HDAC5

Summary

HDAC5 (histone deacetylase 5, HGNC:14068) is a protein-coding gene on chromosome 17q21.31, encoding Histone deacetylase 5 (Q9UQL6). In vitro, it deacetylates 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 belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10014 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 174 total
• Regional missense constraint (gnomAD): 1 of 9 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 9 tissues, sQTL in 5 (q < 0.05)
• ChEMBL bioactivity: 30 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.27 (highly constrained)
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_005474
• Interaction hub: 2,788 STRING partners (top 3% of genes corpus-wide)
• Notable: 174 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14068
Approved symbol	HDAC5
Name	histone deacetylase 5
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0600, NY-CO-9, FLJ90614
Ensembl gene	ENSG00000108840
Ensembl biotype	protein_coding
OMIM	605315
Entrez	10014

Gene structure

Transcript identifiers

Ensembl transcripts: 84 — 62 protein_coding, 17 nonsense_mediated_decay, 5 retained_intron

MANE Select: ENST00000682912

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

ENST00000682912, ENST00000225983, ENST00000336057, ENST00000586339, ENST00000586802, ENST00000587135, ENST00000587776, ENST00000588261, ENST00000588419, ENST00000588703, ENST00000591714, ENST00000592385, ENST00000593013, ENST00000715273, ENST00000864900, ENST00000864901, ENST00000864902, ENST00000864903, ENST00000864904, ENST00000864905, ENST00000864906, ENST00000864907, ENST00000864908, ENST00000864909, ENST00000864910, ENST00000864911, ENST00000864912, ENST00000864913, ENST00000864914, ENST00000864915, ENST00000864916, ENST00000864917, ENST00000864918, ENST00000864919, ENST00000864920, ENST00000864921, ENST00000864922, ENST00000864923, ENST00000864924, ENST00000864925, ENST00000925825, ENST00000925826, ENST00000925827, ENST00000925828, ENST00000925829, ENST00000925830, ENST00000925831, ENST00000925832, ENST00000968358, ENST00000968359, ENST00000968360, ENST00000968361, ENST00000968362, ENST00000968363, ENST00000968364, ENST00000968365, ENST00000968366, ENST00000968367, ENST00000968368, ENST00000968369, ENST00000968370, ENST00000968371, ENST00000968372, ENST00000968373, ENST00000986821, ENST00000986822, ENST00001057569, ENST00001057570, ENST00001057572, ENST00001057573, ENST00001057574, ENST00001057575, ENST00001057576, ENST00001057577, ENST00001057578, ENST00001057579, ENST00001057580, ENST00001057581, ENST00001057582, ENST00001057583, ENST00001057584, ENST00001057585, ENST00001057586, ENST00001141966

RefSeq mRNA: 3 — MANE Select: NM_005474 NM_001015053, NM_001382393, NM_005474

CCDS: CCDS32663, CCDS45696

Canonical transcript exons

ENST00000682912 — 27 exons

Exon	Start	End
ENSE00000731166	44080763	44080882
ENSE00000731172	44079144	44079277
ENSE00000731173	44078795	44078879
ENSE00000731174	44078500	44078665
ENSE00001619144	44093575	44093834
ENSE00001669662	44093314	44093485
ENSE00001711158	44110729	44110800
ENSE00001724889	44092172	44092284
ENSE00001739338	44080107	44080225
ENSE00002261772	44117494	44117704
ENSE00002350210	44080401	44080498
ENSE00002425474	44082585	44082672
ENSE00003478670	44091700	44091831
ENSE00003482191	44088387	44088598
ENSE00003484375	44085022	44085155
ENSE00003521425	44087412	44087696
ENSE00003533985	44092676	44092806
ENSE00003562125	44083545	44083652
ENSE00003586612	44086572	44086737
ENSE00003605327	44084555	44084675
ENSE00003622443	44082765	44082820
ENSE00003650856	44092381	44092527
ENSE00003653051	44083805	44083854
ENSE00003666410	44091270	44091492
ENSE00003691295	44093092	44093206
ENSE00003918270	44076753	44078415
ENSE00003921347	44123504	44123641

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 97.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.1749 / max 773.4901, expressed in 1816 samples.

Highest expression (Bgee): cortical plate, lower esophagus mucosa, skin of leg, skin of abdomen, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

HDAC5 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	3.7e-15	+0.22	17:44103454:T:A
Heart Atrial Appendage	eqtl	6.1e-05	+0.26	17:44869703:G:C
Skin Sun Exposed Lower leg	eqtl	2.4e-03	+0.09	17:43864540:C:A
Cells Cultured fibroblasts	eqtl	3.2e-03	-0.12	17:43632899:A:G
Cells EBV-transformed lymphocytes	eqtl	5.9e-03	-0.22	17:44208372:T:C
Nerve Tibial	eqtl	6.1e-03	-0.10	17:44336113:C:T
Artery Tibial	sqtl	6.4e-03	-0.28	17:44093838:T:C
Esophagus Muscularis	sqtl	7.5e-03	+0.42	17:44017517:A:G
Thyroid	eqtl	1.4e-02	+0.09	17:43989126:A:G
Brain Hypothalamus	sqtl	2.3e-02	+4.23	17:43973623:C:G
Brain Hypothalamus	eqtl	2.8e-02	+0.52	17:44053724:G:A
Brain Frontal Cortex BA9	sqtl	3.6e-02	-0.53	17:44212647:G:A
Adipose Subcutaneous	eqtl	3.7e-02	-0.17	17:44399041:G:A
Thyroid	sqtl	5.0e-02	-1.36	17:43470145:A:G

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
166311	15.8474	1796
166310	12.7901	1744
166307	1.9301	806
166306	0.2162	107
166304	0.1551	71
166309	0.1258	59
166303	0.1101	56

Top tissues by expression

showing 100 of 275 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.07	gold quality
lower esophagus mucosa	UBERON:0035834	96.61	gold quality
skin of leg	UBERON:0001511	96.59	gold quality
skin of abdomen	UBERON:0001416	96.42	gold quality
ganglionic eminence	UBERON:0004023	96.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.96	gold quality
right frontal lobe	UBERON:0002810	95.87	gold quality
popliteal artery	UBERON:0002250	95.78	gold quality
tibial artery	UBERON:0007610	95.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.74	gold quality
apex of heart	UBERON:0002098	95.68	gold quality
cerebellar hemisphere	UBERON:0002245	95.48	gold quality
aorta	UBERON:0000947	95.46	gold quality
mucosa of stomach	UBERON:0001199	95.44	gold quality
adenohypophysis	UBERON:0002196	95.41	gold quality
cerebellar cortex	UBERON:0002129	95.35	gold quality
ascending aorta	UBERON:0001496	95.31	gold quality
thoracic aorta	UBERON:0001515	95.23	gold quality
left ovary	UBERON:0002119	95.18	gold quality
prefrontal cortex	UBERON:0000451	95.10	gold quality
right ovary	UBERON:0002118	94.72	gold quality
cingulate cortex	UBERON:0003027	94.61	gold quality
gastrocnemius	UBERON:0001388	94.60	gold quality
sural nerve	UBERON:0015488	94.56	gold quality
right lung	UBERON:0002167	94.54	gold quality
lower esophagus	UBERON:0013473	94.51	gold quality
descending thoracic aorta	UBERON:0002345	94.50	gold quality
anterior cingulate cortex	UBERON:0009835	94.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.50	gold quality
pituitary gland	UBERON:0000007	94.43	gold quality
body of uterus	UBERON:0009853	94.35	gold quality
muscle of leg	UBERON:0001383	94.32	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.23	gold quality
right atrium auricular region	UBERON:0006631	94.20	gold quality
ventricular zone	UBERON:0003053	94.05	gold quality
ectocervix	UBERON:0012249	94.01	gold quality
endocervix	UBERON:0000458	93.88	gold quality
heart left ventricle	UBERON:0002084	93.85	gold quality
amygdala	UBERON:0001876	93.83	gold quality
right coronary artery	UBERON:0001625	93.77	gold quality
esophagus	UBERON:0001043	93.73	gold quality
zone of skin	UBERON:0000014	93.71	gold quality
nerve	UBERON:0001021	93.68	gold quality
tibial nerve	UBERON:0001323	93.68	gold quality
cerebellum	UBERON:0002037	93.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.57	gold quality
cardiac ventricle	UBERON:0002082	93.39	gold quality
right lobe of thyroid gland	UBERON:0001119	93.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.30	gold quality
esophagus mucosa	UBERON:0002469	93.26	gold quality
granulocyte	CL:0000094	93.03	gold quality
left lobe of thyroid gland	UBERON:0001120	93.01	gold quality
left uterine tube	UBERON:0001303	92.95	gold quality
left coronary artery	UBERON:0001626	92.82	gold quality
stromal cell of endometrium	CL:0002255	92.75	gold quality
cardiac atrium	UBERON:0002081	92.75	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.69	gold quality
neocortex	UBERON:0001950	92.66	gold quality
right uterine tube	UBERON:0001302	92.63	gold quality
heart	UBERON:0000948	92.43	gold quality
frontal cortex	UBERON:0001870	92.40	gold quality
coronary artery	UBERON:0001621	92.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.32	gold quality
hypothalamus	UBERON:0001898	92.26	gold quality
thyroid gland	UBERON:0002046	92.05	gold quality
omental fat pad	UBERON:0010414	92.04	gold quality
peritoneum	UBERON:0002358	92.00	gold quality
blood	UBERON:0000178	91.89	gold quality
upper lobe of left lung	UBERON:0008952	91.71	gold quality
spinal cord	UBERON:0002240	91.65	gold quality
muscle organ	UBERON:0001630	91.58	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.58	gold quality
nucleus accumbens	UBERON:0001882	91.33	gold quality
monocyte	CL:0000576	91.17	gold quality
cerebral cortex	UBERON:0000956	91.07	gold quality
ovary	UBERON:0000992	91.01	gold quality
vagina	UBERON:0000996	90.98	gold quality
central nervous system	UBERON:0001017	90.95	gold quality
brain	UBERON:0000955	90.93	gold quality
forebrain	UBERON:0001890	90.93	gold quality
leukocyte	CL:0000738	90.76	gold quality
gall bladder	UBERON:0002110	90.75	gold quality
mononuclear cell	CL:0000842	90.65	gold quality
telencephalon	UBERON:0001893	90.64	gold quality
minor salivary gland	UBERON:0001830	90.60	gold quality
substantia nigra	UBERON:0002038	90.54	gold quality
caudate nucleus	UBERON:0001873	90.49	gold quality
putamen	UBERON:0001874	90.46	gold quality
body of stomach	UBERON:0001161	90.34	gold quality
upper lobe of lung	UBERON:0008948	90.24	gold quality
left adrenal gland cortex	UBERON:0035825	90.24	gold quality
left adrenal gland	UBERON:0001234	90.21	gold quality
embryo	UBERON:0000922	90.18	gold quality
spleen	UBERON:0002106	89.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.88	gold quality
anatomical system	UBERON:0000467	89.71	gold quality
metanephros cortex	UBERON:0010533	89.61	gold quality
midbrain	UBERON:0001891	89.60	gold quality
multicellular organism	UBERON:0000468	89.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.39
E-MTAB-10137	no	311.66

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Locus coeruleus	tissue	112.1
Hippocampus	tissue	100.5	medium
Postcentral gyrus	tissue	98.5
Nucleus accumbens	tissue	73.8
Skeletal muscle	tissue	63.2	low
Cerebral cortex	tissue	59.4	medium
Motor cortex	tissue	59.4
Insular cortex	tissue	56.7
Prefrontal cortex	tissue	56.2
Thalamus	tissue	56.1
Retrosplenial cortex	tissue	53.3
Hippocampal formation	tissue	52.5
Entorhinal cortex	tissue	52.5
Retrosplenial and cingulate cortex	tissue	50.8
Choroid plexus	tissue	50.5
Pons	tissue	50.3
Somatosensory cortex	tissue	50.3
Temporal cortex	tissue	50.3
Midbrain	tissue	49.6
Superior colliculi	tissue	49.4
Occipital cortex	tissue	47.7
Amygdala	tissue	45.9
Frontal cortex	tissue	45.8
Skin 1	tissue	45.1	medium
Pituitary gland	tissue	44.6
Corpus callosum	tissue	44.6
Cerebellum	tissue	44.2	medium
Substantia nigra	tissue	44.2
Olfactory bulb	tissue	43.4
Hypothalamus	tissue	43.2
Ventral forebrain	tissue	42.2
Medulla oblongata	tissue	39.5
Septum	tissue	39.5
Periaqueductal gray	tissue	38.4
Putamen	tissue	37.4
Basal ganglia	tissue	36.7	low
Caudate putamen	tissue	35.7
Vagina	tissue	35.1	medium
Spinal cord	tissue	34.8
Heart muscle	tissue	33.4	low
Parathyroid gland	tissue	29.3	medium
Tongue	tissue	26.6
Ovary	tissue	26.1	low
Esophagus	tissue	25.9	medium
Adrenal gland	tissue	22.1	medium
Retina	tissue	21.9
Adipose tissue	tissue	21.2	medium
Pancreas	tissue	21.0	medium
Placenta	tissue	21.0	medium
Fallopian tube	tissue	20.9	medium
Spleen	tissue	19.1	medium
Endometrium 1	tissue	19.0	medium
Salivary gland	tissue	18.9	high
Bone marrow	tissue	18.5	high
Lung	tissue	17.7	medium
Cervix	tissue	15.9	medium
Gallbladder	tissue	14.8	medium
Epididymis	tissue	14.3	medium
Prostate	tissue	14.2	medium
Seminal vesicle	tissue	14.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Flocculonodular lobe (143.5), Temporal white matter (142.8), Parieto-temporal junction (white matter) (142.7), Angular gyrus (white matter) (142.4), Piriform cortex (141.9).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets:

Target	Regulation
ERVW-1	Repression
FGF2	Repression
GCM1	Repression
IGF2	Unknown
MEF2A	Repression
SLC2A1	Activation
SLC2A4	Repression
SLIT2	Repression
WT1	Repression
YY1	Activation

Upstream regulators (CollecTRI, top): CAMK1

miRNA regulators (miRDB)

Targeting HDAC5 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 87 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.271, missense Z 3.88 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000682912 splits into 9 regions with different missense tolerance; 1 is missense-constrained (≈2% 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
17:44,078,379–44,078,822	95 / 107.3	0.88	no
17:44,078,823–44,083,834	174 / 352.7	0.49	no
17:44,083,835–44,084,596	31 / 27.0	1.15	no
17:44,084,597–44,086,580	42 / 101.7	0.41	no
17:44,086,581–44,092,479	433 / 531.6	0.81	no
17:44,092,480–44,092,700	8 / 31.9	0.25	yes (p 2.3e-05)
17:44,092,701–44,092,803	56 / 41.3	1.36	no
17:44,092,804–44,093,711	109 / 168.0	0.65	no
17:44,093,712–44,117,515	93 / 98.8	0.94	no

Literature-anchored findings (GeneRIF, showing 40)

• Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor (PMID:11929873)
• Histone deacetylase 5 is not a p53 target gene, but its overexpression inhibits tumor cell growth and induces apoptosis. (PMID:12019172)
• MITR, HDAC4, and HDAC5 associate with heterochromatin protein 1 (HP1), an adaptor protein that recognizes methylated lysines within histone tails and mediates transcriptional repression by recruiting histone methyltransferase (PMID:12242305)
• HDAC5 binds to Ca(2+)/calmodulin and inhibits MEF2a binding (PMID:12626519)
• ICP0 of herpes simplex virus Type 1 is able to overcome the HDAC5 amino-terminal- and MITR-induced MEF2A repression in gene reporter assays (PMID:15194749)
• The HDAC5, a class II HDAC involved in myogenesis, was not detected in the tissues. (PMID:15590418)
• G betagamma binds HDAC5 and inhibits its transcriptional co-repression activity (PMID:16221676)
• novel transcriptional pathway under the control of class II HDACs and suggest a role for these transcriptional repressors as signal-responsive regulators of antigen presentation (PMID:16236793)
• NO-dependent PP2A activation plays a key role in nuclear translocation of class II HDACs HDAC4 and HDAC5 (PMID:17975112)
• AMP-activated protein kinase (AMPK) regulates GLUT4 transcription through the histone deacetylase (HDAC)5 transcriptional repressor. (PMID:18184930)
• Chronic upregulation/activation of CaMKIID, and PKD in heart failure shifts HDAC5 out of the nucleus, derepressing transcription of hypertrophic genes. (PMID:18218981)
• Protein kinase D-HDAC5 pathway plays an important role in VEGF regulation of gene transcription and angiogenesis (PMID:18332134)
• These results indicate that HDAC4 and HDAC5 increase the transactivation function of HIF-1alpha by promoting dissociation of HIF-1alpha from FIH-1 and association with p300. (PMID:19071119)
• HDAC5 represses angiogenic genes, such as FGF2 and Slit2, which causally contribute to capillary-like sprouting of endothelial cells. (PMID:19351956)
• phosphorylation-dependent derepression of HDAC5 mediates flow-induced KLF2 and eNOS expression as well as flow anti-inflammation, and suggest that HDAC5 could be a potential therapeutic target for the prevention of atherosclerosis. (PMID:20042720)
• Findings identify HDAC5 as a substrate of PKA and reveal a cAMP/PKA-dependent pathway that controls HDAC5 nucleocytoplasmic shuttling and represses gene transcription. (PMID:20716686)
• differentiation-dependent GLUT4 gene expression in 3T3-L1 adipocytes is dependent on the nuclear concentration of a class II histone deacetylase (HDAC) protein, HDAC5 (PMID:21047791)
• Ser279 is a critical phosphorylation within the NLS involved in the nuclear import of HDAC5 (PMID:21081666)
• in addition to activation of protein kinase D isozymes by phosphorylating Ser744 and Ser748 at their activation sites, PKCdelta may also play a role in the regulation of HDAC5 by phosphorylation of Ser259 (PMID:21146494)
• Significantly increased methylation of the HDAC5 gene was associated with astrocytomas. (PMID:21508384)
• The results of this study suggested that suggest that HDAC5 provides a delayed braking mechanism on gene expression programs that support the development, but not expression, of cocaine reward behaviors. (PMID:22243750)
• HDAC5 in the maintenance/assembly of pericentric heterochromatin structure and demonstrate that class IIa HDAC5 can represent a potential target for anticancer therapies. (PMID:22301920)
• Loss of HDAC5 impairs memory function but has little impact in a transgenic mouse model of amyloid pathology. (PMID:22914591)
• The current study identified the class II deacetylase HDAC5 as a novel promoting factor of CTG*CAG expansions. (PMID:22941650)
• Data suggest that HDAC5 regulates muscle glucose metabolism and insulin action and that HDAC inhibitors can be used to modulate these parameters in muscle cells. (PMID:22991226)
• Dephosphorylation at a conserved SP motif governs cAMP sensitivity and nuclear localization of class IIa histone deacetylases HDAC4, 5 and 9 (PMID:23297420)
• Nuclear calcium signaling is a regulator of nuclear export of HDAC4 and HDAC5. (PMID:23364788)
• Data indicate there was a link between baseline viral load, age (40 years), IL-28B (rs12979860), HDAC2 (rs3778216), HDAC3 (rs976552) and HDAC5 (rs368328) with sustained virological response (SVR). (PMID:23615070)
• HDAC5 is essential for the length maintenance of long telomeres and its depletion is required for sensitization of cancer cells with long telomeres to chemotherapy. (PMID:23729589)
• findings show N-Myc upregulated HDAC5 expression in neuroblastoma cells; HDAC5 repressed NEDD4 gene expression,increased Aurora A gene expression and consequently upregulated N-Myc protein expression;data identify HDAC5 as a novel co-factor in N-Myc oncogenesis (PMID:23812427)
• At the molecular level, we demonstrated that HDAC5 promoted mRNA expression of twist 1, which has been reported as an oncogene (PMID:24092570)
• These findings suggest that HDAC5 is a key determinant of p53-mediated cell fate decisions in response to genotoxic stress. (PMID:24120667)
• we show that Stat3 binds to the promoter region of PTPN13 and promotes its activity through recruiting HDAC5. Thus, our results suggest a previously unknown Stat3-PTPN13 molecular network controlling squamous cell lung carcinoma development (PMID:24191246)
• In erythroid cells, pull down experiments identified the presence of a novel complex formed by HDAC5, GATA1, EKLF and pERK which was instead undetectable in cells of the megakaryocytic lineage. (PMID:24594363)
• HDAC5 promoted the Six1 expression. (PMID:24706304)
• In C2C12 myoblasts, recombinant human HDAC5 phosphorylation by PKD regulated the expression of diverse metabolic genes and glucose metabolism. (PMID:24732133)
• Studied phosphorylation sites within functional HDAC5 domains, including the deacetylation domain (DAC, Ser755), nuclear export signal (NES, Ser1108), and an acidic domain (AD, Ser611). (PMID:24920159)
• Data reveal a novel role of HDAC5 in modulating the KLF2 transcriptional activation and eNOS expression. (PMID:25096223)
• mRNA and protein levels of HDAC5 were up-regulated in human hepatocellular carcinoma. (PMID:25129440)
• These results suggest a strong regulatory function of HDAC5 in the pro-inflammatory response of macrophages. (PMID:26059794)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdac5	ENSDARG00000075139
mus_musculus	Hdac5	ENSMUSG00000008855
rattus_norvegicus	Hdac5	ENSRNOG00000020905
caenorhabditis_elegans		WBGENE00009657
caenorhabditis_elegans		WBGENE00009663
caenorhabditis_elegans		WBGENE00219378

Paralogs (10): HDAC9 (ENSG00000048052), HDAC7 (ENSG00000061273), HDAC4 (ENSG00000068024), HDAC6 (ENSG00000094631), HDAC10 (ENSG00000100429), HDAC1 (ENSG00000116478), HDAC8 (ENSG00000147099), HDAC11 (ENSG00000163517), HDAC3 (ENSG00000171720), HDAC2 (ENSG00000196591)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1333784) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
cardiac hypertrophy	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
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
Oryza sativa Japonica Group	Q6YV04	95.9%	Diamond
Bos taurus	Q0VCB2	95.8%	Diamond
Arabidopsis thaliana	Q8LRK8	85.9%	Diamond
Caenorhabditis briggsae	Q613L4	82.2%	Diamond
Pseudomonas aeruginosa PAO1	Q9HXM1	75.0%	Diamond
Staphylococcus xylosus	Q56195	68.8%	Diamond
Saccharomyces cerevisiae S288C	P32561	66.6%	Diamond
Dictyostelium discoideum	Q55BW2	64.3%	Diamond
Mycoplana ramosa	Q48935	52.0%	Diamond
Candida albicans SC5314	Q5A960	50.4%	Diamond
Schizosaccharomyces pombe 972h-	P56523	49.0%	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
Methanocaldococcus jannaschii DSM 2661	Q57955	38.1%	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
LSM12	protein-coding	124801
HROB	protein-coding	78995
G6PC3	protein-coding	92579
ASB16-AS1	ncRNA	339201
ASB16	protein-coding	92591
TMEM101	protein-coding	84336
ATXN7L3	protein-coding	56970
TMUB2	protein-coding	79089

Protein

Protein identifiers

Histone deacetylase 5 — Q9UQL6 (reviewed: Q9UQL6)

Alternative names: Antigen NY-CO-9

All UniProt accessions (5): Q9UQL6, K7EJL4, K7EJL6, K7EJZ7, K7ES01

UniProt curated annotations — full annotation on UniProt →

Function. In vitro, it deacetylates 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 MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Serves as a corepressor of RARA and causes its deacetylation. In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response.

Subunit / interactions. Interacts with AHRR, BAHD1, BCOR, HDAC7, HDAC9, CTBP1, MEF2C, NCOR2, NRIP1, PHB2 and a 14-3-3 chaperone protein. Interacts with BCL6, DDIT3/CHOP, GRK5, KDM5B and MYOCD. Interacts with EP300 in the presence of TFAP2C. Interacts with ANKRA2. Interacts with CUL7 (as part of the 3M complex); negatively regulated by ANKRA2. Interacts with ZBTB7B; the interaction allows the recruitment of HDAC4 on CD8 loci for deacetylation and possible inhibition of CD8 genes expression. Interacts with RARA.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed. Expressed in the heart, brain, kidney, pancreas, liver, skeletal muscle, placenta.

Post-translational modifications. Phosphorylated by AMPK, CaMK1, SIK1 and PRKD1 at Ser-259 and Ser-498. The phosphorylation is required for the export to the cytoplasm and inhibition. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import. Phosphorylated by GRK5, leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Ubiquitinated. Polyubiquitination however does not lead to its degradation.

Activity regulation. Inhibited by trichostatin A.

Domain organisation. The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UQL6-1	1	yes
Q9UQL6-2	2
Q9UQL6-3	3

RefSeq proteins (3): NP_001015053, NP_001369322, NP_005465* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000286	HDACs	Family
IPR023696	Ureohydrolase_dom_sf	Homologous_superfamily
IPR023801	His_deacetylse_dom	Domain
IPR024643	Hist_deacetylase_Gln_rich_N	Domain
IPR037138	His_deacetylse_dom_sf	Homologous_superfamily
IPR046949	HDAC4/5/7/9	Family

Pfam: PF00850, PF12203

Catalyzed reactions (Rhea)

• N(6)-acetyl-L-lysyl-[histone] + H2O = L-lysyl-[histone] + acetate (RHEA:58196)

UniProt features (55 total): mutagenesis site 9, sequence conflict 9, region of interest 8, compositionally biased region 7, modified residue 7, binding site 4, splice variant 2, sequence variant 2, helix 2, chain 1, active site 1, cross-link 1, strand 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
5UWI	Crystal Structure of HDAC5 NES Peptide in complex with CRM1-Ran-RanBP1	X-RAY DIFFRACTION	2.14
8Q9P	Crystal Structure of the MADS-box/MEF2 Domain of MEF2D bound to dsDNA and HDAC5 …	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UQL6-F1	64.14	0.33

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles; cytosol; golgi apparatus

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
833

Ligand- & substrate-binding residues (4)

Position	Role
696	Zn(2+)
698	Zn(2+)
704	Zn(2+)
781	Zn(2+)

Post-translational modifications (8)

Type	Positions
Phosphoserine	259, 498, 611, 661, 1108
Phosphothreonine	292
N6-acetyllysine	533
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	35

Mutagenesis-validated functional residues (9)

Position	Phenotype
259	reduces ampk- and camk-dependent phosphorylation and the subsequent nuclear export. abolishes nuclear export; when associated with a-498 …
279	no effect.
291	does not affect phosphorylation by pkc.
292	abolishes phosphorylation by pkc.
498	reduces ampk- and camk-dependent phosphorylation and the subsequent nuclear export. abolishes nuclear export; when associated with a-259.
661	no effect.
713	no effect.
1086	reduces camk-dependent nuclear export.
1092	reduces camk-dependent nuclear export.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 20; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

20 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-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-2122947	NOTCH1 Intracellular Domain Regulates Transcription	electronic
R-HSA-1257604	PIP3 activates AKT signaling	—
R-HSA-6807070	PTEN Regulation	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-8943724	Regulation of PTEN gene transcription	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-157118	Signaling by NOTCH	—
R-HSA-1980143	Signaling by NOTCH1	—

MSigDB gene sets: 322 (showing top): PID_HDAC_CLASSI_PATHWAY, REACTOME_SIGNALING_BY_NOTCH, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_COCAINE, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_B_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN

GO Biological Process (20): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA-templated transcription (GO:0006351), inflammatory response (GO:0006954), response to xenobiotic stimulus (GO:0009410), regulation of myotube differentiation (GO:0010830), negative regulation of myotube differentiation (GO:0010832), response to activity (GO:0014823), neuron differentiation (GO:0030182), B cell differentiation (GO:0030183), cellular response to insulin stimulus (GO:0032869), epigenetic regulation of gene expression (GO:0040029), B cell activation (GO:0042113), response to cocaine (GO:0042220), negative regulation of gene expression, epigenetic (GO:0045814), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to lipopolysaccharide (GO:0071222), negative regulation of cell migration involved in sprouting angiogenesis (GO:0090051), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (16): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription activator activity (GO:0001216), transcription corepressor binding (GO:0001222), chromatin binding (GO:0003682), histone deacetylase activity (GO:0004407), protein kinase C binding (GO:0005080), protein lysine deacetylase activity (GO:0033558), identical protein binding (GO:0042802), histone deacetylase binding (GO:0042826), metal ion binding (GO:0046872), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA-binding transcription factor binding (GO:0140297), histone deacetylase activity, hydrolytic mechanism (GO:0141221), transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607), protein-containing complex (GO:0032991)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Signal Transduction	2
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
Generic Transcription Pathway	1
PTEN Regulation	1
Differentiation of T cells	1
Intracellular signaling by second messengers	1
Signaling by NOTCH	1
RNA Polymerase II Transcription	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Disease	1
PIP3 activates AKT signaling	1
Gene expression (Transcription)	1

GO top-level categories

showing 60 of 69 GO namespaces:

Category	Terms
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
myotube differentiation	2
positive regulation of DNA-templated transcription	2
binding	2
negative regulation of DNA-templated transcription	1
gene expression	1
RNA biosynthetic process	1
defense response	1
response to chemical	1
regulation of striated muscle cell differentiation	1
regulation of myotube differentiation	1
negative regulation of striated muscle cell differentiation	1
response to stimulus	1
cell differentiation	1
generation of neurons	1
lymphocyte differentiation	1
B cell activation	1
response to insulin	1
cellular response to peptide hormone stimulus	1
chromatin remodeling	1
regulation of gene expression	1
lymphocyte activation	1
response to alkaloid	1
response to oxygen-containing compound	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
cell migration involved in sprouting angiogenesis	1
negative regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	1
cellular component organization	1
chromatin organization	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
DNA-binding transcription factor activity	1
transcription coregulator binding	1
protein lysine deacetylase activity	1
histone modifying activity	1
protein kinase binding	1
deacetylase activity	1
catalytic activity, acting on a protein	1
protein binding	1
enzyme binding	1
cation binding	1
DNA-binding transcription factor binding	1
transcription factor binding	1
histone deacetylase activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
catalytic activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 18 of 43 annotations. The rest are phylogenetic / computational / electronic (IEA).

18 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of cell migration involved in sprouting angiogenesis	BP	mutant phenotype
negative regulation of myotube differentiation	BP	mutant phenotype
negative regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nuclear speck	CC	direct assay
nucleus	CC	direct assay
DNA-binding transcription activator activity	MF	mutant phenotype
DNA-binding transcription factor binding	MF	physical interaction
RNA polymerase II cis-regulatory region sequence-specific DNA binding	MF	direct assay
RNA polymerase II-specific DNA-binding transcription factor binding	MF	physical interaction
histone deacetylase activity	MF	direct assay
histone deacetylase binding	MF	physical interaction
identical protein binding	MF	physical interaction
protein kinase C binding	MF	physical interaction
protein lysine deacetylase activity	MF	mutant phenotype
transcription corepressor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,788 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDAC5	MEF2D	Q14814	727
HDAC5	MEF2C	Q06413	712
HDAC5	MEF2A	Q02078	709
HDAC5	SIK1	P57059	678
HDAC5	EP300	Q09472	616
HDAC5	PRKD1	Q15139	606
HDAC5	CREBBP	Q92793	580
HDAC5	PRKD3	O94806	570
HDAC5	FUT7	Q11130	560
HDAC5	SIRT1	Q96EB6	559
HDAC5	ZBTB32	Q9Y2Y4	553
HDAC5	PRKD2	Q9BZL6	547
HDAC5	CAMK4	Q16566	543
HDAC5	SLC2A4	P14672	539
HDAC5	A0A0B4J2F2	A0A0B4J2F2	537

IntAct

Human interaction partners of HDAC5 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

29 partners by confidence:

Partner	Interaction type	MIscore	Records
YWHAZ	physical association	0.800	1
YWHAE	association	0.640	2
ANKRA2	direct interaction	0.590	1
LMO2	physical association	0.560	3
MEF2C	physical association	0.550	2
SFN	physical association	0.550	2
ICP0	physical association	0.520	3
BRMS1	physical association	0.520	2
RUNX3	physical association	0.500	1
H4C16	deacetylation reaction	0.440	1
GATA3	physical association	0.400	4
BUB1B	physical association	0.400	1
HDAC3	physical association	0.400	1
HIF1A	physical association	0.400	1
PKN2	physical association	0.400	1
MEF2D	physical association	0.370	2
HOXC11	physical association	0.370	1
MAFF	physical association	0.370	1
UBE2I	physical association	0.370	1
TBL1X	association	0.350	1
CBY1	physical association	0.000	1
CGN	physical association	0.000	1
EEF1G	physical association	0.000	1
GABARAP	physical association	0.000	1
KCTD3	physical association	0.000	1
KIF13B	physical association	0.000	1
KSR1	physical association	0.000	1
MAX	physical association	0.000	1
ZBTB21	physical association	0.000	1

BioGRID (495 interactions; top human partners by supporting records): YWHAQ (Affinity Capture-Western; 9 records), YWHAE (Affinity Capture-Western; 8 records), HDAC3 (Affinity Capture-Western; 6 records), YWHAB (Affinity Capture-Western; 6 records), MEF2A (Affinity Capture-Western; 5 records), NCOR1 (Affinity Capture-Western; 5 records), REST (Affinity Capture-MS; 5 records), SIK1 (Biochemical Activity; 5 records), YWHAG (Affinity Capture-MS; 5 records), ANKRA2 (Affinity Capture-MS; 4 records), HDAC4 (Affinity Capture-Western; 4 records), PRKD1 (Affinity Capture-Western; 4 records), YWHAH (Affinity Capture-MS; 4 records), YWHAZ (Affinity Capture-MS; 4 records), BCL6 (Affinity Capture-Western; 3 records)

SIGNOR signaling

showing 31 of 43 signaling interactions:

A	Effect	B	Mechanism
HDAC5	down-regulates	RUNX2	deacetylation
PRKAA1	down-regulates	HDAC5	phosphorylation
AURKB	down-regulates	HDAC5	phosphorylation
PRKACA	“up-regulates activity”	HDAC5	phosphorylation
PRKD1	down-regulates	HDAC5	phosphorylation
AMPK	down-regulates	HDAC5	phosphorylation
HDAC5	“down-regulates activity”	RUNX2	deacetylation
CAMK4	down-regulates	HDAC5	phosphorylation
BCOR	“up-regulates activity”	HDAC5	binding
BCORL1	“up-regulates activity”	HDAC5	binding
PRKCD	“down-regulates activity”	HDAC5	phosphorylation
GRK5	“down-regulates activity”	HDAC5	phosphorylation
HDAC5	down-regulates	MEF2A	binding
HDAC5	down-regulates	MEF2C	binding
HDAC5	down-regulates	MEF2D	binding
CAMK1	down-regulates	HDAC5	phosphorylation
CAMK2G	down-regulates	HDAC5	phosphorylation
14-3-3	down-regulates	HDAC5	binding
DYRK1B	“down-regulates activity”	HDAC5	phosphorylation
PRKCA	“down-regulates activity”	HDAC5	phosphorylation
PRKD1	“down-regulates activity”	HDAC5	phosphorylation
vorinostat	“down-regulates activity”	HDAC5	“chemical inhibition”
belinostat	“down-regulates activity”	HDAC5	“chemical inhibition”
“N-[4-[(hydroxyamino)-oxomethyl]phenyl]carbamic acid [6-(diethylaminomethyl)-2-naphthalenyl]methyl ester”	“down-regulates activity”	HDAC5	“chemical inhibition”
N-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide	“down-regulates activity”	HDAC5	“chemical inhibition”
romidepsin	“down-regulates activity”	HDAC5	“chemical inhibition”
6-(1,3-dioxo-2-benzo[de]isoquinolinyl)-N-hydroxyhexanamide	“down-regulates activity”	HDAC5	“chemical inhibition”
“trichostatin A”	“down-regulates activity”	HDAC5	“chemical inhibition”
CUDC-101	“down-regulates activity”	HDAC5	“chemical inhibition”
PRKD3	“up-regulates activity”	HDAC5	phosphorylation
PRKD2	“up-regulates activity”	HDAC5	phosphorylation

Protein complexes (CORUM) (8)

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

8 complexes by size:

Complex	Subunits	Members
★ GNB1-GNG2-HDAC5 complex	3	GNB1, GNG2, HDAC5
★ ACTN4-HDAC5 complex	2	ACTN4, HDAC5
★ BCL6-HDAC5 complex	2	BCL6, HDAC5
★ HDAC5-RARA complex	2	HDAC5, RARA
★ HDAC5-NCOR2 complex	2	HDAC5, NCOR2
★ HDAC5-MEF2A complex	2	HDAC5, MEF2A
★ HDAC5-MEF2C complex	2	HDAC5, MEF2C
★ HDAC5-MEF2D complex	2	HDAC5, MEF2D

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
Cell Cycle	5	6.9×	7e-03
Signaling by Rho GTPases	5	6.6×	8e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	5	6.4×	9e-03

Disease & clinical

Genetic variants

Variant evidence for HDAC5: 174 ClinVar records (0 pathogenic / likely pathogenic); 12 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	132
Likely benign	7
Benign	9

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 2,307):

Position(s)	Effect	Δscore	Sites
17:44078666–44078667	acceptor_loss	1.0000	6
17:44078668	acceptor_gain	1.0000
17:44078674	acceptor_gain	1.0000
17:44078813	donor_gain	1.0000
17:44078880–44078881	acceptor_loss	1.0000	6
17:44078885	acceptor_gain	1.0000
17:44079290	acceptor_gain	1.0000
17:44080105–44080106	donor_loss	1.0000	4
17:44080226–44080227	acceptor_loss	1.0000	6
17:44080399–44080400	donor_loss	1.0000	5

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	9.67e-06
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000121
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000486
Glioblastoma Multiforme (validation)	favorable	0.000515

Disease associations

OMIM: gene MIM:605315 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

GWAS associations

12 associations:

Study	Trait	p-value
GCST006979_871	Heel bone mineral density	2e-40
GCST006288_556	Heel bone mineral density	6e-17
GCST006288_273	Heel bone mineral density	6e-14
GCST010242_12	HDL cholesterol levels	2e-12
GCST012465_21	Bipolar disorder	3e-10
GCST90002395_425	Mean platelet volume	4e-9
GCST010241_289	Apolipoprotein A1 levels	8e-9
GCST000495_10	Bone mineral density (hip)	2e-8
GCST008103_184	Bipolar disorder	2e-8
GCST011102_19	Bipolar disorder	3e-8
GCST006288_325	Heel bone mineral density	3e-6
GCST000494_8	Bone mineral density (spine)	4e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2093865 (PROTEIN FAMILY), CHEMBL2563 (SINGLE PROTEIN), CHEMBL3038483 (PROTEIN FAMILY), CHEMBL4630737 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195544 (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: 485,978 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

30 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL408513	BELINOSTAT	4	8,184
CHEMBL487253	BENDAMUSTINE	4	31,460
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
CHEMBL51085	EBSELEN	3	13,356
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
CHEMBL356066	DACINOSTAT	2	3,152
CHEMBL3622533	FIMEPINOSTAT	2
CHEMBL1801250	NANATINOSTAT	2
CHEMBL2105763	QUISINOSTAT	2
CHEMBL2364628	RICOLINOSTAT	2
CHEMBL3989941	TINOSTAMUSTINE	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 (15 total), top 15:

Ligand	Action	Affinity	Parameter
quisinostat	Inhibition	8.43	pIC50
CUDC-101	Inhibition	7.94	pIC50
pracinostat	Inhibition	7.33	pIC50
TMP269	Inhibition	7.01	pIC50
belinostat	Inhibition	6.76	pKi
CHR-3996	Inhibition	6.7	pIC50
trichostatin A	Inhibition	6.59	pKi
martinostat	Inhibition	6.45	pIC50
dacinostat	Inhibition	6.38	pKi
romidepsin	Inhibition	6.26	pKi
givinostat	Inhibition	6.22	pKi
scriptaid	Inhibition	6.0	pKi
KA1010	Inhibition	5.96	pIC50
vorinostat	Inhibition	5.44	pKi
SS-208	Inhibition	5.16	pIC50

Binding affinities (BindingDB)

2222 measured of 2645 human assays (2691 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
(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
CHEMBL4592929	IC50	0.918 nM
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
CHEMBL4444219	IC50	1.2 nM
CHEMBL1793992	IC50	1.3 nM
CHEMBL99661	IC50	1.4 nM
CHEMBL4212186	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
CHEMBL1793938	IC50	2 nM
CHEMBL4228304	IC50	2 nM
CHEMBL4575813	IC50	2 nM

ChEMBL bioactivities

3598 potent at pChembl≥5 of 3970 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
9.15	Ki	0.7	nM	PANOBINOSTAT
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	VORINOSTAT
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	CHEMBL3692689
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	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

PubChem BioAssay actives

2428 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-[(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-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide	1236447: Inhibition of human HDAC5	ki	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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Estradiol	decreases reaction, decreases expression	3
dorsomorphin	affects cotreatment, decreases expression, affects localization, decreases reaction, increases phosphorylation	2
Resveratrol	decreases reaction, increases phosphorylation, affects cotreatment, decreases expression, affects binding	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cisplatin	affects cotreatment, increases expression	2
Lipopolysaccharides	affects cotreatment, decreases reaction, increases cleavage, increases phosphorylation, increases secretion (+3 more)	2
Nickel	decreases expression	2
Ozone	increases abundance, affects expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
afuresertib	increases expression	1
FR900359	affects phosphorylation	1
Batroxase, Bothrops atrox	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
terbufos	increases methylation	1
sulforaphane	decreases expression	1
cupric chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	decreases expression	1
KN 62	affects localization, decreases reaction, increases phosphorylation	1
perfluorooctane sulfonic acid	increases expression	1
pterostilbene	increases expression, increases phosphorylation, affects binding, decreases reaction, affects reaction	1

ChEMBL screening assays

1686 unique, capped per target: 1670 binding, 11 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_B8H9	Abcam HCT 116 HDAC5 KO	Cancer cell line	Male
CVCL_B8WM	Abcam MCF-7 HDAC5 KO	Cancer cell line	Female
CVCL_B9JJ	Abcam A-549 HDAC5 KO	Cancer cell line	Male
CVCL_SR11	HAP1 HDAC5 (-) 1	Cancer cell line	Male
CVCL_SR12	HAP1 HDAC5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 185 trials:

NCT	Phase	Status	Title
NCT00152750	Phase 4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	Phase 4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	Phase 4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	Phase 4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	Phase 4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	Phase 4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	Phase 4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	Phase 3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	Phase 3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	Phase 3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	Phase 3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	Phase 3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	Phase 3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	Phase 3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	Phase 3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	Phase 3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	Phase 3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	Phase 2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	Phase 2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	Phase 2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	Phase 2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	Phase 2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	Phase 2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	Phase 2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	Phase 2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	Phase 2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	Phase 2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	Phase 2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	Phase 2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	Phase 2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	Phase 2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	Phase 2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	Phase 2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	Phase 2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	Phase 2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	Phase 2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	Phase 2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	Phase 2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	Phase 2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03530293	Phase 2	TERMINATED	Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome
NCT03625453	Phase 2	COMPLETED	Study of ABX-1431 in Adult Patients With Tourette Syndrome or Chronic Motor Tic Disorder
NCT03651726	Phase 2	UNKNOWN	A Study to Examine the Efficacy of a Therapeutic THX-110 for Tourette Syndrome
NCT03732534	Phase 2	TERMINATED	Rollover Study for Continuing NBI-98854 Administration in Pediatric Subjects With Tourette Syndrome
NCT03944447	Phase 2	UNKNOWN	Outcomes Mandate National Integration With Cannabis as Medicine
NCT04007991	Phase 2	COMPLETED	Ecopipam Tablets to Study Tourette’s Syndrome in Children and Adolescents
NCT04354103	Phase 2	TERMINATED	Atomoxetine in Patients With Tourette’s Syndrome
NCT04978428	Phase 2	COMPLETED	Epidiolex in Obsessive Compulsive Disorder and Related Disorders
NCT05126888	Phase 2	NOT_YET_RECRUITING	SCI-110 in the Treatment of Tourette Syndrome
NCT05434546	Phase 2	COMPLETED	A Study to Explore the Effect of Sepranolone in Tourette Syndrome
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06194305	Phase 2	RECRUITING	Multimodal Profiling of Response to Pediatric Comprehensive Behavioral Intervention for Tics
NCT06315751	Phase 2	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Gemlapodect (NOE-105) in Adults and Adolescents With Tourette Syndrome
NCT06678737	Phase 2	RECRUITING	CBIT+TMS R33 Phase
NCT00139308	Phase 1	COMPLETED	High Frequency Stimulation of the GPi or Thalamus in Tourette’s Syndrome
NCT00634556	Phase 1	COMPLETED	Dopaminergic Effects on Cortical Function in Tourette’s (Levodopa Protocol)
NCT00952601	Phase 1	TERMINATED	Pilot Study of the Modified Atkins Diet for Tourette Syndrome
NCT01440023	Phase 1	COMPLETED	Developing Cognitive Training for Tourette Syndrome
NCT01719523	Phase 1	COMPLETED	Open-Trial of EPI-743 for Adults With Tourette Syndrome
NCT02134080	Phase 1	TERMINATED	FAAH Inhibitor Trial for Adults With Tourette Syndrome

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for HDAC5 across ~30M SureChEMBL compounds — explore on Sugi Predict.