ACACA
gene geneOn this page
Also known as ACC1ACC-alphaACCAACCalphaACACalphaAcac1hACC1
Summary
ACACA (acetyl-CoA carboxylase alpha, HGNC:84) is a protein-coding gene on chromosome 17q12, encoding Acetyl-CoA carboxylase 1 (Q13085). Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis. It is a selective cancer dependency (DepMap: 26.6% of cell lines).
Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5’ sequence and encoding distinct isoforms have been found for this gene.
Source: NCBI Gene 31 — RefSeq curated summary.
At a glance
- Gene–disease (curated): acetyl-coa carboxylase deficiency (Moderate, GenCC)
- GWAS associations: 2
- Clinical variants (ClinVar): 480 total — 4 pathogenic (top 7% of genes corpus-wide)
- Regional missense constraint (gnomAD): 7 of 16 regions constrained (≈19% of expected missense variation)
- GTEx eGene: eQTL in 20 tissues, sQTL in 3 (q < 0.05)
- Phenotypes (HPO): 7
- Drug target: yes — 4 via a complex or family; 4 molecules with ChEMBL bioactivity
- Cancer dependency (DepMap): dependent in 26.6% of screened cell lines
- Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.37 (moderately constrained)
- MANE Select transcript:
NM_198834 - Interaction hub: 2,832 STRING partners (top 3% of genes corpus-wide)
- Notable: 480 clinical variants but no curated precision-oncology (CIViC) evidence yet
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:84 |
| Approved symbol | ACACA |
| Name | acetyl-CoA carboxylase alpha |
| Location | 17q12 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | ACC1, ACC-alpha, ACCA, ACCalpha, ACACalpha, Acac1, hACC1 |
| Ensembl gene | ENSG00000278540 |
| Ensembl biotype | protein_coding |
| OMIM | 200350 |
| Entrez | 31 |
Gene structure
Transcript identifiers
Ensembl transcripts: 25 — 12 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 1 non_stop_decay
MANE Select: ENST00000616317
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 8, TSL 2: 3, TSL 3: 5, TSL 4: 3, TSL 5: 4
ENST00000616317, ENST00000612007, ENST00000612120, ENST00000612895, ENST00000612926, ENST00000613146, ENST00000613776, ENST00000614333, ENST00000614428, ENST00000614438, ENST00000614450, ENST00000614482, ENST00000614789, ENST00000615229, ENST00000616352, ENST00000617548, ENST00000617649, ENST00000618053, ENST00000618351, ENST00000618575, ENST00000619245, ENST00000619546, ENST00000621960, ENST00001046176, ENST00001143661
RefSeq mRNA: 5 — MANE Select: NM_198834
NM_198834, NM_198836, NM_198837, NM_198838, NM_198839
CCDS: CCDS11317, CCDS11318, CCDS42302, CCDS42303
Canonical transcript exons
ENST00000616317 — 56 exons
| Exon | Start | End |
|---|---|---|
| ENSE00003711809 | 37234975 | 37235099 |
| ENSE00003712872 | 37121355 | 37121490 |
| ENSE00003713465 | 37125698 | 37125794 |
| ENSE00003713472 | 37240476 | 37240564 |
| ENSE00003715963 | 37155683 | 37155780 |
| ENSE00003717027 | 37257703 | 37257866 |
| ENSE00003718107 | 37224992 | 37225105 |
| ENSE00003718686 | 37088938 | 37089074 |
| ENSE00003719856 | 37248011 | 37248156 |
| ENSE00003720725 | 37283267 | 37283405 |
| ENSE00003723069 | 37111531 | 37111643 |
| ENSE00003726147 | 37243371 | 37243559 |
| ENSE00003726892 | 37263685 | 37263894 |
| ENSE00003728369 | 37181201 | 37181356 |
| ENSE00003729292 | 37226339 | 37226452 |
| ENSE00003730108 | 37200139 | 37200183 |
| ENSE00003730337 | 37192090 | 37192305 |
| ENSE00003730946 | 37221724 | 37221842 |
| ENSE00003731706 | 37130075 | 37130218 |
| ENSE00003731907 | 37206783 | 37206879 |
| ENSE00003731966 | 37161781 | 37162050 |
| ENSE00003732149 | 37277033 | 37277114 |
| ENSE00003732213 | 37258212 | 37258373 |
| ENSE00003732433 | 37223512 | 37223601 |
| ENSE00003732440 | 37275951 | 37276049 |
| ENSE00003732606 | 37210467 | 37210490 |
| ENSE00003732890 | 37179260 | 37179406 |
| ENSE00003734280 | 37252886 | 37253036 |
| ENSE00003734814 | 37191120 | 37191275 |
| ENSE00003735484 | 37193374 | 37193415 |
| ENSE00003736690 | 37252005 | 37252108 |
| ENSE00003736988 | 37246826 | 37246976 |
| ENSE00003737982 | 37274193 | 37274299 |
| ENSE00003738753 | 37129365 | 37129485 |
| ENSE00003740675 | 37084992 | 37087439 |
| ENSE00003740987 | 37245080 | 37245214 |
| ENSE00003741169 | 37241953 | 37242053 |
| ENSE00003741519 | 37207657 | 37207800 |
| ENSE00003741681 | 37200427 | 37200483 |
| ENSE00003742848 | 37096996 | 37097166 |
| ENSE00003743039 | 37270751 | 37270861 |
| ENSE00003743164 | 37248593 | 37248674 |
| ENSE00003743531 | 37122531 | 37122627 |
| ENSE00003744386 | 37149864 | 37149974 |
| ENSE00003744996 | 37097830 | 37097984 |
| ENSE00003745678 | 37113088 | 37113265 |
| ENSE00003746195 | 37205765 | 37205872 |
| ENSE00003748166 | 37188277 | 37188480 |
| ENSE00003748405 | 37151301 | 37151421 |
| ENSE00003748605 | 37330173 | 37330425 |
| ENSE00003749439 | 37259360 | 37259530 |
| ENSE00003750104 | 37277896 | 37278005 |
| ENSE00003750795 | 37339804 | 37339850 |
| ENSE00003752159 | 37244588 | 37244734 |
| ENSE00003786438 | 37284838 | 37284970 |
| ENSE00003843730 | 37406262 | 37406836 |
Expression profiles
Bgee: expression breadth ubiquitous, 134 present calls, max score 96.24.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5962 / max 196.6445, expressed in 1809 samples.
Highest expression (Bgee): cortical plate, adrenal tissue, ganglionic eminence, corpus callosum, ventricular zone.
Genetic regulation across tissues (GTEx eQTL / sQTL)
ACACA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
showing 20 of 23 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Cells Cultured fibroblasts | sqtl | 2.0e-11 | -0.50 | 17:37333831:T:G |
| Nerve Tibial | eqtl | 2.2e-06 | +0.16 | 17:37232521:A:G |
| Cells Cultured fibroblasts | eqtl | 3.9e-06 | +0.12 | 17:37399875:T:A |
| Testis | sqtl | 9.3e-06 | -0.67 | 17:37084509:ACT:A |
| Brain Cortex | eqtl | 6.5e-05 | +0.20 | 17:37491071:A:C |
| Skin Not Sun Exposed Suprapubic | eqtl | 8.1e-05 | +0.13 | 17:37232521:A:G |
| Artery Aorta | eqtl | 8.8e-05 | +0.17 | 17:37383917:C:T |
| Skin Sun Exposed Lower leg | eqtl | 1.2e-04 | +0.11 | 17:37217510:T:C |
| Esophagus Gastroesophageal Junction | eqtl | 4.1e-03 | +0.13 | 17:37335407:G:A |
| Artery Tibial | eqtl | 4.2e-03 | +0.13 | 17:38375601:C:G |
| Esophagus Mucosa | eqtl | 7.3e-03 | +0.12 | 17:36806337:C:A |
| Pancreas | eqtl | 8.7e-03 | +0.19 | 17:37374913:C:G |
| Brain Amygdala | eqtl | 9.3e-03 | +0.22 | 17:37513297:TA:T |
| Adipose Visceral Omentum | eqtl | 9.6e-03 | +0.12 | 17:37474926:G:A |
| Muscle Skeletal | sqtl | 1.7e-02 | -0.95 | 17:38321310:C:T |
| Stomach | eqtl | 2.8e-02 | +0.66 | 17:36497489:T:A |
| Brain Anterior cingulate cortex BA24 | eqtl | 3.0e-02 | +0.15 | 17:37515526:T:C |
| Brain Spinal cord cervical c-1 | eqtl | 3.2e-02 | +1.09 | 17:36521549:T:C |
| Brain Frontal Cortex BA9 | eqtl | 3.3e-02 | +0.63 | 17:37197986:G:A |
| Brain Putamen basal ganglia | eqtl | 3.5e-02 | +0.74 | 17:38279120:G:A |
FANTOM5 promoters
5 alternative TSS:
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 165466 | 21.1174 | 1784 |
| 165470 | 2.9720 | 1413 |
| 165467 | 1.7630 | 873 |
| 165469 | 0.7297 | 455 |
| 165468 | 0.0142 | 3 |
Top tissues by expression
showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| cortical plate | UBERON:0005343 | 96.24 | gold quality |
| adrenal tissue | UBERON:0018303 | 96.11 | gold quality |
| ganglionic eminence | UBERON:0004023 | 95.51 | gold quality |
| corpus callosum | UBERON:0002336 | 95.35 | gold quality |
| ventricular zone | UBERON:0003053 | 95.23 | gold quality |
| superior frontal gyrus | UBERON:0002661 | 93.19 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 92.25 | gold quality |
| prefrontal cortex | UBERON:0000451 | 92.15 | gold quality |
| right adrenal gland | UBERON:0001233 | 92.00 | gold quality |
| frontal cortex | UBERON:0001870 | 91.97 | gold quality |
| right frontal lobe | UBERON:0002810 | 91.51 | gold quality |
| prostate gland | UBERON:0002367 | 91.28 | gold quality |
| cerebral cortex | UBERON:0000956 | 91.06 | gold quality |
| sural nerve | UBERON:0015488 | 90.97 | gold quality |
| adrenal gland | UBERON:0002369 | 90.96 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 90.86 | gold quality |
| colonic epithelium | UBERON:0000397 | 90.83 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 90.67 | gold quality |
| left adrenal gland | UBERON:0001234 | 90.46 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 90.33 | gold quality |
| primary visual cortex | UBERON:0002436 | 90.29 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 90.11 | gold quality |
| esophagus mucosa | UBERON:0002469 | 89.96 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 89.85 | gold quality |
| brain | UBERON:0000955 | 89.73 | gold quality |
| right testis | UBERON:0004534 | 89.65 | gold quality |
| temporal lobe | UBERON:0001871 | 89.50 | gold quality |
| amygdala | UBERON:0001876 | 89.39 | gold quality |
| esophagus | UBERON:0001043 | 89.28 | gold quality |
| hypothalamus | UBERON:0001898 | 89.21 | gold quality |
| left testis | UBERON:0004533 | 89.14 | gold quality |
| nucleus accumbens | UBERON:0001882 | 89.13 | gold quality |
| tonsil | UBERON:0002372 | 89.07 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 88.99 | gold quality |
| Ammon’s horn | UBERON:0001954 | 88.85 | gold quality |
| islet of Langerhans | UBERON:0000006 | 88.79 | gold quality |
| pituitary gland | UBERON:0000007 | 88.79 | gold quality |
| testis | UBERON:0000473 | 88.76 | gold quality |
| putamen | UBERON:0001874 | 88.58 | gold quality |
| caudate nucleus | UBERON:0001873 | 88.55 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 88.51 | gold quality |
| lower esophagus | UBERON:0013473 | 88.47 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 88.44 | gold quality |
| adenohypophysis | UBERON:0002196 | 88.24 | gold quality |
| liver | UBERON:0002107 | 88.13 | gold quality |
| cerebellum | UBERON:0002037 | 88.12 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 88.08 | gold quality |
| urinary bladder | UBERON:0001255 | 88.07 | gold quality |
| substantia nigra | UBERON:0002038 | 88.06 | gold quality |
| cerebellar cortex | UBERON:0002129 | 88.06 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 87.93 | gold quality |
| bone marrow cell | CL:0002092 | 87.87 | gold quality |
| stromal cell of endometrium | CL:0002255 | 87.49 | gold quality |
| right lobe of liver | UBERON:0001114 | 87.27 | gold quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 87.12 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 87.08 | gold quality |
| calcaneal tendon | UBERON:0003701 | 87.01 | gold quality |
| endometrium | UBERON:0001295 | 86.54 | gold quality |
| lung | UBERON:0002048 | 86.53 | gold quality |
| thoracic mammary gland | UBERON:0005200 | 86.01 | gold quality |
| vagina | UBERON:0000996 | 85.99 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 85.99 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 85.98 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 85.75 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 85.74 | gold quality |
| fallopian tube | UBERON:0003889 | 85.72 | gold quality |
| skin of abdomen | UBERON:0001416 | 85.67 | gold quality |
| minor salivary gland | UBERON:0001830 | 85.64 | gold quality |
| saliva-secreting gland | UBERON:0001044 | 85.54 | gold quality |
| pancreas | UBERON:0001264 | 85.49 | gold quality |
| right lung | UBERON:0002167 | 85.45 | gold quality |
| multicellular organism | UBERON:0000468 | 85.43 | gold quality |
| zone of skin | UBERON:0000014 | 85.35 | gold quality |
| muscle tissue | UBERON:0002385 | 85.34 | gold quality |
| fundus of stomach | UBERON:0001160 | 85.19 | gold quality |
| stomach | UBERON:0000945 | 85.13 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 85.09 | gold quality |
| gastrocnemius | UBERON:0001388 | 85.00 | gold quality |
| skin of leg | UBERON:0001511 | 84.98 | gold quality |
| bone marrow | UBERON:0002371 | 84.97 | gold quality |
| colon | UBERON:0001155 | 84.84 | gold quality |
| left uterine tube | UBERON:0001303 | 84.72 | gold quality |
| right uterine tube | UBERON:0001302 | 84.69 | gold quality |
| muscle of leg | UBERON:0001383 | 84.64 | gold quality |
| uterine cervix | UBERON:0000002 | 84.49 | gold quality |
| myometrium | UBERON:0001296 | 84.49 | gold quality |
| right ovary | UBERON:0002118 | 84.44 | gold quality |
| subcutaneous adipose tissue | UBERON:0002190 | 84.41 | gold quality |
| adipose tissue | UBERON:0001013 | 84.38 | gold quality |
| ectocervix | UBERON:0012249 | 84.30 | gold quality |
| right coronary artery | UBERON:0001625 | 84.21 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 84.19 | gold quality |
| body of uterus | UBERON:0009853 | 84.19 | gold quality |
| omental fat pad | UBERON:0010414 | 84.18 | gold quality |
| transverse colon | UBERON:0001157 | 84.17 | gold quality |
| body of stomach | UBERON:0001161 | 84.09 | gold quality |
| left coronary artery | UBERON:0001626 | 84.09 | gold quality |
| intestine | UBERON:0000160 | 84.03 | gold quality |
| popliteal artery | UBERON:0002250 | 84.02 | gold quality |
| tibial artery | UBERON:0007610 | 84.00 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 10.54 |
HPA expression
RNA tissue specificity: Low tissue specificity
showing 60 of 80 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Spinal cord | tissue | 44.1 | |
| Cerebral cortex | tissue | 40.6 | low |
| Somatosensory cortex | tissue | 40.6 | |
| Prefrontal cortex | tissue | 39.8 | |
| Motor cortex | tissue | 39.1 | |
| Insular cortex | tissue | 38.7 | |
| Substantia nigra | tissue | 37.8 | |
| Medulla oblongata | tissue | 37.7 | |
| Thalamus | tissue | 37.7 | |
| Midbrain | tissue | 37.6 | |
| Pons | tissue | 36.7 | |
| Retrosplenial and cingulate cortex | tissue | 36.7 | |
| Hippocampal formation | tissue | 36.6 | |
| Entorhinal cortex | tissue | 36.6 | |
| Occipital cortex | tissue | 36.3 | |
| Temporal cortex | tissue | 35.8 | |
| Retrosplenial cortex | tissue | 35.5 | |
| Hypothalamus | tissue | 34.2 | |
| Corpus callosum | tissue | 34.1 | |
| Postcentral gyrus | tissue | 32.4 | |
| Periaqueductal gray | tissue | 32.3 | |
| Superior colliculi | tissue | 31.4 | |
| Ventral forebrain | tissue | 30.4 | |
| Amygdala | tissue | 30.3 | |
| Septum | tissue | 29.7 | |
| Frontal cortex | tissue | 29.4 | |
| Choroid plexus | tissue | 27.7 | |
| Putamen | tissue | 27.6 | |
| Cerebellum | tissue | 27.3 | medium |
| Basal ganglia | tissue | 27.1 | low |
| Locus coeruleus | tissue | 27.0 | |
| Caudate putamen | tissue | 25.2 | |
| Breast | tissue | 20.9 | medium |
| Hippocampus | tissue | 20.9 | low |
| Olfactory bulb | tissue | 19.9 | |
| Nucleus accumbens | tissue | 19.8 | |
| Pituitary gland | tissue | 18.4 | |
| Adipose tissue | tissue | 14.0 | low |
| Prostate | tissue | 14.0 | medium |
| Vagina | tissue | 13.9 | medium |
| Epididymis | tissue | 13.0 | high |
| Esophagus | tissue | 10.9 | high |
| Parathyroid gland | tissue | 10.2 | high |
| Seminal vesicle | tissue | 9.0 | medium |
| Lung | tissue | 8.9 | high |
| Smooth muscle | tissue | 7.5 | medium |
| Retina | tissue | 7.4 | |
| Testis | tissue | 7.0 | high |
| Liver | tissue | 7.0 | high |
| Skin 1 | tissue | 6.9 | medium |
| Urinary bladder | tissue | 6.8 | high |
| Rectum | tissue | 6.0 | high |
| Cervix | tissue | 5.7 | medium |
| Salivary gland | tissue | 5.7 | medium |
| Adrenal gland | tissue | 5.7 | high |
| Colon | tissue | 5.4 | high |
| Endometrium 1 | tissue | 5.3 | medium |
| Tonsil | tissue | 5.2 | low |
| Thyroid gland | tissue | 5.1 | high |
| Ovary | tissue | 4.9 | low |
Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (44.1), Dorsal spinal cord (37.0), Precentral gyrus (36.9), Subiculum (34.1), White matter (34.1).
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): AR, CEBPA, CEBPB, CREB1, CREBZF, FOXO1, MLXIPL, NR1H3, NR1H4, NRF1, PPARD, SP1, SREBF1, STAT3, STAT5A, THRB, USF1, USF2
miRNA regulators (miRDB)
Targeting ACACA by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
showing 30 of 77 miRNAs:
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-5193 | 100.00 | 67.26 | 1744 |
| HSA-MIR-6758-5P | 100.00 | 66.21 | 1470 |
| HSA-MIR-6856-5P | 100.00 | 65.47 | 1298 |
| HSA-MIR-511-3P | 99.99 | 68.85 | 1467 |
| HSA-MIR-548AW | 99.99 | 72.57 | 3559 |
| HSA-MIR-27A-3P | 99.98 | 72.13 | 2955 |
| HSA-MIR-27B-3P | 99.98 | 72.13 | 2955 |
| HSA-MIR-9985 | 99.98 | 72.11 | 2939 |
| HSA-MIR-3065-5P | 99.97 | 71.56 | 3281 |
| HSA-MIR-6825-5P | 99.96 | 69.81 | 3431 |
| HSA-MIR-4725-3P | 99.96 | 69.53 | 2520 |
| HSA-MIR-6780B-5P | 99.96 | 69.60 | 2562 |
| HSA-MIR-185-3P | 99.95 | 67.01 | 1743 |
| HSA-MIR-1305 | 99.91 | 71.43 | 3443 |
| HSA-MIR-627-3P | 99.90 | 71.42 | 3316 |
| HSA-MIR-4731-5P | 99.89 | 67.23 | 2537 |
| HSA-MIR-4271 | 99.88 | 68.32 | 2244 |
| HSA-MIR-4492 | 99.87 | 68.25 | 3611 |
| HSA-MIR-4659A-3P | 99.80 | 72.62 | 4248 |
| HSA-MIR-4659B-3P | 99.80 | 72.62 | 4248 |
| HSA-MIR-92A-2-5P | 99.75 | 67.01 | 2164 |
| HSA-MIR-1976 | 99.74 | 65.48 | 1127 |
| HSA-MIR-1825 | 99.72 | 68.11 | 1089 |
| HSA-MIR-4422 | 99.72 | 72.07 | 2908 |
| HSA-MIR-1283 | 99.69 | 72.42 | 3009 |
| HSA-MIR-4666B | 99.64 | 68.69 | 1282 |
| HSA-MIR-182-3P | 99.57 | 67.57 | 825 |
| HSA-MIR-6716-5P | 99.56 | 68.62 | 1244 |
| HSA-MIR-7844-5P | 99.55 | 68.56 | 1428 |
| HSA-MIR-7159-5P | 99.53 | 72.12 | 2472 |
Functional genomics
gnomAD constraint: pLI 1, LOEUF 0.374, missense Z 10.2 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD)
ENST00000616317 splits into 16 regions with different missense tolerance; 7 are missense-constrained (≈19% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD
| Region (GRCh38) | Missense obs / exp | o/e | Constrained |
|---|---|---|---|
| 17:37,087,319–37,188,390 | 553 / 1043.6 | 0.53 | no |
| 17:37,188,391–37,192,143 | 35 / 131.8 | 0.27 | yes (p 3.4e-17) |
| 17:37,192,144–37,210,476 | 179 / 283.2 | 0.63 | no |
| 17:37,210,477–37,221,748 | 1 / 16.7 | 0.06 | yes (p 1.2e-04) |
| 17:37,221,749–37,221,791 | 15 / 18.8 | 0.80 | no |
| 17:37,221,792–37,226,446 | 42 / 147.5 | 0.28 | yes (p 3.7e-18) |
| 17:37,226,447–37,252,899 | 316 / 540.9 | 0.58 | no |
| 17:37,252,900–37,258,258 | 35 / 139.4 | 0.25 | yes (p 9.3e-19) |
| 17:37,258,259–37,258,368 | 37 / 49.9 | 0.74 | no |
| 17:37,258,369–37,259,425 | 3 / 29.1 | 0.10 | yes (p 1.3e-06) |
| 17:37,259,426–37,274,217 | 82 / 185.2 | 0.44 | no |
| 17:37,274,218–37,275,998 | 47 / 55.4 | 0.85 | no |
| 17:37,275,999–37,277,985 | 29 / 90.3 | 0.32 | yes (p 1.1e-10) |
| 17:37,277,986–37,283,290 | 0 / 18.0 | 0.00 | yes (p 2.3e-05) |
| 17:37,283,291–37,284,928 | 40 / 92.2 | 0.43 | no |
| 17:37,284,929–37,406,299 | 140 / 147.7 | 0.95 | no |
| DepMap (CRISPR cell-line fitness): dependent in 26.6% of screened cell lines. |
Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): CH-157MN (-1.449), P4E6 (-1.369), Evsa-T (-1.326), PA-TU-8988S (-1.321), MEL-HO (-1.301), NCI-H1993 (-1.291), DEL (-1.286), SF-172 (-1.275), DLD-1 (-1.27), HSC-5 (-1.246), SW 626 (-1.21), ACC-MESO-1 (-1.199), OUMS-23 (-1.16), U-937 (-1.143), IPC-298 (-1.143).
Literature-anchored findings (GeneRIF, showing 40)
- The Stoned proteins may regulate sustainable neurotransmission in vivo by binding to Ca(2+)-bound Synaptotagmin-1 associated synaptic vesicles. (PMID:22701718)
- folding of the T4 major capsid protein requires a gp31-dependent cis-folding mechanism likely inside an enlarged “Anfinsen cage” provided by GroEL and gp31 (PMID:15919824)
- enlarged volume for folding is consistent with the size of the bacteriophage coat protein gp23, which is the major substrate of GroEL-gp31 chaperonin complex (PMID:16549073)
- structures of gp23-chaperonin complexes, showing both the initial captured state and the final, close-to-native state with gp23 encapsulated in the folding chamber (PMID:19122642)
- Human acetyl-CoA carboxylase 1 gene has three promoters and heterogeneity at the 5’-untranslated mRNA region (PMID:12810950)
- Transcription of ACC-alpha from at least three promoters and the potential to generate ACC-alpha isozymes with differential susceptibilities to phosphorylation indicate that the regulation of fatty acid synthesis in human tissues is likely to be complex (PMID:14643797)
- polymorphisms in acetyl-Coenzyme A carboxylase alpha is associated with breast cancer predisposition (PMID:15333468)
- BRCA1 affects lipogenesis through binding to P-ACCA, suggesting a new mechanism by which BRCA1 may exert a tumor suppressor function (PMID:16326698)
- the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263. (PMID:16698035)
- a possible role of the ACC-alpha common sequence variants in susceptibility to breast cancer (PMID:17372234)
- observations provide complete information about the pattern and levels of LKB1 and p-ACC immunostaining in normal tissues and in lung tumors (PMID:17521700)
- the major mechanism of HER2-mediated induction of FASN and ACCalpha in the breast cancer cells used in this study is translational regulation primarily through the mTOR signaling pathway. (PMID:17631500)
- AKR1B10 regulates the stability of acetyl-CoA carboxylase-alpha and is a novel regulator of the biosynthesis of fatty acid, an essential component of the cell membrane, in breast cancer cells (PMID:18056116)
- biochemical analysis of human BRCA1 BRCT domains in complex with a phospho-peptide from human ACC1 (PMID:18452305)
- Differential activation of recombinant ACC1 and ACC2 by citrate is reported. (PMID:18455495)
- AMPK alpha2 activity, AMPK alpha2 Thr172 phosphorylation, and ACC-beta Ser222 phosphorylation were increased immediately after exercise. These increases had all returned to basal levels at 3 and 24 h after exercise. (PMID:18614941)
- Data suggest that increased expression of malonyl CoA decarboxylase, and the decreased expression of acetyl CoA carboxylase and 5’-AMP activated protein kinase are important regulators of the maturation of fatty acid oxidation in the newborn human heart. (PMID:18614968)
- The interaction between BRCA1 and acetyl-CoA-carboxylase is regulated during cell cycle progression. (PMID:19061860)
- ACC was down-regulated in visceral adipose tissue from obese subjects, with and without diabetes mellitus type 2 (PMID:19543203)
- data suggest that cancer cells require active SCD1 to control the rate of glucose-mediated lipogenesis, and that when SCD1 activity is impaired cells downregulate SFA synthesis via AMPK-mediated inactivation of acetyl-CoA carboxylase (PMID:19710915)
- Data show that kidney bean husk extract exhibited antitumor effects accompanied by the increase in p-AMPK and p-Acc as well as antitumor proteins p53 and p21. (PMID:19723093)
- Transient over-expression of CREB1 in HepG2 cells activates ACC1 PII promoter and induces the production of triacylglycerol in response to arachidonic acid (AA), indicating that the effect of AA on ACC1 is possibly regulated via CREB1. (PMID:19842072)
- This study supports the hypothesis that the direct effects of some antipsychotics on hypertriglyceridemia may be at least partially mediated by the ACACA gene. (PMID:19846279)
- data suggest that insulin and glucocorticoid have positive effects on both acetyl-CoA carboxylase alpha(ACC1) and beta(ACC2) gene transcription (PMID:20139635)
- show that MIG12, a 22 kDa cytosolic protein of previously unknown function, binds to ACC and lowers the threshold for citrate activation into the physiological range. (PMID:20457939)
- Human cytomegalovirus infection induces an increase in ACC1 mRNA and protein expression. (PMID:21471234)
- IGF-1 reduced ACCalpha phosphorylation via an ATM/AMPK signaling pathway and suppressed ACCalpha expression through an ERK1/2 (PMID:21638027)
- three major enzymes of the pathway, FASN, ACC, and ACLY, are up-regulated in numerous tumor types. (PMID:21726077)
- Metabolic regulation of invadopodia and invasion by acetyl-CoA carboxylase 1 and de novo lipogenesis. (PMID:22238651)
- Exercise training increased AMPKalpha1 activity in older men, however, AMPKalpha2 activity, and the phosphorylation of AMPK, ACC and mTOR, were not affected (PMID:23000302)
- Single nucleotide polymorphisms in the ACACA and ACLY genes are associated with a relative change in plasma triglycierides following fish oil supplementation. (PMID:23886516)
- Phospho-acetyl-CoA carboxylase protein expression correlates with tumor grade and the disease stage in gastric cancer. (PMID:24924473)
- ACAT1, ACACA, ALDH6A1 and MTHFD1 represent novel biomarkers in adipose tissue associated with type 2 diabetes in obese individuals. (PMID:25099943)
- ACACA may constitute a previously unrecognized target for novel anti-breast cancer stem cell therapies. (PMID:25246709)
- ACC1 and ACLY regulate the levels of ETV4 under hypoxia via increased alpha-ketoglutarate. These results reveal that the ACC1/ACLY-alpha-ketoglutarate-ETV4 axis is a novel means by which metabolic states regulate transcriptional output (PMID:26452058)
- Cetuximab-mediated activation of AMPK and subsequent phosphorylation and inhibition of ACC is followed by a compensatory increase in total ACC, which rewires cancer metabolism from glycolysis-dependent to lipogenesis-dependent. (PMID:27693630)
- acetyl-CoA carboxylase 1 and senescence regulation in human fibroblasts involves oxidant mediated p38 MAPK activation (PMID:27983949)
- Inhibition of Acetyl-CoA Carboxylase 1 (ACC1) and 2 (ACC2) Reduces Proliferation and De Novo Lipogenesis of EGFRvIII Human Glioblastoma Cells (PMID:28081256)
- These data showed that ACC1 gene (ACACA) expression was twofold greater in HCC compared to non-cancerous liver. (PMID:28290443)
- of ACCs decreased polyunsaturated fatty acid (PUFA) concentrations in liver due to reduced malonyl-CoA, which is required for elongation of essential fatty acids. (PMID:28768177)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | acaca | ENSDARG00000078512 |
| mus_musculus | Acaca | ENSMUSG00000020532 |
| rattus_norvegicus | Acaca | ENSRNOG00000034013 |
Paralogs (4): ACACB (ENSG00000076555), MCCC1 (ENSG00000078070), PC (ENSG00000173599), PCCA (ENSG00000175198)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:108451) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| decreased liver triglyceride level | 2 |
| abnormal liver physiology | 1 |
| abnormal lipid level | 1 |
| increased circulating free fatty acids level | 1 |
| hyperglycemia | 1 |
| decreased embryo size | 1 |
| embryonic growth arrest | 1 |
| abnormal glucose homeostasis | 1 |
| increased circulating insulin level | 1 |
| abnormal lipid homeostasis | 1 |
| decreased susceptibility to hepatic steatosis | 1 |
| abnormal T cell physiology | 1 |
| decreased circulating free fatty acids level | 1 |
| decreased circulating ketone body level | 1 |
| embryonic growth retardation | 1 |
| decreased T cell number | 1 |
| decreased fatty acids level | 1 |
| increased circulating aspartate transaminase level | 1 |
| embryonic lethality during organogenesis | 1 |
| decreased memory T cell number | 1 |
| embryonic lethality between implantation and somite formation, complete penetrance | 1 |
| abnormal lipid metabolism | 1 |
| decreased liver enzyme/coenzyme activity | 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 |
|---|---|---|---|
| Escherichia coli K-12 | P24182 | 99.8% | Diamond |
| Escherichia coli O157:H7 | Q8X9B6 | 99.8% | Diamond |
| Saccharomyces cerevisiae JAY291 | C7GRE4 | 99.7% | Diamond |
| Saccharomyces cerevisiae EC1118 | C8ZF72 | 99.7% | Diamond |
| Saccharomyces cerevisiae S288C | P32874 | 99.7% | Diamond |
| Saccharomyces cerevisiae YJM789 | A6ZMR9 | 99.6% | Diamond |
| Saccharomyces cerevisiae RM11-1a | B3LM95 | 99.6% | Diamond |
| Aspergillus terreus | O93918 | 99.6% | Diamond |
| Aspergillus terreus NIH2624 | Q0CLK1 | 99.6% | Diamond |
| Ovis aries | Q28559 | 99.4% | Diamond |
| Bos taurus | Q9TTS3 | 99.4% | Diamond |
| Populus trichocarpa | B9HBA8 | 94.1% | Diamond |
| Aspergillus niger | Q9HES8 | 93.3% | Diamond |
| Gallus gallus | P11029 | 92.7% | Diamond |
| Caenorhabditis elegans | Q19842 | 91.3% | Diamond |
| Arabidopsis thaliana | F4I1L3 | 90.2% | Diamond |
| Mycobacterium leprae TN | P46392 | 86.0% | Diamond |
| Mycobacterium tuberculosis H37Rv | P96890 | 86.0% | Diamond |
| Haemophilus influenzae Rd KW20 | P43873 | 82.1% | Diamond |
| Komagataella pastoris | P78992 | 81.9% | Diamond |
| Ogataea angusta | Q8X1T3 | 81.9% | Diamond |
| Methanothermobacter thermautotrophicus str. Delta H | O27939 | 76.9% | Diamond |
| Archaeoglobus fulgidus DSM 4304 | O30019 | 76.9% | Diamond |
| Allochromatium vinosum DSM 180 | O52058 | 75.3% | Diamond |
| Hydrogenobacter thermophilus TK-6 | D3DJ42 | 75.0% | Diamond |
| Oryza sativa Japonica Group | Q2QMG2 | 75.0% | Diamond |
| Lachancea kluyveri | A5H0J2 | 74.2% | Diamond |
| Pseudomonas aeruginosa PAO1 | P37798 | 71.9% | Diamond |
| Methanocaldococcus jannaschii DSM 2661 | Q58626 | 70.4% | Diamond |
| Schizosaccharomyces pombe 972h- | Q9UUE1 | 69.4% | Diamond |
| Bacillus subtilis subsp. subtilis str. 168 | O34544 | 69.2% | Diamond |
| Dictyostelium discoideum | Q54KE6 | 67.9% | Diamond |
| Nostoc sp. PCC 7120 = FACHB-418 | Q06862 | 66.7% | Diamond |
| Halalkalibacterium halodurans C-125 | Q9KDS9 | 64.6% | Diamond |
| Staphylococcus aureus subsp. aureus Mu50 | A0A0H3JRU9 | 64.1% | Diamond |
| Cryptosporiopsis sp. 8999 | A0A4P8DJE6 | 57.4% | Diamond |
| Aspergillus nidulans FGSC A4 | P38095 | 45.9% | 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 |
|---|---|---|
| MIR2909 | ncRNA | 100422969 |
| AATF | protein-coding | 26574 |
| SNORA90 | snoRNA | 106635523 |
| C17orf78 | protein-coding | 284099 |
| DUSP14 | protein-coding | 11072 |
| SYNRG | protein-coding | 11276 |
| TADA2A | protein-coding | 6871 |
| LHX1-DT | ncRNA | 102723471 |
| LHX1 | protein-coding | 3975 |
| MIR378J | ncRNA | 102465136 |
| DDX52 | protein-coding | 11056 |
Protein
Protein identifiers
Acetyl-CoA carboxylase 1 — Q13085 (reviewed: Q13085)
Alternative names: Acetyl-Coenzyme A carboxylase alpha
All UniProt accessions (10): A0A087WVR6, A0A087WWN5, A0A087WYK6, A0A087WYS8, A0A087X0W4, A0A087X126, A0A087X2F8, A0A0C4DGT1, Q13085, Q59FY4
UniProt curated annotations — full annotation on UniProt →
Function. Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis. This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA.
Subunit / interactions. Monomer, homodimer, and homotetramer. Can form filamentous polymers. Interacts in its inactive phosphorylated form with the BRCT domains of BRCA1 which prevents ACACA dephosphorylation and inhibits lipid synthesis. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity.
Subcellular location. Cytoplasm. Cytosol.
Tissue specificity. Expressed in brain, placenta, skeletal muscle, renal, pancreatic and adipose tissues; expressed at low level in pulmonary tissue; not detected in the liver.
Post-translational modifications. Phosphorylation on Ser-1263 is required for interaction with BRCA1. Phosphorylation at Ser-80 by AMPK inactivates enzyme activity. The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity.
Disease relevance. Acetyl-CoA carboxylase-alpha deficiency (ACACAD) [MIM:613933] An autosomal recessive inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth. The disease is caused by variants affecting the gene represented in this entry.
Activity regulation. Inhibited by phosphorylation. Citrate promotes oligomerization of the protein into filaments that correspond to the most active form of the carboxylase. Inhibited by palmitoyl-CoA.
Cofactor. Binds 2 magnesium or manganese ions per subunit.
Domain organisation. Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain. The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA.
Pathway. Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA: step 1/1.
Isoforms (4)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q13085-1 | 1 | yes |
| Q13085-2 | 2, E5A | |
| Q13085-3 | 3, E5B | |
| Q13085-4 | 4 |
RefSeq proteins (5): NP_942131, NP_942133, NP_942134, NP_942135, NP_942136 (=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000089 | Biotin_lipoyl | Domain |
| IPR001882 | Biotin_BS | Binding_site |
| IPR005479 | CPAse_ATP-bd | Domain |
| IPR005481 | BC-like_N | Domain |
| IPR005482 | Biotin_COase_C | Domain |
| IPR011053 | Single_hybrid_motif | Homologous_superfamily |
| IPR011054 | Rudment_hybrid_motif | Homologous_superfamily |
| IPR011761 | ATP-grasp | Domain |
| IPR011762 | COA_CT_N | Domain |
| IPR011763 | COA_CT_C | Domain |
| IPR011764 | Biotin_carboxylation_dom | Domain |
| IPR013537 | AcCoA_COase_cen | Domain |
| IPR013815 | ATP_grasp_subdomain_1 | Homologous_superfamily |
| IPR016185 | PreATP-grasp_dom_sf | Homologous_superfamily |
| IPR029045 | ClpP/crotonase-like_dom_sf | Homologous_superfamily |
| IPR034733 | AcCoA_carboxyl_beta | Domain |
| IPR049074 | ACCA_BT | Domain |
| IPR049076 | ACCA | Family |
Pfam: PF00289, PF00364, PF01039, PF02785, PF02786, PF08326, PF21385
Enzyme classification (BRENDA)
- EC 6.4.1.2 — acetyl-CoA carboxylase (BRENDA: 88 organisms, 133 substrates, 705 inhibitors, 131 Km, 13 kcat entries)
Substrate kinetics (BRENDA)
10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| ACETYL-COA | 0.0002–1.2 | 39 |
| ATP | 0.015–0.5 | 38 |
| HCO3- | 0.3–12.8 | 27 |
| MALONYL-COA | 0.016–0.75 | 5 |
| PROPIONYL-COA | 0.045–0.144 | 4 |
| BIOCYTIN | 10–70 | 2 |
| BIOTIN | 0.1–3 | 2 |
| BUTYRYL-COA | 0.099–0.143 | 2 |
| ACETODETHIO-COA | 1.25 | 1 |
| MG2+ | 0.83 | 1 |
Catalyzed reactions (Rhea)
- hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + phosphate + H(+) (RHEA:11308)
UniProt features (306 total): strand 92, helix 92, sequence conflict 38, turn 25, modified residue 25, binding site 12, mutagenesis site 8, domain 5, splice variant 3, sequence variant 3, chain 1, region of interest 1, active site 1
Structure
Experimental structures (PDB)
10 structures by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 2YL2 | Crystal structure of human acetyl-CoA carboxylase 1, biotin carboxylase (BC) domain | X-RAY DIFFRACTION | 2.3 |
| 8XKZ | Core region of the citrate-induced human acetyl-CoA carboxylase 1 filament (ACC1-citrate) | ELECTRON MICROSCOPY | 2.55 |
| 8XL1 | Core region of the human acetyl-CoA carboxylase 1 filament in complex with acetyl-CoA … | ELECTRON MICROSCOPY | 2.57 |
| 8XL2 | Human acetyl-CoA carboxylase 1 filament in complex with acetyl-CoA (ACC1-inact) | ELECTRON MICROSCOPY | 2.73 |
| 4ASI | Crystal structure of human ACACA C-terminal domain | X-RAY DIFFRACTION | 2.8 |
| 3COJ | Crystal Structure of the BRCT Domains of Human BRCA1 in Complex with a Phosphorylated … | X-RAY DIFFRACTION | 3.21 |
| 8XL0 | Citrate-induced filament of human acetyl-coenzyme A carboxylase 1 (ACC1-citrate) | ELECTRON MICROSCOPY | 4.14 |
| 6G2H | Filament of acetyl-CoA carboxylase and BRCT domains of BRCA1 (ACC-BRCT) core at 4.6 A … | ELECTRON MICROSCOPY | 4.6 |
| 6G2D | Citrate-induced acetyl-CoA carboxylase (ACC-Cit) filament at 5.4 A resolution | ELECTRON MICROSCOPY | 5.4 |
| 6G2I | Filament of acetyl-CoA carboxylase and BRCT domains of BRCA1 (ACC-BRCT) at 5.9 A … | ELECTRON MICROSCOPY | 5.9 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q13085-F1 | 83.05 | 0.41 |
Human Protein Atlas
Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets
Protein evidence: Evidence at protein level
Subcellular location (HPA, imaging): cytosol; actin filaments; nucleoli fibrillar center
Antibody reliability (HPA): IH approved · IF supported
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1)
| Position | Role |
|---|---|
| 441 |
Ligand- & substrate-binding residues (12)
| Position | Role |
|---|---|
| 424 | Mn(2+) |
| 437 | Mg(2+) |
| 437 | Mn(2+) |
| 439 | Mg(2+) |
| 439 | Mn(2+) |
| 1823 | CoA |
| 2127 | CoA |
| 2129 | CoA |
| 315–320 | ATP |
| 424 | Mg(2+) |
Post-translational modifications (25)
| Type | Positions |
|---|---|
| N-acetylmethionine | 1 |
| Phosphoserine | 5, 23, 25, 29, 34, 48, 50, 53, 78, 80, 488, 835, 1201, 1216, 1218, 1259, 1263, 1273 |
| Phosphothreonine | 58, 610, 1227, 2153 |
| N6-biotinyllysine | 786 |
| N6-acetyllysine | 1334 |
Mutagenesis-validated functional residues (8)
| Position | Phenotype |
|---|---|
| 78 | no effect on interaction with brca1. |
| 344 | no effect on interaction with brca1. |
| 432 | no effect on interaction with brca1. |
| 1201 | no effect on interaction with brca1. |
| 1263 | abolishes interaction with brca1. |
| 1585 | no effect on interaction with brca1. |
| 1952 | no effect on interaction with brca1. |
| 2211 | no effect on interaction with brca1. |
Function
Pathways and Gene Ontology
Reactome pathways
6 curated (TAS) of 18; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
18 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-3371599 | Defective HLCS causes multiple carboxylase deficiency ⚕ | curated |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | curated |
| R-HSA-196780 | Biotin transport and metabolism | curated |
| R-HSA-200425 | Carnitine shuttle | curated |
| R-HSA-163765 | ChREBP activates metabolic gene expression | curated |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | curated |
| R-HSA-3323169 | Defects in biotin (Btn) metabolism ⚕ | — |
| R-HSA-3296482 | Defects in vitamin and cofactor metabolism ⚕ | — |
| R-HSA-1643685 | Disease ⚕ | — |
| R-HSA-5668914 | Diseases of metabolism ⚕ | — |
| R-HSA-8978868 | Fatty acid metabolism | — |
| R-HSA-163685 | Integration of energy metabolism | — |
| R-HSA-1430728 | Metabolism | — |
| R-HSA-556833 | Metabolism of lipids | — |
| R-HSA-8957322 | Metabolism of steroids | — |
| R-HSA-196854 | Metabolism of vitamins and cofactors | — |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | — |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | — |
MSigDB gene sets: 360 (showing top):
GGGACCA_MIR133A_MIR133B, YAATNRNNNYNATT_UNKNOWN, HNF3ALPHA_Q6, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_CELLULAR_RESPONSE_TO_LIPID, AAGTCCA_MIR422B_MIR422A, TTTGTAG_MIR520D, GOBP_CELLULAR_RESPONSE_TO_PROSTAGLANDIN_STIMULUS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, ACTGCAG_MIR173P, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS
GO Biological Process (9): acetyl-CoA metabolic process (GO:0006084), fatty acid biosynthetic process (GO:0006633), fatty-acyl-CoA biosynthetic process (GO:0046949), protein homotetramerization (GO:0051289), malonyl-CoA biosynthetic process (GO:2001295), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), acyl-CoA metabolic process (GO:0006637), lipid biosynthetic process (GO:0008610)
GO Molecular Function (8): acetyl-CoA carboxylase activity (GO:0003989), ATP binding (GO:0005524), identical protein binding (GO:0042802), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), ligase activity (GO:0016874)
GO Cellular Component (2): mitochondrion (GO:0005739), cytosol (GO:0005829)
Reactome top-level categories
12 top-level categories:
| Category | Pathways |
|---|---|
| Metabolism | 3 |
| Fatty acid metabolism | 2 |
| Metabolism of lipids | 2 |
| Integration of energy metabolism | 1 |
| Metabolism of water-soluble vitamins and cofactors | 1 |
| Regulation of cholesterol biosynthesis by SREBP (SREBF) | 1 |
| Defects in biotin (Btn) metabolism | 1 |
| Metabolism of steroids | 1 |
| Metabolism of vitamins and cofactors | 1 |
| Diseases of metabolism | 1 |
| Defects in vitamin and cofactor metabolism | 1 |
| Disease | 1 |
GO top-level categories
31 GO namespaces:
| Category | Terms |
|---|---|
| acyl-CoA biosynthetic process | 2 |
| lipid metabolic process | 2 |
| cytoplasm | 2 |
| acyl-CoA metabolic process | 1 |
| fatty acid metabolic process | 1 |
| lipid biosynthetic process | 1 |
| monocarboxylic acid biosynthetic process | 1 |
| fatty-acyl-CoA metabolic process | 1 |
| fatty acid derivative biosynthetic process | 1 |
| protein homooligomerization | 1 |
| protein tetramerization | 1 |
| malonyl-CoA metabolic process | 1 |
| primary metabolic process | 1 |
| monocarboxylic acid metabolic process | 1 |
| nucleoside phosphate metabolic process | 1 |
| sulfur compound metabolic process | 1 |
| purine-containing compound metabolic process | 1 |
| biosynthetic process | 1 |
| CoA carboxylase activity | 1 |
| adenyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| anion binding | 1 |
| protein binding | 1 |
| cation binding | 1 |
| nucleoside phosphate binding | 1 |
| heterocyclic compound binding | 1 |
| molecular_function | 1 |
| binding | 1 |
| catalytic activity | 1 |
| intracellular membrane-bounded organelle | 1 |
| cellular anatomical structure | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).
3 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| cytosol | CC | direct assay |
| acetyl-CoA carboxylase activity | MF | direct assay |
| identical protein binding | MF | physical interaction |
Protein interactions and networks
STRING
showing 15 of 2,832 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| ACACA | FASN | P49327 | 940 |
| ACACA | SCD | O00767 | 878 |
| ACACA | SREBF1 | P36956 | 860 |
| ACACA | CPT1A | P50416 | 846 |
| ACACA | ACLY | P53396 | 807 |
| ACACA | HLCS | P50747 | 790 |
| ACACA | HMGCR | P04035 | 741 |
| ACACA | ACSL1 | P33121 | 737 |
| ACACA | DGAT1 | O75907 | 730 |
| ACACA | ACOX1 | Q15067 | 720 |
| ACACA | ELOVL6 | Q9H5J4 | 718 |
| ACACA | PPARA | Q07869 | 718 |
| ACACA | DGAT2 | Q96PD7 | 711 |
| ACACA | PPARG | P37231 | 702 |
| ACACA | MLXIPL | Q9NP71 | 700 |
IntAct
Human interaction partners of ACACA in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
14 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| SIRT1 | physical association | 0.590 | 2 |
| AKR1B10 | physical association | 0.560 | 4 |
| EGLN3 | association | 0.530 | 1 |
| BRCA1 | physical association | 0.520 | 2 |
| PIN1 | colocalization | 0.460 | 9 |
| RPL27A | physical association | 0.400 | 1 |
| PCNA | physical association | 0.370 | 1 |
| OAS2 | association | 0.350 | 1 |
| ATXN1 | physical association | 0.000 | 1 |
| CHGB | physical association | 0.000 | 1 |
| CIAO1 | physical association | 0.000 | 1 |
| ILK | physical association | 0.000 | 1 |
| MCC | physical association | 0.000 | 1 |
| MYC | physical association | 0.000 | 1 |
BioGRID (557 interactions; top human partners by supporting records): BRCA1 (Affinity Capture-Western; 12 records), RNF180 (Affinity Capture-Western; 5 records), ACACB (Affinity Capture-MS; 2 records), ADRBK1 (Affinity Capture-MS; 2 records), AKR1B10 (Affinity Capture-MS; 2 records), AURKA (Negative Genetic; 2 records), C12orf49 (Negative Genetic; 2 records), C20orf195 (Affinity Capture-MS; 2 records), CCNF (Proximity Label-MS; 2 records), CD274 (Affinity Capture-MS; 2 records), COPB1 (Co-fractionation; 2 records), CSNK1A1 (Affinity Capture-MS; 2 records), CUL3 (Affinity Capture-MS; 2 records), DCAF6 (Proximity Label-MS; 2 records), EGFR (Affinity Capture-MS; 2 records)
SIGNOR signaling
18 signaling interactions:
| A | Effect | B | Mechanism |
|---|---|---|---|
| AMPK | down-regulates | ACACA | phosphorylation |
| ACACA | down-regulates | “Food intake” | |
| citrate(3-) | “up-regulates activity” | ACACA | binding |
| ACACA | “down-regulates quantity” | acetyl-CoA | “chemical modification” |
| ACACA | “up-regulates quantity” | malonyl-CoA | “chemical modification” |
| AMPK | “down-regulates activity” | ACACA | phosphorylation |
| PPP4C | “up-regulates activity” | ACACA | dephosphorylation |
| SREBF1 | “up-regulates quantity by expression” | ACACA | “transcriptional regulation” |
| COP1 | “down-regulates quantity by destabilization” | ACACA | ubiquitination |
| TRIB3 | “down-regulates quantity by destabilization” | ACACA | binding |
| PRKAA2 | down-regulates | ACACA | phosphorylation |
| MLXIPL | “up-regulates quantity by expression” | ACACA | “transcriptional regulation” |
| PRKAA1 | “down-regulates activity” | ACACA | phosphorylation |
| CSNK2A1 | unknown | ACACA | phosphorylation |
| CSNK2A2 | unknown | ACACA | phosphorylation |
| MID1IP1 | “up-regulates activity” | ACACA | binding |
| BRCA1 | “down-regulates activity” | ACACA | binding |
| PRKACA | “down-regulates activity” | ACACA | phosphorylation |
Disease & clinical
Genetic variants
Variant evidence for ACACA: 480 ClinVar records (4 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.
ClinVar
480 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 4 |
| Likely pathogenic | 0 |
| Uncertain significance | 224 |
| Likely benign | 152 |
| Benign | 41 |
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 |
|---|---|---|---|---|
| 160879 | GRCh38/hg38 17q12(chr17:36357258-37889296)x3 | Pathogenic | criteria provided, multiple submitters, no conflicts | 2 |
| 625612 | GRCh37/hg19 17q12(chr17:34848678-36194230) | Pathogenic | criteria provided, single submitter | 1 |
| 929346 | GRCh37/hg19 17q12(chr17:34815551-36244358)x3 | Pathogenic | criteria provided, single submitter | 1 |
| 2443957 | NM_198834.3(ACACA):c.4969G>A (p.Ala1657Thr) | Pathogenic | no assertion criteria provided | 1 |
Per-variant reference — Sugi Variant
Explore ACACA’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; 42 predictions of 4,940):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 17:37088936–37088937 | donor_loss | 1.0000 | 5 |
| 17:37096994–37096995 | donor_loss | 1.0000 | 5 |
| 17:37097167–37097168 | acceptor_loss | 1.0000 | 5 |
| 17:37097171 | acceptor_gain | 1.0000 | |
| 17:37097828–37097829 | donor_loss | 1.0000 | 3 |
| 17:37111529–37111530 | donor_loss | 1.0000 | 5 |
| 17:37113267 | acceptor_loss | 1.0000 | 3 |
| 17:37121353–37121354 | donor_loss | 1.0000 | 5 |
| 17:37121491–37121492 | acceptor_loss | 1.0000 | 5 |
| 17:37130073–37130074 | donor_loss | 1.0000 | 5 |
AlphaMissense
6,100 missense substitutions predicted likely pathogenic (of 15,734 scored), across 1,393 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 |
|---|---|---|---|
| M785 | 9 | 0.933 | 0.997 |
| M1875 | 9 | 0.879 | 0.975 |
| M787 | 9 | 0.878 | 0.980 |
| M1236 | 9 | 0.874 | 0.999 |
| M1495 | 9 | 0.868 | 0.984 |
| M1483 | 9 | 0.858 | 0.991 |
| M1147 | 9 | 0.796 | 0.982 |
| D1367 | 8 | 0.998 | 0.999 |
| D946 | 8 | 0.997 | 0.999 |
| F1182 | 8 | 0.997 | 1.000 |
| D1418 | 8 | 0.997 | 0.999 |
| D1600 | 8 | 0.996 | 0.999 |
| H559 | 8 | 0.995 | 0.999 |
| F561 | 8 | 0.995 | 1.000 |
| F1104 | 8 | 0.995 | 1.000 |
| D1132 | 8 | 0.995 | 0.998 |
| D1455 | 8 | 0.994 | 0.999 |
| H1140 | 8 | 0.993 | 0.999 |
| H1188 | 8 | 0.993 | 1.000 |
| F936 | 8 | 0.992 | 1.000 |
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 |
|---|---|---|
| Liver Hepatocellular Carcinoma (TCGA) | unfavorable | 9.72e-07 |
Disease associations
OMIM: gene MIM:200350 | disease phenotypes: MIM:613933
GenCC curated gene-disease
1 curated gene-disease records:
| Disease | Classification | Inheritance | Records |
|---|---|---|---|
| acetyl-coa carboxylase deficiency | Moderate | Autosomal recessive | 2 |
Genomics England panels (PanelApp)
Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.
6 panels:
| Panel | Rating |
|---|---|
| Hypotonic infant | green |
| Intellectual disability | green |
| Leukodystrophy, childhood onset | green |
| Likely inborn error of metabolism | green |
| Paediatric disorders | green |
| Unexplained death in infancy and sudden unexplained death in childhood | green |
Mondo (1): acetyl-coa carboxylase deficiency (MONDO:0013493)
HPO phenotypes
7 phenotypes (HPO-id order):
| HPO | Term |
|---|---|
| HP:0000007 | Autosomal recessive inheritance |
| HP:0001252 | Hypotonia |
| HP:0001263 | Global developmental delay |
| HP:0001510 | Growth delay |
| HP:0002151 | Increased circulating lactate concentration |
| HP:0003198 | Myopathy |
| HP:6000430 | Reduced tissue acetyl-CoA carboxylase activity |
GWAS associations
2 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST011494_17 | Daytime nap | 5e-22 |
| GCST001941_16 | Ovarian cancer | 8e-10 |
EFO canonical traits (from GWAS)
1 canonical traits:
| EFO ID | Trait name |
|---|---|
| EFO:0007828 | daytime rest measurement |
MeSH disease descriptors
1 disease descriptors:
| Descriptor | Name | Tree numbers |
|---|---|---|
| C562678 | Acetyl-Coa Carboxylase Deficiency *(supp.)* |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL3351 (SINGLE PROTEIN), CHEMBL3885507 (PROTEIN FAMILY)
Drugs acting on a complex or family that includes this protein
Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes ACACA — the drug acts on the assembly or class, not necessarily on this subunit alone.
4 drugs via a complex or family:
| Drug | Target (ChEMBL) | Members | Max phase |
|---|---|---|---|
| OLUMACOSTAT GLASARETIL | Acetyl-CoA carboxylase | 2 | 3 |
| CLESACOSTAT | Acetyl-CoA carboxylase | 2 | 2 |
| FIRSOCOSTAT | Acetyl-CoA carboxylase | 2 | 2 |
| PF-05175157 | Acetyl-CoA carboxylase | 2 | 2 |
Molecules with ChEMBL bioactivity
Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,150 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
4 molecules by phase:
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL3545313 | BEMPEDOIC ACID | 4 | 839 |
| CHEMBL4567446 | CLESACOSTAT | 2 | 775 |
| CHEMBL3407547 | FIRSOCOSTAT | 2 | 1,258 |
| CHEMBL3359265 | PF-05175157 | 2 | 278 |
PharmGKB: 1 entry (CPIC guideline: no)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — Carboxylases
Most potent curated ligand interactions (5 total), top 5:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| firsocostat | Negative | 8.68 | pIC50 |
| compound 21 [PMID: 23981033] | Inhibition | 8.0 | pIC50 |
| clesacostat | Inhibition | 7.91 | pIC50 |
| CP-640186 | Inhibition | 6.39 | pIC50 |
| TOFA | Inhibition | 4.91 | pIC50 |
Binding affinities (BindingDB)
624 measured of 761 human assays (762 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| CHEMBL6171288 | IC50 | 0.22 nM | |
| 2-[1-[(2R)-2-[[(3aR,6aS)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]furan-5-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimidin-3-yl]-2-methyl-propionic acid | IC50 | 0.23 nM | US-12428432: Thienopyrimidine derivatives having stereo configurations and use thereof in medicine |
| CHEMBL4875701 | EC50 | 0.3 nM | |
| CHEMBL6161060 | IC50 | 0.32 nM | |
| CHEMBL6149358 | IC50 | 0.33 nM | |
| 2-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-4a,7a-dihydrothieno[2,3-d]pyrimidin-3-yl]-2-methylpropanamide | IC50 | 0.37 nM | US-10995099: Compounds and their uses as ACC inhibitors |
| 2-[1-[2-[[(3aR,6aS)-5-methylsulfonyl-1,2,3,3a,4,5,6,6a-octahydropentalen-2-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimid-3-yl]-2-methyl-propanoic acid | IC50 | 0.47 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| (R)-3-((1-(2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxa-1,4-dihydrothieno[2,3-d]pyrimidine-3(2H)-yl)methyl)cyclobutane-1-carboxylic acid | IC50 | 0.487 nM | US-12384798: ACC inhibitor and use thereof |
| 2-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-4a,7a-dihydrothieno[2,3-d]pyrimidin-3-yl]-2-methylpropanoic acid | IC50 | 0.49 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| CHEMBL6146650 | IC50 | 0.52 nM | |
| CHEMBL4073202 | IC50 | 0.58 nM | |
| 2-[1-[2-(2-methoxyphenyl)-2-(1-methylsulfonylpiperidin-4-yl)oxyethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-4aH-thieno[2,3-d]pyrimidin-1-ium-3-yl]-2-methylpropanoic acid | IC50 | 0.63 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| 2-[1-[2-[[(3aR,6aS)-5-cyclopropyl-5-hydroxy-2,3,3a,4,6,6a-hexahydro-1H-pentalen-2-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimid-3-yl]-2-methyl-propanoic acid | IC50 | 0.67 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 3-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-4a,7a-dihydrothieno[2,3-d]pyrimidin-3-yl]-1-methylcyclobutane-1-carboxylic acid | IC50 | 0.68 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| (R)-2-(3-(1-(2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidine-3(2H)-yl)cyclobutyl)acetic acid | IC50 | 0.688 nM | US-12384798: ACC inhibitor and use thereof |
| 3-[1-[2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-4a,7a-dihydrothieno[2,3-d]pyrimidin-3-yl]cyclobutane-1-carboxylic acid | IC50 | 0.69 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| 2-[1-[2-[1-(cyclopropanecarbonyl)piperidin-4-yl]oxy-2-(2-methoxyphenyl)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-4aH-thieno[2,3-d]pyrimidin-1-ium-3-yl]-2-methylpropanoic acid | IC50 | 0.7 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| CHEMBL6164037 | IC50 | 0.71 nM | |
| CHEMBL4060253 | IC50 | 0.76 nM | |
| CHEMBL6174786 | IC50 | 0.79 nM | |
| 2-[1-[2-(2-methoxyphenyl)-2-[(2-methylsulfonyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenteno[c]pyrrole-5-yl)oxy]ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimid-3-yl]-2-methyl-propanoic acid | IC50 | 0.81 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 2-((1R,3R)-3-(1-((R)-2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidine-3(4H)-yl)cyclobutyl)acetic acid | IC50 | 0.836 nM | US-12384798: ACC inhibitor and use thereof |
| CHEMBL6143782 | IC50 | 0.85 nM | |
| 3-methoxy-4-[1-[2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-4a,7a-dihydrothieno[2,3-d]pyrimidin-3-yl]benzoic acid | IC50 | 0.87 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| 2-[1-[2-[[(3aR,6aS)-5-ethyl-5-hydroxy-2,3,3a,4,6,6a-hexahydro-1H-pentalen-2-yl]oxy]-2-(2-methoxyphenyl)ethyl)-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimid-3-yl]-2-methyl-propanoic acid | IC50 | 0.88 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 2-[1-[2-[[(3aR,6aS)-5-hydroxy-5-(trifluoromethyl)-2,3,3a,4,6,6a-hexahydro-1H-pentalen-2-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimid-3-yl]-2-methyl-propanoic acid | IC50 | 0.89 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| CHEMBL4874989 | EC50 | 0.9 nM | |
| 4-[4-(2-tert-butyl-4-oxospiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-1’-carbonyl)-6-(dimethylamino)-2-pyridinyl]benzamide | IC50 | 0.9 nM | US-20240109915: NOVEL ACC INHIBITORS |
| 2-[1-[2-(1-acetylpiperidin-4-yl)oxy-2-(2-methoxyphenyl)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-4aH-thieno[2,3-d]pyrimidin-1-ium-3-yl]-2-methylpropanoic acid | IC50 | 0.91 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| 2-[1-[2-[[(3aS,6aR)-5-hydroxy-1,2,3,3a,4,5,6,6a-octahydropentalen-2-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimid-3-yl]-2-methyl-propanoic acid | IC50 | 0.93 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| CHEMBL6168887 | IC50 | 0.95 nM | |
| CHEMBL4085633 | IC50 | 0.96 nM | |
| CHEMBL4086127 | IC50 | 0.96 nM | |
| CHEMBL4864719 | EC50 | 1 nM | |
| CHEMBL4875627 | EC50 | 1 nM | |
| CHEMBL4859704 | EC50 | 1 nM | |
| CHEMBL4861716 | EC50 | 1 nM | |
| 3-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-4a,7a-dihydrothieno[2,3-d]pyrimidin-3-yl]-1-methylcyclobutane-1-carboxylic acid | IC50 | 1 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| 2-[1-[(2R)-2-[[(3aS,6aS)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]furan-5-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimidin-3-yl]-2-methyl-propionic acid | IC50 | 1.09 nM | US-12428432: Thienopyrimidine derivatives having stereo configurations and use thereof in medicine |
| CHEMBL6166957 | IC50 | 1.1 nM | |
| CHEMBL6173125 | IC50 | 1.1 nM | |
| 3-[1-(cyclopropanecarbonyl)azetidin-3-yl]-1-[2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-4a,7a-dihydrothieno[2,3-d]pyrimidine-2,4-dione | IC50 | 1.12 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| 2-((1S,3S)-3-(1-((R)-2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidine-3(4H)-yl)cyclobutyl)acetic acid | IC50 | 1.12 nM | US-12384798: ACC inhibitor and use thereof |
| 2-[1-[2-[[(1S,3S,5R)-6,8-dioxabicyclo[3.2.1]oct-3-yl]oxy]-2-(2-methoxyphenyl)-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimid-3-yl]-2-methyl-propanoic acid | IC50 | 1.21 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 1-[2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-3-[1-(morpholine-4-carbonyl)azetidin-3-yl]-6-(1,3-oxazol-2-yl)-4a,7a-dihydrothieno[2,3-d]pyrimidine-2,4-dione | IC50 | 1.22 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| CHEMBL4777068 | IC50 | 1.3 nM | |
| CHEMBL5411569 | IC50 | 1.3 nM | |
| 2-tert-butyl-1’-(4-chloro-5-methyl-1H-indazole-7-carbonyl)spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one | IC50 | 1.3 nM | US-20240109915: NOVEL ACC INHIBITORS |
| 3-(1-ethylsulfonylazetidin-3-yl)-1-[2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-4a,7a-dihydrothieno[2,3-d]pyrimidine-2,4-dione | IC50 | 1.35 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| 2-[1-[(2R)-2-[[(3aR,6aR)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]furan-5-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimidin-3-yl]-2-methyl-propionic acid | IC50 | 1.42 nM | US-12428432: Thienopyrimidine derivatives having stereo configurations and use thereof in medicine |
ChEMBL bioactivities
782 potent at pChembl≥5 of 802 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 9.66 | IC50 | 0.22 | nM | CHEMBL6171288 |
| 9.52 | EC50 | 0.3 | nM | CHEMBL4875701 |
| 9.49 | IC50 | 0.32 | nM | CHEMBL6161060 |
| 9.48 | IC50 | 0.33 | nM | CHEMBL6149358 |
| 9.43 | IC50 | 0.37 | nM | CHEMBL6012286 |
| 9.33 | IC50 | 0.47 | nM | CHEMBL5918349 |
| 9.31 | IC50 | 0.49 | nM | FIRSOCOSTAT |
| 9.30 | IC50 | 0.5 | nM | FIRSOCOSTAT |
| 9.28 | IC50 | 0.52 | nM | CHEMBL6146650 |
| 9.24 | IC50 | 0.58 | nM | CHEMBL4073202 |
| 9.20 | IC50 | 0.63 | nM | CHEMBL5923261 |
| 9.17 | IC50 | 0.67 | nM | CHEMBL5768893 |
| 9.17 | IC50 | 0.68 | nM | CHEMBL5814783 |
| 9.16 | IC50 | 0.69 | nM | CHEMBL5840411 |
| 9.15 | IC50 | 0.7 | nM | CHEMBL5986273 |
| 9.15 | IC50 | 0.71 | nM | CHEMBL6164037 |
| 9.14 | IC50 | 0.73 | nM | CHEMBL5814783 |
| 9.12 | IC50 | 0.76 | nM | CHEMBL4060253 |
| 9.10 | IC50 | 0.79 | nM | CHEMBL6174786 |
| 9.09 | IC50 | 0.81 | nM | CHEMBL5788250 |
| 9.07 | IC50 | 0.85 | nM | CHEMBL6143782 |
| 9.06 | IC50 | 0.88 | nM | CHEMBL5963413 |
| 9.06 | IC50 | 0.87 | nM | CHEMBL5991352 |
| 9.05 | EC50 | 0.9 | nM | CHEMBL4874989 |
| 9.05 | IC50 | 0.9 | nM | CHEMBL5404551 |
| 9.05 | IC50 | 0.89 | nM | CHEMBL5900123 |
| 9.04 | IC50 | 0.91 | nM | CHEMBL5856218 |
| 9.03 | IC50 | 0.93 | nM | CHEMBL5769140 |
| 9.02 | IC50 | 0.96 | nM | CHEMBL4085633 |
| 9.02 | IC50 | 0.96 | nM | CHEMBL4086127 |
| 9.02 | IC50 | 0.95 | nM | CHEMBL6168887 |
| 9.00 | EC50 | 1 | nM | CHEMBL4864719 |
| 9.00 | EC50 | 1 | nM | CHEMBL4875627 |
| 9.00 | EC50 | 1 | nM | CHEMBL4859704 |
| 9.00 | EC50 | 1 | nM | CHEMBL4861716 |
| 9.00 | IC50 | 1 | nM | CHEMBL5997686 |
| 8.98 | IC50 | 1.05 | nM | CHEMBL6173125 |
| 8.96 | IC50 | 1.1 | nM | CHEMBL6166957 |
| 8.95 | IC50 | 1.12 | nM | CHEMBL5922268 |
| 8.92 | IC50 | 1.21 | nM | CHEMBL5791009 |
| 8.91 | IC50 | 1.22 | nM | CHEMBL5926678 |
| 8.89 | IC50 | 1.29 | nM | CHEMBL4777068 |
| 8.89 | IC50 | 1.3 | nM | CHEMBL5435853 |
| 8.89 | IC50 | 1.3 | nM | CHEMBL5411569 |
| 8.87 | IC50 | 1.35 | nM | CHEMBL6057395 |
| 8.86 | IC50 | 1.37 | nM | CHEMBL5997686 |
| 8.85 | IC50 | 1.43 | nM | CHEMBL5889718 |
| 8.85 | IC50 | 1.43 | nM | CHEMBL5890205 |
| 8.85 | IC50 | 1.43 | nM | CHEMBL5757590 |
| 8.83 | IC50 | 1.48 | nM | CHEMBL6039150 |
PubChem BioAssay actives
486 with measured affinity, of 737 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 |
|---|---|---|---|---|
| 3-[1-[(2R)-2-(5-fluoro-2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-1-methylcyclobutane-1-carboxylic acid | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0002 | uM |
| 2-[1-[(2R)-2-(5-fluoro-2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-2,4-dioxo-6-(triazol-2-yl)thieno[2,3-d]pyrimidin-3-yl]-2-methyl-N-(1-methylcyclopropyl)sulfonylpropanamide | 1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer | ec50 | 0.0003 | uM |
| 3-[1-[(2R)-2-(4-hydroxycyclohexyl)oxy-2-(2-methoxyphenyl)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-1-methylcyclobutane-1-carboxylic acid | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0003 | uM |
| 1-(fluoromethyl)-3-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]cyclobutane-1-carboxylic acid | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0003 | uM |
| 2-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-2-methylpropanamide | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0004 | uM |
| 3-[1-[(2R)-2-(5-fluoro-2-methoxyphenyl)-2-(4-hydroxycyclohexyl)oxyethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-1-methylcyclobutane-1-carboxylic acid | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0005 | uM |
| 2-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-2-methylpropanoic acid | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0005 | uM |
| [(2S)-1-[[2-[4-[3-(cyclopropylmethoxy)phenoxy]phenyl]-1,3-oxazol-5-yl]oxy]propan-2-yl]urea | 1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry | ic50 | 0.0006 | uM |
| 3-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-1-methylcyclobutane-1-carboxylic acid | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0007 | uM |
| N-[1-[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-benzoxazol-6-yl]ethyl]acetamide | 1472481: Inhibition of ACC1 in human HCT116 cells assessed as reduction of [14C]acetate uptake preincubated for 60 mins followed by addition of [14C]acetate and measured after 2 hrs by scintillation counting analysis | ic50 | 0.0008 | uM |
| 3-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]cyclobutane-1-carboxylic acid | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0008 | uM |
| 1-[[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]methyl]cyclopropane-1-carboxylic acid | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0008 | uM |
| 1-[1-[(2R)-2-[2-(difluoromethoxy)-5-fluorophenyl]-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-2,4-dioxo-6-(triazol-2-yl)thieno[2,3-d]pyrimidin-3-yl]-N-(1-methylcyclopropyl)sulfonylcyclopropane-1-carboxamide | 1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer | ec50 | 0.0009 | uM |
| 4-[4-(2-tert-butyl-4-oxospiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-1’-carbonyl)-6-(dimethylamino)-2-pyridinyl]benzamide | 1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis | ic50 | 0.0009 | uM |
| 1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-3-[1-(2,2,2-trifluoroethyl)azetidin-3-yl]thieno[2,3-d]pyrimidine-2,4-dione | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0009 | uM |
| N-[(2S)-1-[[2-[4-[3-(cyclopropylmethoxy)phenoxy]phenyl]-1,3-oxazol-5-yl]oxy]propan-2-yl]acetamide | 1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry | ic50 | 0.0010 | uM |
| N-[(2S)-1-[[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-oxazol-5-yl]oxy]propan-2-yl]acetamide | 1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry | ic50 | 0.0010 | uM |
| (2R)-2-[1-[(2R)-2-(2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-N-(1-methylcyclopropyl)sulfonylpropanamide | 1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer | ec50 | 0.0010 | uM |
| 2-[1-[(2R)-2-(2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-2-methyl-N-(1-methylcyclopropyl)sulfonylpropanamide | 1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer | ec50 | 0.0010 | uM |
| 1-[1-[(2R)-2-(2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-2,4-dioxo-6-(triazol-2-yl)thieno[2,3-d]pyrimidin-3-yl]-N-(1-methylcyclopropyl)sulfonylcyclopropane-1-carboxamide | 1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer | ec50 | 0.0010 | uM |
| 2-[1-[(2R)-2-(2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-2,4-dioxo-6-(triazol-2-yl)thieno[2,3-d]pyrimidin-3-yl]-2-methyl-N-(1-methylcyclopropyl)sulfonylpropanamide | 1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer | ec50 | 0.0010 | uM |
| 3-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-1-methylcyclobutane-1-carboxamide | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0010 | uM |
| 1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-3-[1-(morpholine-4-carbonyl)azetidin-3-yl]-6-(1,3-oxazol-2-yl)thieno[2,3-d]pyrimidine-2,4-dione | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0011 | uM |
| 1’-[2-(4-aminophenyl)quinoline-4-carbonyl]-2-tert-butylspiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one | 1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay | ic50 | 0.0013 | uM |
| 2-tert-butyl-1’-(4-chloro-5-methyl-1H-indazole-7-carbonyl)spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one | 1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis | ic50 | 0.0013 | uM |
| 2-tert-butyl-1’-(4-chloro-5-methoxy-1H-indole-7-carbonyl)spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one | 1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis | ic50 | 0.0013 | uM |
| 1-[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-benzoxazol-6-yl]ethylurea | 1611142: Inhibition of recombinant human His-tagged ACC1 expressed in baculovirus infected SF9 cells using acetyl-CoA as substrate incubated for 60 mins followed by substrate addition and measured after 30 mins Rapidfire-Mass spectrometry | ic50 | 0.0015 | uM |
| 2-tert-butyl-1’-[5-methoxy-2-(methylamino)quinoline-7-carbonyl]spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one | 1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis | ic50 | 0.0015 | uM |
| 3-[1-(1H-imidazole-2-carbonyl)azetidin-3-yl]-1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)thieno[2,3-d]pyrimidine-2,4-dione | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0015 | uM |
| 2-tert-butyl-1’-[8-methyl-2-(methylamino)quinoline-3-carbonyl]spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one | 1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis | ic50 | 0.0018 | uM |
| 2-tert-butyl-1’-[2-(propylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767840: Inhibition of human ACC1 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3 | ic50 | 0.0018 | uM |
| 3-[1-[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-benzoxazol-6-yl]ethyl]-1,1-dimethylurea | 1611142: Inhibition of recombinant human His-tagged ACC1 expressed in baculovirus infected SF9 cells using acetyl-CoA as substrate incubated for 60 mins followed by substrate addition and measured after 30 mins Rapidfire-Mass spectrometry | ic50 | 0.0021 | uM |
| 1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-3-[1-(pyridine-2-carbonyl)azetidin-3-yl]thieno[2,3-d]pyrimidine-2,4-dione | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0021 | uM |
| N-[1-[2-[4-[3-(cyclopropylmethoxy)phenoxy]phenyl]-1,3-benzoxazol-6-yl]ethyl]acetamide | 1472481: Inhibition of ACC1 in human HCT116 cells assessed as reduction of [14C]acetate uptake preincubated for 60 mins followed by addition of [14C]acetate and measured after 2 hrs by scintillation counting analysis | ic50 | 0.0022 | uM |
| 2-tert-butyl-1’-[2-(4-methylphenyl)quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one | 1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay | ic50 | 0.0022 | uM |
| 2-tert-butyl-1’-(7-ethoxy-1,3-dimethylindazole-5-carbonyl)spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one | 1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis | ic50 | 0.0022 | uM |
| 2-tert-butyl-1’-[2-(methylamino)quinoline-7-carbonyl]spiro[4,6-dihydroindazole-5,4’-piperidine]-7-one | 725837: Inhibition of human recombinant ACC1 | ic50 | 0.0022 | uM |
| 2-tert-butyl-1’-[2-[4-(dimethylamino)phenyl]quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one | 1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay | ic50 | 0.0027 | uM |
| 5-[1’-(1-cyclopropyl-4-methoxy-3-methylindole-6-carbonyl)-4-oxospiro[3H-chromene-2,4’-piperidine]-6-yl]pyridine-3-carboxylic acid | 1546893: Inhibition of ACC1 (unknown origin) | ic50 | 0.0030 | uM |
| 2-tert-butyl-1’-[2-(4-methoxyphenyl)quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one | 1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay | ic50 | 0.0032 | uM |
| 2-tert-butyl-1’-[2-(3,4-dimethoxyphenyl)quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one | 1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay | ic50 | 0.0036 | uM |
| 1-[1-[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-benzoxazol-6-yl]ethyl]-3-methylurea | 1611142: Inhibition of recombinant human His-tagged ACC1 expressed in baculovirus infected SF9 cells using acetyl-CoA as substrate incubated for 60 mins followed by substrate addition and measured after 30 mins Rapidfire-Mass spectrometry | ic50 | 0.0038 | uM |
| N-[4-[2-[4-[3-(cyclopropylmethoxy)phenoxy]phenyl]-1,3-oxazol-5-yl]butan-2-yl]acetamide | 1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry | ic50 | 0.0049 | uM |
| 2-tert-butyl-1’-[2-(dimethylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767840: Inhibition of human ACC1 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3 | ic50 | 0.0050 | uM |
| 1’-(6-methoxyquinoline-3-carbonyl)-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-7-one | 725837: Inhibition of human recombinant ACC1 | ic50 | 0.0050 | uM |
| 3-(1-benzoylazetidin-3-yl)-1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)thieno[2,3-d]pyrimidine-2,4-dione | 2262885: Inhibition of recombinant human ACC1 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0054 | uM |
| 1’-[2-(4-bromophenyl)quinoline-4-carbonyl]-2-tert-butylspiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one | 1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay | ic50 | 0.0057 | uM |
| N-[(2S)-1-[[2-[5-[3-(cyclopropylmethoxy)phenoxy]-2-pyridinyl]-1,3-oxazol-5-yl]oxy]propan-2-yl]acetamide | 1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry | ic50 | 0.0058 | uM |
| 2-tert-butyl-1’-(2-phenylquinoline-4-carbonyl)spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one | 1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay | ic50 | 0.0060 | uM |
| 2-tert-butyl-1’-[2-(methylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767840: Inhibition of human ACC1 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3 | ic50 | 0.0060 | uM |
CTD chemical–gene interactions
185 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| dorsomorphin | affects cotreatment, decreases reaction, increases phosphorylation, increases expression, decreases expression (+1 more) | 9 |
| bisphenol A | increases expression, decreases expression, decreases reaction | 7 |
| Resveratrol | affects cotreatment, increases expression, increases reaction, decreases activity, decreases reaction (+1 more) | 7 |
| Valproic Acid | decreases expression, affects reaction, increases expression, affects expression, affects methylation | 7 |
| T0901317 | decreases reaction, increases expression, decreases phosphorylation, decreases expression | 6 |
| Benzo(a)pyrene | affects cotreatment, decreases expression, affects methylation | 5 |
| Oleic Acid | decreases expression, decreases reaction, increases expression, increases reaction, affects cotreatment | 5 |
| Palmitic Acid | decreases phosphorylation, decreases reaction, increases expression, affects cotreatment, decreases expression | 5 |
| AICA ribonucleotide | increases expression, increases phosphorylation | 4 |
| Cisplatin | affects expression, decreases expression | 4 |
| Glucose | affects cotreatment, increases expression, decreases reaction, increases reaction, increases phosphorylation (+2 more) | 4 |
| Metformin | decreases reaction, increases phosphorylation, decreases expression, increases expression | 4 |
| sodium arsenite | increases expression, decreases expression, affects cotreatment, increases abundance | 3 |
| Arsenic | increases abundance, increases expression, affects methylation, affects cotreatment, decreases expression | 3 |
| Plant Extracts | affects cotreatment, increases expression, increases phosphorylation | 3 |
| Cyclosporine | decreases expression | 3 |
| Cadmium Chloride | decreases expression, decreases phosphorylation, increases abundance, increases expression | 3 |
| nuciferine | increases expression, decreases reaction | 2 |
| arsenite | affects binding, decreases reaction, increases reaction, increases methylation | 2 |
| mono-(2-ethylhexyl)phthalate | affects expression, decreases expression | 2 |
| perfluorooctanoic acid | decreases expression, decreases phosphorylation, increases expression | 2 |
| caryophyllene | affects reaction, decreases reaction, increases phosphorylation, affects cotreatment, decreases expression | 2 |
| cordycepin | decreases expression | 2 |
| 6,8-diallyl 5,7-dihydroxy 2-(2-allyl 3-hydroxy 4-methoxyphenyl)1-H benzo(b)pyran-4-one | increases phosphorylation, decreases reaction, increases reaction, decreases activity | 2 |
| STO 609 | decreases reaction, increases phosphorylation | 2 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, decreases expression | 2 |
| 6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime | decreases expression, increases expression, affects cotreatment | 2 |
| fatostatin | decreases phosphorylation, increases reaction, decreases expression, increases response to substance | 2 |
| bisphenol AF | increases expression | 2 |
| Sunitinib | decreases phosphorylation, increases expression | 2 |
ChEMBL screening assays
71 unique, capped per target: 71 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1048878 | Binding | Inhibition of human recombinant ACC 1 expressed in baculovirus expression system by FAS-coupled assay | Potent biphenyl- and 3-phenyl pyridine-based inhibitors of acetyl-CoA carboxylase. — *Bioorg Med Chem Lett* |
Cellosaurus cell lines
5 cell lines: 5 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_D1V2 | Abcam A-549 ACACA KO | Cancer cell line | Male |
| CVCL_D1ZQ | Abcam HCT 116 ACACA KO | Cancer cell line | Male |
| CVCL_D9X5 | Ubigene HeLa ACACA KO | Cancer cell line | Female |
| CVCL_SB13 | HAP1 ACACA (-) 1 | Cancer cell line | Male |
| CVCL_SB14 | HAP1 ACACA (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
Via MONDO — disease-level, not drug-specific.
51 trials:
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02562170 | Phase 4 | COMPLETED | Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study |
| NCT00673335 | Phase 3 | COMPLETED | Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation |
| NCT00685256 | Phase 3 | COMPLETED | Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children |
| NCT03162276 | Phase 3 | UNKNOWN | Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers |
| NCT00253539 | Phase 2 | COMPLETED | Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer |
| NCT00305695 | Phase 2 | COMPLETED | Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries |
| NCT00321633 | Phase 2 | COMPLETED | Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer |
| NCT01333748 | Phase 2 | COMPLETED | Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer |
| NCT01367639 | Phase 2 | COMPLETED | Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers |
| NCT00535119 | Phase 1 | COMPLETED | Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer |
| NCT00892736 | Phase 1 | COMPLETED | Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy |
| NCT03832985 | Early Phase 1 | COMPLETED | Pediatric Reporting of Adult-Onset Genomic Results |
| NCT00005095 | Not specified | RECRUITING | Specimen and Data Study for Ovarian Cancer Early Detection and Prevention |
| NCT00609505 | Not specified | COMPLETED | Telemedicine vs. Face-to-Face Cancer Genetic Counseling |
| NCT01273909 | Not specified | UNKNOWN | Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment |
| NCT01445275 | Not specified | WITHDRAWN | Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199 |
| NCT01608074 | Not specified | ACTIVE_NOT_RECRUITING | Radical Fimbriectomy for Young BRCA Mutation Carriers |
| NCT02087592 | Not specified | COMPLETED | Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers |
| NCT02302742 | Not specified | RECRUITING | Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry |
| NCT02324062 | Not specified | COMPLETED | Cancer Genetics Hereditary Cancer Panel Testing |
| NCT02516540 | Not specified | UNKNOWN | Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers |
| NCT02653105 | Not specified | ACTIVE_NOT_RECRUITING | Women at Risk of Breast Cancer and OLFM4 |
| NCT02705924 | Not specified | TERMINATED | Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk |
| NCT02760849 | Not specified | ACTIVE_NOT_RECRUITING | Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations |
| NCT02786147 | Not specified | COMPLETED | Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer |
| NCT02956681 | Not specified | COMPLETED | Statewide Communication to Reach Diverse Low Income Women |
| NCT03015376 | Not specified | UNKNOWN | Inherited Susceptible Genes Among Epithelial Ovarian Cancer |
| NCT03050268 | Not specified | RECRUITING | Familial Investigations of Childhood Cancer Predisposition |
| NCT03075540 | Not specified | COMPLETED | Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer |
| NCT03124212 | Not specified | RECRUITING | Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland |
| NCT03246841 | Not specified | ACTIVE_NOT_RECRUITING | Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes. |
| NCT03294343 | Not specified | UNKNOWN | Risk-Reducing Surgeries for Hereditary Ovarian Cancer |
| NCT03421327 | Not specified | COMPLETED | Genetic Risk: Whether, When, and How to Tell Adolescents |
| NCT03510689 | Not specified | COMPLETED | Genetics and Heart Health After Cancer Therapy |
| NCT03511690 | Not specified | COMPLETED | Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment |
| NCT03784859 | Not specified | COMPLETED | Tissue Expansion in Breast Reconstruction Without Drains |
| NCT03979612 | Not specified | UNKNOWN | Evaluation of the Adhesion to the GENEPY Network |
| NCT04197856 | Not specified | UNKNOWN | Direct Information to At-risk Relatives |
| NCT04407611 | Not specified | COMPLETED | Scalable Communication Modalities for Returning Genetic Research Results |
| NCT04508764 | Not specified | TERMINATED | Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome |
| NCT04544501 | Not specified | COMPLETED | Enhance the Use of Genetic Counseling and Testing in Latinas |
| NCT04668521 | Not specified | TERMINATED | Multifactorial Risk Assessment for Breast & Ovarian Cancer Risk Detection |
| NCT05130606 | Not specified | RECRUITING | CONTIGO - A Narrative Intervention to Enhance Genetic Counseling and Testing |
| NCT05306002 | Not specified | COMPLETED | Nutritional Intervention and DNA Damage of Patients With HBOC |
| NCT05409222 | Not specified | UNKNOWN | Study of Quality of Life Post Salpingo-oophorectomy in BRCA1/2 & PALB2 Mutation Carriers (BRCA-HRT) |
| NCT05677048 | Not specified | ACTIVE_NOT_RECRUITING | Feasibility Study: IGNITE-TX (Identifying Individuals for Genetic Testing & Treatment) Intervention |
| NCT05721326 | Not specified | COMPLETED | Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition |
| NCT06892275 | Not specified | RECRUITING | The FYI on MRI: A Multilevel Decision Support Intervention for Screening Breast MRI |
| NCT06914726 | Not specified | ENROLLING_BY_INVITATION | Patient Centered Clinical Decision Support for Hereditary Cancer Syndromes |
| NCT07039552 | Not specified | RECRUITING | Development and Validation of an Ovarian Cancer Risk Prediction Model for Family Members of Ovarian Cancer Probands |
| NCT07236359 | Not specified | NOT_YET_RECRUITING | Evaluation of Well Being and Patient Reported Outcomes After Robotic Single-port Nipple Sparing Mastectomy and Implant Reconstruction |
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for ACACA across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
- Associated diseases: acetyl-coa carboxylase deficiency
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): acetyl-coa carboxylase deficiency, cardiac anomalies - developmental delay - facial dysmorphism syndrome, chromosome 17q12 duplication syndrome