HDAC7

Summary

HDAC7 (histone deacetylase 7, HGNC:14067) is a protein-coding gene on chromosome 12q13.11, encoding Histone deacetylase 7 (Q8WUI4). Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene has sequence homology to members of the histone deacetylase family. This gene is orthologous to mouse HDAC7 gene whose protein promotes repression mediated via the transcriptional corepressor SMRT. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 51564 — RefSeq curated summary.

At a glance

• GWAS associations: 42 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 193 total
• Regional missense constraint (gnomAD): 2 of 6 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 26 tissues, sQTL in 30 (q < 0.05)
• ChEMBL bioactivity: 28 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.34 (highly constrained)
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_015401
• Interaction hub: 2,352 STRING partners (top 5% of genes corpus-wide)
• Notable: 193 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14067
Approved symbol	HDAC7
Name	histone deacetylase 7
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP586J0917
Ensembl gene	ENSG00000061273
Ensembl biotype	protein_coding
OMIM	606542
Entrez	51564

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 26 protein_coding, 12 nonsense_mediated_decay, 5 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000080059

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 6, TSL 3: 4, TSL 4: 10, TSL 5: 8

ENST00000080059, ENST00000354334, ENST00000380610, ENST00000417107, ENST00000417902, ENST00000421231, ENST00000422254, ENST00000425451, ENST00000427332, ENST00000430670, ENST00000433685, ENST00000434070, ENST00000440293, ENST00000445237, ENST00000447463, ENST00000450805, ENST00000459625, ENST00000463732, ENST00000470668, ENST00000471235, ENST00000477203, ENST00000477937, ENST00000485796, ENST00000488927, ENST00000491464, ENST00000547259, ENST00000548080, ENST00000548938, ENST00000549883, ENST00000552960, ENST00000903431, ENST00000903432, ENST00000903433, ENST00000903434, ENST00000903435, ENST00000903436, ENST00000903437, ENST00000903438, ENST00001001839, ENST00001001840, ENST00001001841, ENST00001001842, ENST00001001843, ENST00001041295, ENST00001142890

RefSeq mRNA: 4 — MANE Select: NM_015401 NM_001098416, NM_001308090, NM_001368046, NM_015401

CCDS: CCDS41776, CCDS81685, CCDS8756

Canonical transcript exons

ENST00000080059 — 26 exons

Exon	Start	End
ENSE00000888040	47795906	47796016
ENSE00001853912	47782722	47783886
ENSE00001862271	47819767	47819903
ENSE00003459640	47798108	47798219
ENSE00003460861	47791871	47792004
ENSE00003474618	47795184	47795380
ENSE00003488616	47798562	47798652
ENSE00003491961	47789813	47789920
ENSE00003506538	47788045	47788164
ENSE00003512342	47798785	47798972
ENSE00003581790	47802224	47802274
ENSE00003599876	47789261	47789348
ENSE00003626481	47796207	47796298
ENSE00003641521	47785752	47785885
ENSE00003642796	47795587	47795767
ENSE00003658111	47785387	47785471
ENSE00003662696	47786585	47786703
ENSE00003664202	47789523	47789578
ENSE00003667866	47793369	47793588
ENSE00003674845	47794760	47794933
ENSE00003677330	47791259	47791308
ENSE00003688194	47784079	47784217
ENSE00003690258	47797017	47797142
ENSE00003691273	47787712	47787809
ENSE00003692328	47791586	47791706
ENSE00003785951	47797384	47797499

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 97.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.3751 / max 398.3701, expressed in 1813 samples.

Highest expression (Bgee): sural nerve, mucosa of stomach, metanephros cortex, uterine tube, body of uterus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

HDAC7 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 30 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 56 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	3.7e-36	-0.86	12:47787477:C:T
Skin Sun Exposed Lower leg	sqtl	2.8e-32	-0.90	12:47781787:C:T
Testis	sqtl	3.1e-30	+1.01	12:47786725:C:T
Whole Blood	sqtl	4.8e-21	-0.36	12:47785214:C:T
Pituitary	sqtl	6.0e-21	-1.27	12:47768697:A:T
Nerve Tibial	sqtl	7.9e-19	-0.49	12:47785680:C:T
Breast Mammary Tissue	sqtl	1.1e-17	-0.83	12:47785564:C:T
Lung	sqtl	2.8e-17	-0.31	12:47785619:C:T
Artery Tibial	eqtl	2.3e-15	+0.18	12:47783290:A:G
Spleen	sqtl	3.6e-15	-1.16	12:47787201:C:T
Esophagus Mucosa	sqtl	3.3e-13	-0.60	12:47785695:T:G
Ovary	sqtl	4.4e-12	-0.72	12:47796261:C:T
Adipose Visceral Omentum	sqtl	5.3e-12	-0.38	12:47785214:C:T
Prostate	sqtl	6.8e-12	-1.17	12:47785695:T:G
Artery Aorta	sqtl	1.1e-11	+0.46	12:47785619:C:T
Muscle Skeletal	sqtl	1.7e-11	+0.39	12:47785194:G:C
Thyroid	sqtl	1.4e-09	+0.27	12:47796383:G:A
Colon Sigmoid	sqtl	1.4e-09	-0.79	12:47784123:C:T
Esophagus Mucosa	eqtl	1.5e-09	+0.18	12:47820208:C:T
Heart Atrial Appendage	sqtl	4.5e-09	-0.45	12:47796383:G:A

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
130698	36.7470	1806
130699	5.7667	1648
206684	0.3999	169
130700	0.3339	163
130697	0.0928	23
130701	0.0347	13

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.55	gold quality
mucosa of stomach	UBERON:0001199	97.23	gold quality
metanephros cortex	UBERON:0010533	97.23	gold quality
left uterine tube	UBERON:0001303	97.13	gold quality
body of uterus	UBERON:0009853	97.03	gold quality
apex of heart	UBERON:0002098	97.02	gold quality
upper lobe of left lung	UBERON:0008952	96.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.96	gold quality
lower esophagus	UBERON:0013473	96.94	gold quality
left adrenal gland cortex	UBERON:0035825	96.82	gold quality
endocervix	UBERON:0000458	96.77	gold quality
right ovary	UBERON:0002118	96.77	gold quality
right uterine tube	UBERON:0001302	96.68	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.66	gold quality
peripheral nervous system	UBERON:0000010	96.60	gold quality
nerve	UBERON:0001021	96.60	gold quality
tibial nerve	UBERON:0001323	96.60	gold quality
adrenal cortex	UBERON:0001235	96.56	gold quality
left adrenal gland	UBERON:0001234	96.54	gold quality
left ovary	UBERON:0002119	96.54	gold quality
right lung	UBERON:0002167	96.54	gold quality
right lobe of thyroid gland	UBERON:0001119	96.53	gold quality
right adrenal gland	UBERON:0001233	96.53	gold quality
right coronary artery	UBERON:0001625	96.37	gold quality
right adrenal gland cortex	UBERON:0035827	96.34	gold quality
ascending aorta	UBERON:0001496	96.33	gold quality
thoracic aorta	UBERON:0001515	96.31	gold quality
descending thoracic aorta	UBERON:0002345	96.26	gold quality
omental fat pad	UBERON:0010414	96.26	gold quality
peritoneum	UBERON:0002358	96.25	gold quality
left lobe of thyroid gland	UBERON:0001120	96.13	gold quality
skin of leg	UBERON:0001511	96.13	gold quality
left coronary artery	UBERON:0001626	96.07	gold quality
ectocervix	UBERON:0012249	96.07	gold quality
coronary artery	UBERON:0001621	96.00	gold quality
stromal cell of endometrium	CL:0002255	95.94	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.92	gold quality
upper lobe of lung	UBERON:0008948	95.78	gold quality
aorta	UBERON:0000947	95.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.57	gold quality
thymus	UBERON:0002370	95.55	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.40	gold quality
granulocyte	CL:0000094	95.38	gold quality
skin of abdomen	UBERON:0001416	95.35	gold quality
spleen	UBERON:0002106	95.34	gold quality
gall bladder	UBERON:0002110	95.27	gold quality
popliteal artery	UBERON:0002250	95.23	gold quality
tibial artery	UBERON:0007610	95.23	gold quality
lymph node	UBERON:0000029	95.21	gold quality
right atrium auricular region	UBERON:0006631	95.20	gold quality
thyroid gland	UBERON:0002046	95.17	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.05	gold quality
adrenal gland	UBERON:0002369	94.94	gold quality
minor salivary gland	UBERON:0001830	94.90	gold quality
vena cava	UBERON:0004087	94.87	gold quality
olfactory bulb	UBERON:0002264	94.68	gold quality
cardiac atrium	UBERON:0002081	94.58	gold quality
smooth muscle tissue	UBERON:0001135	94.32	gold quality
esophagus	UBERON:0001043	94.28	gold quality
cardia of stomach	UBERON:0001162	94.26	gold quality
fundus of stomach	UBERON:0001160	94.18	gold quality
saliva-secreting gland	UBERON:0001044	94.08	gold quality
lower esophagus mucosa	UBERON:0035834	94.07	gold quality
heart left ventricle	UBERON:0002084	93.96	gold quality
cardiac ventricle	UBERON:0002082	93.84	gold quality
pericardium	UBERON:0002407	93.76	gold quality
pylorus	UBERON:0001166	93.70	gold quality
colonic epithelium	UBERON:0000397	93.57	gold quality
adenohypophysis	UBERON:0002196	93.51	gold quality
heart	UBERON:0000948	93.37	gold quality
mouth mucosa	UBERON:0003729	93.34	gold quality
body of stomach	UBERON:0001161	93.31	gold quality
type B pancreatic cell	CL:0000169	93.18	silver quality
caecum	UBERON:0001153	93.18	gold quality
pituitary gland	UBERON:0000007	92.94	gold quality
zone of skin	UBERON:0000014	92.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.83	gold quality
uterine cervix	UBERON:0000002	92.80	gold quality
myometrium	UBERON:0001296	92.72	gold quality
stomach	UBERON:0000945	92.56	gold quality
tongue squamous epithelium	UBERON:0006919	92.52	silver quality
renal medulla	UBERON:0000362	92.43	gold quality
vermiform appendix	UBERON:0001154	92.38	gold quality
vagina	UBERON:0000996	92.35	gold quality
body of tongue	UBERON:0011876	92.34	gold quality
esophagus mucosa	UBERON:0002469	92.08	gold quality
ovary	UBERON:0000992	92.04	gold quality
blood	UBERON:0000178	92.00	gold quality
adipose tissue	UBERON:0001013	91.97	gold quality
diaphragm	UBERON:0001103	91.80	silver quality
connective tissue	UBERON:0002384	91.62	gold quality
bone marrow cell	CL:0002092	91.50	gold quality
tongue	UBERON:0001723	91.50	gold quality
saphenous vein	UBERON:0007318	91.38	gold quality
nipple	UBERON:0002030	91.35	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	91.33	gold quality
parotid gland	UBERON:0001831	91.25	silver quality
transverse colon	UBERON:0001157	91.22	gold quality
small intestine	UBERON:0002108	91.04	gold quality
trachea	UBERON:0003126	90.90	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	53.55
E-ANND-3	yes	11.75

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	78.5
Thymus	tissue	74.3
Hippocampus	tissue	34.8
Locus coeruleus	tissue	32.8
Vagina	tissue	32.6
Nucleus accumbens	tissue	31.2
Spleen	tissue	27.1
Appendix	tissue	26.9
Adipose tissue	tissue	25.6
Lymph node	tissue	25.4
Postcentral gyrus	tissue	24.6
Bone marrow	tissue	22.3
Endometrium 1	tissue	21.1
Lung	tissue	20.7
Adrenal gland	tissue	19.1
Parathyroid gland	tissue	18.8
Skin 1	tissue	18.5
Ovary	tissue	18.3
Placenta	tissue	18.3
Pituitary gland	tissue	17.0
Seminal vesicle	tissue	16.2
Urinary bladder	tissue	16.1
Smooth muscle	tissue	15.8
Gallbladder	tissue	15.8
Fallopian tube	tissue	15.7
Salivary gland	tissue	15.2
Skeletal muscle	tissue	15.0
Tonsil	tissue	14.2
Spinal cord	tissue	13.9
Stomach 1	tissue	13.8
Superior colliculi	tissue	13.5
Cervix	tissue	13.4
Epididymis	tissue	12.8
Heart muscle	tissue	12.3
Prostate	tissue	11.6
Substantia nigra	tissue	11.2
Thyroid gland	tissue	11.2
Small intestine	tissue	10.7
Esophagus	tissue	10.3
Medulla oblongata	tissue	9.7
Corpus callosum	tissue	9.7
Pancreas	tissue	9.5
Midbrain	tissue	9.2
Thalamus	tissue	9.0
Tongue	tissue	8.8
Olfactory bulb	tissue	8.7
Pons	tissue	8.4
Periaqueductal gray	tissue	8.4
Colon	tissue	8.3
Duodenum	tissue	8.3
Hippocampal formation	tissue	8.3
Cerebral cortex	tissue	8.2
Hypothalamus	tissue	8.2
Insular cortex	tissue	8.2
Putamen	tissue	7.6
Amygdala	tissue	7.6
Entorhinal cortex	tissue	7.6
Septum	tissue	7.4
Retrosplenial cortex	tissue	7.4
Occipital cortex	tissue	7.4

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Area postrema (66.0), Orbitofrontal gyrus, anterior (54.6), Anterior thalamic nucleus, ventral (53.4), Nucleus rhomboideus (51.5), Dorsal tegmental nucleus (51.4).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets:

Target	Regulation
ACTN4	Repression
AKAP12	Repression
CDKN1A	Activation
CYP7A1	Unknown
ESR1	Repression
HDC	Repression
HIF1A	Activation
MAML1	Unknown
MEF2A	Repression
MEF2C	Repression
MEF2D	Repression
MMP10	Repression
NR4A1	Unknown

Upstream regulators (CollecTRI, top): BCL6, MECP2, MEF2D, NFKB1, RELA, SP1, STAT1

miRNA regulators (miRDB)

Targeting HDAC7 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 61 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-7112-5P	99.59	65.76	104
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-5689	99.50	71.26	1154

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.344, missense Z 2.01 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000080059 splits into 6 regions with different missense tolerance; 2 are missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:47,783,844–47,785,775	98 / 123.9	0.79	no
12:47,785,776–47,785,820	2 / 20.9	0.10	yes (p 3.5e-05)
12:47,785,821–47,791,280	182 / 301.1	0.60	no
12:47,791,281–47,798,156	618 / 701.5	0.88	no
12:47,798,157–47,798,213	7 / 23.0	0.30	yes (p 8.6e-04)
12:47,798,214–47,819,785	161 / 158.5	1.02	no

Literature-anchored findings (GeneRIF, showing 40)

• Characterization of the mouse HDAC7 ortholog. (PMID:10640276)
• Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor (PMID:11929873)
• Interaction of HDAC7 with MEF2D is essential for repression of Nur77. (PMID:12753745)
• HDAC7 phosphorylation is mediated by calcium/calmodulin-dependent kinase I, which also promotes the association of HDAC7 with 14-3-3 and stabilizes HDAC7 (PMID:15166223)
• HDAC7 increased transcriptional activity of HIF-1alpha through the formation of a complex with HIF-1alpha, HDAC7, and p300 (PMID:15280364)
• HDAC7 is sequestered to the cytoplasm from mitochondrial and nuclear compartments upon initiation of apoptosis (PMID:15364908)
• Data indicate that protein kinase D1 regulates the expression of Nur77 during thymocyte activation at least in part by phosphorylating HDAC7. (PMID:15623513)
• a mutant of HDAC7 specifically deficient in phosphorylation by protein kinase D, inhibits T cell receptor-mediated apoptosis of T cell hybridomas (PMID:15738054)
• These results identify HDAC7 as a novel Androgen receptor corepressor whose subcellular and subnuclear compartmentalization can be regulated in an androgen-selective manner. (PMID:16860317)
• Class IIa histone deacetylases (HDACs) are subjected to signal-independent nuclear export that relies on their constitutive phosphorylation. EMK and C-TAK1, are identified as regulators of this process. (PMID:16980613)
• HDAC7 is a key modulator of endothelial cell migration and angiogenesis, at least in part, by regulating platelet-derived growth factor-B (PDGF-B) and its receptor PDGFR-beta gene expression. (PMID:17947801)
• Histone deacetylase 7 associates with Runx2 and represses its activity during osteoblast maturation in a deacetylation-independent manner (PMID:17997710)
• HDAC7 has a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity (PMID:18285338)
• PP2A constitutively dephosphorylates the class IIa member HDAC7 to control its biological functions as a regulator of T cell apoptosis and endothelial cell functions. (PMID:18339811)
• Caspase-8 cleaves histone deacetylase 7 and abolishes its transcription repressor function. (PMID:18458084)
• PML sequesters HDAC7 to relieve repression and up-regulate gene expression (PMID:18463162)
• The data showed alteration of HDACs gene expression in pancreatic cancer. Increased expression of HDAC7 discriminates PA from other pancreatic tumors. (PMID:18506539)
• These results demonstrate that phosphorylation of HDAC7 serves as a molecular switch to mediate VEGF signaling and endothelial function. (PMID:18509061)
• VEGF stimulates HDAC7 phosphorylation and cytoplasmic accumulation modulating MT-MMP1/MMP10 expression and angiogenesis. (PMID:18617643)
• These results demonstrate a novel function of HDAC7 and provide a regulatory mechanism of PML sumoylation. (PMID:18625722)
• recent developments in the crystal structure analysis of human HDAC4, HDAC7, and HDAC8 recent developments in the crystal structure analysis of human HDAC4, HDAC7, and HDAC8 [REVIEW] (PMID:19355988)
• Elevated HDAC7 expression in human osteoarthritis may contribute to cartilage degradation via promoting MMP-13 gene expression. (PMID:19784544)
• these data implicate a novel role for HDAC7 and FoxA1 in estrogen repression of RPRM. (PMID:19917725)
• histone deacetylase 7 has a role in function of misfolded CFTR in cystic fibrosis (PMID:19966789)
• HDAC7 interacts with beta-catenin keeping endothelial cells in a low proliferation stage. (PMID:20224040)
• The expression of HDAC7 protein plays an important role in the apoptosis and vascular tubulogenesis of hepatocellular carcinoma by the upregulation of p21 and HIF-1alpha and the downregulation of cyclin E and MMP10. (PMID:20693714)
• Findings highlight for the first time an unrecognized link between HDAC7 and c-Myc and offer a novel mechanistic insight into the contribution of HDAC7 to tumor progression. (PMID:21120446)
• Data demonstrate that Mitf and HDAC7 interact in RAW 264 cells and osteoclasts. The transcriptional activity of Mitf is repressed by HDAC7. (PMID:21324898)
• HDAC7 reduction in COPD causes a defect of HIF-1alpha induction response to hypoxia with impaired VEGF gene expression. This poor cellular adaptation might play a role in the pathogenesis of COPD. (PMID:22172637)
• demonstrated for the first time that AKAP12 tumor/angiogenesis suppressor gene is an epigenetic target of HDAC7 (PMID:22584896)
• VEGF and PKC promote degradation-independent protein ubiquitination of FLNB to control intracellular trafficking of HDAC7. (PMID:23401860)
• Our findings uncover a novel role for HDAC7 in maintaining the identity of a particular cell type by silencing lineage-inappropriate genes. (PMID:23696748)
• Histone deacetylase 7 promotes Toll-like receptor 4-dependent proinflammatory gene expression in macrophages. (PMID:23853092)
• Authors identified acetyltransferase p300 and deacetylase HDAC7 as enzymes modulating human T cell leukemia virus type 1 Tax protein acetylation. (PMID:23880157)
• Expression of JHDM2A was significantly increased but HDAC2, HDAC7, and SUV39H2 were significantly down-regulated in Systemic Sclerosis B cells relative to controls (PMID:23891737)
• endothelial progenitor cells involved in the angiogenesis might be controlled by VEGF-PKD1-HDAC7 axis, which regulates the EPCs angiogenesis by PKD1, but not the ERK and PI3K pathway (PMID:24189120)
• The transcriptional function of HCS was shown by in vitro pull down and in vivo co-immunoprecipitation assays to depend on its interaction with the histone deacetylases HDAC1, HDAC2 and HDAC7 (PMID:24239178)
• Study identifies the miR-34a-HDAC1/HDAC7-HSP70 K246 axis as a novel molecular signature predictive of therapy resistance. (PMID:25173798)
• identify a new target of ROCK signaling via myosin phosphatase subunit (MYPT1) and histone deacetylase (HDAC7) at the nuclear level (PMID:25511694)
• This study demonstrated a simple and straightforward method of quantifying proneural/mesenchymal markers in glioblastoma. Of note, HDAC7 expression might be a novel therapeutic target in glioblastoma treatment. (PMID:26272600)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdac7b	ENSDARG00000073850
danio_rerio	hdac7a	ENSDARG00000105179
mus_musculus	Hdac7	ENSMUSG00000022475
rattus_norvegicus	Hdac7	ENSRNOG00000055597
caenorhabditis_elegans		WBGENE00009657
caenorhabditis_elegans		WBGENE00009663
caenorhabditis_elegans		WBGENE00219378

Paralogs (10): HDAC9 (ENSG00000048052), HDAC4 (ENSG00000068024), HDAC6 (ENSG00000094631), HDAC10 (ENSG00000100429), HDAC5 (ENSG00000108840), HDAC1 (ENSG00000116478), HDAC8 (ENSG00000147099), HDAC11 (ENSG00000163517), HDAC3 (ENSG00000171720), HDAC2 (ENSG00000196591)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1891835) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
thin ventricular wall	1
abnormal vasculogenesis	1
internal hemorrhage	1
edema	1
abnormal coat/hair pigmentation	1
abnormal cardiovascular system morphology	1
abnormal pharyngeal arch artery morphology	1
increased circulating alkaline phosphatase level	1
dilated heart atrium	1
dilated dorsal aorta	1
abnormal cardinal vein morphology	1
abnormal dorsal aorta morphology	1
pericardial effusion	1
abnormal vascular smooth muscle morphology	1
abnormal vascular endothelial cell morphology	1
embryonic lethality, complete penetrance	1
embryonic lethality during organogenesis, complete penetrance	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Staphylococcus aureus subsp. aureus Mu50	P64375	100.0%	Diamond
Staphylococcus aureus subsp. aureus N315	P64376	100.0%	Diamond
Staphylococcus aureus subsp. aureus MSSA476	Q6G8J2	100.0%	Diamond
Staphylococcus aureus subsp. aureus MW2	Q8NW34	100.0%	Diamond
Staphylococcus aureus subsp. aureus COL	Q5HF39	99.7%	Diamond
Pongo abelii	Q5RB76	99.5%	Diamond
Staphylococcus aureus subsp. aureus MRSA252	Q6GFX3	98.5%	Diamond
Xenopus tropicalis	Q28DV3	98.4%	Diamond
Xenopus laevis	Q6IRL9	98.4%	Diamond
Gallus gallus	P56520	97.4%	Diamond
Cricetulus griseus	Q80ZH1	97.0%	Diamond
Tetraodon nigroviridis	Q4SFA0	96.7%	Diamond
Bos taurus	Q0VCB2	95.8%	Diamond
Arabidopsis thaliana	Q8LRK8	85.9%	Diamond
Caenorhabditis briggsae	Q613L4	82.2%	Diamond
Zea mays	P56521	81.5%	Diamond
Pseudomonas aeruginosa PAO1	Q9HXM1	75.0%	Diamond
Oryza sativa Japonica Group	Q2QWU2	68.6%	Diamond
Schizosaccharomyces pombe 972h-	O59702	66.6%	Diamond
Dictyostelium discoideum	Q55BW2	64.3%	Diamond
Mycoplana ramosa	Q48935	52.0%	Diamond
Saccharomyces cerevisiae S288C	P53973	50.7%	Diamond
Candida albicans SC5314	Q5A960	50.4%	Diamond
Alcaligenaceae bacterium FB188	Q70I53	47.9%	Diamond
Burkholderia pseudomallei 1710b	Q3JUN4	43.5%	Diamond
Archaeoglobus fulgidus DSM 4304	O30107	40.8%	Diamond
Synechocystis sp. PCC 6803 substr. Kazusa	P72702	40.8%	Diamond
Methanothermobacter thermautotrophicus str. Delta H	O27262	39.7%	Diamond
Methanocaldococcus jannaschii DSM 2661	Q57955	38.1%	Diamond
Picosynechococcus sp. PCC 7002	P28606	37.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RPAP3-DT	ncRNA	105369748
LINC02354	ncRNA	107984503
SLC48A1	protein-coding	55652
RPAP3	protein-coding	79657
ENDOU	protein-coding	8909
RAPGEF3	protein-coding	10411
VDR	protein-coding	7421
TMEM106C	protein-coding	79022
COL2A1	protein-coding	1280

Protein

Protein identifiers

Histone deacetylase 7 — Q8WUI4 (reviewed: Q8WUI4)

Alternative names: Histone deacetylase 7A, Protein deacetylase HDAC7

All UniProt accessions (19): Q8WUI4, A0A087WYQ4, C9J102, C9JAH2, C9JBC2, C9JEB6, C9JF80, C9JGF5, C9JH46, C9JKN3, C9JNI4, C9JVZ1, C9JZ79, F8VWY3, H0YH91, H0YHJ5, H0YI15, H0YI41, J3KPH8

UniProt curated annotations — full annotation on UniProt →

Function. Responsible for 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. Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene. Positively regulates the transcriptional repressor activity of FOXP3. Serves as a corepressor of RARA, causing its deacetylation and inhibition of RARE DNA element binding. In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response. Also acetylates non-histone proteins, such as ALKBH5.

Subunit / interactions. Interacts with HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, NCOR1, NCOR2, SIN3A, SIN3B, RBBP4, RBBP7, MTA1L1, SAP30 and MBD3. Interacts with KAT5 and EDNRA. Interacts with the 14-3-3 protein YWHAE, MEF2A, MEF2B and MEF2C. Interacts with ZMYND15. Interacts with KDM5B. Interacts with PML. Interacts with FOXP3. Interacts with RARA.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. May be phosphorylated by CaMK1. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import. Phosphorylation at Ser-155 by MARK2, MARK3 and PRKD1 promotes interaction with 14-3-3 proteins and export from the nucleus. Phosphorylation at Ser-155 is a prerequisite for phosphorylation at Ser-181.

Similarity. Belongs to the histone deacetylase family. HD type 2 subfamily.

Isoforms (10)

UniProt ID	Names	Canonical?
Q8WUI4-1	1	yes
Q8WUI4-2	2
Q8WUI4-3	3
Q8WUI4-4	4
Q8WUI4-5	5
Q8WUI4-6	6
Q8WUI4-7	7
Q8WUI4-8	8
Q8WUI4-9	9
Q8WUI4-10	10

RefSeq proteins (4): NP_001091886, NP_001295019, NP_001354975, NP_056216* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000286	HDACs	Family
IPR023696	Ureohydrolase_dom_sf	Homologous_superfamily
IPR023801	His_deacetylse_dom	Domain
IPR037138	His_deacetylse_dom_sf	Homologous_superfamily
IPR046949	HDAC4/5/7/9	Family

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)

• 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)

UniProt features (106 total): helix 26, modified residue 12, strand 12, sequence conflict 11, region of interest 10, splice variant 10, mutagenesis site 8, turn 4, compositionally biased region 4, binding site 4, chain 1, short sequence motif 1, active site 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
3C10	Crystal structure of catalytic domain of human histone deacetylase HDAC7 in complex with …	X-RAY DIFFRACTION	2
3C0Y	Crystal structure of catalytic domain of human histone deacetylase HDAC7	X-RAY DIFFRACTION	2.1
3C0Z	Crystal structure of catalytic domain of human histone deacetylase HDAC7 in complex with …	X-RAY DIFFRACTION	2.1
8Q9Q	Crystal Structure of the MADS-box/MEF2 Domain of MEF2D bound to dsDNA and HDAC7 …	X-RAY DIFFRACTION	2.11
3ZNR	HDAC7 bound with inhibitor TMP269	X-RAY DIFFRACTION	2.4
3ZNS	HDAC7 bound with TFMO inhibitor tmp942	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUI4-F1	62.90	0.36

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, Plasma proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IF enhanced

Functional residue map

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

Catalytic / active sites (2)

Position	Role
670
843	contributes to catalysis

Ligand- & substrate-binding residues (4)

Position	Role
533	Zn(2+)
535	Zn(2+)
541	Zn(2+)
618	Zn(2+)

Post-translational modifications (12)

Type	Positions
Phosphoserine	109, 155, 181, 283, 358, 364, 405, 486, 487, 507, 595
Phosphothreonine	286

Mutagenesis-validated functional residues (8)

Position	Phenotype
150	abolishes phosphorylation at s-155.
155	abolishes nuclear export; when associated with a-181; a-358 and a-486. abolishes phosphorylation by mark2 and mark3, interaction with …
181	abolishes nuclear export; when associated with a-155; a-358 and a-486.
358	abolishes nuclear export; when associated with a-192; a-1118 and a-486.
486	abolishes nuclear export; when associated with a-192; a-1118 and a-358.
843	enhanced deacetylase activity.
843	6000 fold increase in deacetylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 25; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

25 pathways:

ID	Pathway	Evidence
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants ⚕	curated
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants ⚕	curated
R-HSA-350054	Notch-HLH transcription pathway	curated
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-2894858	Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer ⚕	—
R-HSA-2644602	Signaling by NOTCH1 PEST Domain Mutants in Cancer ⚕	—
R-HSA-2644603	Signaling by NOTCH1 in Cancer ⚕	—
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	electronic
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription	electronic
R-HSA-1257604	PIP3 activates AKT signaling	—
R-HSA-6807070	PTEN Regulation	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-8943724	Regulation of PTEN gene transcription	electronic
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	—
R-HSA-2990846	SUMOylation	—
R-HSA-162582	Signal Transduction	—
R-HSA-157118	Signaling by NOTCH	—
R-HSA-1980143	Signaling by NOTCH1	—

MSigDB gene sets: 291 (showing top): PID_HDAC_CLASSI_PATHWAY, REACTOME_SIGNALING_BY_NOTCH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_DEACYLATION, GOBP_OSTEOBLAST_DIFFERENTIATION, MEF2_02, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION, GOBP_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_PEPTIDYL_LYSINE_MODIFICATION, LIU_VAV3_PROSTATE_CARCINOGENESIS_DN, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA-templated transcription (GO:0006351), protein deacetylation (GO:0006476), protein sumoylation (GO:0016925), negative regulation of interleukin-2 production (GO:0032703), epigenetic regulation of gene expression (GO:0040029), negative regulation of osteoblast differentiation (GO:0045668), regulation of mRNA processing (GO:0050684), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (13): chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), histone deacetylase activity (GO:0004407), protein kinase C binding (GO:0005080), SUMO transferase activity (GO:0019789), protein kinase binding (GO:0019901), protein lysine deacetylase activity (GO:0033558), metal ion binding (GO:0046872), 14-3-3 protein binding (GO:0071889), DNA-binding transcription factor binding (GO:0140297), histone deacetylase activity, hydrolytic mechanism (GO:0141221), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

16 top-level categories:

Category	Pathways
Signaling by NOTCH1 in Cancer	2
Signaling by NOTCH1	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
SUMO E3 ligases SUMOylate target proteins	1
Generic Transcription Pathway	1
PTEN Regulation	1
Differentiation of T cells	1
Intracellular signaling by second messengers	1
Signal Transduction	1
Signaling by NOTCH	1
RNA Polymerase II Transcription	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Post-translational protein modification	1
SUMOylation	1
Disease	1

GO top-level categories

49 GO namespaces:

Category	Terms
cellular anatomical structure	3
negative regulation of DNA-templated transcription	2
binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
gene expression	1
RNA biosynthetic process	1
protein deacylation	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
negative regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
chromatin remodeling	1
regulation of gene expression	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
mRNA processing	1
regulation of mRNA metabolic process	1
cell migration involved in sprouting angiogenesis	1
positive regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
cellular component organization	1
chromatin organization	1
transcription coregulator activity	1
protein lysine deacetylase activity	1
histone modifying activity	1
protein kinase binding	1
ubiquitin-like protein transferase activity	1
kinase binding	1
deacetylase activity	1
catalytic activity, acting on a protein	1
cation binding	1
protein binding	1
transcription factor binding	1
histone deacetylase activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
catalytic activity	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of interleukin-2 production	BP	direct assay
negative regulation of non-canonical NF-kappaB signal transduction	BP	mutant phenotype
negative regulation of osteoblast differentiation	BP	mutant phenotype
positive regulation of cell migration involved in sprouting angiogenesis	BP	mutant phenotype
protein deacetylation	BP	mutant phenotype
regulation of mRNA processing	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nucleus	CC	direct assay
14-3-3 protein binding	MF	direct assay
DNA-binding transcription factor binding	MF	physical interaction
protein kinase C binding	MF	physical interaction
protein kinase binding	MF	physical interaction
protein lysine deacetylase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,352 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDAC7	BCORL1	Q5H9F3	683
HDAC7	MMP10	P09238	677
HDAC7	NR4A1	P22736	640
HDAC7	MEF2A	Q02078	593
HDAC7	MEF2D	Q14814	593
HDAC7	KLRB1	Q12918	591
HDAC7	SIRT1	Q96EB6	542
HDAC7	TIMP1	P01033	508
HDAC7	HSD3B2	P26439	487
HDAC7	NCOR2	Q9Y618	468
HDAC7	NR4A3	Q92570	450
HDAC7	USE1	Q9NZ43	437
HDAC7	NR4A2	P43354	435
HDAC7	KAT5	Q92993	430
HDAC7	CABIN1	Q9Y6J0	425

IntAct

Human interaction partners of HDAC7 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 115 partners by confidence:

Partner	Interaction type	MIscore	Records
YWHAG	physical association	0.890	2
YWHAZ	physical association	0.800	2
SFN	physical association	0.690	2
PRKD2	physical association	0.640	6
EGFR	physical association	0.630	3
MAGI1	direct interaction	0.550	3
CALCOCO2	physical association	0.550	2
ICP0	physical association	0.520	3
PATJ	direct interaction	0.440	9
GRIP1	direct interaction	0.440	5
GRIP2	direct interaction	0.440	5
MAGI2	direct interaction	0.440	5
DLG1	direct interaction	0.440	3
DLG3	direct interaction	0.440	3
DLG4	direct interaction	0.440	3
FRMPD2	direct interaction	0.440	3
IL16	direct interaction	0.440	3
LNX1	direct interaction	0.440	3
MPDZ	direct interaction	0.440	3
PDZK1	direct interaction	0.440	3
SCRIB	direct interaction	0.440	3
WHRN	direct interaction	0.440	3
APBA1	direct interaction	0.440	2
APBA2	direct interaction	0.440	2
DLG2	direct interaction	0.440	2
GRID2IP	direct interaction	0.440	2
LNX2	direct interaction	0.440	2
TJP1	direct interaction	0.440	2
AHNAK	direct interaction	0.440	1
APBA3	direct interaction	0.440	1

BioGRID (251 interactions; top human partners by supporting records): CTNNB1 (Affinity Capture-MS; 10 records), YWHAQ (Affinity Capture-MS; 7 records), YWHAE (Affinity Capture-MS; 6 records), YWHAH (Affinity Capture-MS; 6 records), HIF1A (Two-hybrid; 4 records), MEF2A (Affinity Capture-Western; 4 records), YWHAB (Affinity Capture-MS; 4 records), YWHAG (Affinity Capture-MS; 4 records), YWHAZ (Affinity Capture-MS; 4 records), ACTN4 (Two-hybrid; 3 records), ADNP (Affinity Capture-MS; 3 records), CALCOCO2 (Two-hybrid; 3 records), DCAF10 (Affinity Capture-MS; 3 records), EDNRA (Affinity Capture-Western; 3 records), FLYWCH2 (Affinity Capture-MS; 3 records)

SIGNOR signaling

showing 21 of 42 signaling interactions:

A	Effect	B	Mechanism
PRKD1	down-regulates	HDAC7	phosphorylation
HDAC7	down-regulates	PLAG1	deacetylation
HDAC7	down-regulates	PLAGL2	deacetylation
MAP3K7	down-regulates	HDAC7	phosphorylation
MARK2	down-regulates	HDAC7	phosphorylation
PRKAA1	down-regulates	HDAC7	phosphorylation
AMPK	down-regulates	HDAC7	phosphorylation
PPP2CB	“up-regulates activity”	HDAC7	dephosphorylation
PPP2CA	“up-regulates activity”	HDAC7	dephosphorylation
BCORL1	“up-regulates activity”	HDAC7	binding
PRKD1	unknown	HDAC7	phosphorylation
belinostat	“down-regulates activity”	HDAC7	“chemical inhibition”
panobinostat	“down-regulates activity”	HDAC7	“chemical inhibition”
“N-[4-[(hydroxyamino)-oxomethyl]phenyl]carbamic acid [6-(diethylaminomethyl)-2-naphthalenyl]methyl ester”	“down-regulates activity”	HDAC7	“chemical inhibition”
vorinostat	“down-regulates activity”	HDAC7	“chemical inhibition”
N-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide	“down-regulates activity”	HDAC7	“chemical inhibition”
“trichostatin A”	“down-regulates activity”	HDAC7	“chemical inhibition”
romidepsin	“down-regulates activity”	HDAC7	“chemical inhibition”
6-(1,3-dioxo-2-benzo[de]isoquinolinyl)-N-hydroxyhexanamide	“down-regulates activity”	HDAC7	“chemical inhibition”
PRKD3	“up-regulates activity”	HDAC7	phosphorylation
PRKD2	“up-regulates activity”	HDAC7	phosphorylation

Protein complexes (CORUM) (7)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

7 complexes by size:

Complex	Subunits	Members
★ HDAC7-CTNNB1-YWHAE-YWHAH-YWHAZ complex	5	HDAC7, YWHAE, YWHAH, YWHAZ, CTNNB1
★ FOXP3-HDAC7-KAT5 complex	3	HDAC7, KAT5, FOXP3
★ ACTN4-HDAC7 complex	2	ACTN4, HDAC7
★ ACTN1-HDAC7 complex	2	ACTN1, HDAC7
★ BCL6-HDAC7 complex	2	BCL6, HDAC7
★ HDAC7-RARA complex	2	HDAC7, RARA
★ HDAC7-CTNNB1 complex	2	CTNNB1, HDAC7

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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
Ras activation upon Ca2+ influx through NMDA receptor	5	37.1×	9e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	35.3×	9e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	35.3×	9e-06
Assembly and cell surface presentation of NMDA receptors	10	33.0×	5e-11
Dopamine Neurotransmitter Release Cycle	5	32.2×	1e-05
Protein-protein interactions at synapses	9	31.0×	1e-09
Long-term potentiation	5	30.9×	1e-05
Neurexins and neuroligins	12	30.7×	9e-13

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	59.2×	1e-14
protein localization to synapse	6	42.6×	8e-07
receptor clustering	7	40.5×	1e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	32.1×	4e-07
protein targeting	5	17.0×	8e-04
Rho protein signal transduction	5	11.5×	3e-03
cell-cell adhesion	11	10.3×	1e-06
regulation of small GTPase mediated signal transduction	6	8.0×	4e-03

Disease & clinical

Genetic variants

Variant evidence for HDAC7: 193 ClinVar records (0 pathogenic / likely pathogenic); 42 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	148
Likely benign	9
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 2,269):

Position(s)	Effect	Δscore	Sites
12:47785472–47785473	acceptor_loss	1.0000	5
12:47785474	acceptor_gain	1.0000
12:47785886–47785887	acceptor_loss	1.0000	4
12:47787710–47787711	donor_loss	1.0000	4
12:47787810–47787811	acceptor_loss	1.0000	6
12:47788043–47788044	donor_loss	1.0000	5
12:47788064	donor_gain	1.0000
12:47788165–47788166	acceptor_loss	1.0000	5
12:47788167–47788169	acceptor_gain	1.0000	2
12:47789259–47789260	donor_loss	1.0000	2

AlphaMissense

1,772 missense substitutions predicted likely pathogenic (of 6,363 scored), across 410 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M528	9	0.956	0.996
D801	8	0.995	0.999
D707	8	0.994	0.999
H669	8	0.992	0.998
H670	8	0.992	0.997
H531	8	0.991	0.998
H709	8	0.991	0.998
D705	8	0.990	0.996
H730	8	0.989	0.997
H581	8	0.988	0.995
D624	8	0.984	0.996
H544	8	0.982	0.994
H541	8	0.981	0.996
F800	8	0.977	0.998
D525	8	0.976	0.997
H710	8	0.976	0.989
F738	8	0.972	0.998
D626	8	0.969	0.993
F679	8	0.969	0.999
F682	8	0.969	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000809
Lung Adenocarcinoma (validation)	unfavorable	0.000903

Disease associations

OMIM: gene MIM:606542 | disease phenotypes:

GWAS associations

showing 30 of 42 associations:

Study	Trait	p-value
GCST90002402_43	Platelet count	1e-41
GCST90002402_44	Platelet count	3e-39
GCST90002400_302	Plateletcrit	2e-32
GCST90002400_301	Plateletcrit	3e-28
GCST004603_32	Platelet count	6e-18
GCST90002388_329	Lymphocyte count	2e-17
GCST90002389_462	Lymphocyte percentage of white cells	2e-16
GCST005038_111	Allergic disease (asthma, hay fever or eczema)	3e-16
GCST90002390_132	Mean corpuscular hemoglobin	5e-16
GCST90002399_434	Neutrophil percentage of white cells	6e-15
GCST004607_257	Plateletcrit	1e-13
GCST007799_12	Asthma (adult onset)	2e-13
GCST90002392_59	Mean corpuscular volume	3e-13
GCST90002395_387	Mean platelet volume	3e-13
GCST90002407_425	White blood cell count	3e-12
GCST90002401_145	Platelet distribution width	1e-11
GCST90002396_52	Mean reticulocyte volume	3e-11
GCST90014033_27	Haemorrhoidal disease	6e-11
GCST007611_6	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	7e-11
GCST010043_44	Asthma	7e-11
GCST004627_24	Lymphocyte count	2e-10
GCST007099_123	Systolic blood pressure	2e-10
GCST007993_14	Asthma (adult onset)	2e-10
GCST90020029_1270	Waist circumference adjusted for body mass index	2e-10
GCST90020024_601	A body shape index	2e-9
GCST90002395_388	Mean platelet volume	3e-9
GCST010042_57	Asthma	4e-9
GCST006670_11	Primary sclerosing cholangitis	5e-9
GCST009720_43	Asthma	5e-9
GCST90020027_368	Waist-hip index	5e-9

EFO canonical traits (from GWAS)

17 canonical traits:

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004587	lymphocyte count
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:1002011	adult onset asthma
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004731	eye measurement
EFO:0010729	sun exposure measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007984	platelet component distribution width
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2093865 (PROTEIN FAMILY), CHEMBL2716 (SINGLE PROTEIN), CHEMBL4630738 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193803 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 444,851 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

28 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL408513	BELINOSTAT	4	8,184
CHEMBL118	CELECOXIB	4	113,751
CHEMBL1213492	GIVINOSTAT	4	2,960
CHEMBL483254	PANOBINOSTAT	4	12,172
CHEMBL1469	PHENYLBUTANOIC ACID	4	37,412
CHEMBL343448	ROMIDEPSIN	4	13,626
CHEMBL1746	SODIUM PHENYLBUTYRATE	4	5,678
CHEMBL98	VORINOSTAT	4	51,304
CHEMBL2103863	ABEXINOSTAT	3	2,290
CHEMBL145	CAFFEIC ACID	3	36,727
CHEMBL140	CURCUMIN	3	95,185
CHEMBL27759	ENTINOSTAT	3	6,811
CHEMBL1851943	PRACINOSTAT	3	2,099
CHEMBL235191	TACEDINALINE	3	2,995
CHEMBL3621988	TUCIDINOSTAT	3	2,280
CHEMBL191482	AR-42	2	2,146
CHEMBL284616	CHLOROGENIC ACID	2	42,390
CHEMBL3693786	CITARINOSTAT	2	1,061
CHEMBL356066	DACINOSTAT	2	3,152
CHEMBL3622533	FIMEPINOSTAT	2	2,628
CHEMBL1801250	NANATINOSTAT	2
CHEMBL2105763	QUISINOSTAT	2
CHEMBL2364628	RICOLINOSTAT	2
CHEMBL598797	CUDC-101	1
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1
CHEMBL353581	PYROXAMIDE	1
CHEMBL609583	R-306465	1
CHEMBL99	TRICHOSTATIN	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Histone deacetylases (HDACs)

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
panobinostat	Inhibition	7.85	pEC50
TMP269	Inhibition	7.37	pIC50
belinostat	Inhibition	7.12	pKi
quisinostat	Inhibition	6.92	pIC50
trichostatin A	Inhibition	6.71	pKi
givinostat	Inhibition	6.62	pKi
CUDC-101	Inhibition	6.43	pIC50
KA1010	Inhibition	6.01	pIC50
romidepsin	Inhibition	5.9	pKi
scriptaid	Inhibition	5.65	pKi
SS-208	Inhibition	5.08	pIC50
dacinostat	Inhibition	5.02	pKi

Binding affinities (BindingDB)

2096 measured of 2501 human assays (2547 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
GNF-Pf-1011	IC50	0.001 nM
CHEMBL4237803	KI	0.075 nM
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	IC50	0.08 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
JNJ-26481585	IC50	0.1 nM
CHEMBL113303	IC50	0.11 nM
CHEMBL3622726	IC50	0.12 nM
4sc-202	IC50	0.16 nM
CHEMBL4532398	IC50	0.19 nM
(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
CHEMBL1793991	IC50	0.2 nM
CHEMBL4241370	KI	0.27 nM
CHEMBL1836142	IC50	0.28 nM
(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
CHEMBL5199116	IC50	0.3 nM
CHEMBL5170036	IC50	0.3 nM
CHEMBL5433552	IC50	0.34 nM
CHEMBL5395502	IC50	0.43 nM
HC toxin	KI	0.44 nM
CHEMBL3828518	IC50	0.45 nM
CHEMBL3827517	IC50	0.55 nM
CHEMBL99392	KI	0.6 nM
CHEMBL3827814	IC50	0.65 nM
(6S,9S,12S,14aR)-6-((S)-sec-Butyl)-9-(1-methoxy-1H-indol-3-ylmethyl)-12-(6-oxo-octyl)-decahydro-4a,7,10,13-tetraaza-benzocyclododecene-5,8,11,14-tetraone	IC50	0.7 nM
(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
(S)-N8-hydroxy-2-(2-(5-methoxy-2-methyl-1H-indol-3-yl)acetamido)-N1-(2-(2-phenyl-1H-indol-3-yl)ethyl)octanediamide	IC50	0.8 nM
CHEMBL2047540	IC50	0.9 nM
CHEMBL4592929	IC50	0.918 nM
(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
HDAC inhibitor, Compound 1	IC50	1 nM
CHEMBL3310505	IC50	1 nM
CHEMBL3758184	IC50	1 nM
CHEMBL3827281	IC50	1 nM
CHEMBL3827894	IC50	1 nM
CHEMBL1793823	IC50	1 nM
CHEMBL1793947	IC50	1 nM
CHEMBL4467135	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
CHEMBL1836145	IC50	1.2 nM
CHEMBL4444219	IC50	1.2 nM
CHEMBL1793992	IC50	1.3 nM
CHEMBL99661	IC50	1.4 nM
N-[[4-(propylaminocarbamoyl)phenyl]methyl]-1H-indole-2-carboxamide	IC50	1.5 nM	US-20240327418: MULTI-TARGET INHIBITOR TARGETING HDAC AND NAD SYNTHESIS AND USE OF MULTI-TARGET INHIBITOR
(E)-3-[4-[(cyclohexylmethylamino)methyl]phenyl]-N-hydroxyprop-2-enamide	IC50	1.8 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
CHEMBL3759186	IC50	1.8 nM
6-(6-Methoxynaphthalyl)Triazolylhexahydroxamic Acid	IC50	1.8 nM
CHEMBL4517151	IC50	1.8 nM
6-(3-Biphenyl)Triazolylhexahydroxamic Acid	IC50	1.9 nM
BRD2492	IC50	2 nM

ChEMBL bioactivities

3434 potent at pChembl≥5 of 3844 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.77	IC50	0.17	nM	CHEMBL5433552
9.70	IC50	0.2	nM	CHEMBL2371007
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
9.52	IC50	0.3	nM	CHEMBL2370998
9.52	IC50	0.3	nM	CHEMBL5199116
9.52	IC50	0.3	nM	CHEMBL5170036
9.52	IC50	0.3	nM	CHEMBL1793822
9.46	IC50	0.35	nM	VORINOSTAT
9.40	IC50	0.4	nM	CHEMBL2371000
9.40	IC50	0.4	nM	CHEMBL1793816
9.08	IC50	0.83	nM	PANOBINOSTAT
9.05	IC50	0.9	nM	CHEMBL605110
9.02	IC50	0.95	nM	CHEMBL595479
9.00	IC50	1	nM	CHEMBL3758184
9.00	IC50	1	nM	APICIDIN
9.00	IC50	1	nM	CHEMBL2371003
9.00	IC50	1	nM	ROMIDEPSIN
9.00	IC50	1	nM	CHEMBL4467135
9.00	IC50	1	nM	CHEMBL3692689
9.00	IC50	1	nM	CHEMBL595711
9.00	IC50	1	nM	CHEMBL595910
9.00	IC50	1	nM	CHEMBL1793947
9.00	IC50	1	nM	CHEMBL1793810
9.00	IC50	1	nM	CHEMBL1793823
8.99	IC50	1.03	nM	CHEMBL1214760
8.98	IC50	1.05	nM	CHEMBL594544
8.92	IC50	1.2	nM	CHEMBL604796
8.92	IC50	1.2	nM	CHEMBL608416
8.92	IC50	1.2	nM	CHEMBL594544
8.89	IC50	1.3	nM	CHEMBL1793992
8.85	IC50	1.4	nM	CHEMBL99661
8.85	IC50	1.42	nM	TRICHOSTATIN
8.82	IC50	1.5	nM	TRICHOSTATIN
8.82	IC50	1.5	nM	CHEMBL5280445
8.82	IC50	1.5	nM	CHEMBL594743
8.82	IC50	1.5	nM	CHEMBL593846
8.82	IC50	1.5	nM	CHEMBL594542
8.77	Ki	1.7	nM	QUISINOSTAT
8.77	IC50	1.7	nM	CHEMBL595908
8.74	IC50	1.8	nM	CHEMBL478727
8.74	IC50	1.8	nM	CHEMBL26159
8.74	IC50	1.8	nM	CHEMBL595910
8.72	IC50	1.9	nM	CHEMBL477093
8.70	IC50	2	nM	CHEMBL99392
8.70	IC50	2	nM	CHEMBL150237
8.70	IC50	2	nM	CHEMBL4228565
8.70	IC50	2	nM	CHEMBL4228304

PubChem BioAssay actives

2425 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-(4-methylphenyl)sulfonylpiperazin-1-yl]-1,3-thiazole-5-carboxamide	1941741: Inhibition of HDAC (unknown origin)	ic50	0.0001	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
(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
(3S,6S,9S,12R)-3-[(2S)-butan-2-yl]-9-(7-hydroxy-6-oxooctyl)-6-[(1-methoxyindol-3-yl)methyl]-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	90356: Inhibitory concentration against human Histone deacetylase in Hela cells	ic50	0.0003	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-(4-phenylphenyl)but-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0009	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-(4-methoxyphenyl)but-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	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
7-(5-bromo-2-oxo-3H-indol-1-yl)-N-hydroxyheptanamide	2237987: Inhibition of HDAC in human HeLa cells nuclear extract	ic50	0.0010	uM
N-hydroxy-6-[(2S,5S,8S,11S)-8-(1H-indol-3-ylmethyl)-2-methyl-11-(2-methylpropyl)-3,6,9,13-tetraoxo-1,4,7,10-tetrazacyclotridec-5-yl]hexanamide	447991: Inhibition of HDAC in human HeLa cell nuclear extract after 30 mins by fluorimetric assay	ic50	0.0010	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-(4-methylphenyl)but-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0010	uM
6-[(5S,8S,11R)-11-[(2S)-butan-2-yl]-8-(1H-indol-2-ylmethyl)-3,6,9,13-tetraoxo-1,4,7,10-tetrazacyclotridec-5-yl]-N-hydroxyhexanamide	487230: Inhibition of HDAC in human HeLa cells	ic50	0.0010	uM
7-[4-[4-[[[(2S,3R,4S,6R)-2-[[(2R,4R,5R,6R,8R,11R,12S,19R,20R)-11-ethyl-4-methoxy-2,4,6,8,12,19-hexamethyl-7,9,14-trioxo-10,13-dioxa-15,18-diazatricyclo[10.6.2.015,20]icos-1(18)-en-5-yl]oxy]-3-hydroxy-6-methyloxan-4-yl]-methylamino]methyl]phenyl]triazol-1-yl]-N-hydroxyheptanamide	499799: Inhibition of HDAC in human HeLa cell nuclear extracts	ic50	0.0010	uM
(E)-N-hydroxy-3-[4-oxo-1’-(2-phenylethyl)spiro[3H-chromene-2,3’-piperidine]-6-yl]prop-2-enamide	1273866: Inhibition of HDAC in human HeLa cells nuclear extract using Fluor de lys as substrate after 15 mins by fluorometric analysis	ic50	0.0010	uM
2-[4-[(E)-4-(3-fluorophenyl)-1-hydroxybut-3-en-2-yl]piperazin-1-yl]-N-hydroxypyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0012	uM
2-[4-[(E)-4-(4-chlorophenyl)-1-hydroxybut-3-en-2-yl]piperazin-1-yl]-N-hydroxypyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0012	uM
N’-hydroxy-N-[(2R)-4-(methylamino)-3-oxo-1-phenylbutan-2-yl]octanediamide	90195: Concentration required to inhibit Histone Deacetylase (HDAC) from K562 erythroleukemia cells	ic50	0.0014	uM
(2E,4E,6R)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide	1273502: Inhibition of HDAC in human HeLa cell nuclear extract using BML-KI104 Fluor de Lys as substrate by fluorescence-based assay	ic50	0.0014	uM
N-hydroxy-2-[4-(naphthalen-2-ylmethyl)piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0015	uM
N-hydroxy-2-[4-[(E)-1-methoxy-4-phenylbut-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0015	uM
N-hydroxy-2-[4-[[[(E)-1-hydroxy-4-phenylbut-3-en-2-yl]amino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0015	uM
N-hydroxy-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide	1399820: Inhibition of human recombinant HDAC7 using fluorogenic HDAC substrate class 2a after 45 mins by fluorimetrc method	ki	0.0017	uM
N-hydroxy-2-[4-[(E)-4-phenylbut-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0017	uM
N-hydroxy-6-[4-(6-methoxynaphthalen-2-yl)triazol-1-yl]hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0018	uM
N-hydroxy-6-[4-(3-phenylphenyl)triazol-1-yl]hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0019	uM
2-[2-[2-[[(2E)-3-(3-bromo-4-hydroxyphenyl)-2-hydroxyiminopropanoyl]amino]ethyldisulfanyl]ethylamino]-2-oxoacetic acid	90530: Inhibitory concentration against isolated Histone deacetylase	ic50	0.0020	uM
(3S,6S,9S,12R)-3-[(2S)-butan-2-yl]-6-(1H-indol-3-ylmethyl)-9-(6-oxooctyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	81887: Inhibitory activity against histone deacetylase (HDAC) enzyme derived from partially purified extracts of human HeLa cells using [3H]11 as radioligand	ic50	0.0020	uM
6-[4-[[5-chloro-4-(4-chloroanilino)pyrimidin-2-yl]amino]pyrazol-1-yl]-N-hydroxyhexanamide	1550094: Inhibition of HDAC in human HeLa nuclear extract using Boc-Lys(acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	0.0020	uM
7-[4-[[5-chloro-4-(4-chloroanilino)pyrimidin-2-yl]amino]pyrazol-1-yl]-N-hydroxyheptanamide	1550094: Inhibition of HDAC in human HeLa nuclear extract using Boc-Lys(acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	0.0020	uM
4-[(E)-3-[[(2S)-1-(4-bromoanilino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-oxoprop-1-enyl]-N-hydroxybenzamide	1390020: Inhibition of HDAC in human HeLa cell nuclear extract using Boc-Lys (acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by fluorescence assay	ic50	0.0020	uM
4-[(E)-3-[[(2S)-1-(4-fluoroanilino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-oxoprop-1-enyl]-N-hydroxybenzamide	1390020: Inhibition of HDAC in human HeLa cell nuclear extract using Boc-Lys (acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by fluorescence assay	ic50	0.0020	uM
2-(6-ethoxy-3-pyridinyl)-N-[7-(hydroxyamino)-7-oxoheptyl]-9-(2-methoxy-3-pyridinyl)-8-oxo-7H-purine-6-carboxamide	2079009: Inhibition of HDAC in human HeLa cells nuclear extract	ic50	0.0020	uM
2-[4-[(E)-4-(2-fluorophenyl)-1-hydroxybut-3-en-2-yl]piperazin-1-yl]-N-hydroxypyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0020	uM
N-hydroxy-7-[5-(4-methoxyphenyl)-1,3-oxazol-2-yl]heptanamide	316872: Inhibition of HDAC from human K562 cells	ic50	0.0021	uM
N-hydroxy-6-[4-(4-methoxyphenyl)triazol-1-yl]hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0021	uM
tert-butyl (8R,9R,12S)-12-[[6-(hydroxyamino)-6-oxohexyl]carbamoyl]-9-(2-methylpropyl)-2-oxa-11-azabicyclo[12.2.2]octadeca-1(16),14,17-triene-8-carboxylate	90195: Concentration required to inhibit Histone Deacetylase (HDAC) from K562 erythroleukemia cells	ic50	0.0021	uM
N-hydroxy-6-(4-quinolin-2-yltriazol-1-yl)hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0021	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-[4-(trifluoromethyl)phenyl]but-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0021	uM
6-[4-(4-bromoanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyhexanamide	1720096: Inhibition of HDAC (unknown origin)	ic50	0.0022	uM
7-[4-(4-bromoanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyheptanamide	1275247: Inhibition of HDAC in human HeLa cell nuclear extracts preincubated for 15 mins followed by addition of Fluor de Lys as substrate for 1 hr by fluorometric assay	ic50	0.0022	uM
N-hydroxy-6-[4-(4-pyridin-4-ylphenyl)triazol-1-yl]hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0023	uM
N-hydroxy-7-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]heptanamide	316872: Inhibition of HDAC from human K562 cells	ic50	0.0025	uM
7-[5-(4-bromophenyl)-1,3-oxazol-2-yl]-N-hydroxyheptanamide	316872: Inhibition of HDAC from human K562 cells	ic50	0.0027	uM
(E)-N-hydroxy-3-[4-[2-(2-methyl-1H-indol-3-yl)ethylsulfamoyl]phenyl]prop-2-enamide	1187258: Inhibition of HDAC in human HeLa cells nuclear extracts incubated for 30 mins by fluorescent assay	ic50	0.0028	uM
6-[4-(2,4-dichloroanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyhexanamide	1256443: Inhibition of human HDAC in HeLa cell nuclear extract by fluorometric assay using Fluor de Lys substrate	ic50	0.0028	uM
7-[4-(2,4-dichloroanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyheptanamide	1915571: Inhibition of HDAC (unknown origin)	ic50	0.0028	uM
N-hydroxy-7-[4-(2-methylphenyl)triazol-1-yl]heptanamide	456795: Inhibition of HDAC in human HeLa cell nuclear extracts after 15 mins by fluorescence assay	ic50	0.0028	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Vorinostat	affects cotreatment, decreases expression	3
Air Pollutants	increases abundance, increases oxidation, affects expression, increases expression, affects cotreatment	3
Valproic Acid	affects expression, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression	2
Estradiol	affects expression, decreases expression, increases reaction	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Particulate Matter	increases abundance, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
propionaldehyde	decreases expression	1
bisphenol A	increases expression	1
arsenite	decreases methylation	1
sodium arsenite	affects expression, decreases expression, increases reaction	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
monomethylarsonous acid	increases expression, affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1

ChEMBL screening assays

1710 unique, capped per target: 1695 binding, 10 admet, 4 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

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8HB	Abcam HCT 116 HDAC7 KO	Cancer cell line	Male
CVCL_B8WP	Abcam MCF-7 HDAC7 KO	Cancer cell line	Female
CVCL_F6HW	EDITGENE HDAC7 Knockout HAP1 Cell Line	Cancer cell line	Male
CVCL_SR16	HAP1 HDAC7 (-) 1	Cancer cell line	Male
CVCL_SR17	HAP1 HDAC7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for HDAC7 across ~30M SureChEMBL compounds — explore on Sugi Predict.