROSCOPY	2.92
4BKX	X-RAY DIFFRACTION	3
5ICN	X-RAY DIFFRACTION	3.3
8VPQ	ELECTRON MICROSCOPY	3.3
8VRT	ELECTRON MICROSCOPY	3.42
8VOJ	ELECTRON MICROSCOPY	3.77
6Z2J	ELECTRON MICROSCOPY	4
6Z2K	ELECTRON MICROSCOPY	4.5
7AO8	ELECTRON MICROSCOPY	4.5
7AO9	ELECTRON MICROSCOPY	6.1
7AOA	ELECTRON MICROSCOPY	19.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13547-F1	86.41	0.76

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): 141

Ligand- & substrate-binding residues (6): 176; 178; 264; 270; 27; 31

Post-translational modifications (20): 74, 220, 261, 273, 393, 406, 409, 421, 423, 432, 74, 438, 444, 444, 456, 457, 473, 476, 476, 480

Mutagenesis-validated functional residues (13):

Position	Phenotype
136–138	impaired protein deacetylase activity without affecting the protein decrotonylase activity.
141	abolishes histone deacetylase and decrotonylase activities.
287	abolishes interaction with chfr; when associated with i-297.
297	abolishes interaction with chfr; when associated with y-287.
391–482	strongly decreases deacetylase activity, and disrupts interaction with nurd and sin3 complexes.
421	strongly decreases deacetylase activity, and disrupts interaction with nurd and sin3 complexes.
421	slightly decreases deacetylase activity.
423	strongly decreases deacetylase activity, and disrupts interaction with nurd and sin3 complexes.
423	decreases deacetylase activity.
424–426	abolished histone deacetylase and decrotonylase activities.
424	slightly decreases deacetylase activity, no effect on interaction with nurd and sin3 complexes.
425	no effect on deacetylase activity, no effect on interaction with nurd and sin3 complexes.
426	decreases deacetylase activity, and disrupts interaction with nurd and sin3 complexes.

Function

Pathways and Gene Ontology

Reactome pathways

42 pathways

ID	Pathway
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-1538133	G0 and Early G1
R-HSA-193670	p75NTR negatively regulates cell cycle via SC1
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3214815	HDACs deacetylate histones
R-HSA-350054	Notch-HLH transcription pathway
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4641265	Repression of WNT target genes
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-69205	G1/S-Specific Transcription
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9022538	Loss of MECP2 binding ability to 5mC-DNA
R-HSA-9022692	Regulation of MECP2 expression and activity
R-HSA-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-9022702	MECP2 regulates transcription of neuronal ligands
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9701898	STAT3 nuclear events downstream of ALK signaling

MSigDB gene sets: 632 (showing top): GOBP_CIRCADIAN_RHYTHM, PID_HDAC_CLASSI_PATHWAY, REACTOME_SIGNALING_BY_NOTCH, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, MORF_SMC1L1, PID_TELOMERASE_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION

GO Biological Process (43): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), regulation of transcription by RNA polymerase II (GO:0006357), endoderm development (GO:0007492), positive regulation of cell population proliferation (GO:0008284), epidermal cell differentiation (GO:0009913), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), hippocampus development (GO:0021766), neuron differentiation (GO:0030182), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), heterochromatin formation (GO:0031507), circadian regulation of gene expression (GO:0032922), positive regulation of intracellular estrogen receptor signaling pathway (GO:0033148), cellular response to platelet-derived growth factor stimulus (GO:0036120), odontogenesis of dentin-containing tooth (GO:0042475), regulation of cell fate specification (GO:0042659), embryonic digit morphogenesis (GO:0042733), negative regulation of apoptotic process (GO:0043066), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), host-mediated suppression of viral transcription (GO:0043922), negative regulation of gene expression, epigenetic (GO:0045814), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of smooth muscle cell proliferation (GO:0048661), oligodendrocyte differentiation (GO:0048709), positive regulation of oligodendrocyte differentiation (GO:0048714), negative regulation of androgen receptor signaling pathway (GO:0060766), hair follicle placode formation (GO:0060789), eyelid development in camera-type eye (GO:0061029), fungiform papilla formation (GO:0061198), negative regulation of canonical Wnt signaling pathway (GO:0090090), negative regulation of stem cell population maintenance (GO:1902455), positive regulation of stem cell population maintenance (GO:1902459), regulation of stem cell differentiation (GO:2000736), negative regulation of intrinsic apoptotic signaling pathway (GO:2001243)

GO Molecular Function (28): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), RNA polymerase II core promoter sequence-specific DNA binding (GO:0000979), core promoter sequence-specific DNA binding (GO:0001046), transcription corepressor binding (GO:0001222), p53 binding (GO:0002039), transcription corepressor activity (GO:0003714), histone deacetylase activity (GO:0004407), enzyme binding (GO:0019899), protein lysine deacetylase activity (GO:0033558), Krueppel-associated box domain binding (GO:0035851), histone deacetylase binding (GO:0042826), metal ion binding (GO:0046872), NF-kappaB binding (GO:0051059), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), E-box binding (GO:0070888), DNA-binding transcription factor binding (GO:0140297), histone deacetylase activity, hydrolytic mechanism (GO:0141221), histone decrotonylase activity (GO:0160009), protein lysine delactylase activity (GO:0160216), promoter-specific chromatin binding (GO:1990841), transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), chromatin binding (GO:0003682), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811), nucleosomal DNA binding (GO:0031492), protein decrotonylase activity (GO:0160008)

GO Cellular Component (13): histone deacetylase complex (GO:0000118), chromatin (GO:0000785), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), NuRD complex (GO:0016581), transcription repressor complex (GO:0017053), protein-containing complex (GO:0032991), neuronal cell body (GO:0043025), Sin3-type complex (GO:0070822), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
G0 and Early G1	2
TCF dependent signaling in response to WNT	2
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	2
Mitotic G1 phase and G1/S transition	1
p75 NTR receptor-mediated signalling	1
Signaling by NOTCH1	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Chromatin modifying enzymes	1
Generic Transcription Pathway	1
Positive epigenetic regulation of rRNA expression	1
Negative epigenetic regulation of rRNA expression	1
SUMO E3 ligases SUMOylate target proteins	1
Degradation of beta-catenin by the destruction complex	1
Regulation of TP53 Activity	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of gene expression	3
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
gene expression	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
protein binding	2
histone modifying activity	2
catalytic activity, acting on a protein	2
chromatin	2
histone deacetylase complex	2
transcription regulator complex	2
regulation of transcription by RNA polymerase II	1
cellular component organization	1
chromatin organization	1
constitutive heterochromatin formation	1
regulation of DNA-templated transcription	1
tissue development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
epidermis development	1
epithelial cell differentiation	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
pallium development	1
limbic system development	1
anatomical structure development	1
cell differentiation	1
generation of neurons	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1

Protein interactions and networks

STRING

6794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDAC1	RCOR1	Q9UKL0	998
HDAC1	DNMT1	P26358	998
HDAC1	RBBP4	P31149	998
HDAC1	KDM1A	O60341	998
HDAC1	SIN3A	Q96ST3	998
HDAC1	NCOR1	O75376	997
HDAC1	SAP30	O75446	997
HDAC1	RBBP7	Q16576	997
HDAC1	EZH2	Q15910	996
HDAC1	MTA1	Q13330	996
HDAC1	SAP18	O00422	996
HDAC1	SIN3B	O75182	996
HDAC1	MECP2	P51608	996
HDAC1	CHD4	Q14839	996
HDAC1	EHMT2	Q96KQ7	996
HDAC1	SUDS3	Q9H7L9	996
HDAC1	NCOR2	Q9Y618	996

IntAct

567 interactions, top by confidence:

A	B	Type	Score
RB1	HDAC1	psi-mi:“MI:0914”(association)	0.960
RB1	HDAC1	psi-mi:“MI:0915”(physical association)	0.960
HDAC1	RB1	psi-mi:“MI:0914”(association)	0.960
RB1	HDAC1	psi-mi:“MI:0407”(direct interaction)	0.960
HDAC1	RB1	psi-mi:“MI:2364”(proximity)	0.960
HDAC1	RCOR1	psi-mi:“MI:0915”(physical association)	0.950
HDAC1	HDAC2	psi-mi:“MI:0915”(physical association)	0.950
HDAC1	MTA2	psi-mi:“MI:0915”(physical association)	0.950
MTA1	HDAC1	psi-mi:“MI:0915”(physical association)	0.940
HDAC1	SIN3A	psi-mi:“MI:0915”(physical association)	0.930
CHD4	HDAC1	psi-mi:“MI:0403”(colocalization)	0.930
HDAC1	RBBP4	psi-mi:“MI:0914”(association)	0.920
MBD3	HDAC1	psi-mi:“MI:0915”(physical association)	0.910
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
CHD3	HDAC1	psi-mi:“MI:0403”(colocalization)	0.850
RYBP	BMI1	psi-mi:“MI:0914”(association)	0.850
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
BRMS1	HDAC1	psi-mi:“MI:0915”(physical association)	0.830
HDAC1	BRMS1	psi-mi:“MI:0915”(physical association)	0.830

BioGRID (2918): HDAC1 (Affinity Capture-Western), HDAC1 (Affinity Capture-Western), HDAC1 (Affinity Capture-Western), HDAC1 (Affinity Capture-Western), CUL4B (Affinity Capture-Western), DDB1 (Affinity Capture-Western), HDAC1 (Co-fractionation), HDAC1 (Affinity Capture-MS), SIN3A (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), CHFR (Affinity Capture-Western), HDAC1 (Biochemical Activity), HDAC1 (Affinity Capture-Western), DDIT3 (Affinity Capture-Western), HDAC1 (Reconstituted Complex)

ESM2 similar proteins: A0A0K0JFP3, O09106, O13298, O13648, O15379, O17695, O22446, O42227, O59702, O74429, O88895, P32561, P53096, P53973, P56517, P56518, P56519, P56520, P56521, P56523, P70288, Q09440, Q13547, Q20296, Q28DV3, Q32PJ8, Q4QQW4, Q4SFA0, Q55BW2, Q55FN5, Q5RAG0, Q5RB76, Q61E36, Q6IRL9, Q6P6W3, Q6YV04, Q7Y0Y6, Q7Y0Y8, Q803C3, Q8H0W2

Diamond homologs: B1H369, B1WC68, O09106, O13298, O15379, O17695, O22446, O30107, O42227, O59702, O88895, P32561, P39067, P53096, P56517, P56518, P56519, P56520, P56521, P56524, P70288, P83038, Q02959, Q09440, Q0VCB2, Q12214, Q13547, Q28DV3, Q32PJ8, Q3JUN4, Q4QQW4, Q4SFA0, Q54X15, Q55BW2, Q55FN5, Q5R902, Q5RAG0, Q5RB76, Q6GPA7, Q6IRL9

SIGNOR signaling

82 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	HDAC1	phosphorylation
HDAC1	down-regulates	MYOD1	binding
BCL3	up-regulates	HDAC1	binding
HDAC1	up-regulates	CCND1	binding
HDAC1	“down-regulates quantity by repression”	CEBPA	“transcriptional regulation”
PPARG	down-regulates	HDAC1	relocalization
HDAC1	down-regulates	RELA	binding
DDX5	up-regulates	HDAC1	binding
“N-[4-[(hydroxyamino)-oxomethyl]phenyl]carbamic acid [6-(diethylaminomethyl)-2-naphthalenyl]methyl ester”	down-regulates	HDAC1	“chemical inhibition”
CUDC-907	down-regulates	HDAC1	“chemical inhibition”
entinostat	down-regulates	HDAC1	“chemical inhibition”
N-hydroxy-2-[4-[[(1-methyl-3-indolyl)methylamino]methyl]-1-piperidinyl]-5-pyrimidinecarboxamide	down-regulates	HDAC1	“chemical inhibition”
N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide	down-regulates	HDAC1	“chemical inhibition”
E2F1	up-regulates	HDAC1	binding
HDAC1	“form complex”	SMAD7/HDAC1/E2F-1	binding
HDAC3	up-regulates	HDAC1	binding
3-[(dimethylamino)methyl]-N-[2-[4-[(hydroxyamino)-oxomethyl]phenoxy]ethyl]-2-benzofurancarboxamide	down-regulates	HDAC1	“chemical inhibition”
HDAC1	up-regulates	FLI1	deacetylation
HDAC1	down-regulates	CEBPA	“transcriptional regulation”
HDAC1	down-regulates	NfKb-p65/p50	binding
HDAC1	“form complex”	“CoREST-HDAC complex”	binding
TFAP4	“up-regulates activity”	HDAC1	binding
SMARCAD1	“up-regulates activity”	HDAC1	binding
CSNK2A2	“up-regulates activity”	HDAC1	phosphorylation
NKX3-1	“down-regulates activity”	HDAC1	binding
BCOR	“up-regulates activity”	HDAC1	binding
HDAC1	“down-regulates quantity by repression”	DNMT1	“transcriptional regulation”
HDAC1	“down-regulates quantity by repression”	ESR1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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
Regulation of TP53 Activity through Acetylation	12	53.2×	1e-16
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	11	40.6×	7e-14
Regulation of PTEN gene transcription	22	38.1×	4e-27
Transcriptional Regulation by E2F6	11	31.3×	1e-12
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	20	28.4×	5e-22
HDACs deacetylate histones	23	26.8×	8e-25
RNA Polymerase I Transcription Initiation	12	26.1×	1e-12
PTEN Regulation	10	22.2×	8e-10

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	11	67.4×	3e-16
negative regulation of stem cell population maintenance	8	49.0×	3e-10
negative regulation of gene expression via chromosomal CpG island methylation	5	42.1×	8e-06
DNA methylation-dependent constitutive heterochromatin formation	6	26.1×	8e-06
positive regulation of stem cell population maintenance	9	24.8×	1e-08
protein localization to chromatin	5	23.2×	1e-04
chromatin remodeling	31	18.1×	7e-28
circadian regulation of gene expression	8	15.0×	6e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	31
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
208751	NM_004964.3(HDAC1):c.461A>G (p.Asn154Ser)	Likely pathogenic

SpliceAI

2176 predictions. Top by Δscore:

Variant	Effect	Δscore
1:32292197:A:T	donor_gain	1.0000
1:32292215:GACG:G	donor_gain	1.0000
1:32292217:CGGT:C	donor_loss	1.0000
1:32292218:GGT:G	donor_loss	1.0000
1:32292219:G:GG	donor_gain	1.0000
1:32292219:G:T	donor_loss	1.0000
1:32292220:T:A	donor_loss	1.0000
1:32302619:AGGG:A	acceptor_gain	1.0000
1:32302620:GGGG:G	acceptor_gain	1.0000
1:32302734:G:GG	donor_gain	1.0000
1:32316655:T:TA	acceptor_gain	1.0000
1:32316662:TAGC:T	acceptor_loss	1.0000
1:32316663:A:AG	acceptor_gain	1.0000
1:32316663:AGC:A	acceptor_gain	1.0000
1:32316664:G:GA	acceptor_gain	1.0000
1:32316664:GC:G	acceptor_gain	1.0000
1:32316664:GCG:G	acceptor_gain	1.0000
1:32316664:GCGC:G	acceptor_gain	1.0000
1:32316664:GCGCC:G	acceptor_gain	1.0000
1:32316778:GAGAT:G	donor_gain	1.0000
1:32316779:AGAT:A	donor_gain	1.0000
1:32316779:AGATG:A	donor_loss	1.0000
1:32316780:GAT:G	donor_gain	1.0000
1:32316780:GATG:G	donor_gain	1.0000
1:32316781:AT:A	donor_gain	1.0000
1:32316783:G:GG	donor_gain	1.0000
1:32316783:GTAAG:G	donor_loss	1.0000
1:32316784:T:G	donor_loss	1.0000
1:32324476:A:AG	acceptor_gain	1.0000
1:32324477:A:G	acceptor_gain	1.0000

AlphaMissense

3217 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:32302629:G:A	G20R	1.000
1:32302629:G:C	G20R	1.000
1:32302630:G:A	G20E	1.000
1:32302630:G:T	G20V	1.000
1:32302641:T:C	Y24H	1.000
1:32302644:G:A	G25R	1.000
1:32302644:G:C	G25R	1.000
1:32302645:G:A	G25E	1.000
1:32302653:C:G	H28D	1.000
1:32302654:A:G	H28R	1.000
1:32302655:C:A	H28Q	1.000
1:32302655:C:G	H28Q	1.000
1:32302660:T:A	M30K	1.000
1:32302660:T:C	M30T	1.000
1:32302660:T:G	M30R	1.000
1:32302661:G:A	M30I	1.000
1:32302661:G:C	M30I	1.000
1:32302661:G:T	M30I	1.000
1:32302662:A:G	K31E	1.000
1:32302664:G:C	K31N	1.000
1:32302664:G:T	K31N	1.000
1:32302666:C:A	P32H	1.000
1:32302666:C:G	P32R	1.000
1:32302668:C:G	H33D	1.000
1:32302672:G:C	R34P	1.000
1:32302678:G:C	R36P	1.000
1:32302681:T:A	M37K	1.000
1:32302681:T:C	M37T	1.000
1:32302681:T:G	M37R	1.000
1:32302693:T:C	L41S	1.000

dbSNP variants (sampled 300 via entrez): RS1000005850 (1:32315064 T>C), RS1000043838 (1:32294024 C>CA), RS1000112357 (1:32322444 T>C,G), RS1000164454 (1:32308468 A>T), RS1000170130 (1:32296424 G>A), RS1000204115 (1:32332236 A>G), RS1000230321 (1:32328107 A>C), RS1000266721 (1:32315356 T>A,C), RS1000337342 (1:32301634 G>A), RS1000619193 (1:32303088 G>T), RS1000619725 (1:32308739 C>T), RS1000873378 (1:32296806 A>G), RS1000902347 (1:32308514 T>A,G), RS1000912348 (1:32308953 C>T), RS1001020965 (1:32290370 G>C)

Disease associations

OMIM: gene MIM:601241 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	Disputed	AD

Mondo (1): congenital heart disease (MONDO:0005453)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (17): CHEMBL2093865 (PROTEIN FAMILY), CHEMBL2111429 (PROTEIN FAMILY), CHEMBL3038483 (PROTEIN FAMILY), CHEMBL325 (SINGLE PROTEIN), CHEMBL3430896 (PROTEIN FAMILY), CHEMBL3430897 (PROTEIN FAMILY), CHEMBL3885589 (PROTEIN FAMILY), CHEMBL3885590 (PROTEIN COMPLEX), CHEMBL4106143 (PROTEIN COMPLEX), CHEMBL4106187 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

48 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 856,187 (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
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1469	PHENYLBUTANOIC ACID	4	37,081
CHEMBL1746	SODIUM PHENYLBUTYRATE	4	5,577
CHEMBL343448	ROMIDEPSIN	4	12,963
CHEMBL408513	BELINOSTAT	4	7,765
CHEMBL483254	PANOBINOSTAT	4	11,666
CHEMBL98	VORINOSTAT	4	50,361
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL109	VALPROIC ACID	4	65,937
CHEMBL1213492	GIVINOSTAT	4	2,827
CHEMBL1487	ATORVASTATIN	4	68,788
CHEMBL178	DAUNORUBICIN	4	203,756
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL329522	EXIFONE	4	1,547
CHEMBL487253	BENDAMUSTINE	4	30,877
CHEMBL503	LOVASTATIN	4	92,462
CHEMBL140	CURCUMIN	3	93,882
CHEMBL145	CAFFEIC ACID	3	36,305
CHEMBL1851943	PRACINOSTAT	3	1,998
CHEMBL235191	TACEDINALINE	3	2,950
CHEMBL27759	ENTINOSTAT	3
CHEMBL3621988	TUCIDINOSTAT	3
CHEMBL2103863	ABEXINOSTAT	3
CHEMBL1801250	NANATINOSTAT	2
CHEMBL191482	AR-42	2
CHEMBL284616	CHLOROGENIC ACID	2
CHEMBL356066	DACINOSTAT	2
CHEMBL3622533	FIMEPINOSTAT	2
CHEMBL1232461	MOLIBRESIB	2
CHEMBL14227	BUTYRIC ACID	2

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1741981	Efficacy	3	corticosteroids	Asthma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1741981	HDAC1	3	3.25	1	corticosteroids

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 3.5.1.- Histone deacetylases (HDACs)

Most potent curated ligand interactions (36 total), top 25:

Ligand	Action	Affinity	Parameter
romidepsin	Inhibition	11.82	pKi
apicidin	Inhibition	10.4	pKi
quisinostat	Inhibition	9.96	pIC50
compound 25ap [PMID: 37796543]	Inhibition	9.92	pIC50
trichostatin A	Inhibition	9.7	pKi
martinostat	Inhibition	9.52	pIC50
dacinostat	Inhibition	9.26	pKi
vorinostat	Inhibition	8.89	pKi
scriptaid	Inhibition	8.82	pKi
fimepinostat	Inhibition	8.77	pIC50
panobinostat	Inhibition	8.52	pEC50
CHR-3996	Inhibition	8.52	pIC50
CUDC-101	Inhibition	8.35	pIC50
abexinostat	Inhibition	8.15	pIC50
mocetinostat	Inhibition	8.05	pKi
givinostat	Inhibition	7.55	pEC50
RGFP109	Inhibition	7.49	pKi
citarinostat	Inhibition	7.46	pIC50
belinostat	Inhibition	7.39	pEC50
resminostat	Inhibition	7.37	pIC50
pracinostat	Inhibition	7.31	pIC50
ricolinostat	Inhibition	7.24	pIC50
ACY-738	Inhibition	7.03	pIC50
BML-281	Inhibition	7.0	pIC50
suprastat	Inhibition	6.93	pIC50

Binding affinities (BindingDB)

1653 measured of 2418 human assays (2422 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-N-((S)-1-(4-chloro-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-ethyl-6-azaspiro[2.5]octane-1-carboxamide	IC50	0.049 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-((S)-1-(4-chloro-2-(2-fluorophenyl)-1H-imidazol-5-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide	IC50	0.083 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
Quinolone-based HDAC inhibitor 4i	IC50	0.1 nM
(2S)-N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	IC50	0.1 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
2-(dimethylamino)-N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]acetamide	IC50	0.11 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-chloro-2-(2-fluorophenyl)-1H-imidazol-5-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.12 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-2-carboxamide	IC50	0.13 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.13 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-[(1S)-1-[4-chloro-2-(4-fluorophenyl)-1H-imidazol-5-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-(dimethylamino)acetamide	IC50	0.14 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(1S)-6-ethyl-N-{(1S)-1-[5-(2- fluorophenyl)isoxazol-3-yl]-7- isoxazol-3-yl-7-oxoheptyl}-6- azaspiro[2.5]octane-1- carboxamide	IC50	0.14 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-((S)-1-(4-chloro-5-(4- fluorophenyl)-1H-imidazol-2-yl)-7- (isoxazol-3-yl)-7-oxoheptyl)-6- methyl-6-azaspiro[2.5]octane-1- carboxamide 2,3- dihydroxysuccinate	IC50	0.14 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	IC50	0.16 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-((S)-1-(4-cyano-2-(4- fluorophenyl)-1H-imidazol-5- yl)-7-(oxazol-2-yl)-7- oxoheptyl)-6-methyl-6- azaspiro[2.5]octane-1- carboxamide	IC50	0.16 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
2-(dimethylamino)-N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]acetamide	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-((S)-7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-chloro-5-(4- fluorophenyl)-1H-imidazol-2-yl)-7- (isoxazol-3-yl)-7-oxoheptyl)-1- methylazetidine-3-carboxamide 2,3-dihydroxysuccinate	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-cyano-2-(4- fluorophenyl)-1H-imidazol-5- yl)-7-(oxazol-2-yl)-7- oxoheptyl)thiazole-5- carboxamide	IC50	0.19 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(E)-N-hydroxy-3-[4-[[2-(1-methylindol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide	IC50	0.2 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
1-methyl-N-[(1S)-1-[5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]azetidine-3-carboxamide	IC50	0.2 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-(1-(5-(2-fluorophenyl)oxazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.2 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-chloro-5-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-2-(dimethylamino)acetamide	IC50	0.2 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-chloro-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)thiazole-5-carboxamide	IC50	0.22 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	IC50	0.23 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(2S)-6-methyl-N-[(1S)-1-[5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-6-azaspiro[2.5]octane-2-carboxamide	IC50	0.24 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(7-(isoxazol-3-yl)-1-(5-(7-methoxy-1-methyl-2-oxo-1,2-dihydroquinolin-6-yl)-1H-imidazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.24 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
2-(dimethylamino)-N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]propanamide	IC50	0.25 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-(4-fluorophenyl)- 1H-imidazol-2-yl)-7-(oxazol-2- yl)-7-oxoheptyl)-1- methylpiperidine-4- carboxamide	IC50	0.26 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-2-(dimethylamino)-N-(1-(5-(2-ethyl-7-methoxy-1-oxo-1,2-dihydroisoquinolin-6-yl)-1H-imidazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)acetamide	IC50	0.26 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-cyano-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-2-(dimethylamino)acetamide	IC50	0.28 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(E)-3-[4-[[1-adamantylmethyl(methyl)amino]methyl]phenyl]-N-hydroxyprop-2-enamide	IC50	0.3 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
4-(dimethylamino)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]butanamide	IC50	0.3 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.3 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-methylpiperidine-4-carboxamide	IC50	0.34 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-(4-fluorophenyl)- 1H-imidazol-2-yl)-7-(oxazol-2- yl)-7-oxoheptyl)thiazole-5- carboxamide	IC50	0.37 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
2-(dimethylamino)-N-[(1S)-1-[5-(7-methoxy-1-methyl-2-oxoquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]acetamide	IC50	0.37 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
2-(azetidin-1-yl)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]acetamide	IC50	0.38 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
2-(dimethylamino)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]acetamide	IC50	0.39 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
2-(dimethylamino)-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]acetamide	IC50	0.4 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-((S)-1-(5-(7-methoxy-2-methylquinolin-6-yl)oxazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide	IC50	0.41 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(2-(5-(2-fluorophenyl)-1H-imidazol-2-yl)-8-(isoxazol-3-yl)-8-oxooctan-2-yl)-1-methylazetidine-3-carboxamide	IC50	0.41 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(5-(7-methoxy-2-methylquinolin-6-yl)oxazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.45 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
8-[4-amino-3-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]-N-hydroxyoctanamide	IC50	0.47 nM	US-9695181: Hydroximic acid derivatives and medical applications therof
(S)-6-(2-(1-amino-7-(isoxazol-3-yl)-7-oxoheptyl)-1H-imidazol-4-yl)-1-methylquinolin-2(1H)-one	IC50	0.51 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-2-(dimethylamino)-N-(1-(5-(2-ethyl-7-methoxy-1-oxo-1,2-dihydroisoquinolin-6-yl)-1H-imidazol-2-yl)-7-(oxazol-2-yl)-7-oxoheptyl)acetamide	IC50	0.51 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
1-(dimethylamino)-N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]cyclobutane-1-carboxamide	IC50	0.54 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
2,2,2-trifluoro-N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]acetamide	IC50	0.55 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-pyrrolidin-1-ylacetamide	IC50	0.56 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-6-ethyl-N-((S)-2-(5-(2-fluorophenyl)-1H-imidazol-2-yl)-8-(isoxazol-3-yl)-8-oxooctan-2-yl)-6-azaspiro[2.5]octane-1-carboxamide	IC50	0.56 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL114184
10.52	Ki	0.03	nM	QUISINOSTAT
10.40	Ki	0.04	nM	APICIDIN
10.30	IC50	0.05	nM	CHEMBL4861467
10.25	Ki	0.056	nM	CHEMBL4250302
10.24	Ki	0.057	nM	CHEMBL4239232
10.21	IC50	0.062	nM	CHEMBL432618
10.20	Ki	0.063	nM	CHEMBL4237636
10.12	Ki	0.075	nM	CHEMBL4237803
10.10	IC50	0.08	nM	CHEMBL4641682
10.09	IC50	0.082	nM	CHEMBL321689
10.09	IC50	0.082	nM	CHEMBL6133082
10.07	IC50	0.085	nM	CHEMBL4649205
10.01	Ki	0.097	nM	CHEMBL4251203
10.00	IC50	0.1	nM	CHEMBL4641682
10.00	IC50	0.1	nM	QUISINOSTAT
9.98	IC50	0.105	nM	CHEMBL6145619
9.96	IC50	0.109	nM	CHEMBL432243
9.96	IC50	0.11	nM	CHEMBL113303
9.96	IC50	0.11	nM	QUISINOSTAT
9.96	IC50	0.11	nM	CHEMBL4568666
9.96	IC50	0.11	nM	CHEMBL4644038
9.96	IC50	0.11	nM	CHEMBL4876610
9.96	IC50	0.11	nM	CHEMBL4878197
9.96	IC50	0.11	nM	TRAPOXIN B
9.94	IC50	0.116	nM	CHEMBL6169315
9.92	IC50	0.12	nM	FR-135313
9.90	IC50	0.125	nM	CHEMBL6174035
9.85	IC50	0.142	nM	CHEMBL5618643
9.82	Ki	0.15	nM	CHEMBL4246561
9.82	IC50	0.15	nM	CHEMBL4438063
9.82	IC50	0.15	nM	TRICHOSTATIN
9.80	IC50	0.16	nM	CHEMBL4637689
9.80	IC50	0.16	nM	DOMATINOSTAT
9.77	IC50	0.17	nM	CHEMBL4862152
9.77	IC50	0.17	nM	CHEMBL5433552
9.72	IC50	0.19	nM	CHEMBL4532398
9.72	IC50	0.19	nM	CHEMBL4642518
9.70	IC50	0.2	nM	CHEMBL2047701
9.70	IC50	0.2	nM	ROMIDEPSIN
9.70	IC50	0.2	nM	CHEMBL3126833
9.70	IC50	0.2	nM	CHEMBL3317812
9.70	Ki	0.2	nM	TRICHOSTATIN
9.70	IC50	0.2	nM	CHEMBL2371007
9.70	IC50	0.2	nM	CHEMBL4634501
9.70	IC50	0.2	nM	CHEMBL4746782
9.70	IC50	0.2	nM	CHEMBL4780309
9.70	IC50	0.2	nM	ENTINOSTAT
9.70	IC50	0.2	nM	CHEMBL4860000
9.70	IC50	0.2	nM	CHEMBL5288006

PubChem BioAssay actives

3185 with measured affinity, of 6100 total; 50 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
N-hydroxy-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide	1236442: Inhibition of human HDAC1	ki	<0.0001	uM
N-hydroxy-2-[4-(4-methylphenyl)sulfonylpiperazin-1-yl]-1,3-thiazole-5-carboxamide	1941741: Inhibition of HDAC (unknown origin)	ic50	0.0001	uM
1-[5-(hydroxyamino)-5-oxopentyl]-N-(4-methyl-1,3-thiazol-2-yl)-4-oxoquinoline-3-carboxamide	1794854: HDAC Activity screening from Article 10.3109/14756366.2013.827675: “Quinolone-based HDAC inhibitors.”	ic50	0.0001	uM
N-hydroxy-6-[[2-(4-methylanilino)-3,4-dioxocyclobuten-1-yl]amino]heptanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0001	uM
(6R)-6-[[3,4-dioxo-2-[[2-(trifluoromethyl)-1H-indol-6-yl]amino]cyclobuten-1-yl]amino]-N-hydroxyheptanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0001	uM
N-hydroxy-6-[[2-(4-methoxyanilino)-3,4-dioxocyclobuten-1-yl]amino]hexanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0001	uM
N-hydroxy-6-[[2-(4-methylanilino)-3,4-dioxocyclobuten-1-yl]amino]hexanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0001	uM
N-hydroxy-6-[[2-(4-methoxyanilino)-3,4-dioxocyclobuten-1-yl]amino]-6-methylheptanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0001	uM
N-hydroxy-5-[1-[[2-(4-methoxyanilino)-3,4-dioxocyclobuten-1-yl]amino]cyclobutyl]pentanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0001	uM
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	1664940: Inhibition of full length human recombinant FLAG-tagged HDAC1 expressed in HEK293F cells using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay	ic50	0.0001	uM
(2S)-6-(cyclopropylmethyl)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1662500: Inhibition of HDAC1 (unknown origin)	ic50	0.0001	uM
(2S)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-propan-2-yl-6-azaspiro[2.5]octane-2-carboxamide	1662500: Inhibition of HDAC1 (unknown origin)	ic50	0.0001	uM
(3S,6S)-6-(6-oxooctyl)-21-oxa-5,8,18,25,32-pentazahexacyclo[23.2.2.17,10.111,15.114,18.01,3]dotriaconta-7,9,11(31),12,14,16-hexaene-4,30-dione	1754652: Inhibition of HDAC1 (unknown origin)	ic50	0.0001	uM
(3S,6S)-12-methoxy-6-(6-oxooctyl)-5,8,18,27,34-pentazahexacyclo[25.2.2.17,10.111,15.114,18.01,3]tetratriaconta-7,9,11,13,15(33),16-hexaene-4,32-dione	1754652: Inhibition of HDAC1 (unknown origin)	ic50	0.0001	uM
(3S,9S,12R)-3-benzyl-6,6-dimethyl-9-[6-(oxiran-2-yl)-6-oxohexyl]-1,4,7,10-tetrazabicyclo[10.3.0]pentadecane-2,5,11-trione	1622972: Inhibition of HDAC1 (unknown origin)	ic50	0.0001	uM
(5R,8S,11S)-8-(1H-imidazol-5-ylmethyl)-5-methyl-11-[(E)-4-sulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione	1185952: Inhibition of HDAC1 (unknown origin) incubated at 37 degC for 30 mins	ic50	0.0002	uM
(5R,8S,11S)-8-[(4-hydroxyphenyl)methyl]-5-methyl-11-[(E)-4-sulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione	1185952: Inhibition of HDAC1 (unknown origin) incubated at 37 degC for 30 mins	ic50	0.0002	uM
(2R)-N-[4-[1-[7-(hydroxyamino)-7-oxoheptyl]-4-morpholin-4-ylpyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-2-methylmorpholine-4-carboxamide	1614126: Inhibition of recombinant full length HDAC1 (unknown origin) using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by fluorescence assay	ic50	0.0002	uM
6-[[3,4-dioxo-2-[4-(trifluoromethyl)anilino]cyclobuten-1-yl]amino]-N-hydroxyhexanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0002	uM
N-[(1S)-1-[5-(2-fluorophenyl)-1,3-oxazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	1664940: Inhibition of full length human recombinant FLAG-tagged HDAC1 expressed in HEK293F cells using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay	ic50	0.0002	uM
(2S)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1662500: Inhibition of HDAC1 (unknown origin)	ic50	0.0002	uM
(3S,6S)-6-(6-oxooctyl)-5,8,18,27,34-pentazahexacyclo[25.2.2.17,10.111,15.114,18.01,3]tetratriaconta-7,9,11(33),12,14,16-hexaene-4,32-dione	1754652: Inhibition of HDAC1 (unknown origin)	ic50	0.0002	uM
7-[6-(4-aminophenyl)-4-morpholin-4-ylpyrazolo[5,4-d]pyrimidin-1-yl]-N-hydroxyheptanamide	1614126: Inhibition of recombinant full length HDAC1 (unknown origin) using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by fluorescence assay	ic50	0.0002	uM
(5R,8S,11S)-8-benzyl-5-methyl-11-[(E)-4-sulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione	1185952: Inhibition of HDAC1 (unknown origin) incubated at 37 degC for 30 mins	ic50	0.0003	uM
(5R,8S,11S)-5-methyl-11-[(E)-4-[[(E)-4-[(5R,8S,11S)-5-methyl-6,9,13-trioxo-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-11-yl]but-3-enyl]disulfanyl]but-1-enyl]-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione	1188977: Inhibition of HDAC1 (unknown origin) incubated for 30 mins in presence of BSA and DTT by fluorescence assay	ic50	0.0003	uM
6-[[3,4-dioxo-2-[4-(trifluoromethyl)anilino]cyclobuten-1-yl]amino]-N-hydroxy-6-methylheptanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0003	uM
6-[[3,4-dioxo-2-[4-(trifluoromethyl)anilino]cyclobuten-1-yl]amino]-N-hydroxyheptanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0003	uM
N-hydroxy-6-[[2-(4-methoxyanilino)-3,4-dioxocyclobuten-1-yl]amino]heptanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0003	uM
6-[(2-anilino-3,4-dioxocyclobuten-1-yl)amino]-N-hydroxyhexanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0003	uM
N-hydroxy-6-[[2-[(2-methyl-1H-indol-6-yl)amino]-3,4-dioxocyclobuten-1-yl]amino]hexanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0003	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916027: Inhibition of recombinant human HDAC1 using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-6-methyl-N-[(1S)-1-[5-(2-methyl-1-oxoisoquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1754652: Inhibition of HDAC1 (unknown origin)	ic50	0.0003	uM
(2S)-6-cyclobutyl-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916027: Inhibition of recombinant human HDAC1 using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(7-ethyl-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916027: Inhibition of recombinant human HDAC1 using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1,3-oxazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916027: Inhibition of recombinant human HDAC1 using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(3S,6S)-6-(6-oxooctyl)-22-oxa-5,8,18,26,33-pentazahexacyclo[24.2.2.17,10.111,15.114,18.01,3]tritriaconta-7,9,11(32),12,14,16-hexaene-4,31-dione	1754652: Inhibition of HDAC1 (unknown origin)	ic50	0.0003	uM
tert-butyl (2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[[(E)-4-[(5R,8S,11S)-5-methyl-6,9,13-trioxo-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-11-yl]but-3-enyl]disulfanyl]propanoate	1188977: Inhibition of HDAC1 (unknown origin) incubated for 30 mins in presence of BSA and DTT by fluorescence assay	ic50	0.0004	uM
N-hydroxy-2-[[2-(4-methoxyphenyl)-9-methyl-6-morpholin-4-ylpurin-8-yl]methyl-methylamino]pyrimidine-5-carboxamide	1312847: Inhibition of full length C-terminal His/FLAG-tagged human recombinant HDAC1 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0004	uM
(3S,6R,9S,12R)-6,9-dimethyl-3-[6-[(2S)-oxiran-2-yl]-6-oxohexyl]-1,4,7,10-tetrazabicyclo[10.3.0]pentadecane-2,5,8,11-tetrone	1972856: Binding affinity to HDAC1 (unknown origin) assessed as inhibition constant(ki,1)	ki	0.0004	uM
N-hydroxy-6-[[2-(3-methylanilino)-3,4-dioxocyclobuten-1-yl]amino]hexanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0004	uM
7-[2-(4-fluoro-3-hydroxyphenyl)-6-morpholin-4-ylpurin-9-yl]-N-hydroxyheptanamide	1702055: Inhibition of HDAC1 in human HeLa nuclear extract using Boc-Lys(Ac)-AMC as substrate measured after 2 hrs by fluorescence based assay	ic50	0.0005	uM
N-hydroxy-2-[methyl-[(9-methyl-6-morpholin-4-yl-2-pyridin-3-ylpurin-8-yl)methyl]amino]pyrimidine-5-carboxamide	1312847: Inhibition of full length C-terminal His/FLAG-tagged human recombinant HDAC1 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0005	uM
7-cyclopentyl-2-[4-[[6-(hydroxyamino)-6-oxohexyl]carbamoyl]anilino]-N,N-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide	1469380: Inhibition of HDAC1 (unknown origin)	ic50	0.0005	uM
6-[[3,4-dioxo-2-[4-(trifluoromethyl)anilino]cyclobuten-1-yl]amino]-N-hydroxyoctanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0005	uM
6-[[2-[4-(dimethylamino)-3-methoxyanilino]-3,4-dioxocyclobuten-1-yl]amino]-N-hydroxyhexanamide	1399812: Inhibition of human recombinant HDAC1 using Fluor de Lys as substrate after 2 hrs by fluorescence method	ki	0.0005	uM
(5R,8S,11S)-11-[(Z)-2-fluoro-4-sulfanylbut-1-enyl]-5-methyl-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione	1566037: Inhibition of recombinant full length C-terminal FLAG/His-tagged human HDAC1 expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay	ic50	0.0005	uM
4-[9-[7-(hydroxyamino)-7-oxoheptyl]-6-morpholin-4-ylpurin-2-yl]benzamide	1702055: Inhibition of HDAC1 in human HeLa nuclear extract using Boc-Lys(Ac)-AMC as substrate measured after 2 hrs by fluorescence based assay	ic50	0.0006	uM
tert-butyl 4-[[(5R,8S,11S)-5-methyl-6,9,13-trioxo-11-[(E)-4-sulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-8-yl]methyl]imidazole-1-carboxylate	1185952: Inhibition of HDAC1 (unknown origin) incubated at 37 degC for 30 mins	ic50	0.0006	uM
N-hydroxy-2-[[2-(3-hydroxyphenyl)-9-methyl-6-morpholin-4-ylpurin-8-yl]methyl-methylamino]pyrimidine-5-carboxamide	1312847: Inhibition of full length C-terminal His/FLAG-tagged human recombinant HDAC1 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0006	uM
2-[[2-(4-aminophenyl)-9-methyl-6-morpholin-4-ylpurin-8-yl]methyl-methylamino]-N-hydroxypyrimidine-5-carboxamide	1312847: Inhibition of full length C-terminal His/FLAG-tagged human recombinant HDAC1 expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression, decreases activity, decreases methylation (+1 more)	7
trichostatin A	decreases activity, decreases expression, decreases reaction, increases expression	6
Estradiol	affects cotreatment, decreases reaction, increases expression, affects binding, increases reaction (+1 more)	5
sodium arsenite	affects expression, decreases reaction, increases expression, decreases expression	4
Curcumin	affects localization, decreases reaction, decreases expression	4
Resveratrol	increases reaction, affects binding, decreases reaction, increases acetylation, increases activity (+1 more)	3
Decitabine	affects binding, decreases reaction	3
Arsenic Trioxide	decreases expression, increases phosphorylation, affects binding, affects cotreatment, increases reaction	3
Vorinostat	decreases reaction, increases expression, decreases activity, decreases expression	3
bisphenol A	affects expression, affects splicing	2
hydroquinone	increases expression, decreases reaction	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects localization, decreases reaction, decreases expression, increases degradation	2
Doxorubicin	affects binding, increases reaction, decreases expression	2
Hydrogen Peroxide	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression, affects binding, increases reaction, affects cotreatment, decreases reaction	2
Theophylline	increases activity, increases expression	2
Cyclosporine	decreases expression	2
Genistein	affects binding, increases reaction, decreases expression, decreases reaction	2
Butyric Acid	increases expression, affects binding, decreases reaction	2
Particulate Matter	decreases expression, increases abundance, decreases reaction, increases degradation, increases expression	2
FR900359	affects phosphorylation	1
napabucasin	decreases expression	1
TAK-243	decreases sumoylation	1
2,4,6-tribromophenol	increases expression	1
honokiol	affects binding, decreases activity	1
benzo(b)fluoranthene	decreases expression	1
chlamydocin	decreases activity	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
withaferin A	decreases expression	1
decabromobiphenyl ether	increases expression	1

ChEMBL screening assays

3675 unique, capped per target: 3604 binding, 57 admet, 13 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003756	Binding	Inhibition of HDAC in human NB4 cells assessed as induction of histone H3 acetylation after 6 hrs by Western blot analysis	Design, synthesis and preliminary biological evaluation of new hydroxamate histone deacetylase inhibitors as potential antileukemic agents. — Bioorg Med Chem Lett
CHEMBL4346553	ADMET	Inhibition of HDAC in HUVEC using Boc-Lys(Ac)-AMC as substrate preincubated for 12 hrs followed by substrate addition and measured after 4 hrs by fluorimetry	Discovery of Novel Fungal Lanosterol 14α-Demethylase (CYP51)/Histone Deacetylase Dual Inhibitors to Treat Azole-Resistant Candidiasis. — J Med Chem
CHEMBL5049470	Functional	In vivo inhibition of HDAC in HEL cells xenografted in BALB/C mouse assessed as upregulation of caspase-9 levels at 5 to 10 mg/kg by immunohistochemical staining method	Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy. — J Med Chem

Cellosaurus cell lines

15 cell lines: 11 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2L7	SEES3-1V human HDAC1, clone1	Embryonic stem cell	Male
CVCL_A2L8	SEES3-1V human HDAC1, clone2	Embryonic stem cell	Male
CVCL_A2L9	SEES3-1V human HDAC1, clone3	Embryonic stem cell	Male
CVCL_B8H6	Abcam HCT 116 HDAC1 KO	Cancer cell line	Male
CVCL_B8WJ	Abcam MCF-7 HDAC1 KO	Cancer cell line	Female
CVCL_B9JG	Abcam A-549 HDAC1 KO	Cancer cell line	Male
CVCL_D7R4	Ubigene A-549 HDAC1 KO	Cancer cell line	Male
CVCL_D8MA	Ubigene HCT 116 HDAC1 KO	Cancer cell line	Male
CVCL_D9G3	Ubigene HEK293 HDAC1 KO	Transformed cell line	Female
CVCL_E0E6	Ubigene HeLa HDAC1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE