HDAC2

Summary

HDAC2 (histone deacetylase 2, HGNC:4853) is a protein-coding gene on chromosome 6q21, encoding Histone deacetylase 2 (Q92769). Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

This gene product belongs to the histone deacetylase family. Histone deacetylases act via the formation of large multiprotein complexes, and are responsible for the deacetylation of lysine residues at the N-terminal regions of core histones (H2A, H2B, H3 and H4). This protein forms transcriptional repressor complexes by associating with many different proteins, including YY1, a mammalian zinc-finger transcription factor. Thus, it plays an important role in transcriptional regulation, cell cycle progression and developmental events. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3066 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 61 total
• Druggable target: yes — 41 molecules with ChEMBL bioactivity
• Transcription factor: yes — 28 downstream targets (CollecTRI)
• MANE Select transcript: NM_001527

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4853
Approved symbol	HDAC2
Name	histone deacetylase 2
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	RPD3, YAF1, KDAC2
Ensembl gene	ENSG00000196591
Ensembl biotype	protein_coding
OMIM	605164
Entrez	3066

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 23 protein_coding, 5 retained_intron

ENST00000368632, ENST00000425835, ENST00000518690, ENST00000518756, ENST00000519065, ENST00000519108, ENST00000520170, ENST00000520746, ENST00000520895, ENST00000521163, ENST00000521233, ENST00000521610, ENST00000522371, ENST00000523240, ENST00000523334, ENST00000523628, ENST00000524334, ENST00000869750, ENST00000869751, ENST00000869752, ENST00000916845, ENST00000916846, ENST00000916847, ENST00000916848, ENST00000916849, ENST00000916850, ENST00000916851, ENST00000952494

RefSeq mRNA: 1 — MANE Select: NM_001527 NM_001527

CCDS: CCDS43493

Canonical transcript exons

ENST00000519065 — 14 exons

Exon	Start	End
ENSE00000975531	113958649	113958766
ENSE00000975532	113956619	113956693
ENSE00001084361	113949168	113949260
ENSE00002092091	113933028	113941088
ENSE00002133903	113970857	113971148
ENSE00003497597	113944280	113944410
ENSE00003529625	113959906	113960018
ENSE00003533415	113943351	113943506
ENSE00003545171	113941708	113941765
ENSE00003565277	113953277	113953418
ENSE00003585974	113946008	113946148
ENSE00003665730	113956013	113956151
ENSE00003675004	113948979	113949087
ENSE00003675635	113945362	113945470

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.3119 / max 506.2534, expressed in 1824 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75222	81.7831	1823
75221	2.8869	1169
75224	1.7796	805
75225	0.4323	235
75223	0.4300	240

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.55	gold quality
cortical plate	UBERON:0005343	99.54	gold quality
embryo	UBERON:0000922	99.25	gold quality
ventricular zone	UBERON:0003053	99.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.72	gold quality
stromal cell of endometrium	CL:0002255	97.91	gold quality
adrenal tissue	UBERON:0018303	97.34	gold quality
right testis	UBERON:0004534	97.10	gold quality
islet of Langerhans	UBERON:0000006	96.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.84	gold quality
testis	UBERON:0000473	96.73	gold quality
left testis	UBERON:0004533	96.69	gold quality
rectum	UBERON:0001052	96.34	gold quality
right ovary	UBERON:0002118	96.23	gold quality
left ovary	UBERON:0002119	96.18	gold quality
endometrium	UBERON:0001295	96.15	gold quality
ovary	UBERON:0000992	96.10	gold quality
body of uterus	UBERON:0009853	95.97	gold quality
smooth muscle tissue	UBERON:0001135	95.93	gold quality
body of pancreas	UBERON:0001150	95.88	gold quality
left uterine tube	UBERON:0001303	95.85	gold quality
ectocervix	UBERON:0012249	95.85	gold quality
popliteal artery	UBERON:0002250	95.79	gold quality
tibial artery	UBERON:0007610	95.79	gold quality
endocervix	UBERON:0000458	95.76	gold quality
monocyte	CL:0000576	95.67	gold quality
pancreas	UBERON:0001264	95.59	gold quality
skin of abdomen	UBERON:0001416	95.55	gold quality
right coronary artery	UBERON:0001625	95.49	gold quality
aorta	UBERON:0000947	95.44	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	28.77
E-CURD-114	yes	8.70
E-MTAB-7303	no	474.39
E-GEOD-93593	no	7.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

28 targets.

Target	Regulation
ALOX5	Activation
APAF1	Repression
BMP7	Repression
CAD	Unknown
CCL2	Unknown
CCNE1	Repression
CD1D	Repression
CDH1	Repression
CDKN1A	Unknown
COL1A2	Repression
CXCL8	Repression
DELEC1	Unknown
DNMT1	Repression
GRM2	Unknown
HPGD	Repression
IGF1	Unknown
KLF4	Repression
MUC5AC	Repression
MYC	Unknown
MYCN	Unknown
PHB1	Repression
SNAI2	Repression
SP1	Repression
TGFBR2	Repression
TNFSF10	Repression
TP63	Unknown
TWIST1	Repression
VEGFA	Unknown

Upstream regulators (CollecTRI, top): HIF1A, MYC, MYCN, RFX5, SFPQ, TP53, YY1

miRNA regulators (miRDB)

185 targeting HDAC2, 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-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
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-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• Phosphatase inhibition leads to histone deacetylases 1 and 2 phosphorylation and disruption of corepressor interactions (PMID:11919195)
• Regulation by protein kinase CK2 (PMID:12082111)
• Data show that Daxx associates with proteins critical for transcriptional repression, such as histone deacetylase 2 and Dek, a chromatin-associated protein reported to change the topology of DNA in chromatin in vitro. (PMID:12140263)
• HDAC2 is phosphorylated by CK2 and recruited by Sp1 or Sp3 (PMID:12176973)
• The MLL repression domain specifically interacts with HDAC2. (PMID:12829790)
• IkappaBalpha regulates the transcriptional activity of homeodomain-containing proteins positively through cytoplasmic sequestration of HDAC1 and HDAC3 (PMID:12972430)
• HDAC2 binds to HoxA10 and has a role in repressing gene transcription in undifferentiated myeloid cells (PMID:14512427)
• 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)
• Increased HDAC2 expression is associated with colon cancer (PMID:15144953)
• PELP1 recruits HDAC2 and masks histones using two separate domains (PMID:15456770)
• involved in the early events of carcinogenesis, so candidate marker for tumor progression, target for cancer therapy (PMID:15665816)
• A rationale for targeting HIF-1 alpha with histone dacetylase inhibitors against class II isozymes as anticancer agents in renal carcinoma cells. (PMID:16951198)
• Brg1 and HDAC2 have roles in GR trans-repression of the pituitary POMC gene and misexpression in Cushing disease (PMID:17043312)
• Transgenic HDAC2 regulates expression of many fetal cardiac isoforms, including glycogen synthase kinase 3 beta. (PMID:17322895)
• High expression of HDAC2 is associated with cancer tissues (PMID:17786334)
• unmodified HDAC2 is associated with the coding region of transcribed genes, whereas phosphorylated HDAC2 is primarily recruited to promoters (PMID:17827154)
• CK2 may be a key mediator for HDAC1 and HDAC2 activation under hypoxia in tumor cells (PMID:17935135)
• we showed that the known effects of HDACs on differentiation and proliferation of cancer cells observed in vitro can also be confirmed in vivo. The class I HDAC isoforms 1, 2 and 3 are differentially expressed in prostate cancer. (PMID:18212746)
• HDAC2 mutations have a role in human tumorigenesis through the derepression of key genes from multiple cellular transformation pathways (PMID:18264134)
• depletion of HDAC2 results in simultaneous depletion of ER and PR, and potentiates the effects of antihormonal therapy in ER-positive cells (PMID:18316616)
• Strong prognostic impact of HDAC isoforms in colorectal cancer. (PMID:18347167)
• LPA enhances survival of cancer cells by increasing HDAC1 and HDAC2 activity and reducing histone acetylation (PMID:18408217)
• High expression of HDAC2 is more common in aggressive than indolent cutaneous T-cell lymphoma. (PMID:18671804)
• Recruitment of HDAC-1 and -2 by TNF-alpha, and a consequent deacetylation of histone H3 at the YKL-40 promoter occurs only in glioma cells. (PMID:18708058)
• Frequent HDAC2 mutations are found in MSI tumors and HDAC2 plays a major role in mediating apoptotic response to HDAC inhibitors through direct regulation of APAF1. (PMID:18834886)
• In HCT116 cells, HDAC2 was shown to localize to the APAF1 promoter, and siRNA-mediated down-regulation of HDAC2 induced APAF1 expression, suggesting HDAC2 directly represses APAF1 expression. (PMID:18851967)
• class I histone deacetylase (HDACs), specifically HDAC2, and the transcriptional repressor Snail play a central role in the suppression of 15-hydroxyprostaglandin dehydrogenase expression. (PMID:19010907)
• P/CAF deacetylation by HDAC3 and in a minor degree by HDAC1, HDAC2, or HDAC4 leads to cytoplasmic accumulation of P/CAF. (PMID:19015268)
• TSA treatment enhances the association of CIITA with the transcription factor RFX5, which ameliorates the down-regulation of CIITA recruitment to target promoters by HDAC2. (PMID:19041327)
• the TGFbeta pathway activation leads to recruitment of a KLF14-mSin3A-HDAC2 repressor complex to the TGFbetaRII promoter, as well as the remodeling of chromatin to increase histone marks that associate with transcriptional silencing. (PMID:19088080)
• findings show class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates (PMID:19099586)
• Transcription analysis and genome-wide histone modification studies on these mutants suggested that K36me2 is sufficient to target Rpd3S in vivo, thereby maintaining a functional Set2-Rpd3S pathway. (PMID:19155214)
• Reduced levels of HDAC2 was associated with breast cancer progression. (PMID:19383825)
• nitration of distinct tyrosine residues modifies both the expression and activity of HDAC2, having an impact on epigenetic regulation. (PMID:19410558)
• Reduced HDAC2 and HDAC2 activity, but not HDAC2 mRNA, is observed in cells deficient in CFTR. (PMID:19411311)
• deletion of a single HDAC is not sufficient to induce cell death, but HDAC1 and 2 play redundant and essential roles in tumor cell survival (PMID:19416910)
• HDAC2, is overexpressed in diffuse large B-cell lymphoma and peripheral T-cell lymphoma relative to normal lymphoid tissue (PMID:19438744)
• IL-8 and MCP-1 were differently regulated by hypoxia. (PMID:19446037)
• HDAC2 also plays an important role in cell proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (PMID:19531758)
• The data indicate that the carboxy-terminal domain serves a novel function within HDAC1 and HDAC2, to mediate repression of cartilage-specific gene expression in human chondrocytes. (PMID:19561124)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hdac2	ENSMUSG00000019777
rattus_norvegicus	Hdac2	ENSRNOG00000000604
drosophila_melanogaster	HDAC1	FBGN0015805
caenorhabditis_elegans		WBGENE00009657
caenorhabditis_elegans		WBGENE00009663
caenorhabditis_elegans		WBGENE00219378

Paralogs (10): HDAC9 (ENSG00000048052), HDAC7 (ENSG00000061273), HDAC4 (ENSG00000068024), HDAC6 (ENSG00000094631), HDAC10 (ENSG00000100429), HDAC5 (ENSG00000108840), HDAC1 (ENSG00000116478), HDAC8 (ENSG00000147099), HDAC11 (ENSG00000163517), HDAC3 (ENSG00000171720)

Protein

Protein identifiers

Histone deacetylase 2 — Q92769 (reviewed: Q92769)

Alternative names: Protein deacylase HDAC2

All UniProt accessions (10): Q92769, E5RFI6, E5RFP9, E5RG37, E5RGV4, E5RH52, E5RHE7, E5RJ04, E5RK19, H3BM24

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. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. 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. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Component of the SIN3B complex that represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2. Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A. In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, 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 RCOR/GFI/KDM1A/HDAC complex. Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Part of a complex containing the core histones H2A, H2B, H3 and H4, DEK and unphosphorylated DAXX. Part of a complex containing ATR and CHD4. Forms a heterologous complex at least with YY1. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 and HDAC2. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2. Component of a histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2. Forms a complex comprising APPL1, RUVBL2, APPL2, CTNNB1 and HDAC1. Interacts directly with GFI1. Interacts directly with GFI1B. Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with ATR. Interacts with BCL6 (non-acetylated form). Interacts with BEND3. Interacts with CBFA2T3. Interacts with CDK2AP1. Interacts with CHD4. Interacts with CHD5. Interacts with CHFR. Interacts with CRY1. Interacts with DNMT1. Interacts with GATAD2A. Interacts with HCFC1. Interacts with HDAC7. Interacts with HDAC10. Interacts with INSM1. Interacts with KDM4A. Interacts with MACROH2A1 (via the non-histone region). Interacts with MBD3L2. Interacts with MTA1, with a preference for sumoylated MTA1. Interacts with NACC2. Interacts with NRIP1. Interacts with PELP1. Interacts with PIMREG. Interacts with PRDM6. Interacts with PWWP2B. Interacts with SAP30. Interacts with SAP30L. Interacts with SETDB1. Interacts with SIX3. Interacts with SMARCAD1. Interacts with SNW1. Interacts with SPHK2. Interacts with SPEN/MINT. Interacts (CK2 phosphorylated form) with SP3. Interacts with SUV39H1. Interacts with TSHZ3 (via its N-terminus). Interacts with ZMYND8. Interacts with ZNF431. Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression. Identified in a complex with HDAC1, KCTD19, DNTTIP1 and ZNF541. Component of the SIN3B complex, which includes SIN3B, HDAC2, PHF12 and MORF4L1; interacts directly with all subunits.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed; lower levels in brain and lung.

Post-translational modifications. S-nitrosylated by GAPDH. In neurons, S-nitrosylation at Cys-262 and Cys-274 does not affect enzyme activity, but induces HDAC2 release from chromatin. This in turn increases acetylation of histones surrounding neurotrophin-dependent gene promoters and promotes their transcription. In embryonic cortical neurons, S-Nitrosylation regulates dendritic growth and branching.

Activity regulation. Inositol tetraphosphate (1D-myo-inositol 1,4,5,6-tetrakisphosphate) may act as an intermolecular glue between HDAC2 and N-Cor repressor complex components.

Cofactor. Binds 2 Ca(2+) ions per subunit.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q92769-1	1	yes
Q92769-3	2

RefSeq proteins (1): NP_001518* (*=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), 5 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)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] + H2O = 2-hydroxy-2-methylpropanoate + L-lysyl-[protein] (RHEA:69176)
• N(6)-[(S)-lactoyl]-L-lysyl-[protein] + H2O = (S)-lactate + L-lysyl-[protein] (RHEA:81387)

UniProt features (80 total): helix 17, binding site 15, strand 13, modified residue 8, cross-link 7, sequence conflict 5, turn 5, compositionally biased region 3, region of interest 2, sequence variant 2, chain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

48 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7KBG	X-RAY DIFFRACTION	1.26
6WBZ	X-RAY DIFFRACTION	1.32
6WBW	X-RAY DIFFRACTION	1.46
7LTL	X-RAY DIFFRACTION	1.49
6XEB	X-RAY DIFFRACTION	1.5
7ZZP	X-RAY DIFFRACTION	1.52
6WHN	X-RAY DIFFRACTION	1.54
7MOT	X-RAY DIFFRACTION	1.54
7MOZ	X-RAY DIFFRACTION	1.54
6XDM	X-RAY DIFFRACTION	1.56
7ZZT	X-RAY DIFFRACTION	1.56
4LY1	X-RAY DIFFRACTION	1.57
7LTK	X-RAY DIFFRACTION	1.59
9K0G	X-RAY DIFFRACTION	1.62
7JS8	X-RAY DIFFRACTION	1.63
5IWG	X-RAY DIFFRACTION	1.66
7MOX	X-RAY DIFFRACTION	1.69
6XEC	X-RAY DIFFRACTION	1.7
7MOS	X-RAY DIFFRACTION	1.7
5IX0	X-RAY DIFFRACTION	1.72
7ZZW	X-RAY DIFFRACTION	1.73
8A0B	X-RAY DIFFRACTION	1.75
7MOY	X-RAY DIFFRACTION	1.78
9JWJ	X-RAY DIFFRACTION	1.78
7LTG	X-RAY DIFFRACTION	1.8
9NTB	X-RAY DIFFRACTION	1.8
4LXZ	X-RAY DIFFRACTION	1.85
7ZZU	X-RAY DIFFRACTION	1.85
7ZZS	X-RAY DIFFRACTION	1.88
7ZZO	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92769-F1	86.01	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): 142

Ligand- & substrate-binding residues (15): 177; 177; 179; 179; 188; 191; 194; 198; 199; 223; 265; 271 …

Post-translational modifications (15): 75, 221, 262, 274, 394, 407, 422, 424, 75, 439, 452, 458, 462, 478, 481

Function

Pathways and Gene Ontology

Reactome pathways

26 pathways

ID	Pathway
R-HSA-193670	p75NTR negatively regulates cell cycle via SC1
R-HSA-2122947	NOTCH1 Intracellular Domain 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-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-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9022692	Regulation of MECP2 expression and activity
R-HSA-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9701898	STAT3 nuclear events downstream of ALK signaling
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 601 (showing top): GOBP_CIRCADIAN_RHYTHM, MORF_MTA1, GOBP_DENDRITE_DEVELOPMENT, PID_HDAC_CLASSI_PATHWAY, MORF_DNMT1, GOBP_NEGATIVE_REGULATION_OF_DENDRITIC_SPINE_DEVELOPMENT, REACTOME_SIGNALING_BY_NOTCH, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_BEHAVIOR, PID_TELOMERASE_PATHWAY, GOBP_RESPONSE_TO_COCAINE

GO Biological Process (51): negative regulation of transcription by RNA polymerase II (GO:0000122), response to amphetamine (GO:0001975), cardiac muscle hypertrophy (GO:0003300), chromatin remodeling (GO:0006338), positive regulation of cell population proliferation (GO:0008284), response to xenobiotic stimulus (GO:0009410), epidermal cell differentiation (GO:0009913), positive regulation of epithelial to mesenchymal transition (GO:0010718), obsolete negative regulation of transcription by competitive promoter binding (GO:0010944), negative regulation of neuron projection development (GO:0010977), dendrite development (GO:0016358), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), response to caffeine (GO:0031000), heterochromatin formation (GO:0031507), response to lipopolysaccharide (GO:0032496), positive regulation of interleukin-1 production (GO:0032732), positive regulation of tumor necrosis factor production (GO:0032760), circadian regulation of gene expression (GO:0032922), positive regulation of intracellular estrogen receptor signaling pathway (GO:0033148), cellular response to heat (GO:0034605), response to nicotine (GO:0035094), response to cocaine (GO:0042220), 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), positive regulation of proteolysis (GO:0045862), 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), behavioral response to ethanol (GO:0048149), positive regulation of oligodendrocyte differentiation (GO:0048714), progesterone receptor signaling pathway (GO:0050847), response to hyperoxia (GO:0055093), hair follicle placode formation (GO:0060789), negative regulation of dendritic spine development (GO:0061000), eyelid development in camera-type eye (GO:0061029), fungiform papilla formation (GO:0061198), cellular response to hydrogen peroxide (GO:0070301)

GO Molecular Function (23): transcription coregulator binding (GO:0001221), chromatin binding (GO:0003682), RNA binding (GO:0003723), histone deacetylase activity (GO:0004407), enzyme binding (GO:0019899), heat shock protein binding (GO:0031072), protein lysine deacetylase activity (GO:0033558), histone binding (GO:0042393), histone deacetylase binding (GO:0042826), NF-kappaB binding (GO:0051059), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), histone deacetylase activity, hydrolytic mechanism (GO:0141221), histone decrotonylase activity (GO:0160009), protein de-2-hydroxyisobutyrylase activity (GO:0160010), protein lysine delactylase activity (GO:0160216), promoter-specific chromatin binding (GO:1990841), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811), deacetylase activity (GO:0019213), nucleosomal DNA binding (GO:0031492), DNA-binding transcription factor binding (GO:0140297), protein decrotonylase activity (GO:0160008)

GO Cellular Component (11): histone deacetylase complex (GO:0000118), chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), NuRD complex (GO:0016581), protein-containing complex (GO:0032991), ESC/E(Z) complex (GO:0035098), Sin3-type complex (GO:0070822), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-19 pathways:

Category	Pathways
Transcriptional Regulation by MECP2	2
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
Regulation of TP53 Activity	1
RNA Polymerase I Promoter Clearance	1
PTEN Regulation	1
FOXO-mediated transcription	1
Nervous system development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	3
neuron projection development	2
binding	2
histone modifying activity	2
catalytic activity, acting on a protein	2
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	2
deacylase activity	2
histone deacetylase complex	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
response to amine	1
striated muscle hypertrophy	1
chromatin organization	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to chemical	1
epidermis development	1
epithelial cell differentiation	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
regulation of neuron projection development	1
negative regulation of cell projection organization	1
anatomical structure development	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
response to purine-containing compound	1
response to alkaloid	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1

Protein interactions and networks

STRING

5447 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDAC2	RCOR1	Q9UKL0	998
HDAC2	SAP30	O75446	997
HDAC2	DNMT1	P26358	997
HDAC2	RBBP4	P31149	997
HDAC2	RBBP7	Q16576	997
HDAC2	SIN3A	Q96ST3	997
HDAC2	KDM1A	O60341	997
HDAC2	MTA1	Q13330	995
HDAC2	SAP18	O00422	995
HDAC2	SUDS3	Q9H7L9	995
HDAC2	MECP2	P51608	994
HDAC2	CHD4	Q14839	994
HDAC2	MTA2	O94776	993
HDAC2	CHD3	Q12873	993
HDAC2	SIN3B	O75182	992

IntAct

387 interactions, top by confidence:

A	B	Type	Score
HDAC1	HDAC2	psi-mi:“MI:0915”(physical association)	0.950
NCOR2	HDAC3	psi-mi:“MI:0915”(physical association)	0.950
SUZ12	EED	psi-mi:“MI:0914”(association)	0.910
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
KDM1A	HDAC1	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
KDM1A	HDAC2	psi-mi:“MI:0914”(association)	0.890
HDAC2	SIN3A	psi-mi:“MI:0915”(physical association)	0.880
SIN3A	HDAC2	psi-mi:“MI:0407”(direct interaction)	0.880
DNTTIP1	HDAC1	psi-mi:“MI:0914”(association)	0.880
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
PLK1	SPAG9	psi-mi:“MI:0914”(association)	0.790
CHD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
GATAD2B	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
CTBP1	KDM1A	psi-mi:“MI:0914”(association)	0.790
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
CHD4	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
EHMT2	WIZ	psi-mi:“MI:0914”(association)	0.730
HDAC2	BRMS1	psi-mi:“MI:0915”(physical association)	0.720
BRMS1	HDAC2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (1752): HDAC2 (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), CUL4B (Affinity Capture-Western), DDB1 (Affinity Capture-Western), HDAC2 (Co-fractionation), HDAC2 (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), CHFR (Reconstituted Complex), DDX5 (Affinity Capture-Western), DDX17 (Affinity Capture-Western), HDAC2 (Affinity Capture-RNA), HDAC2 (Affinity Capture-RNA), HDAC2 (Affinity Capture-RNA)

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

51 interactions.

A	Effect	B	Mechanism
CCND1	up-regulates	HDAC2	binding
HDAC2	up-regulates	CCND1	binding
CSNK2A1	up-regulates	HDAC2	phosphorylation
N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide	down-regulates	HDAC2	“chemical inhibition”
3-[(dimethylamino)methyl]-N-[2-[4-[(hydroxyamino)-oxomethyl]phenoxy]ethyl]-2-benzofurancarboxamide	down-regulates	HDAC2	“chemical inhibition”
HDAC2	“form complex”	“CoREST-HDAC complex”	binding
CSNK2A1	“up-regulates activity”	HDAC2	phosphorylation
CSNK2A2	“up-regulates activity”	HDAC2	phosphorylation
HDAC2	“down-regulates quantity by repression”	TWIST1	“transcriptional regulation”
HDAC2	“down-regulates quantity by repression”	SNAI2	“transcriptional regulation”
HDAC2	“down-regulates quantity by repression”	CIITA	deacetylation
“valproic acid”	“down-regulates activity”	HDAC2	“chemical inhibition”
JWOGUUIOCYMBPV-GMFLJSBRSA-N	“down-regulates activity”	HDAC2	“chemical inhibition”
HDAC2	“up-regulates activity”	ZNF318	binding
(S)-N-Hydroxy-4-(3-methyl-2-phenylbutanamido)benzamide	“down-regulates activity”	HDAC2	“chemical inhibition”
HDAC2	“form complex”	“MBD2/NuRD complex”	binding
HDAC2	“form complex”	“MBD3/NuRD complex”	binding
HDAC2	“form complex”	“BHC complex”	binding
HDAC2	“form complex”	“MECP2/SIN3A/HDAC complex”	binding
HDAC2	down-regulates	Epigenetic_regulation
PPP2CA	“down-regulates activity”	HDAC2	dephosphorylation
PBK	“up-regulates activity”	HDAC2	phosphorylation
NOS1	“down-regulates activity”	HDAC2	s-nitrosylation
HDAC2	“down-regulates quantity by repression”	HPGD	“transcriptional regulation”
ABL1	“up-regulates quantity by stabilization”	HDAC2	phosphorylation
belinostat	“down-regulates activity”	HDAC2	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 189 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	10	32.4×	2e-11
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	10	27.0×	1e-10
Regulation of PTEN gene transcription	20	25.3×	2e-20
Transcriptional Regulation by E2F6	10	20.8×	1e-09
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	19	19.7×	1e-17
HDACs deacetylate histones	21	17.9×	2e-18
RNA Polymerase I Transcription Initiation	11	17.5×	1e-09
Notch-HLH transcription pathway	6	17.4×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	10	45.6×	1e-12
negative regulation of stem cell population maintenance	9	41.0×	6e-11
negative regulation of androgen receptor signaling pathway	5	27.9×	6e-05
DNA methylation-dependent constitutive heterochromatin formation	7	22.6×	2e-06
positive regulation of stem cell population maintenance	10	20.5×	6e-09
chromatin remodeling	31	13.5×	1e-23
heterochromatin formation	8	12.2×	3e-05
negative regulation of transforming growth factor beta receptor signaling pathway	11	11.4×	4e-07

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2245 predictions. Top by Δscore:

Variant	Effect	Δscore
6:113941703:TTTAC:T	donor_loss	1.0000
6:113941705:TA:T	donor_loss	1.0000
6:113941706:A:AC	donor_gain	1.0000
6:113941706:AC:A	donor_gain	1.0000
6:113941707:C:A	donor_loss	1.0000
6:113941707:C:CC	donor_gain	1.0000
6:113941707:CC:C	donor_gain	1.0000
6:113941763:CGT:C	acceptor_gain	1.0000
6:113941764:GT:G	acceptor_gain	1.0000
6:113941766:C:CC	acceptor_gain	1.0000
6:113941766:CTAA:C	acceptor_loss	1.0000
6:113941767:T:G	acceptor_loss	1.0000
6:113943347:TGACC:T	donor_loss	1.0000
6:113943348:GACC:G	donor_loss	1.0000
6:113943349:ACCT:A	donor_loss	1.0000
6:113943380:T:C	donor_gain	1.0000
6:113943502:TCGAA:T	acceptor_gain	1.0000
6:113943503:CGAA:C	acceptor_gain	1.0000
6:113943503:CGAAC:C	acceptor_gain	1.0000
6:113943504:GAA:G	acceptor_gain	1.0000
6:113943505:AA:A	acceptor_gain	1.0000
6:113943506:ACT:A	acceptor_loss	1.0000
6:113943507:C:CC	acceptor_gain	1.0000
6:113943507:CT:C	acceptor_loss	1.0000
6:113943510:C:CT	acceptor_gain	1.0000
6:113943512:CAGAA:C	acceptor_gain	1.0000
6:113943513:A:T	acceptor_gain	1.0000
6:113943516:A:AC	acceptor_gain	1.0000
6:113943516:A:C	acceptor_gain	1.0000
6:113943518:A:C	acceptor_gain	1.0000

AlphaMissense

3233 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:113945388:G:C	N355K	1.000
6:113945388:G:T	N355K	1.000
6:113945422:A:G	L344P	1.000
6:113945427:G:C	F342L	1.000
6:113945427:G:T	F342L	1.000
6:113945429:A:G	F342L	1.000
6:113945437:C:T	G339E	1.000
6:113945439:A:C	F338L	1.000
6:113945439:A:T	F338L	1.000
6:113945441:A:G	F338L	1.000
6:113945444:A:G	Y337H	1.000
6:113945457:A:C	N332K	1.000
6:113945457:A:T	N332K	1.000
6:113945467:A:C	L329W	1.000
6:113945467:A:G	L329S	1.000
6:113946038:C:G	A318P	1.000
6:113946051:C:A	W313C	1.000
6:113946051:C:G	W313C	1.000
6:113946053:A:G	W313R	1.000
6:113946053:A:T	W313R	1.000
6:113946054:A:C	C312W	1.000
6:113946058:C:G	R311P	1.000
6:113946061:G:T	A310D	1.000
6:113946064:A:T	V309D	1.000
6:113946066:A:C	N308K	1.000
6:113946066:A:T	N308K	1.000
6:113946071:G:T	R307S	1.000
6:113946080:A:G	Y304H	1.000
6:113946082:C:A	G303V	1.000
6:113946082:C:T	G303D	1.000

dbSNP variants (sampled 300 via entrez): RS1000022111 (6:113958305 G>A), RS1000053525 (6:113946405 C>CT), RS1000074788 (6:113947052 C>T), RS1000120100 (6:113941583 C>A,T), RS1000191206 (6:113936445 T>C), RS1000252820 (6:113936596 C>A), RS1000336855 (6:113948171 T>C), RS1000526421 (6:113951828 A>G), RS1000533857 (6:113932557 G>A), RS1000636592 (6:113937546 A>G,T), RS1000655458 (6:113969535 G>C), RS1000830810 (6:113963062 A>G), RS1000862358 (6:113971854 C>T), RS1000869104 (6:113967419 A>G), RS1000990933 (6:113937701 A>G)

Disease associations

OMIM: gene MIM:605164 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003178_2	Event free survival in diffuse large B-cell lymphoma treated with immunochemotherapy	7.000000e-07
GCST009391_1150	Metabolite levels	9.000000e-06
GCST009391_698	Metabolite levels	3.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0000482	event free survival time
EFO:0007754	response to immunochemotherapy
EFO:0010457	Alpha ketoglutarate measurement
EFO:0007745	lactate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (12): CHEMBL1937 (SINGLE PROTEIN), CHEMBL2093865 (PROTEIN FAMILY), CHEMBL2111429 (PROTEIN FAMILY), CHEMBL3430896 (PROTEIN FAMILY), CHEMBL3430897 (PROTEIN FAMILY), CHEMBL3885591 (PROTEIN COMPLEX), CHEMBL4296128 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523988 (PROTEIN FAMILY), CHEMBL4630743 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465383 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

41 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 635,296 (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
CHEMBL109	VALPROIC ACID	4	65,937
CHEMBL1213492	GIVINOSTAT	4	2,827
CHEMBL1469	PHENYLBUTANOIC ACID	4	37,081
CHEMBL1487	ATORVASTATIN	4	68,788
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL343448	ROMIDEPSIN	4	12,963
CHEMBL408513	BELINOSTAT	4	7,765
CHEMBL483254	PANOBINOSTAT	4	11,666
CHEMBL487253	BENDAMUSTINE	4	30,877
CHEMBL503	LOVASTATIN	4	92,462
CHEMBL98	VORINOSTAT	4	50,361
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1746	SODIUM PHENYLBUTYRATE	4	5,577
CHEMBL140	CURCUMIN	3	93,882
CHEMBL1851943	PRACINOSTAT	3	1,998
CHEMBL2103863	ABEXINOSTAT	3	2,195
CHEMBL235191	TACEDINALINE	3	2,950
CHEMBL27759	ENTINOSTAT	3	6,584
CHEMBL3621988	TUCIDINOSTAT	3	2,182
CHEMBL51085	EBSELEN	3	13,237
CHEMBL145	CAFFEIC ACID	3
CHEMBL1232461	MOLIBRESIB	2
CHEMBL14227	BUTYRIC ACID	2
CHEMBL1801250	NANATINOSTAT	2
CHEMBL2105763	QUISINOSTAT	2
CHEMBL2364628	RICOLINOSTAT	2
CHEMBL272980	MOCETINOSTAT	2
CHEMBL356066	DACINOSTAT	2
CHEMBL3622533	FIMEPINOSTAT	2
CHEMBL3693786	CITARINOSTAT	2

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

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 (27 total), top 25:

Ligand	Action	Affinity	Parameter
romidepsin	Inhibition	10.42	pKi
santacruzamate A	Inhibition	9.92	pIC50
quisinostat	Inhibition	9.48	pIC50
trichostatin A	Inhibition	9.19	pKi
dacinostat	Inhibition	8.85	pKi
vorinostat	Inhibition	8.8	pKi
martinostat	Inhibition	8.7	pIC50
scriptaid	Inhibition	8.66	pKi
panobinostat	Inhibition	8.52	pEC50
CHR-3996	Inhibition	8.4	pIC50
fimepinostat	Inhibition	8.3	pIC50
CUDC-101	Inhibition	7.9	pIC50
mocetinostat	Inhibition	7.47	pKi
citarinostat	Inhibition	7.35	pIC50
ricolinostat	Inhibition	7.32	pIC50
givinostat	Inhibition	7.25	pEC50
apicidin	Inhibition	6.92	pEC50
belinostat	Inhibition	6.9	pEC50
ACY-738	Inhibition	6.89	pIC50
tacedinaline	Inhibition	6.82	pKi
suprastat	Inhibition	6.75	pIC50
BML-281	Inhibition	6.62	pIC50
domatinostat	Inhibition	6.43	pIC50
marbostat-100	Inhibition	6.11	pKi
entinostat	Inhibition	5.94	pEC50

Binding affinities (BindingDB)

423 measured of 637 human assays (638 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(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
(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
(E)-3-[4-[(1-adamantylmethylamino)methyl]-3-fluorophenyl]-N-hydroxyprop-2-enamide	IC50	0.78 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
(E)-3-[4-[[1-adamantylmethyl(methyl)amino]methyl]-3-fluorophenyl]-N-hydroxyprop-2-enamide	IC50	0.78 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-hydroxy-6-(8-methoxy-6,11,11-trioxobenzo[b][1,4]benzothiazepin-5-yl)hexanamide	IC50	0.8 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(morpholine-4-carbonyl)piperidin-4-yl]amino]benzamide	IC50	0.9 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
(E)-3-[4-[(1-adamantylmethylamino)methyl]phenyl]-N-hydroxyprop-2-enamide	IC50	0.95 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
Panobinostat	IC50	1 nM
N-hydroxy-6-(8-methoxy-6-oxobenzo[b][1,4]benzothiazepin-5-yl)hexanamide	IC50	1.2 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(4-methylpiperazine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	1.2 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
(E)-3-[4-[(cyclohexylmethylamino)methyl]-3-fluorophenyl]-N-hydroxyprop-2-enamide	IC50	1.64 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
BRD2492	IC50	2 nM
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-methyl-1-(morpholine-4-carbonyl)piperidin-4-yl]amino]benzamide	IC50	2 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
NVP-LAQ824	IC50	2.6 nM
N-hydroxy-2-[[1-[2-(1H-indol-3-yl)acetyl]-4-phenylpiperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	3 nM	US-9278963: Pyrimidine hydroxy amide compounds as histone deacetylase inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-8-cyclopropyl-7-piperazin-1-ylquinoline-3-carboxamide	IC50	3.1 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-methyl-1-(piperazine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	3.2 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-methyl-1-(4-methylpiperazine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	3.2 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-ethyl-1-(piperazine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	3.9 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-2-piperazin-1-ylquinoline-6-carboxamide	IC50	4 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-methyl-1-(pyrrolidine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	4 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(pyrrolidine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	4.7 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
(E)-3-[2-butyl-1-[2-(dimethylamino)ethyl]benzimidazol-5-yl]-N-hydroxyprop-2-enamide	IC50	4.7 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
CHEBI:46024	IC50	4.9 nM
2-[[1-(2,6-difluorophenyl)cyclopropyl]amino]-N-hydroxypyrimidine-5-carboxamide	IC50	5 nM	US-8614223: Pyrimidine hydroxy amide compounds as protein deacetylase inhibitors and methods of use thereof
(E)-N-hydroxy-3-[3-[methyl(2-phenylethyl)sulfamoyl]phenyl]prop-2-enamide	IC50	5 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(oxane-4-carbonyl)piperidin-4-yl]amino]benzamide	IC50	5 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
(E)-3-[4-[[cyclohexylmethyl(methyl)amino]methyl]-3-fluorophenyl]-N-hydroxyprop-2-enamide	IC50	5.43 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
R-TSA	IC50	5.76 nM
N-hydroxy-2-[[4-phenyl-1-(phenylcarbamothioyl)piperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	5.9 nM	US-9278963: Pyrimidine hydroxy amide compounds as histone deacetylase inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-2-cyclopropyl-1-(2-morpholin-4-ylethyl)pyrrolo[2,3-b]pyridine-5-carboxamide	IC50	6 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(1-hydroxycyclohexanecarbonyl)piperidin-4-yl]amino]benzamide	IC50	6 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-[7-(hydroxyamino)-7-oxoheptyl]-4-(methylamino)benzamide	IC50	6.1 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-thiophen-2-ylphenyl)-2-[[4-methyl-1-(propan-2-ylcarbamoyl)piperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	6.5 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-phenylphenyl)-1-(2-morpholin-4-ylethyl)pyrrolo[2,3-b]pyridine-5-carboxamide	IC50	6.8 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
2-[[1-[2-fluoro-5-(trifluoromethyl)phenyl]cyclopropyl]amino]-N-hydroxypyrimidine-5-carboxamide	IC50	7 nM	US-8614223: Pyrimidine hydroxy amide compounds as protein deacetylase inhibitors and methods of use thereof
N-(2-amino-5-thiophen-2-ylphenyl)-2-piperazin-1-ylquinoxaline-6-carboxamide	IC50	7 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
3-[(dimethylamino)methyl]-N-{2-[4-(hydroxycarbamoyl)phenoxy]ethyl}-1-benzofuran-2-carboxamide	KI	7 nM
N-(2-amino-5-thiophen-2-ylphenyl)-2-[[1-(4-methylpiperazine-1-carbonyl)-4-propan-2-ylpiperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	7 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(1-hydroxycyclopentanecarbonyl)piperidin-4-yl]amino]benzamide	IC50	7 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-phenylphenyl)-1-[2-(4-methylpiperazin-1-yl)ethyl]indazole-5-carboxamide	IC50	7.1 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
N-(2-amino-5-pyridin-4-ylphenyl)-4-[[4-methyl-1-(pyrrolidine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	7.1 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-2-[[4-methyl-1-(piperazine-1-carbonyl)piperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	7.3 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
4-(dimethylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide	IC50	7.3 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-phenylphenyl)-1-(2-morpholin-4-ylethyl)indazole-5-carboxamide	IC50	7.4 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
N-(2-amino-5-phenylphenyl)-8-cyclopropyl-7-piperazin-1-ylquinoline-3-carboxamide	IC50	7.8 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
HDAC inhibitor, Compound 2	IC50	7.93 nM
N-(2-amino-5-phenylphenyl)-2-[(1-methylpiperidin-4-yl)amino]pyrimidine-5-carboxamide	IC50	8 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-2-[[4-methyl-1-(4-methylpiperazine-1-carbonyl)piperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	8.5 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-2-[[4-methyl-1-(morpholine-4-carbonyl)piperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	9 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors

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
10.42	Ki	0.038	nM	ROMIDEPSIN
10.40	Ki	0.04	nM	CHEMBL2408247
10.22	Ki	0.06	nM	CHEMBL2408242
10.22	Ki	0.06	nM	QUISINOSTAT
10.21	IC50	0.062	nM	CHEMBL432618
10.09	IC50	0.082	nM	CHEMBL321689
10.00	Ki	0.1	nM	OXAMFLATIN
9.96	IC50	0.109	nM	CHEMBL432243
9.96	IC50	0.11	nM	CHEMBL113303
9.95	IC50	0.112	nM	CHEMBL3086767
9.92	Ki	0.12	nM	CHEMBL2408243
9.92	IC50	0.119	nM	CHEMBL3086767
9.92	Ki	0.12	nM	APICIDIN
9.89	Ki	0.13	nM	CHEMBL2408245
9.89	Ki	0.13	nM	CHEMBL99392
9.77	IC50	0.17	nM	CHEMBL5433552
9.75	IC50	0.179	nM	VORINOSTAT
9.74	IC50	0.18	nM	CHEMBL4080164
9.70	IC50	0.2	nM	CHEMBL2371007
9.70	IC50	0.2	nM	CHEMBL5274004
9.70	IC50	0.2	nM	CHEMBL5395502
9.70	IC50	0.2	nM	CHEMBL1793811
9.70	IC50	0.2	nM	CHEMBL1793991
9.70	IC50	0.2	nM	CHEMBL1793985
9.66	Ki	0.22	nM	CHEMBL2408246
9.64	Ki	0.23	nM	CHEMBL2408241
9.62	IC50	0.239	nM	CHEMBL6145619
9.60	Ki	0.25	nM	CHEMBL2408238
9.59	Ki	0.26	nM	CHEMBL2408237
9.52	IC50	0.3	nM	CHEMBL2370998
9.52	IC50	0.3	nM	QUISINOSTAT
9.52	IC50	0.3	nM	CHEMBL4861467
9.52	IC50	0.3	nM	CHEMBL5199116
9.52	IC50	0.3	nM	CHEMBL5170036
9.52	IC50	0.3	nM	CHEMBL1793822
9.51	IC50	0.31	nM	CHEMBL4878197
9.48	IC50	0.33	nM	QUISINOSTAT
9.46	Ki	0.35	nM	CHEMBL5413269
9.46	IC50	0.35	nM	VORINOSTAT
9.46	IC50	0.343	nM	CHEMBL6169315
9.43	IC50	0.373	nM	CHEMBL6174035
9.43	IC50	0.372	nM	CHEMBL6133082
9.42	IC50	0.38	nM	CHEMBL5618867
9.40	IC50	0.4	nM	CHEMBL2371000
9.40	IC50	0.4	nM	CHEMBL5220926
9.40	IC50	0.4	nM	CHEMBL1793816
9.38	Ki	0.42	nM	CHEMBL2408240
9.37	IC50	0.43	nM	CHEMBL4860000
9.33	IC50	0.47	nM	CHEMBL4641682

PubChem BioAssay actives

2908 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
(E)-5-[4-(benzenesulfonamido)phenyl]-N-hydroxypent-2-en-4-ynamide	1236443: Inhibition of human HDAC2	ki	0.0001	uM
6-tert-butyl-2-hydroxycyclohepta-2,4,6-trien-1-one	760389: Inhibition of human recombinant HDAC2 by Michaelis-Menten equation analysis	ki	0.0001	uM
2-hydroxy-6-phenylcyclohepta-2,4,6-trien-1-one	760389: Inhibition of human recombinant HDAC2 by Michaelis-Menten equation analysis	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
N-hydroxy-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide	1236443: Inhibition of human HDAC2	ki	0.0001	uM
(E)-N-hydroxy-3-[3-[methyl(2-phenylethyl)sulfamoyl]phenyl]prop-2-enamide	1949483: Inhibition of HDAC2 (unknown origin)	ic50	0.0002	uM
(E)-N-hydroxy-3-[3-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide;hydrochloride	1466055: Inhibition of recombinant human full length HDAC2 using Fluor-de-Lys as substrate after 60 mins by spectrofluorimetric analysis	ic50	0.0002	uM
7-[4-[[4-[3-(tert-butylsulfamoyl)anilino]-5-methylpyrimidin-2-yl]amino]-2-fluorophenoxy]-N-hydroxyheptanamide	2031064: Inhibition of HDAC in human HeLa cells nuclear extract incubated for 30 mins by multiplate reader analysis	ic50	0.0002	uM
7-[4-[[4-[3-(tert-butylsulfamoyl)anilino]-5-methylpyrimidin-2-yl]amino]phenoxy]-N-hydroxyheptanamide	2031064: Inhibition of HDAC in human HeLa cells nuclear extract incubated for 30 mins by multiplate reader analysis	ic50	0.0002	uM
2-hydroxy-3-phenylcyclohepta-2,4,6-trien-1-one	760389: Inhibition of human recombinant HDAC2 by Michaelis-Menten equation analysis	ki	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	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells 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)-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	1754653: Inhibition of HDAC2 (unknown origin)	ic50	0.0003	uM
(2S)-6-(cyclopropylmethyl)-N-[(1S)-1-[5-(7-methoxyquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1768794: Inhibition of human recombinant FLAG-tagged HDAC2 expressed in Sf9 cells incubated for 30 mins by Fluor De Lys assay	ic50	0.0003	uM
(2S)-6-(cyclopropylmethyl)-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells 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
(9S,12R)-3-[(2S)-butan-2-yl]-9-(6-hydroxy-5-oxoheptyl)-6-[(1-methoxyindol-3-yl)methyl]-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	1847765: Inhibition of HDAC (unknown origin)	ic50	0.0003	uM
(9S,12R)-3-[(2S)-butan-2-yl]-6-(1H-indol-3-ylmethyl)-9-(5-oxoheptyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	1847765: Inhibition of HDAC (unknown origin)	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(2-cyclopropyl-7-methoxyquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-(cyclopropylmethyl)-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells 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-(cyclopropylmethyl)-N-[(1S)-1-[5-(2-ethyl-7-methoxyquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells 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-ethyl-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0004	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	1754653: Inhibition of HDAC2 (unknown origin)	ic50	0.0004	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	1188978: Inhibition of HDAC2 (unknown origin) incubated for 30 mins in presence of BSA and DTT by fluorescence assay	ic50	0.0005	uM
(E)-N-hydroxy-3-[4-[2-(1-methylindol-4-yl)ethylsulfamoyl]phenyl]prop-2-enamide	1466055: Inhibition of recombinant human full length HDAC2 using Fluor-de-Lys as substrate after 60 mins by spectrofluorimetric analysis	ic50	0.0005	uM
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	1664941: Inhibition of full length human recombinant FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 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	0.0005	uM
(2R)-N-[4-[1-[7-(hydroxyamino)-7-oxoheptyl]-4-morpholin-4-ylpyrazolo[5,4-d]pyrimidin-6-yl]phenyl]-2-methylmorpholine-4-carboxamide	1614127: Inhibition of recombinant full length human HDAC2 expressed in baculovirus expression system using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by fluorescence assay	ic50	0.0006	uM
(2S)-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-propan-2-yl-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0006	uM
(2S)-N-[(1S)-1-[5-(2-cyclopropyl-7-methoxyquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0006	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	1662501: Inhibition of HDAC2 (unknown origin)	ic50	0.0007	uM
(2S)-6-(cyclopropylmethyl)-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1,3-oxazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1768794: Inhibition of human recombinant FLAG-tagged HDAC2 expressed in Sf9 cells incubated for 30 mins by Fluor De Lys assay	ic50	0.0007	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(7-methoxy-1-methyl-2-oxoquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0007	uM
(2S)-N-[(1S)-1-[5-(2,7-dimethylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0007	uM
2-hydroxy-3-(4-methoxyphenyl)cyclohepta-2,4,6-trien-1-one	760389: Inhibition of human recombinant HDAC2 by Michaelis-Menten equation analysis	ki	0.0008	uM
N-[(1S)-1-[5-(2-fluorophenyl)-1,3-oxazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	1664941: Inhibition of full length human recombinant FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 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	0.0008	uM
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	1664941: Inhibition of full length human recombinant FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 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	0.0008	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	1188978: Inhibition of HDAC2 (unknown origin) incubated for 30 mins in presence of BSA and DTT by fluorescence assay	ic50	0.0009	uM
(E)-N-hydroxy-3-[4-[2-(1H-indol-4-yl)ethylsulfamoyl]phenyl]prop-2-enamide	1466055: Inhibition of recombinant human full length HDAC2 using Fluor-de-Lys as substrate after 60 mins by spectrofluorimetric analysis	ic50	0.0009	uM
(3S,6S,22E)-6-(6-oxooctyl)-5,8,20,25,31-pentazaheptacyclo[23.2.2.17,10.111,15.01,3.014,19.016,20]hentriaconta-7,9,11(30),12,14,22-hexaen-4-one	1754653: Inhibition of HDAC2 (unknown origin)	ic50	0.0009	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-phenylbut-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0010	uM
2-[4-[(E)-4-(4-fluorophenyl)-1-hydroxybut-3-en-2-yl]piperazin-1-yl]-N-hydroxypyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0010	uM
(3S,6R,9S,12R)-3-[(2S)-butan-2-yl]-6-[(1-methoxyindol-2-yl)methyl]-9-(6-oxooctyl)-1,4,10-triazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	1622995: Inhibition of HDAC (unknown origin)	ic50	0.0010	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	1185953: Inhibition of HDAC2 (unknown origin) incubated at 37 degC for 30 mins	ic50	0.0011	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	1185953: Inhibition of HDAC2 (unknown origin) incubated at 37 degC for 30 mins	ic50	0.0011	uM
N’-[(5-bromothiophen-2-yl)methyl]-N-hydroxy-N’-[4-(2-morpholin-4-ylethoxy)phenyl]heptanediamide	1927783: Inhibition of HDAC2 (unknown origin)	ic50	0.0011	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1,3-oxazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0011	uM
(2S)-N-[(1S)-1-[5-(2-cyclopropylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0011	uM
(2S)-N-[(1S)-1-[5-(9H-carbazol-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1694524: Inhibition of HDAC2 (unknown origin) using compound purified by traditional preparative HPLC work-flow	ic50	0.0011	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	1972804: Binding affinity to HDAC2 (unknown origin) assessed as inhibition constant	ki	0.0012	uM
N-hydroxy-5-[5-[1-(3,4,5-trimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl]-1,3,4-oxadiazol-2-yl]pentanamide	1890511: Inhibition of HDAC2 (unknown origin)	ic50	0.0012	uM
(E)-N-hydroxy-3-[4-[[2-(1-(111C)methylindol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide	1949483: Inhibition of HDAC2 (unknown origin)	ic50	0.0012	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	1916028: Inhibition of human full length FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0013	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	1185953: Inhibition of HDAC2 (unknown origin) incubated at 37 degC for 30 mins	ic50	0.0014	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	decreases reaction, increases expression, decreases activity	4
Valproic Acid	decreases expression, increases reaction, decreases activity, increases degradation	4
sodium arsenite	decreases reaction, increases expression, decreases expression, affects cotreatment, increases abundance	3
Vorinostat	affects binding, decreases activity, affects cotreatment, decreases expression	3
bisphenol A	affects expression, decreases expression	2
sulforaphane	affects cotreatment, decreases expression	2
hydroquinone	increases expression, decreases reaction	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, increases degradation, increases ubiquitination, affects cotreatment, decreases expression	2
Resveratrol	affects cotreatment, increases expression, increases metabolic processing	2
Arsenic Trioxide	affects expression, increases methylation	2
Arsenic	decreases methylation, increases abundance, affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Curcumin	decreases reaction, increases degradation, decreases expression, decreases activity	2
Doxorubicin	increases reaction, decreases expression, affects binding, decreases reaction	2
Rotenone	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
Batroxase, Bothrops atrox	increases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
honokiol	affects binding, decreases activity	1
4-biphenylamine	decreases expression, decreases reaction	1
deoxynivalenol	increases expression	1
methoxyacetic acid	decreases activity	1
malealdehyde	affects expression	1
3,3’-diindolylmethane	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
nonylphenol	affects reaction, increases expression, decreases acetylation, decreases expression	1

ChEMBL screening assays

2775 unique, capped per target: 2743 binding, 24 admet, 7 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002514	Binding	Inhibition of human C-terminal FLAG-tagged HDAC2 in HEK293 cells	Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties. — J Med Chem
CHEMBL3860977	ADMET	Inhibition of HDAC2 (unknown origin)	Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer’s Disease. — J Med Chem
CHEMBL5049469	Functional	In vivo inhibition of HDAC2 in HEL cells xenografted in BALB/C mouse assessed as upregulation of acetyl-H4 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: 8 cancer cell line, 4 transformed cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2M0	SEES3-1V human HDAC2, clone1	Embryonic stem cell	Male
CVCL_A2M1	SEES3-1V human HDAC2, clone2	Embryonic stem cell	Male
CVCL_A2M2	SEES3-1V human HDAC2, clone3	Embryonic stem cell	Male
CVCL_B2YJ	Abcam HEK293T HDAC2 KO 1	Transformed cell line	Female
CVCL_B2YK	Abcam HEK293T HDAC2 KO 2	Transformed cell line	Female
CVCL_B2YL	Abcam HEK293T HDAC2 KO 3	Transformed cell line	Female
CVCL_B8H7	Abcam HCT 116 HDAC2 KO	Cancer cell line	Male
CVCL_B8WK	Abcam MCF-7 HDAC2 KO	Cancer cell line	Female
CVCL_B9JH	Abcam A-549 HDAC2 KO	Cancer cell line	Male
CVCL_D7R5	Ubigene A-549 HDAC2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism