ACSS2

Summary

ACSS2 (acyl-CoA synthetase short chain family member 2, HGNC:15814) is a protein-coding gene on chromosome 20q11.22, encoding Acetyl-coenzyme A synthetase, cytoplasmic (Q9NR19). Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids.

This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55902 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 124 total — 3 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 25 tissues, sQTL in 10 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.79 (unconstrained)
• MANE Select transcript: NM_018677
• Interaction hub: 2,022 STRING partners (top 7% of genes corpus-wide)
• Notable: 124 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15814
Approved symbol	ACSS2
Name	acyl-CoA synthetase short chain family member 2
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	ACS, ACSA, AceCS, dJ1161H23.1
Ensembl gene	ENSG00000131069
Ensembl biotype	protein_coding
OMIM	605832
Entrez	55902

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 43 protein_coding, 24 nonsense_mediated_decay, 9 protein_coding_CDS_not_defined, 4 retained_intron

MANE Select: ENST00000360596

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

ENST00000360596, ENST00000253382, ENST00000461051, ENST00000464399, ENST00000467019, ENST00000468550, ENST00000470315, ENST00000473172, ENST00000475459, ENST00000476922, ENST00000477932, ENST00000480274, ENST00000480978, ENST00000481284, ENST00000481971, ENST00000484354, ENST00000488172, ENST00000490046, ENST00000490464, ENST00000491533, ENST00000493250, ENST00000493805, ENST00000494727, ENST00000497927, ENST00000871368, ENST00000871369, ENST00000871370, ENST00000871371, ENST00000871372, ENST00000871373, ENST00000871374, ENST00000871375, ENST00000871376, ENST00000871377, ENST00000871378, ENST00000871379, ENST00000871380, ENST00000918462, ENST00000918463, ENST00000918464, ENST00000957793, ENST00000957794, ENST00000957795, ENST00000957796, ENST00000957797, ENST00000957798, ENST00000957799, ENST00000957800, ENST00000957801, ENST00000957802, ENST00000957803, ENST00000957804, ENST00001008122, ENST00001008123, ENST00001008125, ENST00001018038, ENST00001018039, ENST00001018041, ENST00001018042, ENST00001018044, ENST00001018045, ENST00001018048, ENST00001018049, ENST00001018050, ENST00001018054, ENST00001018055, ENST00001018056, ENST00001018057, ENST00001018058, ENST00001018059, ENST00001018060, ENST00001018061, ENST00001018063, ENST00001065442, ENST00001093061, ENST00001106181, ENST00001115715, ENST00001123265, ENST00001123266, ENST00001132188

RefSeq mRNA: 3 — MANE Select: NM_018677 NM_001076552, NM_001242393, NM_018677

CCDS: CCDS13243, CCDS42868

Canonical transcript exons

ENST00000360596 — 18 exons

Exon	Start	End
ENSE00001893210	34876612	34876823
ENSE00003482804	34921330	34921462
ENSE00003499545	34921006	34921139
ENSE00003501527	34920539	34920709
ENSE00003508396	34913096	34913187
ENSE00003522612	34925698	34925766
ENSE00003531165	34919435	34919572
ENSE00003568105	34921544	34921600
ENSE00003580028	34923323	34923431
ENSE00003584160	34926877	34926951
ENSE00003591254	34913753	34913825
ENSE00003591834	34921786	34921866
ENSE00003630254	34914096	34914171
ENSE00003645627	34926105	34926281
ENSE00003662143	34882794	34882989
ENSE00003675474	34914323	34914437
ENSE00003786779	34913393	34913496
ENSE00003846039	34927087	34927959

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.1695 / max 1855.6799, expressed in 1806 samples.

Highest expression (Bgee): ileal mucosa, ileum, mucosa of transverse colon, rectum, hindlimb stylopod muscle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACSS2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 35 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	1.6e-22	+0.30	20:34879914:T:C
Skin Not Sun Exposed Suprapubic	sqtl	2.7e-19	-0.50	20:34877769:C:A
Brain Cerebellum	eqtl	7.0e-17	+0.43	20:34828733:C:T
Skin Sun Exposed Lower leg	sqtl	5.2e-16	-0.42	20:34899066:T:C
Lung	sqtl	9.0e-14	-0.36	20:34939180:T:C
Brain Caudate basal ganglia	eqtl	2.6e-12	+0.29	20:34848071:T:C
Cells Cultured fibroblasts	eqtl	3.0e-11	-0.13	20:34877769:C:A
Brain Cerebellar Hemisphere	eqtl	3.7e-11	+0.27	20:34950718:A:G
Muscle Skeletal	sqtl	9.5e-07	+0.16	20:34934251:T:C
Muscle Skeletal	eqtl	4.6e-06	-0.13	20:35135088:A:AT
Brain Nucleus accumbens basal ganglia	eqtl	4.9e-06	+0.21	20:34837105:C:G
Esophagus Gastroesophageal Junction	eqtl	8.2e-05	+0.16	20:34920785:G:T
Esophagus Muscularis	eqtl	1.5e-04	+0.14	20:34934339:T:C
Breast Mammary Tissue	sqtl	2.1e-04	+0.77	20:35591187:G:A
Brain Cortex	eqtl	3.3e-04	+0.18	20:34699621:T:C
Stomach	eqtl	6.5e-04	+0.12	20:34832174:C:A
Heart Atrial Appendage	eqtl	1.5e-03	-0.15	20:34639257:T:C
Brain Substantia nigra	eqtl	1.6e-03	+0.21	20:34950718:A:G
Brain Hypothalamus	eqtl	6.2e-03	+0.88	20:34863274:C:A
Brain Putamen basal ganglia	eqtl	7.3e-03	+0.15	20:34865112:G:A

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
184266	15.7609	1666
184265	8.8896	1769
184264	1.6378	1099
184261	0.3500	99
184267	0.1838	62
184260	0.1648	79
184262	0.1060	65
184263	0.0767	46

Top tissues by expression

showing 100 of 259 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.31	gold quality
ileum	UBERON:0002116	99.21	silver quality
mucosa of transverse colon	UBERON:0004991	98.93	gold quality
rectum	UBERON:0001052	98.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.93	gold quality
transverse colon	UBERON:0001157	97.71	gold quality
mucosa of stomach	UBERON:0001199	97.65	gold quality
tibialis anterior	UBERON:0001385	97.65	gold quality
right adrenal gland cortex	UBERON:0035827	97.51	gold quality
right lung	UBERON:0002167	97.49	gold quality
gastrocnemius	UBERON:0001388	97.42	gold quality
apex of heart	UBERON:0002098	97.40	gold quality
upper arm skin	UBERON:0004263	97.40	gold quality
kidney epithelium	UBERON:0004819	97.35	gold quality
right adrenal gland	UBERON:0001233	97.27	gold quality
pancreatic ductal cell	CL:0002079	97.19	gold quality
colonic epithelium	UBERON:0000397	97.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.14	gold quality
muscle of leg	UBERON:0001383	97.09	gold quality
upper lobe of left lung	UBERON:0008952	96.95	gold quality
left adrenal gland	UBERON:0001234	96.93	gold quality
left adrenal gland cortex	UBERON:0035825	96.93	gold quality
lower esophagus mucosa	UBERON:0035834	96.89	gold quality
body of stomach	UBERON:0001161	96.78	gold quality
upper lobe of lung	UBERON:0008948	96.76	gold quality
small intestine	UBERON:0002108	96.72	gold quality
adrenal cortex	UBERON:0001235	96.70	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.60	gold quality
heart left ventricle	UBERON:0002084	96.59	gold quality
right lobe of liver	UBERON:0001114	96.58	gold quality
adipose tissue	UBERON:0001013	96.49	gold quality
adrenal gland	UBERON:0002369	96.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.39	gold quality
omental fat pad	UBERON:0010414	96.36	gold quality
peritoneum	UBERON:0002358	96.32	gold quality
cardiac ventricle	UBERON:0002082	96.26	gold quality
descending thoracic aorta	UBERON:0002345	96.25	gold quality
right atrium auricular region	UBERON:0006631	96.18	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.14	gold quality
skin of abdomen	UBERON:0001416	96.12	gold quality
cardiac atrium	UBERON:0002081	95.80	gold quality
stomach	UBERON:0000945	95.77	gold quality
thoracic aorta	UBERON:0001515	95.73	gold quality
intestine	UBERON:0000160	95.71	gold quality
heart	UBERON:0000948	95.71	gold quality
ascending aorta	UBERON:0001496	95.70	gold quality
deltoid	UBERON:0001476	95.69	gold quality
skin of leg	UBERON:0001511	95.66	gold quality
adult mammalian kidney	UBERON:0000082	95.65	gold quality
colon	UBERON:0001155	95.60	gold quality
large intestine	UBERON:0000059	95.56	gold quality
duodenum	UBERON:0002114	95.44	gold quality
metanephros cortex	UBERON:0010533	95.29	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.25	gold quality
right uterine tube	UBERON:0001302	95.15	gold quality
skeletal muscle tissue	UBERON:0001134	95.05	gold quality
left coronary artery	UBERON:0001626	95.05	gold quality
nerve	UBERON:0001021	95.04	gold quality
tibial nerve	UBERON:0001323	95.04	gold quality
coronary artery	UBERON:0001621	94.93	gold quality
adrenal tissue	UBERON:0018303	94.83	gold quality
liver	UBERON:0002107	94.70	gold quality
ectocervix	UBERON:0012249	94.66	gold quality
right coronary artery	UBERON:0001625	94.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.62	gold quality
quadriceps femoris	UBERON:0001377	94.57	gold quality
esophagus mucosa	UBERON:0002469	94.57	gold quality
left ventricle myocardium	UBERON:0006566	94.57	gold quality
muscle tissue	UBERON:0002385	94.56	gold quality
cerebellar hemisphere	UBERON:0002245	94.54	gold quality
monocyte	CL:0000576	94.51	gold quality
zone of skin	UBERON:0000014	94.48	gold quality
cortex of kidney	UBERON:0001225	94.40	gold quality
cerebellar cortex	UBERON:0002129	94.38	gold quality
esophagus	UBERON:0001043	94.30	gold quality
lower esophagus	UBERON:0013473	94.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.18	gold quality
leukocyte	CL:0000738	94.16	gold quality
fundus of stomach	UBERON:0001160	94.16	gold quality
colonic mucosa	UBERON:0000317	94.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.14	gold quality
minor salivary gland	UBERON:0001830	94.07	gold quality
vastus lateralis	UBERON:0001379	93.85	gold quality
lung	UBERON:0002048	93.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.82	gold quality
saliva-secreting gland	UBERON:0001044	93.81	gold quality
kidney	UBERON:0002113	93.77	gold quality
aorta	UBERON:0000947	93.73	gold quality
right ovary	UBERON:0002118	93.71	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.70	gold quality
body of uterus	UBERON:0009853	93.69	gold quality
left ovary	UBERON:0002119	93.67	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.49	gold quality
cerebellum	UBERON:0002037	93.30	gold quality
epithelial cell of pancreas	CL:0000083	93.25	silver quality
mouth mucosa	UBERON:0003729	93.08	gold quality
left uterine tube	UBERON:0001303	92.98	gold quality
endocervix	UBERON:0000458	92.94	gold quality
spinal cord	UBERON:0002240	92.88	gold quality
body of pancreas	UBERON:0001150	92.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	109.9	medium
Tongue	tissue	92.7
Adipose tissue	tissue	65.0	not detected
Duodenum	tissue	60.5	medium
Colon	tissue	51.0	medium
Frontal cortex	tissue	49.9
Heart muscle	tissue	46.6	medium
Small intestine	tissue	44.1	medium
Liver	tissue	43.8	low
Caudate putamen	tissue	40.3
Salivary gland	tissue	35.9	low
Stomach 1	tissue	35.5	medium
Epididymis	tissue	32.4	low
Rectum	tissue	30.8	medium
Locus coeruleus	tissue	29.6
Cerebellum	tissue	27.4	low
Breast	tissue	25.5	low
Choroid plexus	tissue	25.4
Spinal cord	tissue	24.1
Adrenal gland	tissue	22.3	medium
Lung	tissue	21.8	low
Fallopian tube	tissue	20.8	low
Kidney	tissue	20.5	not detected
Nucleus accumbens	tissue	19.7
Parathyroid gland	tissue	18.4	low
Medulla oblongata	tissue	18.0
Esophagus	tissue	17.5	not detected
Hippocampus	tissue	17.5	medium
Postcentral gyrus	tissue	17.4
Pons	tissue	17.0
Vagina	tissue	16.8	not detected
Placenta	tissue	16.1	low
Midbrain	tissue	15.9
Thalamus	tissue	15.6
Seminal vesicle	tissue	15.3
Superior colliculi	tissue	15.3
Skin 1	tissue	15.2	low
Substantia nigra	tissue	15.2
Corpus callosum	tissue	15.0
Hypothalamus	tissue	14.6
Pancreas	tissue	14.0	low
Periaqueductal gray	tissue	13.9
Endometrium 1	tissue	12.8	not detected
Cerebral cortex	tissue	12.1	low
Somatosensory cortex	tissue	12.1
Prostate	tissue	11.5	low
Occipital cortex	tissue	11.5
Hippocampal formation	tissue	11.1
Septum	tissue	10.9
Ovary	tissue	10.6	low
Smooth muscle	tissue	10.5	not detected
Entorhinal cortex	tissue	10.1
Appendix	tissue	10.1	medium
Gallbladder	tissue	10.0	low
Testis	tissue	9.9	medium
Temporal cortex	tissue	9.6
Motor cortex	tissue	9.2
Retrosplenial cortex	tissue	9.2
Prefrontal cortex	tissue	9.1
Thyroid gland	tissue	9.0	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Parieto-temporal junction (white matter) (44.8), Temporal white matter (43.4), Corpus callosum, genu (white matter) (40.3), Principal sensory trigeminal nucleus (38.8), Pontine nuclei (38.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3, SREBF1, SREBF2

miRNA regulators (miRDB)

Targeting ACSS2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 37 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-12126	98.09	64.82	637
HSA-MIR-1245B-3P	98.01	68.91	1387

Functional genomics

gnomAD constraint: pLI 5.55e-10, LOEUF 0.785, missense Z 1.67 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000360596 — one region, missense o/e 0.83.

Literature-anchored findings (GeneRIF, showing 29)

• Because the activity of a bacterial ortholog of AceCS2, called ACS, is controlled via deacetylation by a bacterial sirtuin protein, our observation highlights the conservation of a metabolic regulatory pathway from bacteria to humans (PMID:16788062)
• The patterns of (18)F-FDG and (11)C-acetate uptake seemed to complement each other in both human HCC and HCC cell lines. (PMID:19617323)
• Ritonavir (at 100 mg once daily and 100 mg twice daily significantly down-regulated acyl-CoA synthetase short-chain family member 2 in 20 healthy individuals. (PMID:20353815)
• During hypoxia, ACSS2 modulates interactions of the acetylase/coactivator CBP with the stress-responsive transcription factor, HIF-2. These interactions include acetylation of HIF-2 by CBP as well as stable HIF-2/CBP complex formation, both of which are required for maximal HIF-2 signaling. Thus, ACSS2 links changes in metabolism that occur during stress with activation of a selective nuclear signaling pathway. (PMID:25108527)
• Observations suggest that ACSS2 is expressed to a significant extent in particular tumor types, including triple-negative breast cancers. (PMID:25525877)
• Study shows that ACSS2 is upregulated in the human orthotopic tumor and primary human tumors, as well as a murine glioma model; the tumors do not oxidize [U-(13)C]glutamine. In vivo oxidation of [1,2-(13)C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. (PMID:25525878)
• Study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. (PMID:25584894)
• Loss of ACSS2 expression is associated with with gastric cancer. (PMID:26381042)
• ACSS2 is essential for glucose-independent acetate-mediated cell survival and tumor growth. (PMID:27539851)
• these findings suggest that downregulation of acetyl-CoA synthetase-2 expression is a metabolic hallmark of tumor progression and aggressive behavior in colorectal carcinoma. (PMID:27713423)
• The nuclear-cytosolic acetyl-CoA synthetase 2 recaptures acetate released from histone deacetylation for recycling by histone acetyltransferases. (PMID:28099844)
• ACLY and ACSS2 are both activated to produce cytosolic Ac-CoA from glucose carbon for lipogenesis during human cytomegalovirus infection. (PMID:28167750)
• In a Honduran population, the odds of having nonsyndromic cleft lip/palate (NSCLP) among carriers of the ACSS2 variant was 4.0 with a carrier frequency of 7.1% in unrelated affected and 1.9% in unrelated unaffected individuals. In a Colombian population, the odds of having NSCLP among carriers of the ACSS2 variant was 2.6 with a carrier frequency of 10.0% in unrelated affected and 4.1% in unrelated unaffected individuals. (PMID:28543373)
• Results suggest that ACSS2 gene is associated with human alcoholism and ethanol intake in a free-choice animal model, and even the compulsive-like behavior associated with ethanol use. Finally, slight alterations in metabolism could be responsible for the difference between ethanol non-preferring, ethanol-preferring and compulsive-like ethanol consumption. (PMID:28550509)
• In the nucleus, ACSS2 binds to transcription factor EB and translocates to lysosomal and autophagy gene promoter regions, where ACSS2 incorporates acetate generated from histone acetylation turnover to locally produce acetyl-CoA for histone H3 acetylation in these regions and promote lysosomal biogenesis, autophagy, cell survival, and brain tumorigenesis. (PMID:28552616)
• A novel biologic role for ACSS2 in recycling of nuclear acetate for histone acetylation to promote lysosomal and autophagy-related gene expression and counteract nutritional stress, highlighting the importance of ACSS2 in maintaining autophagy and lysosome-mediated cellular energy homeostasis during tumor development. (PMID:28820290)
• Exogenous acetate augments Acss2/HIF-2 dependent cancer growth and metastasis in cell culture and mouse models (PMID:29281714)
• ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1. (PMID:29444517)
• ACSS2-driven histone crotonylation reverses HIV latency (PMID:29457784)
• High ACSS2 expression is associated with renal cell carcinoma. (PMID:29503142)
• the alternative transcription start site selection of ACSS2 was significantly different between hepatocellular carcinoma and corresponding adjacent tissues. (PMID:31076106)
• Low ACSS2 expression is associated with Abdominal Aortic Aneurysm. (PMID:31730405)
• Silencing ACSS2 expression inhibits migration and invasion of cervical cancer cells induced by nutrient stress, which is related to down-regulated Wnt/beta-catenin signaling pathway activity. (PMID:31814569)
• Mammalian acetate-dependent acetyl CoA synthetase 2 contains multiple protein destabilization and masking elements. (PMID:34343565)
• O-GlcNAc transferase regulates glioblastoma acetate metabolism via regulation of CDK5-dependent ACSS2 phosphorylation. (PMID:35190642)
• Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis and Muscle Wasting Through Metabolic Reprogramming in Pancreatic Cancer. (PMID:35777482)
• ACSS2-mediated NF-kappaB activation promotes alkaliptosis in human pancreatic cancer cells. (PMID:36707625)
• ACSS2 gene variants determine kidney disease risk by controlling de novo lipogenesis in kidney tubules. (PMID:38051585)
• Proteomic profiling reveals ACSS2 facilitating metabolic support in acute myeloid leukemia. (PMID:38851813)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	acss2	ENSDARG00000037781
mus_musculus	Acss2	ENSMUSG00000027605
rattus_norvegicus	Acss2	ENSRNOG00000018755
drosophila_melanogaster	AcCoAS	FBGN0012034
caenorhabditis_elegans		WBGENE00007969

Paralogs (13): ACSM3 (ENSG00000005187), ACSM2B (ENSG00000066813), AACS (ENSG00000081760), ACSS3 (ENSG00000111058), ACSS1 (ENSG00000154930), AASDH (ENSG00000157426), ACSM1 (ENSG00000166743), ACSF2 (ENSG00000167107), ACSM6 (ENSG00000173124), ACSF3 (ENSG00000176715), ACSM5 (ENSG00000183549), ACSM2A (ENSG00000183747), ACSM4 (ENSG00000215009)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1890410) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal kidney cortex morphology	1
decreased circulating creatinine level	1
decreased blood urea nitrogen level	1
abnormal long-term spatial reference memory	1
decreased interleukin-1 beta secretion	1
decreased susceptibility to endotoxin shock	1
impaired contextual conditioning behavior	1
impaired cued conditioning behavior	1
abnormal epigenetic regulation of gene expression	1
decreased pyroptosis	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
Mycobacterium tuberculosis H37Rv	O53551	100.0%	Diamond
Staphylococcus aureus subsp. aureus COL	Q5HIA1	100.0%	Diamond
Staphylococcus aureus subsp. aureus MSSA476	Q6GBR2	100.0%	Diamond
Staphylococcus aureus subsp. aureus MW2	Q7A1Q0	100.0%	Diamond
Staphylococcus aureus subsp. aureus N315	Q7A769	100.0%	Diamond
Mycobacterium tuberculosis variant bovis AF2122/97	Q7TWC5	100.0%	Diamond
Staphylococcus aureus subsp. aureus Mu50	Q99W34	100.0%	Diamond
Staphylococcus aureus subsp. aureus Mu3	Q9KWK5	100.0%	Diamond
Pseudomonas aeruginosa UCBPP-PA14	A0A0H2ZF83	99.3%	Diamond
Pseudomonas aeruginosa PAO1	Q9HWG3	99.3%	Diamond
Staphylococcus aureus subsp. aureus MRSA252	Q6GJ94	98.0%	Diamond
Saccharomyces cerevisiae S288C	Q01574	81.7%	Diamond
Eremothecium gossypii ATCC 10895	Q758X0	77.3%	Diamond
Sulfurisphaera tokodaii str. 7	Q973W5	76.4%	Diamond
Chlorobaculum tepidum TLS	Q8KBY0	58.8%	Diamond
Arabidopsis thaliana	B9DGD6	58.6%	Diamond
Cryptosporidium parvum	Q27549	52.9%	Diamond
Thauera aromatica	Q8GQN9	51.7%	Diamond
Bacillus anthracis	Q81RQ7	39.2%	Diamond
Penicillium expansum	A0A0A2J5U8	38.3%	Diamond
Streptomyces venezuelae ATCC 10712	F2RB81	35.3%	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
MMP24-AS1-EDEM2	protein-coding	111089941
TRPC4AP	protein-coding	26133
GSS	protein-coding	2937
EDEM2	protein-coding	55741
MIR499A	ncRNA	574501
MYH7B	protein-coding	57644
MIR499B	ncRNA	100616134
GGT7	protein-coding	2686
NCOA6	protein-coding	23054
TP53INP2	protein-coding	58476

Protein

Protein identifiers

Acetyl-coenzyme A synthetase, cytoplasmic — Q9NR19 (reviewed: Q9NR19)

Alternative names: Acetate–CoA ligase, Acetyl-CoA synthetase, Acetyl-CoA synthetase 1, Acyl-CoA synthetase short-chain family member 2, Acyl-activating enzyme, Lactyl-CoA synthetase, Propionyl-CoA synthetase

All UniProt accessions (10): B4DEH9, C9IYL0, C9J7L5, C9JXD9, C9JY31, F8WBQ7, F8WC73, F8WCJ4, F8WDJ9, Q9NR19

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids. Acetate is the preferred substrate. Can also utilize propionate with a much lower affinity. Catalyzes the conversion of lactate into lactoyl-CoA. Does not catalyze the conversion of butyrate or crotonate to their corresponding acyl-CoAs. Nuclear ACSS2 promotes glucose deprivation-induced lysosomal biogenesis and autophagy, tumor cell survival and brain tumorigenesis. Glucose deprivation results in AMPK-mediated phosphorylation of ACSS2 leading to its translocation to the nucleus where it binds to TFEB and locally produces acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes thereby activating their transcription. The regulation of genes associated with autophagy and lysosomal activity through ACSS2 is important for brain tumorigenesis and tumor survival. Acts as a chromatin-bound transcriptional coactivator that up-regulates histone acetylation and expression of neuronal genes. Can be recruited to the loci of memory-related neuronal genes to maintain a local acetyl-CoA pool, providing the substrate for histone acetylation and promoting the expression of specific genes, which is essential for maintaining long-term spatial memory.

Subunit / interactions. Monomer. Interacts with TFEB. AMPK-mediated phosphorylated form at Ser-659 interacts with KPNA1; this interaction results in nuclear translocation of ACSS2. Interacts with the ‘Thr-172’ phosphorylated form of PRKAA2. Interacts with CREBBP.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Post-translational modifications. Reversibly acetylated at Lys-661. The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3. Glucose deprivation results in its AMPK-dependent phosphorylation at Ser-659, which leads to exposure of its nuclear localization signal, required for its interaction with KPNA1 and subsequent translocation to the nucleus.

Activity regulation. Inhibited by acetylation at Lys-661 and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3.

Similarity. Belongs to the ATP-dependent AMP-binding enzyme family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NR19-1	1	yes
Q9NR19-2	2

RefSeq proteins (3): NP_001070020, NP_001229322, NP_061147* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000873	AMP-dep_synth/lig_dom	Domain
IPR011904	Ac_CoA_lig	Family
IPR020845	AMP-binding_CS	Conserved_site
IPR025110	AMP-bd_C	Domain
IPR032387	ACAS_N	Domain
IPR042099	ANL_N_sf	Homologous_superfamily
IPR045851	AMP-b_sf	Homologous_superfamily

Pfam: PF00501, PF13193, PF16177

Enzyme classification (BRENDA)

• EC 6.2.1.1 — acetate-CoA ligase (BRENDA: 56 organisms, 173 substrates, 59 inhibitors, 236 Km, 149 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ACETATE	0.035–11000	53
ATP	0.017–17	41
COA	0.011–1.2	36
PROPIONATE	0.62–188.8	16
BUTYRATE	0.19–151.9	12
VALERATE	0.4–11.1	7
4-METHYLVALERATE	0.07–7.6	6
ACETYL-COA	0.0037–1.8	6
HEPTANOATE	0.71–10.2	6
HEXANOATE	0.13–12.6	6
OCTANOATE	2.1–48	6
3-METHYLVALERATE	0.04–125	5
ISOBUTYRATE	0.15–219	5
PROPANOATE	3.1–10.5	5
SODIUM ACETATE	0.25–4.66	5

Catalyzed reactions (Rhea)

• propanoate + ATP + CoA = propanoyl-CoA + AMP + diphosphate (RHEA:20373)
• acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate (RHEA:23176)
• (S)-lactate + ATP + CoA = (S)-lactoyl-CoA + AMP + diphosphate (RHEA:86695)

UniProt features (32 total): modified residue 9, binding site 8, mutagenesis site 7, sequence conflict 3, region of interest 2, chain 1, splice variant 1, short sequence motif 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR19-F1	90.14	0.74

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol; plasma membrane; vesicles

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.

Ligand- & substrate-binding residues (8)

Position	Role
575	CoA
636	CoA
219–222	CoA
363	CoA
439–441	ATP
463–468	ATP
552	ATP
567	ATP

Post-translational modifications (9)

Type	Positions
Phosphoserine	28, 30, 36, 263, 265, 267, 659
N6-acetyllysine	418, 661

Mutagenesis-validated functional residues (7)

Position	Phenotype
202	reduced acetate-binding but no effect on lactate binding.
315	reduced acetate-binding but no effect on lactate binding.
358	loss of lactate-binding but no effect on acetate-binding.
363	loss of catalytic activity but no effect on its nuclear translocation upon glucose deprivation. loss of ability to promote gene …
363	abolishes lactyl-coa synthetase activity.
659	no effect on catalytic activity. loss of ampk-mediated phosphorylation, interaction with kpna1 and nuclear translocation upon glucose …
664–665	no effect on catalytic activity. loss of interaction with kpna1 and nuclear translocation upon glucose deprivation. loss of ability to …

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-71384	Ethanol oxidation	curated
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis	curated
R-HSA-211859	Biological oxidations	—
R-HSA-1430728	Metabolism	—
R-HSA-1592230	Mitochondrial biogenesis	—
R-HSA-1852241	Organelle biogenesis and maintenance	—
R-HSA-211945	Phase I - Functionalization of compounds	—

MSigDB gene sets: 204 (showing top): GOBP_MEMORY, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_COGNITION, GOBP_BEHAVIOR, NIKOLSKY_BREAST_CANCER_20Q11_AMPLICON, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (9): ethanol catabolic process (GO:0006068), acetyl-CoA biosynthetic process (GO:0006085), DNA-templated transcription (GO:0006351), long-term memory (GO:0007616), lipid biosynthetic process (GO:0008610), acetate biosynthetic process (GO:0019413), propionate biosynthetic process (GO:0019542), lipid metabolic process (GO:0006629), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (9): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), acetyl-CoA synthetase activity (GO:0003987), ATP binding (GO:0005524), AMP binding (GO:0016208), propionate-CoA ligase activity (GO:0050218), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759), cytosol (GO:0005829)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Mitochondrial biogenesis	1
Phase I - Functionalization of compounds	1
Organelle biogenesis and maintenance	1
Metabolism	1
Biological oxidations	1

GO top-level categories

36 GO namespaces:

Category	Terms
cellular anatomical structure	3
binding	2
adenyl ribonucleotide binding	2
anion binding	2
ethanol metabolic process	1
primary alcohol catabolic process	1
acetyl-CoA metabolic process	1
acyl-CoA biosynthetic process	1
gene expression	1
RNA biosynthetic process	1
memory	1
lipid metabolic process	1
biosynthetic process	1
acetate metabolic process	1
monocarboxylic acid biosynthetic process	1
propionate metabolic process	1
short-chain fatty acid biosynthetic process	1
primary metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
CoA-ligase activity	1
purine ribonucleoside triphosphate binding	1
cation binding	1
short-chain fatty acid-CoA ligase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
mitochondrion	1
intracellular organelle lumen	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
lipid biosynthetic process	BP	mutant phenotype
cytosol	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
acetyl-CoA synthetase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,022 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSS2	ACSL1	P33121	882
ACSS2	ACSL5	Q9ULC5	848
ACSS2	ACSL6	Q9UKU0	845
ACSS2	ACLY	P53396	825
ACSS2	FASN	P49327	695
ACSS2	ACOT12	Q8WYK0	658
ACSS2	ACACA	Q13085	657
ACSS2	FABP3	P05413	594
ACSS2	SLC25A1	P53007	576
ACSS2	SREBF1	P36956	568
ACSS2	ACACB	O00763	542
ACSS2	SCD	O00767	530
ACSS2	PKM	P14618	530
ACSS2	HMGCS1	Q01581	530
ACSS2	IDH2	P48735	529

IntAct

Human interaction partners of ACSS2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
C	physical association	0.370	1
UPF1	physical association	0.000	1

BioGRID (20 interactions; top human partners by supporting records): BRD4 (Affinity Capture-MS), CAD (Co-fractionation), CTR9 (Affinity Capture-MS), DDX58 (Affinity Capture-RNA), MAPKAPK3 (Co-fractionation), MAT2A (Co-fractionation), PARK2 (Affinity Capture-MS), PRPS1 (Co-fractionation), PRPS2 (Affinity Capture-MS), RAN (Cross-Linking-MS (XL-MS)), RNF128 (Affinity Capture-MS), SUCLG2 (Affinity Capture-MS), TOPBP1 (Proximity Label-MS), TRIM67 (Affinity Capture-MS), UPF1 (Two-hybrid)

SIGNOR signaling

12 signaling interactions:

A	Effect	B	Mechanism
PRKAA1	“up-regulates activity”	ACSS2	phosphorylation
AMPK	“up-regulates activity”	ACSS2	phosphorylation
ACSS2	“up-regulates quantity”	acetyl-CoA(4-)	“chemical modification”
ACSS2	“down-regulates quantity”	acetate	“chemical modification”
ACSS2	“down-regulates quantity”	“coenzyme A(4-)”	“chemical modification”
ACSS2	“up-regulates quantity by expression”	CTSA	“transcriptional regulation”
ACSS2	“up-regulates quantity by expression”	GBA	“transcriptional regulation”
ACSS2	“up-regulates quantity by expression”	GUSB	“transcriptional regulation”
ACSS2	“up-regulates quantity by expression”	LAMP1	“transcriptional regulation”
ACSS2	“up-regulates quantity by expression”	PPM1D	“transcriptional regulation”
ACSS2	“up-regulates quantity by expression”	BECN1	“transcriptional regulation”
ACSS2	“up-regulates quantity by expression”	MAP1LC3B	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for ACSS2: 124 ClinVar records (4 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	78
Likely benign	14
Benign	7

Top pathogenic / likely-pathogenic (4)

Showing all 4 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
1526690	GRCh37/hg19 20p11.21-q11.22(chr20:25442597-33761550)x3	Pathogenic	criteria provided, single submitter	1
3248260	NC_000020.10:g.(?31368130)(34287210_?)del	Pathogenic	criteria provided, single submitter	1
1808687	GRCh37/hg19 20q11.21-11.23(chr20:29833535-34815537)x3	Likely pathogenic	criteria provided, single submitter	1
153447	GRCh38/hg38 20q11.21-11.23(chr20:32062768-35906606)x3	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ACSS2’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; 28 predictions of 1,643):

Position(s)	Effect	Δscore	Sites
20:34882971	donor_gain	1.0000
20:34913498	donor_loss	1.0000
20:34919563	donor_gain	1.0000
20:34923321–34923322	acceptor_loss	1.0000	6
20:34923432–34923433	donor_loss	1.0000	5
20:34926098	acceptor_gain	1.0000
20:34926103	acceptor_gain	1.0000
20:34876824–34876825	donor_loss	0.9900	5
20:34882786	acceptor_gain	0.9900
20:34882792–34882793	acceptor_loss	0.9900	6

AlphaMissense

1,859 missense substitutions predicted likely pathogenic (of 4,601 scored), across 467 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D358	8	0.989	0.998
F191	8	0.988	1.000
H365	8	0.981	0.997
D552	8	0.978	0.993
S317	8	0.976	0.999
D570	8	0.968	0.990
D463	8	0.964	0.989
H328	8	0.959	0.996
D569	8	0.959	0.988
F312	8	0.955	0.994
F345	8	0.942	0.988
H577	8	0.932	0.995
H187	8	0.926	0.987
D109	8	0.909	0.960
F541	8	0.904	0.977
D679	8	0.886	0.971
F494	8	0.858	0.926
D286	8	0.849	0.897
D351	8	0.830	0.963
F493	8	0.793	0.938

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	3.14e-06

Disease associations

OMIM: gene MIM:605832 | disease phenotypes: MIM:266130

GenCC curated gene-disease

Mondo (1): glutathione synthetase deficiency with 5-oxoprolinuria (MONDO:0009947)

Orphanet (1): Glutathione synthetase deficiency with 5-oxoprolinuria (Orphanet:289846)

GWAS associations

9 associations:

Study	Trait	p-value
GCST007876_74	Estimated glomerular filtration rate	7e-18
GCST010142_10	Fish- and plant-related diet	8e-12
GCST90020028_1985	Hip circumference adjusted for BMI	1e-11
GCST006941_38	Irritable mood	1e-10
GCST012227_58	Hip circumference adjusted for BMI	4e-10
GCST005962_5	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3e-8
GCST005956_47	Waist-to-hip ratio adjusted for BMI	8e-8
GCST008103_135	Bipolar disorder	3e-6
GCST005958_8	Waist-to-hip ratio adjusted for BMI (age >50)	6e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009594	irritability measurement
EFO:0008111	diet measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523467 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs17309872	Efficacy	3	carboplatin;cisplatin;docetaxel;gemcitabine;paclitaxel	Non-Small Cell Lung Carcinoma
rs6088638	Toxicity	3	ethanol	Alcohol abuse

PharmGKB variants

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17309872	ACSS2, GSS	3	3.00	1	carboplatin;cisplatin;docetaxel;gemcitabine;paclitaxel
rs6088638	ACSS2	3	1.75	1	ethanol

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

2 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs17309872	carboplatin, cisplatin, docetaxel, gemcitabine, paclitaxel	Efficacy	Genotype AT is associated with decreased overall survival due to carboplatin, cisplatin, docetaxel, gemcitabine or paclitaxel in people with Carcinoma, Non-Small-Cell Lung as compared to genotype AA.	PMID:21636554
rs6088638	ethanol	Toxicity	Allele T is associated with increased risk of Alcoholism due to ethanol as compared to allele C.	PMID:28550509

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Acyl-CoA synthetases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
example 265 [WO2019097515A1]	Inhibition	8.35	pIC50

Binding affinities (BindingDB)

207 measured of 321 human assays (321 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4467131	IC50	0.0028 nM
6-chloro-3-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-2-[hydroxy(diphenyl)methyl]pyrazolo[1,5-a]pyridine-5-carboxamide	IC50	0.01 nM	US-20230271956: AMIDE DERIVATIVES
1-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-2-[hydroxy(dithiophen-2-yl)methyl]-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	IC50	0.01 nM	US-20230271956: AMIDE DERIVATIVES
1-ethyl-N-(4-ethyl-1,3-oxazol-2-yl)-2-[hydroxy(diphenyl)methyl]-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	IC50	0.01 nM	US-20230271956: AMIDE DERIVATIVES
1-ethyl-N-(5-ethyl-1,3-oxazol-2-yl)-2-[hydroxy(diphenyl)methyl]-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	IC50	0.01 nM	US-20230271956: AMIDE DERIVATIVES
2-[[4-(difluoromethoxy)phenyl]-(2-fluorophenyl)-hydroxymethyl]-1-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	IC50	0.01 nM	US-20230271956: AMIDE DERIVATIVES
2-[bis(2-fluorophenyl)-hydroxymethyl]-1-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	IC50	0.01 nM	US-20230271956: AMIDE DERIVATIVES
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-phenyl-(1,3-thiazol-2-yl)methanol	IC50	0.01 nM	US-20240009175
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-phenyl-thiophen-2-ylmethanol	IC50	0.01 nM	US-20240009175
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-phenyl-pyridin-2-ylmethanol	IC50	0.01 nM	US-20240009175
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-bis(2-fluorophenyl)methanol	IC50	0.01 nM	US-20240009175
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-diphenylmethanol	IC50	0.01 nM	US-20240009175
CHEMBL4550594	IC50	0.33 nM
CHEMBL4449652	IC50	0.463 nM
CHEMBL4535842	IC50	1 nM
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-phenyl-pyrimidin-2-ylmethanol	IC50	1 nM	US-20240009175
CHEMBL4473187	IC50	1.1 nM
CHEMBL4463979	IC50	2.1 nM
CHEMBL4560160	IC50	2.7 nM
CHEMBL4548954	IC50	3.2 nM
CHEMBL4476365	IC50	3.9 nM
CHEMBL4466204	IC50	4 nM
CHEMBL4539904	IC50	4.5 nM
CHEMBL4437243	IC50	5 nM
2-[Bis-(2-fluoro-phenyl)-hydroxy-methyl]-6-chloro-3-ethyl-pyrazolo[1,5-a]pyridine-5-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
2-[Bis-(2-fluoro-phenyl)-hydroxy-methyl]-3-ethyl-6-methyl-pyrazolo[1,5-a]pyridine-5-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
2-[Bis-(2-fluoro-phenyl)-hydroxy-methyl]-3-ethyl-pyrazolo[1,5-a]pyridine-5-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
2-[bis(2-fluorophenyl)-hydroxymethyl]-6-chloro-3-ethyl-N-(1-ethylpyrazol-4-yl)pyrazolo[1,5-a]pyridine-5-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
2-[Bis-(2-fluoro-phenyl)-hydroxy-methyl]-3-ethyl-6-methoxy-pyrazolo[1,5-a]pyridine-5-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
3-Ethyl-2-(hydroxy-diphenyl-methyl)-pyrazolo[1,5-a]pyridine-5-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
3-Ethyl-2-(hydroxy-diphenyl-methyl)-6-methoxy-pyrazolo[1,5-a]pyridine-5-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
7-Chloro-3-ethyl-2-(hydroxy-diphenylmethyl)-imidazo[1,2-a]pyridine-6-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
3-Ethyl-7-fluoro-2-(hydroxy-diphenylmethyl)-imidazo[1,2-a]pyridine-6-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
3-Ethyl-2-(hydroxy-diphenyl-methyl)-7-methoxy-imidazo[1,2-a]pyridine-6-carboxylic acid (1-ethyl-1H-pyrazol-4-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
3-Ethyl-2-(hydroxy-diphenyl-methyl)-7-methoxy-imidazo[1,2-a]pyridine-6-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
3-Ethyl-2-(hydroxy-diphenyl-methyl)-imidazo[1,2-a]pyridine-6-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
3-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-2-[hydroxy-(5-methylthiophen-2-yl)-phenylmethyl]-7-methoxyimidazo[1,2-a]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
2-[Bis-(2-fluoro-phenyl)-hydroxy-methyl]-3-ethyl-7-methoxy-imidazo[1,2-a]pyridine-6-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
2-[Bis-(2-fluoro-phenyl)-hydroxy-methyl]-3-ethyl-7-methoxy-imidazo[1,2-a]pyridine-6-carboxylic acid (1-ethyl-1H-pyrazol-4-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
2-[Bis-(2-fluoro-phenyl)-hydroxy-methyl]-7-chloro-3-ethyl-imidazo[1,2-a]pyridine-6-carboxylic acid (1-ethyl-1H-[1,2,4]triazol-3-yl)-amide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
1-[2-(dimethylamino)ethyl]-N-(1-ethyl-1H-1,2,4-triazol-3-yl)-2-(hydroxydiphenylmethyl)-5-methoxy-1H-imidazo[4,5-b]pyridine-6-carboxamide trifluoroacetate	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
1-ethyl-N-(1-ethyl-1H-1,2,4-triazol-3-yl)-2-[hydroxy(phenyl)(quinolin-2-yl)methyl]-5-methoxy-1H-imidazo[4,5-b]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
1-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-2-[hydroxy(diphenyl)methyl]-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
1-ethyl-N-(1-ethyl-1H-1,2,4-triazol-3-yl)-2-[hydroxybis(thiophen-3-yl)methyl]-5-methoxy-1H-imidazo[4,5-b]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
1-ethyl-N-(1-ethyl-1H-1,2,4-triazol-3-yl)-2-[hydroxy(phenyl)(thiophen-3-yl)methyl]-5-methoxy-1H-imidazo[4,5-b]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
N-(1-ethyl-1H-1,2,4-triazol-3-yl)-2-(hydroxydiphenylmethyl)-5-methoxy-1-(2-methoxyethyl)-1H-imidazo[4,5-b]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
1-ethyl-N-(1-ethyl-1H-1,2,4-triazol-3-yl)-2-[hydroxy(phenyl)(1,3-thiazol-2-yl)methyl]-5-methoxy-1H-imidazo[4,5-b]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
1-ethyl-N-(1-ethyl-1H-1,2,4-triazol-3-yl)-2-[hydroxy(phenyl)(pyridazin-3-yl)methyl]-5-methoxy-1H-imidazo[4,5-b]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
1-ethyl-N-(1-ethyl-1H-1,2,4-triazol-3-yl)-2-[hydroxy(phenyl)(thiophen-2-yl)methyl]-5-methoxy-1H-imidazo[4,5-b]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors
N-(1-ethyl-1H-1,2,4-triazol-3-yl)-2-(hydroxydiphenylmethyl)-1-(2-hydroxyethyl)-5-methoxy-1H-imidazo[4,5-b]pyridine-6-carboxamide	IC50	5.5 nM	US-10611763: Histone demethylase inhibitors

ChEMBL bioactivities

272 potent at pChembl≥5 of 272 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL4846168
11.00	IC50	0.01	nM	CHEMBL4873965
11.00	IC50	0.01	nM	CHEMBL4850648
11.00	IC50	0.01	nM	CHEMBL4876400
11.00	IC50	0.01	nM	CHEMBL4867121
11.00	IC50	0.01	nM	CHEMBL4848186
11.00	IC50	0.01	nM	CHEMBL4870590
11.00	IC50	0.01	nM	CHEMBL4853889
11.00	IC50	0.01	nM	CHEMBL4855352
11.00	IC50	0.01	nM	CHEMBL4859117
11.00	IC50	0.01	nM	CHEMBL4862805
9.48	IC50	0.33	nM	CHEMBL4550594
9.34	IC50	0.4626	nM	CHEMBL4449652
9.00	IC50	1	nM	CHEMBL4535842
9.00	IC50	1	nM	CHEMBL4867121
9.00	IC50	1	nM	CHEMBL4848186
9.00	IC50	1	nM	CHEMBL4873965
9.00	IC50	1	nM	CHEMBL4876400
9.00	IC50	1	nM	CHEMBL4850648
9.00	IC50	1	nM	CHEMBL4855352
9.00	IC50	1	nM	CHEMBL4859117
9.00	IC50	1	nM	CHEMBL4870878
9.00	IC50	1	nM	CHEMBL4862805
9.00	IC50	1	nM	CHEMBL4870590
8.96	IC50	1.1	nM	CHEMBL4473187
8.68	IC50	2.1	nM	CHEMBL4463979
8.57	IC50	2.66	nM	CHEMBL4560160
8.49	IC50	3.2	nM	CHEMBL4548954
8.41	IC50	3.9	nM	CHEMBL4476365
8.40	IC50	4	nM	CHEMBL4466204
8.35	IC50	4.5	nM	CHEMBL4539904
8.30	IC50	5	nM	CHEMBL4437243
7.30	IC50	50	nM	CHEMBL4520185
7.30	IC50	50	nM	CHEMBL4570201
7.30	IC50	50	nM	CHEMBL4515458
7.30	IC50	50	nM	CHEMBL4546463
7.30	IC50	50	nM	CHEMBL4572762
7.30	IC50	50	nM	CHEMBL4582559
7.30	IC50	50	nM	CHEMBL4570193
7.30	IC50	50	nM	CHEMBL4513710
7.30	IC50	50	nM	CHEMBL4546851
7.30	IC50	50	nM	CHEMBL4531943
7.30	IC50	50	nM	CHEMBL4557579
7.30	IC50	50	nM	CHEMBL4555596
7.30	IC50	50	nM	CHEMBL4529333
7.30	IC50	50	nM	CHEMBL4559252
7.30	IC50	50	nM	CHEMBL4531805
7.30	IC50	50	nM	CHEMBL4536668
7.30	IC50	50	nM	CHEMBL4539409
7.30	IC50	50	nM	CHEMBL4534808

PubChem BioAssay actives

48 with measured affinity, of 48 total; 24 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-[3-(1,1-difluoroethyl)phenyl]-1-[4-(difluoromethoxy)-3-pyridin-4-ylphenyl]-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	<0.0001	uM
2-[[4-(difluoromethoxy)phenyl]-(2-fluorophenyl)-hydroxymethyl]-1-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	1772177: Inhibition of human recombinant ACSS2 incubated for 180 mins by AMP Glo assay	ic50	<0.0001	uM
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-phenyl-(1,3-thiazol-2-yl)methanol	1782628: Inhibition of ACSS2 in human HCT-15 cells assessed as inhibition of 14C acetate incorporation into fatty acids measured after 24 hrs by scintillation counting based cellular lipids assay	ic50	<0.0001	uM
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-diphenylmethanol	1782627: Inhibition of human recombinant ACSS2 assessed as AMP release using Coenzyme A/ATP as co-substrates by AMP Glo assay	ic50	<0.0001	uM
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-phenyl-thiophen-2-ylmethanol	1782628: Inhibition of ACSS2 in human HCT-15 cells assessed as inhibition of 14C acetate incorporation into fatty acids measured after 24 hrs by scintillation counting based cellular lipids assay	ic50	<0.0001	uM
6-chloro-3-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-2-[hydroxy(diphenyl)methyl]pyrazolo[1,5-a]pyridine-5-carboxamide	1772177: Inhibition of human recombinant ACSS2 incubated for 180 mins by AMP Glo assay	ic50	<0.0001	uM
1-ethyl-N-(4-ethyl-1,3-oxazol-2-yl)-2-[hydroxy(diphenyl)methyl]-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	1772178: Inhibition of ACSS2 in human HCT-15 cells assessed as inhibition of 14C acetate incorporation into fatty acids by microbeta scintillation counting analysis	ic50	<0.0001	uM
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-phenyl-pyridin-2-ylmethanol	1782628: Inhibition of ACSS2 in human HCT-15 cells assessed as inhibition of 14C acetate incorporation into fatty acids measured after 24 hrs by scintillation counting based cellular lipids assay	ic50	<0.0001	uM
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-bis(2-fluorophenyl)methanol	1782627: Inhibition of human recombinant ACSS2 assessed as AMP release using Coenzyme A/ATP as co-substrates by AMP Glo assay	ic50	<0.0001	uM
1-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-2-[hydroxy(dithiophen-2-yl)methyl]-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	1772178: Inhibition of ACSS2 in human HCT-15 cells assessed as inhibition of 14C acetate incorporation into fatty acids by microbeta scintillation counting analysis	ic50	<0.0001	uM
2-[bis(2-fluorophenyl)-hydroxymethyl]-1-ethyl-N-(1-ethyl-1,2,4-triazol-3-yl)-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	1772177: Inhibition of human recombinant ACSS2 incubated for 180 mins by AMP Glo assay	ic50	<0.0001	uM
1-ethyl-N-(5-ethyl-1,3-oxazol-2-yl)-2-[hydroxy(diphenyl)methyl]-5-methoxyimidazo[4,5-b]pyridine-6-carboxamide	1772177: Inhibition of human recombinant ACSS2 incubated for 180 mins by AMP Glo assay	ic50	<0.0001	uM
N-[3-(1,1-difluoroethyl)phenyl]-1-[4-(difluoromethoxy)-3-pyridin-3-ylphenyl]-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0003	uM
N-[3-(1,1-difluoropropyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0005	uM
N-[3-(1,1-difluoroethyl)phenyl]-1-(3,4-dimethoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0010	uM
[1-ethyl-5-methoxy-6-(2H-tetrazol-5-yl)imidazo[4,5-b]pyridin-2-yl]-phenyl-pyrimidin-2-ylmethanol	1782627: Inhibition of human recombinant ACSS2 assessed as AMP release using Coenzyme A/ATP as co-substrates by AMP Glo assay	ic50	0.0010	uM
N-[3-(1,1-difluoroethyl)phenyl]-1-[4-methoxy-3-(1,3-oxazol-2-yl)phenyl]-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0011	uM
methyl 3-[4-[[3-(furan-2-yl)phenyl]carbamoyl]-3-methyl-5-oxo-4H-pyrazol-1-yl]benzoate	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0021	uM
N-[3-(1,1-difluoroethyl)phenyl]-1-[4-(difluoromethoxy)phenyl]-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0027	uM
N-[3-(furan-2-yl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0032	uM
N-[3-(furan-2-yl)phenyl]-1-(6-methoxy-3-pyridinyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0039	uM
N-[3-(1,1-difluoroethyl)phenyl]-3-methyl-5-oxo-1-phenyl-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0040	uM
N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0045	uM
N-[3-(1,1-difluoroethyl)phenyl]-1-(6-methoxy-3-pyridinyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide	1570321: Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	ic50	0.0050	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation, affects expression	4
Benzo(a)pyrene	decreases expression, increases methylation	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
bisphenol A	increases expression, affects expression, decreases methylation	3
perfluorooctane sulfonic acid	decreases expression	3
Cisplatin	affects cotreatment, increases expression, decreases response to substance	3
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	increases expression	2
cupric chloride	decreases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Glucose	increases expression	2
Nickel	decreases expression	2
Oxygen	affects expression, increases expression	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance, affects expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases expression, decreases methylation, affects expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
methyleugenol	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
deoxynivalenol	decreases expression	1
glycidyl methacrylate	decreases expression	1
dodecyldimethylamine oxide	increases expression	1
beta-lapachone	decreases expression	1
methylparaben	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4368259	Binding	Inhibition of ACSS2 in human MDA-MB-468 cells assessed as 13C-acetate incorporation incubated for 5 hrs measured under hypoxic conditions by LCMS analysis	Inhibition of ACSS2 for Treatment of Cancer and Neuropsychiatric Diseases. — *ACS Med Chem Lett*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SB26	HAP1 ACSS2 (-) 1	Cancer cell line	Male
CVCL_XL00	HAP1 ACSS2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

1 trials:

NCT	Phase	Status	Title
NCT03655223	Not specified	ACTIVE_NOT_RECRUITING	Early Check: Expanded Screening in Newborns

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ACSS2 across ~30M SureChEMBL compounds — explore on Sugi Predict.