HDAC9

Summary

HDAC9 (histone deacetylase 9, HGNC:14065) is a protein-coding gene on chromosome 7p21.1, encoding Histone deacetylase 9 (Q9UKV0). 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 the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined.

Source: NCBI Gene 9734 — RefSeq curated summary.

At a glance

• Gene–disease (curated): auriculocondylar syndrome 4 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 87 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 168 total — 2 pathogenic, 1 likely-pathogenic
• Regional missense constraint (gnomAD): 2 of 7 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 14 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 13
• ChEMBL bioactivity: 28 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.38 (moderately constrained)
• Transcription factor: yes — 19 downstream targets (CollecTRI)
• MANE Select transcript: NM_178425
• Interaction hub: 5,492 STRING partners (top 1% of genes corpus-wide)
• Notable: 168 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14065
Approved symbol	HDAC9
Name	histone deacetylase 9
Location	7p21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0744, HDAC, MITR, HD7, HDAC7B
Ensembl gene	ENSG00000048052
Ensembl biotype	protein_coding
OMIM	606543
Entrez	9734

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 42 protein_coding, 8 protein_coding_CDS_not_defined, 4 retained_intron, 2 nonsense_mediated_decay

MANE Select: ENST00000686413

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 6, TSL 2: 7, TSL 3: 9, TSL 4: 3, TSL 5: 4

ENST00000686413, ENST00000401921, ENST00000405010, ENST00000406072, ENST00000406451, ENST00000411993, ENST00000413380, ENST00000413509, ENST00000417496, ENST00000425071, ENST00000428307, ENST00000430454, ENST00000432645, ENST00000433709, ENST00000441542, ENST00000441986, ENST00000446646, ENST00000455069, ENST00000456174, ENST00000461159, ENST00000461409, ENST00000471887, ENST00000474742, ENST00000476135, ENST00000483142, ENST00000490851, ENST00000496026, ENST00000523867, ENST00000524023, ENST00000622668, ENST00000681273, ENST00000681950, ENST00000707077, ENST00000707080, ENST00000707081, ENST00000707082, ENST00000868968, ENST00000868969, ENST00000868970, ENST00000868971, ENST00000868972, ENST00000935502, ENST00001006097, ENST00001006098, ENST00001006099, ENST00001006100, ENST00001006101, ENST00001019012, ENST00001019013, ENST00001019014, ENST00001071301, ENST00001071302, ENST00001071303, ENST00001113640, ENST00001113641, ENST00001131246

RefSeq mRNA: 39 — MANE Select: NM_178425 NM_001204144, NM_001204145, NM_001204146, NM_001204147, NM_001204148, NM_001321868, NM_001321869, NM_001321870, NM_001321871, NM_001321872, NM_001321873, NM_001321874, NM_001321875, NM_001321876, NM_001321877, NM_001321878, NM_001321879, NM_001321884, NM_001321885, NM_001321886, NM_001321887, NM_001321888, NM_001321889, NM_001321890, NM_001321891, NM_001321893, NM_001321894, NM_001321895, NM_001321896, NM_001321897, NM_001321898, NM_001321899, NM_001321900, NM_001321901, NM_001321902, NM_014707, NM_058176, NM_178423, NM_178425

CCDS: CCDS47553, CCDS47554, CCDS47555, CCDS47557, CCDS56465, CCDS56466, CCDS56467, CCDS56468, CCDS75565, CCDS83163, CCDS94058, CCDS94059

Canonical transcript exons

ENST00000686413 — 26 exons

Exon	Start	End
ENSE00002620825	18996023	19002416
ENSE00003469169	18634627	18634742
ENSE00003470295	18835467	18835586
ENSE00003494307	18591516	18591642
ENSE00003494780	18829461	18829548
ENSE00003496922	18874478	18874596
ENSE00003497085	18767106	18767155
ENSE00003516851	18666213	18666476
ENSE00003517875	18749005	18749138
ENSE00003524474	18496262	18496324
ENSE00003533224	18793345	18793452
ENSE00003573192	18935809	18935942
ENSE00003591924	18629350	18629481
ENSE00003597797	18727580	18727757
ENSE00003608932	18647785	18647998
ENSE00003618602	18954146	18954230
ENSE00003639067	18593908	18594029
ENSE00003643746	18585281	18585522
ENSE00003644906	18762157	18762277
ENSE00003662548	18975806	18975953
ENSE00003665477	18648466	18648683
ENSE00003667557	18829161	18829216
ENSE00003668270	18835900	18835997
ENSE00003680086	18644671	18644793
ENSE00003790684	18590336	18590486
ENSE00003936346	18495749	18496023

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 94.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6630 / max 1106.6858, expressed in 1483 samples.

Highest expression (Bgee): oocyte, monocyte, secondary oocyte, mononuclear cell, leukocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

HDAC9 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	5.9e-15	+0.32	7:18297334:G:A
Esophagus Muscularis	eqtl	1.7e-12	-0.22	7:18292730:G:A
Cells Cultured fibroblasts	eqtl	2.2e-11	-0.13	7:18991407:G:A
Artery Tibial	sqtl	5.5e-05	-0.40	7:18189259:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.3e-04	-0.12	7:18899671:C:A
Nerve Tibial	eqtl	1.4e-04	-0.12	7:18237831:C:G
Testis	eqtl	1.7e-04	-0.43	7:18142069:CAAGTTCT:C
Skin Sun Exposed Lower leg	eqtl	1.4e-03	+0.11	7:18989134:C:T
Adipose Subcutaneous	eqtl	2.2e-03	-0.17	7:18164395:T:C
Adipose Visceral Omentum	eqtl	3.2e-03	-0.17	7:18311768:A:C
Vagina	sqtl	1.5e-02	-2.22	7:17394013:G:A
Testis	sqtl	1.6e-02	-1.08	7:18151729:G:A
Esophagus Mucosa	eqtl	1.8e-02	+0.48	7:18348800:A:AGC
Brain Cerebellum	eqtl	2.7e-02	+0.21	7:18565177:G:A
Brain Substantia nigra	eqtl	3.4e-02	-0.98	7:17524038:T:C
Muscle Skeletal	eqtl	3.7e-02	+0.24	7:17868620:A:ATT
Minor Salivary Gland	eqtl	3.9e-02	-0.28	7:18785348:C:T

FANTOM5 promoters

showing 10 of 33 alternative TSS:

Promoter ID	TPM avg	Samples expressed
77384	5.9103	818
77397	5.0656	813
77394	2.9617	801
77375	2.9222	352
77396	1.4204	588
77368	1.0529	274
77383	0.7748	341
77391	0.6106	247
77366	0.3461	159
77389	0.3410	151

Top tissues by expression

showing 100 of 290 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.38	gold quality
monocyte	CL:0000576	94.21	gold quality
secondary oocyte	CL:0000655	93.93	gold quality
mononuclear cell	CL:0000842	93.76	gold quality
leukocyte	CL:0000738	92.93	gold quality
endothelial cell	CL:0000115	92.12	gold quality
choroid plexus epithelium	UBERON:0003911	91.62	gold quality
parotid gland	UBERON:0001831	90.81	gold quality
ganglionic eminence	UBERON:0004023	90.74	gold quality
cortical plate	UBERON:0005343	90.53	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.28	gold quality
ventricular zone	UBERON:0003053	90.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.68	gold quality
epithelium of nasopharynx	UBERON:0001951	89.00	gold quality
corpus callosum	UBERON:0002336	88.78	gold quality
superficial temporal artery	UBERON:0001614	88.23	gold quality
calcaneal tendon	UBERON:0003701	88.23	gold quality
bone marrow cell	CL:0002092	87.44	gold quality
islet of Langerhans	UBERON:0000006	87.07	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.07	gold quality
colonic epithelium	UBERON:0000397	86.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.61	gold quality
lymph node	UBERON:0000029	86.58	gold quality
orbitofrontal cortex	UBERON:0004167	86.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.04	gold quality
middle temporal gyrus	UBERON:0002771	85.98	gold quality
mucosa of stomach	UBERON:0001199	85.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.39	gold quality
left testis	UBERON:0004533	85.30	gold quality
lower esophagus	UBERON:0013473	85.29	gold quality
prefrontal cortex	UBERON:0000451	85.28	gold quality
cartilage tissue	UBERON:0002418	85.10	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.82	gold quality
tonsil	UBERON:0002372	84.47	gold quality
right testis	UBERON:0004534	84.46	gold quality
descending thoracic aorta	UBERON:0002345	84.31	gold quality
testis	UBERON:0000473	84.27	gold quality
sural nerve	UBERON:0015488	84.14	gold quality
thoracic aorta	UBERON:0001515	83.44	gold quality
ascending aorta	UBERON:0001496	83.39	gold quality
biceps brachii	UBERON:0001507	83.38	gold quality
CA1 field of hippocampus	UBERON:0003881	83.37	gold quality
germinal epithelium of ovary	UBERON:0001304	83.36	gold quality
amniotic fluid	UBERON:0000173	83.26	gold quality
superior frontal gyrus	UBERON:0002661	83.08	gold quality
vastus lateralis	UBERON:0001379	83.05	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.96	gold quality
smooth muscle tissue	UBERON:0001135	82.58	gold quality
body of uterus	UBERON:0009853	82.30	gold quality
cauda epididymis	UBERON:0004360	82.28	gold quality
embryo	UBERON:0000922	81.88	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.79	gold quality
entorhinal cortex	UBERON:0002728	81.77	gold quality
aorta	UBERON:0000947	81.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.50	gold quality
frontal cortex	UBERON:0001870	81.45	gold quality
neocortex	UBERON:0001950	81.41	gold quality
primary visual cortex	UBERON:0002436	81.41	gold quality
cerebral cortex	UBERON:0000956	81.19	gold quality
blood vessel layer	UBERON:0004797	81.06	gold quality
gall bladder	UBERON:0002110	80.98	gold quality
skeletal muscle tissue	UBERON:0001134	80.92	gold quality
vermiform appendix	UBERON:0001154	80.88	gold quality
spinal cord	UBERON:0002240	80.80	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.75	gold quality
saphenous vein	UBERON:0007318	80.71	gold quality
seminal vesicle	UBERON:0000998	80.69	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.54	gold quality
postcentral gyrus	UBERON:0002581	80.51	gold quality
occipital lobe	UBERON:0002021	80.50	gold quality
popliteal artery	UBERON:0002250	80.48	gold quality
tibial artery	UBERON:0007610	80.45	gold quality
muscle tissue	UBERON:0002385	80.32	gold quality
diaphragm	UBERON:0001103	80.24	silver quality
medial globus pallidus	UBERON:0002477	80.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.00	gold quality
stromal cell of endometrium	CL:0002255	79.95	gold quality
quadriceps femoris	UBERON:0001377	79.93	gold quality
cingulate cortex	UBERON:0003027	79.83	gold quality
parietal lobe	UBERON:0001872	79.82	gold quality
dorsal plus ventral thalamus	UBERON:0001897	79.77	gold quality
anterior cingulate cortex	UBERON:0009835	79.60	gold quality
myometrium	UBERON:0001296	79.59	gold quality
pigmented layer of retina	UBERON:0001782	79.50	gold quality
caecum	UBERON:0001153	79.42	gold quality
spleen	UBERON:0002106	79.26	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	79.05	gold quality
bone marrow	UBERON:0002371	78.96	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.95	gold quality
right coronary artery	UBERON:0001625	78.85	gold quality
adrenal tissue	UBERON:0018303	78.72	gold quality
temporal lobe	UBERON:0001871	78.66	gold quality
globus pallidus	UBERON:0001875	78.57	gold quality
granulocyte	CL:0000094	78.55	gold quality
substantia nigra	UBERON:0002038	78.46	gold quality
telencephalon	UBERON:0001893	78.43	gold quality
adipose tissue	UBERON:0001013	78.41	gold quality
forebrain	UBERON:0001890	78.36	gold quality
central nervous system	UBERON:0001017	78.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	27.49
E-MTAB-9801	yes	7.66
E-ANND-3	yes	6.60

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	119.9
Olfactory bulb	tissue	52.1
Cerebral cortex	tissue	44.5	medium
Motor cortex	tissue	44.5
Prefrontal cortex	tissue	44.3
Retrosplenial and cingulate cortex	tissue	42.8
Retrosplenial cortex	tissue	42.3
Hippocampal formation	tissue	38.9
Entorhinal cortex	tissue	38.5
Spinal cord	tissue	38.3
Postcentral gyrus	tissue	36.3
Superior colliculi	tissue	35.9
Temporal cortex	tissue	35.1
Insular cortex	tissue	33.5
Occipital cortex	tissue	33.1
Midbrain	tissue	32.5
Thalamus	tissue	31.7
Locus coeruleus	tissue	30.9
Medulla oblongata	tissue	30.6
Corpus callosum	tissue	29.7
Amygdala	tissue	28.4
Hippocampus	tissue	27.6	not detected
Somatosensory cortex	tissue	27.5
Substantia nigra	tissue	26.2
Pons	tissue	25.8
Periaqueductal gray	tissue	24.5
Retina	tissue	23.7
Hypothalamus	tissue	21.8
Frontal cortex	tissue	21.0
Ventral forebrain	tissue	20.0
Nucleus accumbens	tissue	19.6
Septum	tissue	18.6
Basal ganglia	tissue	17.8	low
Cerebellum	tissue	17.6	medium
Lymph node	tissue	17.4	high
Tonsil	tissue	17.4	high
Putamen	tissue	17.1
Spleen	tissue	16.3	low
Skeletal muscle	tissue	15.6	medium
Heart muscle	tissue	13.1	low
Seminal vesicle	tissue	13.0	high
Endometrium 1	tissue	11.9	high
Smooth muscle	tissue	11.6	medium
Adrenal gland	tissue	11.2	high
Prostate	tissue	9.9	medium
Cervix	tissue	9.3	high
Fallopian tube	tissue	8.5	high
Caudate putamen	tissue	8.2
Appendix	tissue	8.2	medium
Stomach 1	tissue	8.1	medium
Adipose tissue	tissue	7.6	medium
Salivary gland	tissue	6.7	medium
Gallbladder	tissue	6.3	high
Thymus	tissue	6.2
Placenta	tissue	5.9	high
Pituitary gland	tissue	5.6
Epididymis	tissue	5.6	high
Bone marrow	tissue	5.4	high
Tongue	tissue	5.3
Rectum	tissue	5.2	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Centromedial thalamic nucleus (48.6), Pulvinar (44.9), Nucleus rhomboideus (44.3), Ventral posterolateral thalamic nucleus (41.3), Lateral thalamic nuclei (40.6).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

19 targets:

Target	Regulation
APP	Unknown
CDKN2A	Activation
CFLAR	Activation
CITED2	Repression
DIRAS3	Repression
ESR1	Repression
HSPA5	Repression
IGFBP1	Repression
IL18	Unknown
LPL	Repression
MEF2A	Repression
MMP13	Activation
MYEF2	Repression
NFKB1	Repression
PRL	Repression
RELA	Repression
STAT6	Repression
TNFRSF10B	Repression
TP53	Repression

Upstream regulators (CollecTRI, top): GATA4, NR4A1, SALL3

miRNA regulators (miRDB)

Targeting HDAC9 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 161 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
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-3924	100.00	72.09	2394
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4775	99.98	75.00	6394

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.377, missense Z 1.48 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000686413 splits into 7 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
7:18,496,303–18,591,580	136 / 183.5	0.74	no
7:18,591,581–18,594,006	79 / 65.8	1.20	no
7:18,594,007–18,629,369	1 / 16.2	0.06	yes (p 1.6e-04)
7:18,629,370–18,648,575	264 / 273.8	0.96	no
7:18,648,576–18,648,617	4 / 16.9	0.24	yes (p 1.7e-03)
7:18,648,618–18,749,023	256 / 219.2	1.17	no
7:18,749,024–18,996,059	407 / 521.5	0.78	no

Literature-anchored findings (GeneRIF, showing 40)

• Chromosomal organization on chromsome 7 (PMID:12054582)
• ICP0 of Herpes simplex virus Type 1 interacts with and controls the repressor activity of class II HDAC7 (PMID:15194749)
• The crystal structure of a histone deacetylase 9 (HDAC9)/myocyte enhancer factor-2 (MEF2)/DNA complex reveals that HDAC9 binds to a hydrophobic groove of the MEF2 dimer. (PMID:15567413)
• Moraxella catarrhalis-induced cytokine expression is regulated by acetylation of histone residues and controlled by histone deacetylase activity. (PMID:16399788)
• The role of ACTN4 in MEF2A transcription via HDAC7 antagonism is reported. (PMID:16980305)
• FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression (PMID:17360565)
• Endogenous HDAC activity plays a crucial role in maintaining the balance of pre-established T(H)1-like and T(H)2-like responses, inhibiting excessive T(H)2 immunity. (PMID:17980413)
• amino enhancer of split has apoptotic activity in neurons and suggest that neuroprotection by histone deacetylase-related protein is mediated by the inhibition of this activity through direct interaction. (PMID:18438919)
• Analysis of chromatin modification patterns shows that HDAC are recruited to the c-myc promoter leading to appearance of repressive chromatin marks. (PMID:19522008)
• HDAC suppresses the activation of PPARgamma in the gastric carcinoma cell line SGC-7901. (PMID:19624894)
• Results demonstrate that histone deacetylase inhibitors (HDACIs) in different combinations with RA, act as cell growth inhibitors. (PMID:19723072)
• Histone deacetylase 9 (HDAC9) regulates the functions of the ATDC (TRIM29) protein (PMID:20947501)
• enforced HDAC9 expression increased gamma-globin mRNA levels by 2.5-fold with a simultaneous 7-fold increase in HbF. (PMID:21078662)
• Histone deacetylases 9 and 10 are required for homologous recombination. (PMID:21247901)
• MITR plays a master switch role to balance osteogenic and adipogenic differentiation of MSCs through regulation of PPARgamma-2 transcriptional activity. (PMID:21247904)
• HDAC9 acts as an epigenetic switch in effector T cell-mediated systemic autoimmunity. (PMID:21708950)
• Data indicate a pronounced deregulation of HDAC genes HDAC9 and HDAC11 in patients with Philadelphia-negative chronic myeloproliferative neoplasms: essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). (PMID:21806350)
• Treated the seminoma-like cell line TCam-2 with the HDAC-inhibitor Depsipeptide. (PMID:21987446)
• The results show that hdac9 is the third androgenic alopecia susceptibility gene (PMID:22032556)
• The results imply that HDAC9 is involved in the transcriptional regulation of human odontoblasts in vivo. (PMID:22297573)
• We identified a new association for large vessel stroke within HDAC9 on chromosome 7p21.1. (PMID:22306652)
• LBH589 and TSA may translationally regulate some HDAC encoding genes in pancreatic tumors. (PMID:22487525)
• Regression models consistently identified rs2522129, rs2675231, and rs2389963 as having among the highest predictive values for explaining differences related to brain volume measures (PMID:22884548)
• We propose that CtBP2 is an ovarian cancer oncogene that regulates gene expression program by modulating HDAC activity. (PMID:22945647)
• HDAC9 promotes angiogenesis and transcriptionally represses the endothelial cell miR-17-92 cluster. (PMID:23288173)
• Dephosphorylation at a conserved SP motif governs cAMP sensitivity and nuclear localization of class IIa histone deacetylases HDAC4, 5 and 9 (PMID:23297420)
• SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension (PMID:23393555)
• Our results are consistent with the 7p21.1 association acting via promoting atherosclerosis, and consistent with alterations in HDAC9 expression mediating this increased risk. (PMID:23449258)
• In vivo sorafenib + HDAC inhibitor toxicity against tumors was increased. (PMID:23674352)
• study reports gene expression in skeletal muscle tissue of women with metabolic syndrome is enriched in inflammatory response-related genes; IL6R, HDAC9 and CD97 expression correlated negatively with insulin sensitivity; suggests a role for these 3 inflammatory genes in development of skeletal muscle insulin resistance in women (PMID:23771909)
• These data suggest that HDAC9 variants may be selected for during cutaneous squamous cell carcinoma tumorigenesis (PMID:23784969)
• HDAC9 gene is significantly associated with large-vessel stroke risk in Chinese population. (PMID:23828597)
• These results suggest that HDAC9 may be a suppressor and its downregulation might promote the progression process, especially in lung adenocarcinomas. (PMID:24427341)
• The hydroxamic acid pan-HDAC inhibitor TSA synergistically inhibit the viability. (PMID:24562770)
• The results elucidate the genetic etiology of lung adenocarcinoma by demonstrating that SNP rs10248565 in the HDAC9 gene may be a potential biomarker of cancer susceptibility. (PMID:24650256)
• Gene expression studies in peripheral blood mononuclear cells revealed increased mRNA levels of HDAC9. Analysis of human atherosclerotic plaques revealed no association between rs2107595 and specific plaque characteristics. (PMID:25388417)
• Data show that miR-376a and HDAC9 expression are inversely correlated in hepatocellular carcinoma and suggest that HDAC9-mediated epigenetic modification may contribute to the down-regulation of the miR-376 cluster in hepatocellular carcinoma. (PMID:25613642)
• HDAC9 promotes tumor formation of glioblastoma via TAZ-mediated EGFR pathway activation. (PMID:25760078)
• the results of this study suggest that targeting HDACs by ST-3595 might represent as a novel and promising anti-pancreatic cancer strategy. (PMID:26084607)
• results indicate that HDAC9 variant rs2107595 may be not associated with IS risk in southern Han Chinese (PMID:26093197)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdac9b	ENSDARG00000056642
mus_musculus	Hdac9	ENSMUSG00000004698
rattus_norvegicus	Hdac9	ENSRNOG00000004158
drosophila_melanogaster	HDAC4	FBGN0041210
caenorhabditis_elegans		WBGENE00001837
caenorhabditis_elegans		WBGENE00009657
caenorhabditis_elegans		WBGENE00009663
caenorhabditis_elegans		WBGENE00219378

Paralogs (10): HDAC7 (ENSG00000061273), 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:1931221) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
cardiac hypertrophy	1
heart left ventricle 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
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
Oryza sativa Japonica Group	Q6YV04	95.9%	Diamond
Arabidopsis thaliana	Q8LRK8	85.9%	Diamond
Caenorhabditis briggsae	Q613L4	82.2%	Diamond
Zea mays	P56521	81.5%	Diamond
Pseudomonas aeruginosa PAO1	Q9I6H0	69.1%	Diamond
Mycoplana ramosa	Q48935	52.0%	Diamond
Saccharomyces cerevisiae S288C	P53973	50.7%	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
Methanothermobacter thermautotrophicus str. Delta H	O27262	39.7%	Diamond
Methanocaldococcus jannaschii DSM 2661	Q57955	38.1%	Diamond
Dictyostelium discoideum	Q54VQ7	38.0%	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
PRPS1L1	protein-coding	221823
MIR1302-6	ncRNA	100302140
LINC02889	ncRNA	101927630
LINC02888	ncRNA	102659288
SNX13	protein-coding	23161
TWIST1	protein-coding	7291
HDAC9-AS1	ncRNA	105375176
FERD3L	protein-coding	222894

Protein

Protein identifiers

Histone deacetylase 9 — Q9UKV0 (reviewed: Q9UKV0)

Alternative names: Histone deacetylase 7B, Histone deacetylase-related protein, MEF2-interacting transcription repressor MITR

All UniProt accessions (15): A0A7P0T8F4, A0A7P0TAB5, A0A9L9PXL9, A0A9L9PXM4, A0A9L9PY57, A0A9L9PY89, B5MCF1, B7Z3P7, C9IZS0, C9J1W4, C9J835, C9JD56, C9JLX1, Q9UKV0, F8WDS2

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. Represses MEF2-dependent transcription. Isoform 3 lacks active site residues and therefore is catalytically inactive. Represses MEF2-dependent transcription by recruiting HDAC1 and/or HDAC3. Seems to inhibit skeletal myogenesis and to be involved in heart development. Protects neurons from apoptosis, both by inhibiting JUN phosphorylation by MAPK10 and by repressing JUN transcription via HDAC1 recruitment to JUN promoter.

Subunit / interactions. Homodimer. Interacts with CTBP1. The phosphorylated form interacts with 14-3-3. Interacts with HDAC1 and HDAC3, and probably with HDAC4 and HDAC5. Interacts with MEF2, MAPK10, ETV6, NCOR1 and BCL6. Interacts with FOXP3 in the absence of T-cell stimulation.

Subcellular location. Nucleus.

Tissue specificity. Broadly expressed, with highest levels in brain, heart, muscle and testis. Isoform 3 is present in human bladder carcinoma cells (at protein level).

Post-translational modifications. Phosphorylated on Ser-220 and Ser-450; which promotes 14-3-3-binding, impairs interaction with MEF2, and antagonizes antimyogenic activity. Phosphorylated on Ser-240; which impairs nuclear accumulation. Isoform 7 is phosphorylated on Tyr-1010. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import. Sumoylated.

Disease relevance. Auriculocondylar syndrome 4 (ARCND4) [MIM:620457] An autosomal dominant form of auriculocondylar syndrome, a craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia. Glossoptosis, masticatory abnormalities, orthodontic problems, and malocclusion occur in a majority of affected subjects. The disease may be caused by variants affecting the gene represented in this entry. A chromosomal aberration involving HDAC9 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with TGFB2 resulting in lack of HDAC9 protein.

Activity regulation. Inhibited by Trichostatin A (TSA) and suberoylanilide hydroxamic acid.

Miscellaneous. Major form in most tissues. Inactive due to lack of active site residues. Excluded from the nucleus. Does not interact with ETV6.

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

Isoforms (11)

UniProt ID	Names	Canonical?
Q9UKV0-1	1	yes
Q9UKV0-2	2
Q9UKV0-3	3, HDRP, MITR
Q9UKV0-4	4, HDAC9a
Q9UKV0-5	5, HDAC9b, HDAC9fl
Q9UKV0-6	6
Q9UKV0-7	7
Q9UKV0-8	8
Q9UKV0-9	9
Q9UKV0-10	10
Q9UKV0-11	11

RefSeq proteins (39): NP_001191073, NP_001191074, NP_001191075, NP_001191076, NP_001191077, NP_001308797, NP_001308798, NP_001308799, NP_001308800, NP_001308801, NP_001308802, NP_001308803, NP_001308804, NP_001308805, NP_001308806, NP_001308807, NP_001308808, NP_001308813, NP_001308814, NP_001308815, NP_001308816, NP_001308817, NP_001308818, NP_001308819, NP_001308820, NP_001308822, NP_001308823, NP_001308824, NP_001308825, NP_001308826, NP_001308827, NP_001308828, NP_001308829, NP_001308830, NP_001308831, NP_055522, NP_478056, NP_848510, NP_848512* (*=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

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-[histone] + H2O = L-lysyl-[histone] + acetate (RHEA:58196)

UniProt features (47 total): splice variant 11, region of interest 9, sequence conflict 9, compositionally biased region 5, modified residue 5, binding site 4, chain 1, active site 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
8Q9N	Crystal Structure of the MADS-box/MEF2 Domain of MEF2D bound to dsDNA and MITR …	X-RAY DIFFRACTION	1.51
8Q9R	Crystal structure of MADS-box/MEF2D N-terminal domain bound to dsDNA and HDAC9 …	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKV0-F1	64.48	0.33

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; mitotic chromosome

Antibody reliability (HPA): IH uncertain · IF approved

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
783

Ligand- & substrate-binding residues (4)

Position	Role
646	Zn(2+)
648	Zn(2+)
654	Zn(2+)
731	Zn(2+)

Post-translational modifications (5)

Type	Positions
Phosphoserine	22, 220, 240, 451, 554

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 16; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 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-2122947	NOTCH1 Intracellular Domain Regulates Transcription	electronic
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-162582	Signal Transduction	—
R-HSA-157118	Signaling by NOTCH	—
R-HSA-1980143	Signaling by NOTCH1	—

MSigDB gene sets: 516 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, PID_HDAC_CLASSI_PATHWAY, REACTOME_SIGNALING_BY_NOTCH, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, WWTAAGGC_UNKNOWN, HARRIS_HYPOXIA, GOBP_INFLAMMATORY_RESPONSE, GOBP_STEROL_HOMEOSTASIS, RORA1_01, GOBP_B_CELL_ACTIVATION, NKX25_02, GCANCTGNY_MYOD_Q6

GO Biological Process (17): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of cytokine production (GO:0001818), DNA-templated transcription (GO:0006351), inflammatory response (GO:0006954), heart development (GO:0007507), B cell differentiation (GO:0030183), cellular response to insulin stimulus (GO:0032869), epigenetic regulation of gene expression (GO:0040029), B cell activation (GO:0042113), cholesterol homeostasis (GO:0042632), negative regulation of gene expression, epigenetic (GO:0045814), negative regulation of DNA-templated transcription (GO:0045892), regulation of skeletal muscle fiber development (GO:0048742), regulation of striated muscle cell differentiation (GO:0051153), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (14): transcription corepressor activity (GO:0003714), histone deacetylase activity (GO:0004407), protein kinase C binding (GO:0005080), histone H3K14 deacetylase activity, hydrolytic mechanism (GO:0031078), histone H3K9 deacetylase activity, hydrolytic mechanism (GO:0032129), protein lysine deacetylase activity (GO:0033558), histone H4K16 deacetylase activity, hydrolytic mechanism (GO:0034739), 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), protein binding (GO:0005515), hydrolase activity (GO:0016787), histone deacetylase activity, hydrolytic mechanism (GO:0141221)

GO Cellular Component (6): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), histone methyltransferase complex (GO:0035097)

Reactome top-level categories

12 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
Generic Transcription Pathway	1
Differentiation of T cells	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
Disease	1
Gene expression (Transcription)	1

GO top-level categories

60 GO namespaces:

Category	Terms
histone deacetylase activity, hydrolytic mechanism	3
negative regulation of DNA-templated transcription	2
negative regulation of gene expression	2
histone H3K deacetylase activity	2
nucleoplasm	2
nuclear protein-containing complex	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cytokine production	1
regulation of cytokine production	1
negative regulation of multicellular organismal process	1
gene expression	1
RNA biosynthetic process	1
defense response	1
animal organ development	1
circulatory system development	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
sterol homeostasis	1
epigenetic regulation of gene expression	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of myotube differentiation	1
skeletal muscle fiber development	1
regulation of cell development	1
striated muscle cell differentiation	1
regulation of muscle cell differentiation	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
cellular component organization	1
chromatin organization	1
transcription coregulator activity	1
protein lysine deacetylase activity	1
histone modifying activity	1
protein kinase binding	1
deacetylase activity	1
catalytic activity, acting on a protein	1
histone H4K deacetylase activity	1
enzyme binding	1
cation binding	1
DNA-binding transcription factor binding	1
transcription factor binding	1
binding	1
catalytic activity	1
histone deacetylase activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
catalytic complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
protein-containing complex	1
intracellular anatomical structure	1
methyltransferase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 37 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to insulin stimulus	BP	direct assay
cholesterol homeostasis	BP	direct assay
negative regulation of DNA-templated transcription	BP	direct assay
negative regulation of cytokine production	BP	direct assay
negative regulation of gene expression, epigenetic	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of cell migration involved in sprouting angiogenesis	BP	mutant phenotype
cytoplasm	CC	direct assay
nucleus	CC	direct assay
transcription regulator complex	CC	direct assay
DNA-binding transcription factor binding	MF	direct assay
RNA polymerase II-specific DNA-binding transcription factor binding	MF	direct assay
histone H4K16 deacetylase activity, hydrolytic mechanism	MF	direct assay
histone deacetylase activity	MF	direct assay
histone deacetylase binding	MF	direct assay
protein kinase C binding	MF	physical interaction
protein lysine deacetylase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 5,492 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDAC9	SIN3A	Q96ST3	862
HDAC9	EP300	Q09472	845
HDAC9	NCOR1	O75376	832
HDAC9	H4C16	P02304	817
HDAC9	H4C7	Q99525	812
HDAC9	SIRT1	Q96EB6	810
HDAC9	H3C14	Q71DI3	810
HDAC9	H3-5	Q6NXT2	810
HDAC9	H3-4	Q16695	810
HDAC9	H3-7	Q5TEC6	810
HDAC9	H3-3A	P06351	809
HDAC9	H3C1	P02295	809
HDAC9	KAT2B	Q92831	802
HDAC9	DNMT1	P26358	799
HDAC9	KAT2A	Q92830	795

IntAct

Human interaction partners of HDAC9 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
BCL6	physical association	0.560	1
MEF2C	physical association	0.550	3
ANKRA2	direct interaction	0.440	1
FOXP3	physical association	0.400	2
ETV6	physical association	0.400	1
NCOR1	physical association	0.400	1
IGLL5	association	0.350	1
ZC3H11A	association	0.350	1
NRIP1	physical association	0.000	1
WNK1	physical association	0.000	1
YWHAE	physical association	0.000	1

BioGRID (106 interactions; top human partners by supporting records): PKD1 (Reconstituted Complex; 5 records), HDAC1 (Affinity Capture-Western; 4 records), TRIM29 (Biochemical Activity; 3 records), CTBP1 (Reconstituted Complex; 2 records), GLS (Affinity Capture-Western; 2 records), HDAC3 (Reconstituted Complex; 2 records), HDAC6 (Affinity Capture-Western; 2 records), MAML1 (Affinity Capture-Western; 2 records), MAPK10 (Affinity Capture-Western; 2 records), MAPK8 (Affinity Capture-Western; 2 records), MAPK9 (Affinity Capture-Western; 2 records), MEF2A (Affinity Capture-Western; 2 records), MEF2C (Two-hybrid; 2 records), NCOR1 (Reconstituted Complex; 2 records), PPARG (Affinity Capture-Western; 2 records)

SIGNOR signaling

showing 13 of 17 signaling interactions:

A	Effect	B	Mechanism
AURKB	down-regulates	HDAC9	phosphorylation
HDAC9	down-regulates	MEF2C	binding
DYRK1B	down-regulates	HDAC9	phosphorylation
belinostat	“down-regulates activity”	HDAC9	“chemical inhibition”
panobinostat	“down-regulates activity”	HDAC9	“chemical inhibition”
entinostat	“down-regulates activity”	HDAC9	“chemical inhibition”
vorinostat	“down-regulates activity”	HDAC9	“chemical inhibition”
N-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide	“down-regulates activity”	HDAC9	“chemical inhibition”
“trichostatin A”	“down-regulates activity”	HDAC9	“chemical inhibition”
“N-[4-[(hydroxyamino)-oxomethyl]phenyl]carbamic acid [6-(diethylaminomethyl)-2-naphthalenyl]methyl ester”	“down-regulates activity”	HDAC9	“chemical inhibition”
romidepsin	“down-regulates activity”	HDAC9	“chemical inhibition”
6-(1,3-dioxo-2-benzo[de]isoquinolinyl)-N-hydroxyhexanamide	“down-regulates activity”	HDAC9	“chemical inhibition”
CUDC-101	“down-regulates activity”	HDAC9	“chemical inhibition”

Protein complexes (CORUM) (11)

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

11 complexes by size:

Complex	Subunits	Members
★ FOXP3-HDAC9-KAT5 complex	3	FOXP3, HDAC9, KAT5
★ ETV6-HDAC9 complex	2	ETV6, HDAC9
★ HDAC3-HDAC9 complex	2	HDAC3, HDAC9
★ HDAC4-HDAC9 complex	2	HDAC4, HDAC9
★ HDAC1-HDAC9 complex	2	HDAC1, HDAC9
★ HDAC9-ZBTB16 complex	2	HDAC9, ZBTB16
★ HDAC9-SIN3A complex	2	HDAC9, SIN3A
★ HDAC9-SIN3B complex	2	HDAC9, SIN3B
★ HDAC9-NCOR1 complex	2	HDAC9, NCOR1
★ BCL6-HDAC9 complex	2	BCL6, HDAC9
★ HDAC9-SMARCA4 complex	2	HDAC9, SMARCA4

Disease & clinical

Genetic variants

Variant evidence for HDAC9: 168 ClinVar records (3 pathogenic / likely pathogenic); 87 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	108
Likely benign	10
Benign	12

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
58533	GRCh38/hg38 7p21.1(chr7:17930595-18209019)x1	Pathogenic	criteria provided, single submitter	1
2580891	NC_000007.14:g.18437239_18867540dup	Pathogenic	no assertion criteria provided	1
2664509	GRCh37/hg19 7p21.1(chr7:17930686-19059254)x1	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore HDAC9’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 3,966):

Position(s)	Effect	Δscore	Sites
7:18545099	donor_gain	1.0000
7:18585270	acceptor_gain	1.0000
7:18590330	acceptor_gain	1.0000
7:18590334	acceptor_gain	1.0000
7:18593906–18593907	acceptor_loss	1.0000	3
7:18593907	acceptor_gain	1.0000
7:18594030–18594031	donor_loss	1.0000	5
7:18666439	donor_gain	1.0000
7:18666477–18666478	donor_loss	1.0000	6
7:18749003–18749004	acceptor_loss	1.0000	6

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000107

Disease associations

OMIM: gene MIM:606543 | disease phenotypes: MIM:620457

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
auriculocondylar syndrome 4	Limited	Autosomal dominant
auriculocondylar syndrome	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
auriculocondylar syndrome	Disputed	AD

Mondo (2): auriculocondylar syndrome 4 (MONDO:0957543), auriculocondylar syndrome (MONDO:0000107)

HPO phenotypes

13 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000162	Glossoptosis
HP:0000175	Cleft palate
HP:0000293	Full cheeks
HP:0000324	Facial asymmetry
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0001263	Global developmental delay
HP:0002104	Apnea
HP:0003577	Congenital onset
HP:0004451	Postauricular skin tag
HP:0030022	Question mark ear

GWAS associations

showing 30 of 87 associations:

Study	Trait	p-value
GCST006661_329	Male-pattern baldness	5e-70
GCST90002400_189	Plateletcrit	4e-41
GCST007096_69	Pulse pressure	1e-37
GCST003983_4	Male-pattern baldness	1e-36
GCST010866_93	Coronary artery disease	1e-31
GCST005575_14	Moyamoya disease	1e-29
GCST90002402_359	Platelet count	1e-28
GCST010703_75	Brain morphology (MOSTest)	3e-26
GCST008839_77	Height	1e-25
GCST007705_32	Pulse pressure	7e-21
GCST90000025_1033	Appendicular lean mass	1e-19
GCST90002401_500	Platelet distribution width	8e-19
GCST001706_2	Stroke (ischemic)	2e-16
GCST010158_1	Large artery stroke (CCS or TOAST classification)	4e-16
GCST003996_40	Monobrow	7e-16
GCST007097_156	Pulse pressure	3e-15
GCST006661_180	Male-pattern baldness	5e-15
GCST010479_31	Coronary artery disease	1e-14
GCST004607_117	Plateletcrit	2e-14
GCST006661_6	Male-pattern baldness	2e-14
GCST010702_136	Subcortical volume (MOSTest)	2e-14
GCST007705_29	Pulse pressure	6e-14
GCST010160_1	Large artery stroke (TOAST classification)	8e-14
GCST007099_190	Systolic blood pressure	9e-14
GCST004787_16	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	3e-13
GCST006009_16	Pulse pressure	5e-13
GCST001548_2	Male-pattern baldness	1e-12
GCST010161_1	Large artery stroke (CCSp classification)j	1e-12
GCST002288_1	Large artery stroke	3e-12
GCST002290_3	Coronary artery disease or large artery stroke	3e-12

EFO canonical traits (from GWAS)

26 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0003940	physical activity
EFO:0000180	HIV-1 infection
EFO:1001253	maculopapular eruption
EFO:0005763	pulse pressure measurement
EFO:0007865	loneliness measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0007906	synophrys measurement
EFO:0007985	platelet crit
EFO:0006797	neurofibrillary tangles measurement
EFO:0006798	neuritic plaque measurement
EFO:0004357	electroencephalogram measurement
EFO:0004350	reasoning
EFO:0006335	systolic blood pressure
EFO:0009764	eye colour measurement
EFO:0006917	spontaneous preterm birth
EFO:0010103	response to peginterferon alfa-2a
EFO:0007006	depressive symptom measurement
EFO:0010272	abdominal aortic calcification measurement
EFO:0004771	visual cortical surface area measurement
EFO:0004346	neuroimaging measurement
EFO:0008255	particulate matter air pollution measurement
EFO:0004980	appendicular lean mass
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C538270	Auriculo-condylar syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2093865 (PROTEIN FAMILY), CHEMBL4145 (SINGLE PROTEIN), CHEMBL5169076 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465556 (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: 455,326 (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
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
CHEMBL4283683	DOMATINOSTAT	2	808
CHEMBL3622533	FIMEPINOSTAT	2
CHEMBL1801250	NANATINOSTAT	2
CHEMBL2105763	QUISINOSTAT	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 (13 total), top 13:

Ligand	Action	Affinity	Parameter
panobinostat	Inhibition	8.52	pEC50
TMP269	Inhibition	7.64	pIC50
quisinostat	Inhibition	7.49	pIC50
vorinostat	Inhibition	7.19	pKi
CUDC-101	Inhibition	7.17	pIC50
belinostat	Inhibition	6.6	pKi
givinostat	Inhibition	6.41	pKi
entinostat	Inhibition	6.3	pEC50
KA1010	Inhibition	6.25	pIC50
trichostatin A	Inhibition	6.1	pKi
romidepsin	Inhibition	5.96	pKi
scriptaid	Inhibition	5.1	pKi
dacinostat	Inhibition	5.05	pKi

Binding affinities (BindingDB)

2063 measured of 2414 human assays (2460 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
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
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
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
6-{[2-(9H-Fluoren-9-yliden)acetyl]amino}-N-hydroxyhexanamide	IC50	1.6 nM
(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

ChEMBL bioactivities

3530 potent at pChembl≥5 of 3904 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
9.30	IC50	0.5	nM	ENTINOSTAT
9.08	IC50	0.83	nM	PANOBINOSTAT
9.05	IC50	0.9	nM	CHEMBL3692689
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
8.96	IC50	1.1	nM	CHEMBL2414098
8.92	IC50	1.2	nM	CHEMBL604796
8.92	IC50	1.2	nM	CHEMBL608416
8.92	IC50	1.2	nM	CHEMBL594544
8.92	Ki	1.2	nM	PANOBINOSTAT
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

PubChem BioAssay actives

2468 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
Vorinostat	2031064: Inhibition of HDAC in human HeLa cells nuclear extract incubated for 30 mins by multiplate reader analysis	ic50	0.0003	uM
pyridin-3-ylmethyl N-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]carbamate	1740018: Inhibition of recombinant human HDAC9 using pan-HDAC substrate incubated for 3 hrs by fluorescence method	ic50	0.0005	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-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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	6
Valproic Acid	affects expression, increases expression, increases methylation, affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	4
bisphenol A	affects methylation, decreases expression	3
(+)-JQ1 compound	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
entinostat	decreases expression, affects cotreatment	2
monomethylarsonous acid	increases expression, decreases reaction	2
Vorinostat	decreases expression, decreases reaction, increases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Silicon Dioxide	increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
oxybenzone	increases expression	1
titanium dioxide	decreases expression	1
malealdehyde	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
benzo(e)pyrene	decreases methylation	1
ferrous chloride	increases expression	1
hydroquinone	increases expression	1
diallyl trisulfide	increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
brequinar	increases expression	1
astragaloside A	decreases expression, decreases reaction, increases reaction, increases expression, increases phosphorylation	1

ChEMBL screening assays

1625 unique, capped per target: 1612 binding, 8 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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SR22	HAP1 HDAC9 (-) 1	Cancer cell line	Male
CVCL_SR23	HAP1 HDAC9 (-) 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 HDAC9 across ~30M SureChEMBL compounds — explore on Sugi Predict.