ACACB
gene geneOn this page
Also known as HACC275ACC2ACCBACC-betaACCbetaACACbeta
Summary
ACACB (acetyl-CoA carboxylase beta, HGNC:85) is a protein-coding gene on chromosome 12q24.11, encoding Acetyl-CoA carboxylase 2 (O00763). Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism.
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. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine-palmitoyl-CoA transferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis.
Source: NCBI Gene 32 — RefSeq curated summary.
At a glance
- Gene–disease (curated): isolated cleft palate (Limited, GenCC)
- GWAS associations: 12
- Clinical variants (ClinVar): 574 total (top 6% of genes corpus-wide)
- Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈1% of expected missense variation)
- GTEx eGene: eQTL in 29 tissues, sQTL in 8 (q < 0.05)
- Drug target: yes — 4 via a complex or family; 4 molecules with ChEMBL bioactivity
- Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.84 (unconstrained)
- MANE Select transcript:
NM_001093 - Interaction hub: 1,978 STRING partners (top 8% of genes corpus-wide)
- Notable: 574 clinical variants but no curated precision-oncology (CIViC) evidence yet
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:85 |
| Approved symbol | ACACB |
| Name | acetyl-CoA carboxylase beta |
| Location | 12q24.11 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | HACC275, ACC2, ACCB, ACC-beta, ACCbeta, ACACbeta |
| Ensembl gene | ENSG00000076555 |
| Ensembl biotype | protein_coding |
| OMIM | 601557 |
| Entrez | 32 |
Gene structure
Transcript identifiers
Ensembl transcripts: 18 — 8 protein_coding, 7 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined
MANE Select: ENST00000338432
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 9, TSL 4: 1, TSL 5: 2
ENST00000338432, ENST00000377848, ENST00000377854, ENST00000396233, ENST00000534852, ENST00000536440, ENST00000537279, ENST00000537347, ENST00000538526, ENST00000539864, ENST00000542524, ENST00000543080, ENST00000544651, ENST00000544726, ENST00000546328, ENST00001114101, ENST00001114102, ENST00001142479
RefSeq mRNA: 9 — MANE Select: NM_001093
NM_001093, NM_001412734, NM_001412735, NM_001412736, NM_001412737, NM_001412738, NM_001412739, NM_001412741, NM_001412742
CCDS: CCDS31898
Canonical transcript exons
ENST00000338432 — 53 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000410836 | 109237165 | 109237380 |
| ENSE00000754740 | 109233748 | 109233847 |
| ENSE00000754741 | 109233938 | 109234045 |
| ENSE00000754742 | 109235313 | 109235369 |
| ENSE00000754743 | 109235606 | 109235647 |
| ENSE00000754745 | 109241078 | 109241281 |
| ENSE00000754752 | 109253015 | 109253158 |
| ENSE00000754753 | 109254214 | 109254334 |
| ENSE00000754755 | 109256140 | 109256236 |
| ENSE00000754756 | 109258268 | 109258364 |
| ENSE00000754757 | 109258973 | 109259108 |
| ENSE00000834688 | 109247606 | 109247703 |
| ENSE00001507550 | 109242437 | 109242592 |
| ENSE00002235090 | 109116587 | 109116704 |
| ENSE00002248873 | 109216796 | 109216920 |
| ENSE00002312587 | 109216618 | 109216706 |
| ENSE00002318749 | 109266236 | 109268226 |
| ENSE00002414906 | 109239830 | 109239985 |
| ENSE00003466998 | 109265389 | 109265525 |
| ENSE00003559754 | 109232669 | 109232806 |
| ENSE00003598675 | 109264232 | 109264386 |
| ENSE00003607535 | 109265110 | 109265280 |
| ENSE00003633552 | 109252046 | 109252156 |
| ENSE00003648656 | 109262357 | 109262469 |
| ENSE00003666060 | 109245626 | 109245748 |
| ENSE00003674468 | 109260480 | 109260657 |
| ENSE00003681964 | 109176153 | 109176263 |
| ENSE00003692777 | 109249984 | 109250104 |
| ENSE00003711752 | 109179917 | 109180087 |
| ENSE00003712327 | 109246179 | 109246448 |
| ENSE00003713917 | 109179088 | 109179297 |
| ENSE00003715175 | 109185579 | 109185740 |
| ENSE00003715301 | 109227371 | 109227489 |
| ENSE00003716931 | 109222507 | 109222620 |
| ENSE00003717197 | 109171805 | 109171914 |
| ENSE00003722000 | 109191847 | 109191950 |
| ENSE00003725709 | 109139397 | 109140058 |
| ENSE00003726799 | 109166861 | 109166993 |
| ENSE00003728112 | 109212836 | 109212936 |
| ENSE00003729382 | 109172275 | 109172356 |
| ENSE00003729412 | 109222799 | 109222912 |
| ENSE00003731216 | 109187999 | 109188162 |
| ENSE00003732315 | 109223815 | 109223904 |
| ENSE00003732419 | 109193648 | 109193729 |
| ENSE00003733707 | 109175931 | 109176040 |
| ENSE00003737429 | 109199402 | 109199552 |
| ENSE00003737693 | 109209165 | 109209353 |
| ENSE00003745712 | 109167896 | 109168034 |
| ENSE00003745866 | 109191613 | 109191763 |
| ENSE00003748551 | 109174132 | 109174230 |
| ENSE00003754435 | 109197008 | 109197153 |
| ENSE00003754629 | 109201567 | 109201701 |
| ENSE00003754769 | 109206710 | 109206856 |
Expression profiles
Bgee: expression breadth ubiquitous, 288 present calls, max score 99.00.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1992 / max 2046.7781, expressed in 957 samples.
Highest expression (Bgee): tendon of biceps brachii, adipose tissue, subcutaneous adipose tissue, mucosa of stomach, renal medulla.
Genetic regulation across tissues (GTEx eQTL / sQTL)
ACACB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 8 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
showing 20 of 37 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Cells Cultured fibroblasts | eqtl | 1.6e-59 | -0.40 | 12:109154678:T:C |
| Thyroid | eqtl | 7.0e-28 | -0.36 | 12:109112798:A:G |
| Testis | eqtl | 1.3e-27 | +0.58 | 12:109267806:A:G |
| Whole Blood | eqtl | 1.2e-21 | -0.42 | 12:109154678:T:C |
| Pancreas | eqtl | 1.5e-20 | +0.37 | 12:109139930:C:T |
| Cells EBV-transformed lymphocytes | eqtl | 1.1e-12 | -0.67 | 12:109154678:T:C |
| Colon Sigmoid | eqtl | 3.5e-10 | -0.22 | 12:109242198:T:A |
| Lung | eqtl | 2.5e-08 | -0.23 | 12:109137386:A:G |
| Heart Atrial Appendage | eqtl | 5.5e-06 | -0.14 | 12:109242198:T:A |
| Skin Not Sun Exposed Suprapubic | eqtl | 2.1e-05 | -0.11 | 12:109428805:CT:C |
| Liver | eqtl | 2.6e-05 | -0.25 | 12:109203773:G:C |
| Esophagus Muscularis | eqtl | 1.0e-04 | -0.15 | 12:109242198:T:A |
| Artery Tibial | eqtl | 2.0e-04 | -0.13 | 12:109154753:C:G |
| Nerve Tibial | eqtl | 2.3e-04 | -0.24 | 12:109132129:C:T |
| Testis | sqtl | 3.4e-04 | +0.38 | 12:109266520:C:T |
| Adrenal Gland | eqtl | 4.1e-04 | -0.29 | 12:109130476:G:A |
| Esophagus Muscularis | sqtl | 5.3e-04 | +0.27 | 12:109242198:T:A |
| Muscle Skeletal | eqtl | 6.4e-04 | +0.08 | 12:109124430:A:G |
| Kidney Cortex | eqtl | 1.5e-03 | +1.64 | 12:108968090:A:C |
| Adipose Visceral Omentum | sqtl | 1.5e-03 | -0.48 | 12:109207167:G:T |
FANTOM5 promoters
showing 10 of 21 alternative TSS:
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 127929 | 9.1512 | 174 |
| 127930 | 3.9813 | 160 |
| 127935 | 2.8392 | 731 |
| 127933 | 0.5175 | 270 |
| 127928 | 0.4740 | 80 |
| 127925 | 0.4437 | 59 |
| 127936 | 0.3080 | 152 |
| 127927 | 0.2362 | 51 |
| 127924 | 0.2344 | 57 |
| 127922 | 0.2338 | 46 |
Top tissues by expression
showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| tendon of biceps brachii | UBERON:0008188 | 99.00 | gold quality |
| adipose tissue | UBERON:0001013 | 98.17 | gold quality |
| subcutaneous adipose tissue | UBERON:0002190 | 98.05 | gold quality |
| mucosa of stomach | UBERON:0001199 | 97.81 | gold quality |
| renal medulla | UBERON:0000362 | 97.64 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 97.62 | gold quality |
| connective tissue | UBERON:0002384 | 97.59 | gold quality |
| omental fat pad | UBERON:0010414 | 97.52 | gold quality |
| peritoneum | UBERON:0002358 | 97.48 | gold quality |
| pericardium | UBERON:0002407 | 97.46 | gold quality |
| gastrocnemius | UBERON:0001388 | 97.36 | gold quality |
| muscle of leg | UBERON:0001383 | 96.71 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 96.66 | gold quality |
| apex of heart | UBERON:0002098 | 96.56 | gold quality |
| medial globus pallidus | UBERON:0002477 | 95.82 | gold quality |
| muscle organ | UBERON:0001630 | 95.66 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 95.35 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 95.06 | gold quality |
| sural nerve | UBERON:0015488 | 95.03 | gold quality |
| lower esophagus | UBERON:0013473 | 95.01 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 94.96 | gold quality |
| synovial joint | UBERON:0002217 | 94.91 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 94.85 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 94.83 | gold quality |
| liver | UBERON:0002107 | 94.79 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 94.72 | gold quality |
| deltoid | UBERON:0001476 | 94.43 | gold quality |
| gluteal muscle | UBERON:0002000 | 94.37 | gold quality |
| adrenal tissue | UBERON:0018303 | 94.32 | gold quality |
| globus pallidus | UBERON:0001875 | 94.26 | gold quality |
| cardia of stomach | UBERON:0001162 | 94.23 | gold quality |
| parietal pleura | UBERON:0002400 | 94.21 | gold quality |
| right lobe of liver | UBERON:0001114 | 94.18 | gold quality |
| cardiac ventricle | UBERON:0002082 | 94.12 | gold quality |
| heart left ventricle | UBERON:0002084 | 94.12 | gold quality |
| right atrium auricular region | UBERON:0006631 | 94.07 | gold quality |
| body of tongue | UBERON:0011876 | 93.89 | gold quality |
| cardiac atrium | UBERON:0002081 | 93.83 | gold quality |
| triceps brachii | UBERON:0001509 | 93.76 | gold quality |
| muscle tissue | UBERON:0002385 | 93.69 | gold quality |
| vena cava | UBERON:0004087 | 93.67 | gold quality |
| fundus of stomach | UBERON:0001160 | 93.58 | gold quality |
| mammary gland | UBERON:0001911 | 93.57 | gold quality |
| thoracic mammary gland | UBERON:0005200 | 93.50 | gold quality |
| tibial nerve | UBERON:0001323 | 93.21 | gold quality |
| heart | UBERON:0000948 | 93.01 | gold quality |
| colonic epithelium | UBERON:0000397 | 92.92 | gold quality |
| biceps brachii | UBERON:0001507 | 92.91 | gold quality |
| tibialis anterior | UBERON:0001385 | 92.88 | gold quality |
| buccal mucosa cell | CL:0002336 | 92.53 | silver quality |
| vastus lateralis | UBERON:0001379 | 92.31 | gold quality |
| pleura | UBERON:0000977 | 92.30 | gold quality |
| heart right ventricle | UBERON:0002080 | 92.19 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 91.97 | gold quality |
| adrenal cortex | UBERON:0001235 | 91.91 | gold quality |
| quadriceps femoris | UBERON:0001377 | 91.70 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 91.67 | gold quality |
| urethra | UBERON:0000057 | 91.61 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 91.41 | gold quality |
| cranial nerve II | UBERON:0000941 | 91.29 | gold quality |
| adrenal gland | UBERON:0002369 | 91.28 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 91.14 | gold quality |
| thyroid gland | UBERON:0002046 | 91.11 | gold quality |
| right adrenal gland | UBERON:0001233 | 91.10 | gold quality |
| inferior olivary complex | UBERON:0002127 | 90.97 | gold quality |
| sigmoid colon | UBERON:0001159 | 90.91 | gold quality |
| tendon | UBERON:0000043 | 90.89 | gold quality |
| pylorus | UBERON:0001166 | 90.86 | gold quality |
| diaphragm | UBERON:0001103 | 90.72 | gold quality |
| left adrenal gland | UBERON:0001234 | 90.70 | gold quality |
| dorsal motor nucleus of vagus nerve | UBERON:0002870 | 90.68 | gold quality |
| body of stomach | UBERON:0001161 | 90.30 | gold quality |
| metanephros cortex | UBERON:0010533 | 90.29 | gold quality |
| stomach | UBERON:0000945 | 90.28 | gold quality |
| tongue | UBERON:0001723 | 90.00 | gold quality |
| transverse colon | UBERON:0001157 | 89.93 | gold quality |
| skin of hip | UBERON:0001554 | 89.89 | gold quality |
| left ventricle myocardium | UBERON:0006566 | 89.61 | gold quality |
| superficial temporal artery | UBERON:0001614 | 89.60 | gold quality |
| cortex of kidney | UBERON:0001225 | 89.57 | gold quality |
| mammary duct | UBERON:0001765 | 89.44 | gold quality |
| body of uterus | UBERON:0009853 | 89.44 | gold quality |
| myocardium | UBERON:0002349 | 89.38 | gold quality |
| colon | UBERON:0001155 | 89.36 | gold quality |
| epithelium of mammary gland | UBERON:0003244 | 89.36 | gold quality |
| choroid plexus epithelium | UBERON:0003911 | 89.33 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 89.31 | gold quality |
| visceral pleura | UBERON:0002401 | 89.17 | gold quality |
| large intestine | UBERON:0000059 | 88.91 | gold quality |
| seminal vesicle | UBERON:0000998 | 88.89 | gold quality |
| body of pancreas | UBERON:0001150 | 88.73 | gold quality |
| endocervix | UBERON:0000458 | 88.64 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 88.57 | gold quality |
| right ovary | UBERON:0002118 | 88.53 | gold quality |
| intestine | UBERON:0000160 | 88.52 | gold quality |
| kidney | UBERON:0002113 | 88.46 | gold quality |
| small intestine | UBERON:0002108 | 88.33 | gold quality |
| layer of synovial tissue | UBERON:0007616 | 88.30 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 88.29 | gold quality |
| left ovary | UBERON:0002119 | 88.15 | gold quality |
Single-cell (SCXA)
Detected in 3 experiment(s), a significant marker in 3.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-2 | yes | 11146.67 |
| E-ANND-3 | yes | 9.04 |
| E-HCAD-25 | yes | 4.94 |
HPA expression
RNA tissue specificity: Tissue enhanced
showing 60 of 77 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Adipose tissue | tissue | 171.9 | high |
| Choroid plexus | tissue | 72.1 | |
| Tongue | tissue | 57.4 | |
| Skeletal muscle | tissue | 42.4 | not detected |
| Liver | tissue | 37.5 | medium |
| Nucleus accumbens | tissue | 30.2 | |
| Hippocampus | tissue | 29.6 | not detected |
| Locus coeruleus | tissue | 29.0 | |
| Pancreas | tissue | 18.2 | low |
| Postcentral gyrus | tissue | 17.2 | |
| Parathyroid gland | tissue | 17.0 | not detected |
| Adrenal gland | tissue | 16.6 | not detected |
| Heart muscle | tissue | 15.6 | not detected |
| Thyroid gland | tissue | 12.7 | low |
| Salivary gland | tissue | 11.8 | not detected |
| Breast | tissue | 11.6 | medium |
| Seminal vesicle | tissue | 11.0 | not detected |
| Pituitary gland | tissue | 10.7 | |
| Vagina | tissue | 10.5 | not detected |
| Kidney | tissue | 10.4 | low |
| Gallbladder | tissue | 10.3 | not detected |
| Esophagus | tissue | 10.0 | not detected |
| Ovary | tissue | 9.8 | not detected |
| Colon | tissue | 9.5 | low |
| Stomach 1 | tissue | 9.4 | not detected |
| Small intestine | tissue | 9.1 | low |
| Smooth muscle | tissue | 8.8 | not detected |
| Endometrium 1 | tissue | 8.1 | not detected |
| Duodenum | tissue | 7.9 | low |
| Rectum | tissue | 7.8 | low |
| Fallopian tube | tissue | 7.6 | not detected |
| Prostate | tissue | 7.1 | not detected |
| Lung | tissue | 6.3 | not detected |
| Cervix | tissue | 5.6 | not detected |
| Urinary bladder | tissue | 5.3 | low |
| Spleen | tissue | 5.3 | not detected |
| Skin 1 | tissue | 4.8 | not detected |
| Thymus | tissue | 4.2 | |
| Lymph node | tissue | 3.6 | not detected |
| Bone marrow | tissue | 3.4 | not detected |
| Epididymis | tissue | 3.3 | not detected |
| Superior colliculi | tissue | 3.1 | |
| Appendix | tissue | 3.1 | |
| Testis | tissue | 3.0 | high |
| Tonsil | tissue | 2.8 | not detected |
| Placenta | tissue | 2.4 | not detected |
| Spinal cord | tissue | 2.4 | |
| Retina | tissue | 1.6 | |
| Substantia nigra | tissue | 1.4 | |
| Frontal cortex | tissue | 1.1 | |
| Pons | tissue | 1.0 | |
| Medulla oblongata | tissue | 1.0 | |
| Hypothalamus | tissue | 1.0 | |
| Periaqueductal gray | tissue | 1.0 | |
| Hippocampal formation | tissue | 0.9 | |
| Midbrain | tissue | 0.8 | |
| Thalamus | tissue | 0.8 | |
| Septum | tissue | 0.8 | |
| Amygdala | tissue | 0.7 | |
| Cerebral cortex | tissue | 0.6 | not detected |
Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Globus pallidus, externus (60.8), Globus pallidus, internus (59.3), Periaquaductal grey, lateral (57.4), Central amygdala (56.8), Posterior thalamic nucleus (56.6).
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): CEBPA, MYF6, MYOD1, MYOG, NRF1, RARA, RXRA, SP1, SREBF1, USF1
miRNA regulators (miRDB)
Targeting ACACB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
showing 30 of 82 miRNAs:
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-5011-5P | 100.00 | 83.46 | 5820 |
| HSA-MIR-190A-3P | 100.00 | 80.35 | 5520 |
| HSA-MIR-7110-3P | 100.00 | 73.18 | 2486 |
| HSA-MIR-4455 | 100.00 | 65.48 | 1587 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-1250-3P | 99.96 | 70.04 | 4038 |
| HSA-MIR-450B-5P | 99.92 | 71.48 | 3175 |
| HSA-MIR-497-5P | 99.92 | 71.83 | 2674 |
| HSA-MIR-1305 | 99.91 | 71.43 | 3443 |
| HSA-MIR-15A-5P | 99.90 | 72.80 | 2787 |
| HSA-MIR-15B-5P | 99.90 | 72.78 | 2798 |
| HSA-MIR-16-5P | 99.90 | 72.80 | 2780 |
| HSA-MIR-195-5P | 99.90 | 72.81 | 2805 |
| HSA-MIR-95-5P | 99.89 | 72.17 | 3973 |
| HSA-MIR-424-5P | 99.89 | 71.90 | 2641 |
| HSA-MIR-6838-5P | 99.89 | 71.94 | 2690 |
| HSA-MIR-548E-5P | 99.89 | 72.73 | 4486 |
| HSA-MIR-153-5P | 99.89 | 73.86 | 6317 |
| HSA-MIR-4728-5P | 99.85 | 69.39 | 4718 |
| HSA-MIR-548AR-3P | 99.85 | 71.26 | 3889 |
| HSA-MIR-6844 | 99.82 | 70.69 | 2423 |
| HSA-MIR-6785-5P | 99.82 | 68.68 | 4428 |
| HSA-MIR-4319 | 99.76 | 69.83 | 2586 |
| HSA-MIR-6745 | 99.74 | 65.33 | 1321 |
| HSA-MIR-4306 | 99.72 | 70.50 | 3630 |
| HSA-MIR-10393-3P | 99.72 | 66.56 | 961 |
| HSA-MIR-6801-5P | 99.72 | 66.50 | 981 |
Functional genomics
gnomAD constraint: pLI 2.74e-49, LOEUF 0.843, missense Z 3.11 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD)
ENST00000338432 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD
| Region (GRCh38) | Missense obs / exp | o/e | Constrained |
|---|---|---|---|
| 12:109,139,406–109,250,092 | 2265 / 2561.3 | 0.88 | no |
| 12:109,250,093–109,252,088 | 6 / 23.0 | 0.26 | yes (p 4.0e-04) |
| 12:109,252,089–109,266,359 | 579 / 684.6 | 0.85 | no |
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)
- binding of T4 gene 32 protein to single- and double-stranded DNA is electrostatically regulated (PMID:15994897)
- UvsW-catalyzed unwinding of recombination intermediates such as D-loops and static X-DNA (Holliday junction mimic) to ssDNA products is enhanced by the gp32 protein. (PMID:23732982)
- Gp59-DNA interactions are needed to load Gp41 onto nascent or collapsed replication forks lacking clusters of Gp32 and to coordinate bidirectional replication from T4 origins. (PMID:24338568)
- Characterization of structural and thermodynamic aspects of gp32 binding cooperativity that are central to the function of this single stranded DNA binding protein with the T4 DNA replication. (PMID:26275774)
- The results show that single gp32 molecules interact most directly and specifically near the 3’-end of these ssDNA oligomers, thus defining the polarity of gp32 binding with respect to the ssDNA lattice, and that only 2-3 nts are directly involved in this tight binding interaction. (PMID:26275775)
- the C-domain of bacteriophage T4 gene 32 protein has a role in ssDNA binding and dsDNA helix-destabilization (PMID:29634784)
- Dynamic structure of T4 gene 32 protein filaments facilitates rapid noncooperative protein dissociation. (PMID:37449435)
- The effect of a 3-month low-intensity endurance training program on fat oxidation and expression (PMID:12086953)
- elevation of AMPK via phosphorylation is not sufficient to maintain elevated ACCbeta Ser(221) phosphorylation during exercise (PMID:12413941)
- down-regulation of acetyl coa carboxylase 2 (ACC2) mRNA, induced by the lowering of plasma insulin concentration, is related to improvement of insulin sensitivity (PMID:14627750)
- differential regulation of ACCbeta gene expression between tissues (PMID:15590647)
- The expression, purification, and characterization of ACC2 were investigated. (PMID:17223360)
- observations provide complete information about the pattern and levels of LKB1 and p-ACC immunostaining in normal tissues and in lung tumors (PMID:17521700)
- Differential activation of recombinant ACC1 and ACC2 by citrate is reported. (PMID:18455495)
- Human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. (PMID:19190759)
- The human ACC2 CT-domain C-terminus is comprised of three intertwined alpha-helices that extend outwards from the enzyme on the opposite side to the ligand-binding site. (PMID:19390150)
- results point towards major differences in ACC tissue distribution between humans and rats (PMID:19618481)
- the crystal structures of the biotin carboxylase domain of human ACC2 phosphorylated by AMP-activated protein kinase was reported. (PMID:19900410)
- data suggest that insulin and glucocorticoid have positive effects on both acetyl-CoA carboxylase alpha(ACC1) and beta(ACC2) gene transcription (PMID:20139635)
- These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes. (PMID:20168990)
- ACACB overexpression in renal proximal tubular epithelial cell increased proinflammatory cytokine expression, such as IL-6, at least partly by increasing mRNA stability through a p38 MAPK-dependent pathway. (PMID:20514549)
- The acetyl-coenzyme A carboxylase beta (ACACB) gene is associated with nephropathy in Chinese patients with type 2 diabetes. (PMID:20519229)
- This study demonstrates that NRF-1 is a novel transcriptional inhibitor of the human ACCbeta gene promoter in the mammalian heart. (PMID:20599696)
- The -368 C/T single-nucleotide polymorphism in ACACB P-II binds HepG2 nuclear proteins that affect promoter activity in an allele-specific fashion. (PMID:20799892)
- Acetyl-CoA carboxylase beta (ACC2) plays a key role in fatty acid synthesis and oxidation pathways. (PMID:20855566)
- A gene polymorphism in acetyl-coenzyme A carboxylase beta may be associated with the C-reactive protein level in a prediabetic and diabetic population. (PMID:21553357)
- Common variants within the ACACB locus appear to regulate adipose gene expression (PMID:21887335)
- In conclusion, common polymorphisms of ACACB gene are associated with obesity and, independently, with type 2 diabetes in postmenopausal women (PMID:21908218)
- Structure-guided inhibitor design for human acetyl-coenzyme A carboxylase by interspecies active site conversion. (PMID:21953464)
- TT genotypes of ACACB gene (rs2268388) and CC genotype of AGTR1 gene (rs5186) confers the risk of diabetic nephropathy in Asian Indian patients with T2DM. (PMID:23081748)
- Its involvement in the development of diabetic nephropathy is explained by the promotion of the so-called micro-inflammation associated with the diabetic state. (PMID:23156397)
- These data support a role for ACACB in obesity and potential roles for altered lipid metabolism in susceptibility to diabetic nephropathy. (PMID:23460794)
- Our meta-analysis supports that the apolipoprotein E epsilon2 allele and acetyl-CoA carboxylase beta rs2268388 C>T might act as promotion factors of nephropathy in type 2 diabetes. (PMID:25262148)
- The knockdown of ACC2 reduced palmitic acid -induced autophagy and thus protects the cells from palmitic acid - induced lipotoxicity with attenuated lipid accumulation and rescued cell viability. (PMID:26022126)
- A significant association exists of ACACB gene polymorphism and diabetic nephropathy among Caucasian patients with diabetes. (PMID:26030797)
- PHD3 loss in cancer enables metabolic reliance on fatty acid oxidation via deactivation of ACC2. (PMID:27635760)
- 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)
- Inhibition of Acetyl-CoA Carboxylase 1 (ACC1) and 2 (ACC2) Reduces Proliferation and De Novo Lipogenesis of EGFRvIII Human Glioblastoma Cells (PMID:28081256)
- ACC2 gene (ACACB) expression was decreased by 25% in HCC tissue compared to non-cancerous liver tissue. (PMID:28290443)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | acacb | ENSDARG00000061994 |
| mus_musculus | Acacb | ENSMUSG00000042010 |
| rattus_norvegicus | Acacb | ENSRNOG00000000658 |
| drosophila_melanogaster | ACC | FBGN0033246 |
Paralogs (4): MCCC1 (ENSG00000078070), PC (ENSG00000173599), PCCA (ENSG00000175198), ACACA (ENSG00000278540)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:2140940) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 27 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| abnormal lipid homeostasis | 2 |
| increased fatty acid oxidation | 2 |
| decreased heart enzyme/coenzyme level | 2 |
| decreased body weight | 1 |
| polyphagia | 1 |
| increased circulating triglyceride level | 1 |
| abnormal glucose homeostasis | 1 |
| increased circulating insulin level | 1 |
| small heart | 1 |
| increased circulating ketone body level | 1 |
| decreased circulating free fatty acids level | 1 |
| abnormal behavior | 1 |
| decreased fatty acids level | 1 |
| increased oxygen consumption | 1 |
| abnormal energy expenditure | 1 |
| decreased circulating glucose level | 1 |
| decreased circulating leptin level | 1 |
| decreased subcutaneous adipose tissue amount | 1 |
| decreased liver triglyceride level | 1 |
| decreased total body fat amount | 1 |
| decreased respiratory quotient | 1 |
| decreased liver glycogen level | 1 |
| increased skeletal muscle glycogen level | 1 |
| abnormal aerobic respiration | 1 |
| increased fatty acid beta-oxidation | 1 |
+2 more (showing top 25).
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 |
| Arabidopsis thaliana | F4I1L3 | 90.2% | Diamond |
| Sus scrofa | P0DTA4 | 88.6% | 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 |
| Glycine max | Q42777 | 71.7% | 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 |
| Nostoc sp. PCC 7120 = FACHB-418 | Q06862 | 66.7% | Diamond |
| Caenorhabditis elegans | O17732 | 65.6% | 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 |
| Ruegeria pomeroyi DSS-3 | Q5LUF3 | 52.5% | Diamond |
| Dictyostelium discoideum | Q54J08 | 43.5% | 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 |
|---|---|---|
| FOXN4 | protein-coding | 121643 |
| MYO1H | protein-coding | 283446 |
| KCTD10 | protein-coding | 83892 |
| UBE3B | protein-coding | 89910 |
| LINC01486 | ncRNA | 101928138 |
| ALKBH2 | protein-coding | 121642 |
| UNG | protein-coding | 7374 |
| USP30-AS1 | ncRNA | 100131733 |
| USP30 | protein-coding | 84749 |
Protein
Protein identifiers
Acetyl-CoA carboxylase 2 — O00763 (reviewed: O00763)
Alternative names: ACC-beta
All UniProt accessions (6): A0A087WUA1, F5H5C3, F8W8T8, O00763, H0YGH5, S4R3S7
UniProt curated annotations — full annotation on UniProt →
Function. Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism. Catalyzes 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. Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation. Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage.
Subunit / interactions. Monomer, homodimer, and homotetramer. Forms filamentous polymers. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity in a citrate-dependent manner.
Subcellular location. Mitochondrion.
Tissue specificity. Widely expressed with highest levels in heart, skeletal muscle, liver, adipose tissue, mammary gland, adrenal gland and colon. Isoform 3 is expressed in skeletal muscle, adipose tissue and liver (at protein level). Isoform 3 is detected at high levels in adipose tissue with lower levels in heart, liver, skeletal muscle and testis.
Post-translational modifications. The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity. Phosphorylation at Ser-222 by AMPK inactivates the enzyme. Required for the maintenance of skeletal muscle lipid and glucose homeostasis.
Activity regulation. Activity is increased by oligomerization of the protein into filaments. The oligomerization and the activity of the enzyme are inhibited by phosphorylation at Ser-222. Inhibited by its product, malonyl-CoA. Activated by citrate. Activation by MID1IP1 is citrate-dependent. Soraphen A, inhibits the enzyme by preventing the formation of active filamentous oligomers.
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 (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| O00763-1 | 1, Long | yes |
| O00763-2 | 2, Short | |
| O00763-3 | 3, ACC2.v2 |
RefSeq proteins (9): NP_001084, NP_001399663, NP_001399664, NP_001399665, NP_001399666, NP_001399667, NP_001399668, NP_001399670, NP_001399671 (=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000089 | Biotin_lipoyl | Domain |
| 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 6.3.4.14 — biotin carboxylase (BRENDA: 52 organisms, 95 substrates, 41 inhibitors, 87 Km, 31 kcat entries)
- EC 6.4.1.2 — acetyl-CoA carboxylase (BRENDA: 88 organisms, 133 substrates, 705 inhibitors, 131 Km, 13 kcat entries)
Substrate kinetics (BRENDA)
18 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| ACETYL-COA | 0.0002–1.2 | 39 |
| ATP | 0.015–0.5 | 38 |
| BIOTIN | 22.7–1234 | 31 |
| HCO3- | 0.3–12.8 | 27 |
| ATP | 0.0025–21 | 18 |
| HCO3- | 0.37–57.5 | 17 |
| ADP | 0.0013–0.83 | 8 |
| CARBAMOYL PHOSPHATE | 0.51–11.2 | 5 |
| 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 |
| BIOTIN-CARBOXYL-CARRIER PROTEIN | 0.16 | 1 |
| CO2 | 62.2 | 1 |
Catalyzed reactions (Rhea)
- hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + phosphate + H(+) (RHEA:11308)
UniProt features (186 total): helix 61, strand 56, modified residue 19, binding site 12, sequence conflict 8, turn 7, domain 5, sequence variant 4, compositionally biased region 3, splice variant 3, region of interest 3, mutagenesis site 2, transit peptide 1, chain 1, active site 1
Structure
Experimental structures (PDB)
11 structures by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 3GLK | The biotin carboxylase (BC) domain of human Acetyl-CoA Carboxylase 2 (ACC2) | X-RAY DIFFRACTION | 2.1 |
| 3GID | The biotin carboxylase (BC) domain of human Acetyl-CoA Carboxylase 2 (ACC2) in complex … | X-RAY DIFFRACTION | 2.3 |
| 3TDC | Crystal Structure of Human Acetyl-CoA carboxylase 2 | X-RAY DIFFRACTION | 2.41 |
| 2HJW | Crystal Structure of the BC domain of ACC2 | X-RAY DIFFRACTION | 2.5 |
| 3JRX | Crystal structure of the BC domain of ACC2 in complex with soraphen A | X-RAY DIFFRACTION | 2.5 |
| 3JRW | Phosphorylated BC domain of ACC2 | X-RAY DIFFRACTION | 2.6 |
| 5KKN | Crystal structure of human ACC2 BC domain in complex with ND-646, the primary amide of … | X-RAY DIFFRACTION | 2.6 |
| 4HQ6 | BC domain in the presence of citrate | X-RAY DIFFRACTION | 2.7 |
| 3FF6 | Human ACC2 CT domain with CP-640186 | X-RAY DIFFRACTION | 3.19 |
| 2DN8 | Solution Structure of RSGI RUH-053, an Apo-Biotin Carboxy Carrier Protein from Human … | SOLUTION NMR | |
| 2KCC | Solution Structure of biotinoyl domain from human acetyl-CoA carboxylase 2 | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-O00763-F1 | 79.29 | 0.29 |
Human Protein Atlas
Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted intracellular proteins, Plasma proteins
Protein evidence: Evidence at protein level
Antibody reliability (HPA): IH enhanced
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1)
| Position | Role |
|---|---|
| 584 |
Ligand- & substrate-binding residues (12)
| Position | Role |
|---|---|
| 458–463 | ATP |
| 567 | Mg(2+) |
| 567 | Mn(2+) |
| 580 | Mg(2+) |
| 580 | Mn(2+) |
| 582 | Mg(2+) |
| 582 | Mn(2+) |
| 1934 | CoA |
| 2238 | CoA |
| 2240 | CoA |
Post-translational modifications (19)
| Type | Positions |
|---|---|
| Phosphoserine | 35, 91, 95, 169, 175, 192, 195, 200, 220, 222, 469, 1340, 1360, 1405 |
| Phosphothreonine | 70, 207, 753, 1342 |
| N6-biotinyllysine | 929 |
Mutagenesis-validated functional residues (2)
| Position | Phenotype |
|---|---|
| 277 | loss of regulation of oligomerization by phosphorylation at s-222. |
| 671 | altered regulation of oligomerization by phosphorylation at s-222. |
Function
Pathways and Gene Ontology
Reactome pathways
4 curated (TAS) of 12; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
12 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| 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-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: 255 (showing top):
GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_STORAGE, WANG_CLIM2_TARGETS_UP, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_HEART_GROWTH, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS
GO Biological Process (16): acetyl-CoA metabolic process (GO:0006084), fatty acid biosynthetic process (GO:0006633), positive regulation of lipid storage (GO:0010884), regulation of glucose metabolic process (GO:0010906), response to nutrient levels (GO:0031667), negative regulation of fatty acid beta-oxidation (GO:0031999), protein homotetramerization (GO:0051289), fatty acid homeostasis (GO:0055089), positive regulation of heart growth (GO:0060421), energy homeostasis (GO:0097009), malonyl-CoA biosynthetic process (GO:2001295), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), acyl-CoA metabolic process (GO:0006637), negative regulation of fatty acid oxidation (GO:0046322), negative regulation of lipid catabolic process (GO:0050995)
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 (4): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829)
Reactome top-level categories
8 top-level categories:
| Category | Pathways |
|---|---|
| Metabolism | 3 |
| Metabolism of lipids | 2 |
| Integration of energy metabolism | 1 |
| Metabolism of water-soluble vitamins and cofactors | 1 |
| Fatty acid metabolism | 1 |
| Regulation of cholesterol biosynthesis by SREBP (SREBF) | 1 |
| Metabolism of steroids | 1 |
| Metabolism of vitamins and cofactors | 1 |
GO top-level categories
54 GO namespaces:
| Category | Terms |
|---|---|
| intracellular membrane-bounded organelle | 2 |
| cytoplasm | 2 |
| acyl-CoA metabolic process | 1 |
| fatty acid metabolic process | 1 |
| lipid biosynthetic process | 1 |
| monocarboxylic acid biosynthetic process | 1 |
| regulation of lipid storage | 1 |
| lipid storage | 1 |
| positive regulation of cellular process | 1 |
| positive regulation of lipid localization | 1 |
| glucose metabolic process | 1 |
| regulation of carbohydrate metabolic process | 1 |
| regulation of small molecule metabolic process | 1 |
| response to stimulus | 1 |
| fatty acid beta-oxidation | 1 |
| regulation of fatty acid beta-oxidation | 1 |
| negative regulation of fatty acid oxidation | 1 |
| negative regulation of lipid catabolic process | 1 |
| protein homooligomerization | 1 |
| protein tetramerization | 1 |
| lipid homeostasis | 1 |
| positive regulation of organ growth | 1 |
| heart growth | 1 |
| regulation of heart growth | 1 |
| multicellular organismal-level homeostasis | 1 |
| acyl-CoA biosynthetic process | 1 |
| malonyl-CoA metabolic process | 1 |
| primary metabolic process | 1 |
| lipid metabolic process | 1 |
| monocarboxylic acid metabolic process | 1 |
| nucleoside phosphate metabolic process | 1 |
| sulfur compound metabolic process | 1 |
| purine-containing compound metabolic process | 1 |
| fatty acid oxidation | 1 |
| negative regulation of fatty acid metabolic process | 1 |
| regulation of fatty acid oxidation | 1 |
| negative regulation of catabolic process | 1 |
| lipid catabolic process | 1 |
| negative regulation of lipid metabolic process | 1 |
| regulation of lipid catabolic 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 |
| mitochondrial membrane | 1 |
| organelle outer membrane | 1 |
| cellular anatomical structure | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 28 annotations. The rest are phylogenetic / computational / electronic (IEA).
6 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| acetyl-CoA metabolic process | BP | direct assay |
| protein homotetramerization | BP | direct assay |
| mitochondrion | CC | direct assay |
| nucleus | CC | direct assay |
| acetyl-CoA carboxylase activity | MF | direct assay |
| identical protein binding | MF | physical interaction |
Protein interactions and networks
STRING
showing 15 of 1,978 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| ACACB | CPT1A | P50416 | 852 |
| ACACB | FASN | P49327 | 839 |
| ACACB | SCARB1 | Q8WTV0 | 690 |
| ACACB | ACLY | P53396 | 661 |
| ACACB | ACSL1 | P33121 | 640 |
| ACACB | CLPP | Q16740 | 623 |
| ACACB | SCD | O00767 | 622 |
| ACACB | SREBF1 | P36956 | 590 |
| ACACB | LEP | P41159 | 569 |
| ACACB | ACOX1 | Q15067 | 559 |
| ACACB | FABP3 | P05413 | 552 |
| ACACB | HMGCR | P04035 | 549 |
| ACACB | PPARA | Q07869 | 548 |
| ACACB | DGAT2 | Q96PD7 | 543 |
| ACACB | ACSS2 | Q9NR19 | 542 |
IntAct
Human interaction partners of ACACB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
showing 30 of 40 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| HLCS | enzymatic reaction | 0.620 | 4 |
| MID1IP1 | association | 0.530 | 2 |
| PEX14 | direct interaction | 0.440 | 1 |
| BCDIN3D | physical association | 0.400 | 1 |
| HMGA1 | physical association | 0.400 | 1 |
| MOXD1 | physical association | 0.400 | 1 |
| RGS1 | physical association | 0.400 | 1 |
| BAG5 | association | 0.350 | 1 |
| C2CD6 | association | 0.350 | 1 |
| CDK17 | association | 0.350 | 1 |
| CDK7 | association | 0.350 | 1 |
| CDKL1 | association | 0.350 | 1 |
| COP1 | association | 0.350 | 1 |
| CSNK1G3 | association | 0.350 | 1 |
| DAPK3 | association | 0.350 | 1 |
| DOCK5 | association | 0.350 | 1 |
| DUSP22 | association | 0.350 | 1 |
| ELP3 | association | 0.350 | 1 |
| HPCAL4 | association | 0.350 | 1 |
| IFNE | association | 0.350 | 1 |
| INAVA | association | 0.350 | 1 |
| LGALS3BP | association | 0.350 | 1 |
| METTL2A | association | 0.350 | 1 |
| NPAP1 | association | 0.350 | 1 |
| NPTXR | association | 0.350 | 1 |
| NT5DC1 | association | 0.350 | 1 |
| NXPH3 | association | 0.350 | 1 |
| PPARD | association | 0.350 | 1 |
| PPM1H | association | 0.350 | 1 |
| PRKG1 | association | 0.350 | 1 |
BioGRID (151 interactions; top human partners by supporting records): ACACA (Affinity Capture-MS; 2 records), CCNF (Proximity Label-MS; 2 records), HLCS (Co-crystal Structure; 2 records), MID1IP1 (Affinity Capture-MS; 2 records), RFWD2 (Affinity Capture-MS; 2 records), RGS1 (Affinity Capture-MS; 2 records), TOPBP1 (Proximity Label-MS; 2 records), ACAA1 (Affinity Capture-MS), ALS2CR11 (Affinity Capture-MS), ANKRD28 (Proximity Label-MS), ANLN (Affinity Capture-MS), ARF4 (Proximity Label-MS), ARL10 (Proximity Label-MS), ARL5A (Proximity Label-MS), ATG16L1 (Proximity Label-MS)
SIGNOR signaling
showing 7 of 8 signaling interactions:
| A | Effect | B | Mechanism |
|---|---|---|---|
| PRKAA2 | “down-regulates activity” | ACACB | phosphorylation |
| ACACB | “down-regulates quantity” | acetyl-CoA | “chemical modification” |
| ACACB | “up-regulates quantity” | malonyl-CoA | “chemical modification” |
| COP1 | “down-regulates quantity by destabilization” | ACACB | ubiquitination |
| TRIB3 | “down-regulates quantity by destabilization” | ACACB | binding |
| MID1IP1 | “up-regulates activity” | ACACB | binding |
| TFEB | “up-regulates quantity by expression” | ACACB | “transcriptional regulation” |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 40 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| protein phosphorylation | 6 | 11.3× | 4e-03 |
Disease & clinical
Genetic variants
Variant evidence for ACACB: 574 ClinVar records (0 pathogenic / likely pathogenic); 12 GWAS associations.
ClinVar
574 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 400 |
| Likely benign | 77 |
| Benign | 32 |
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 4,339):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 12:109166950 | donor_gain | 1.0000 | |
| 12:109166994–109166995 | donor_loss | 1.0000 | 4 |
| 12:109167894–109167895 | acceptor_loss | 1.0000 | 5 |
| 12:109168035–109168036 | donor_loss | 1.0000 | 5 |
| 12:109171798 | acceptor_gain | 1.0000 | |
| 12:109171915–109171916 | donor_loss | 1.0000 | 5 |
| 12:109180088–109180089 | donor_loss | 1.0000 | 5 |
| 12:109188149 | donor_gain | 1.0000 | |
| 12:109191611–109191612 | acceptor_gain | 1.0000 | 2 |
| 12:109191611–109191612 | acceptor_loss | 1.0000 | 3 |
AlphaMissense
5,740 missense substitutions predicted likely pathogenic (of 16,205 scored), across 1,466 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 |
|---|---|---|---|
| M1986 | 9 | 0.878 | 0.981 |
| M609 | 9 | 0.841 | 0.991 |
| D303 | 8 | 0.994 | 0.998 |
| H702 | 8 | 0.986 | 0.997 |
| F674 | 8 | 0.984 | 0.999 |
| F684 | 8 | 0.982 | 0.998 |
| D697 | 8 | 0.982 | 0.996 |
| F704 | 8 | 0.981 | 0.998 |
| D1719 | 8 | 0.979 | 0.990 |
| F1325 | 8 | 0.978 | 0.998 |
| D1537 | 8 | 0.978 | 0.994 |
| D1574 | 8 | 0.978 | 0.996 |
| F287 | 8 | 0.977 | 0.997 |
| F1079 | 8 | 0.973 | 0.998 |
| D1794 | 8 | 0.970 | 0.991 |
| F700 | 8 | 0.969 | 0.997 |
| H693 | 8 | 0.968 | 0.994 |
| F1541 | 8 | 0.965 | 0.995 |
| D2166 | 8 | 0.965 | 0.993 |
| D520 | 8 | 0.964 | 0.989 |
HPA cancer prognostics
RNA cancer specificity: Cancer enhanced (Kidney Chromophobe)
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
5 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Kidney Renal Clear Cell Carcinoma (validation) | favorable | 2.19e-05 |
| Kidney Renal Papillary Cell Carcinoma (TCGA) | favorable | 5.48e-05 |
| Pancreatic Adenocarcinoma (TCGA) | favorable | 0.000116 |
| Kidney Renal Clear Cell Carcinoma (TCGA) | favorable | 0.000251 |
| Thyroid Carcinoma (TCGA) | unfavorable | 0.000314 |
Disease associations
OMIM: gene MIM:601557 | disease phenotypes:
GenCC curated gene-disease
1 curated gene-disease records:
| Disease | Classification | Inheritance | Records |
|---|---|---|---|
| isolated cleft palate | Limited | Unknown |
Mondo (1): isolated cleft palate (MONDO:0007336)
GWAS associations
12 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST90013406_19 | Liver enzyme levels (alkaline phosphatase) | 9e-28 |
| GCST010142_53 | Fish- and plant-related diet | 2e-19 |
| GCST010135_28 | Oily fish consumption | 7e-17 |
| GCST010140_4 | Pork consumption | 7e-17 |
| GCST010142_72 | Fish- and plant-related diet | 4e-13 |
| GCST010142_60 | Fish- and plant-related diet | 5e-13 |
| GCST010135_36 | Oily fish consumption | 6e-11 |
| GCST010140_12 | Pork consumption | 6e-11 |
| GCST010244_228 | Triglyceride levels | 1e-9 |
| GCST012477_2 | Invasive cervical cancer | 3e-9 |
| GCST006613_107 | Triglycerides | 3e-8 |
| GCST010142_93 | Fish- and plant-related diet | 4e-8 |
EFO canonical traits (from GWAS)
3 canonical traits:
| EFO ID | Trait name |
|---|---|
| EFO:0004530 | triglyceride measurement |
| EFO:0008111 | diet measurement |
| EFO:0004533 | alkaline phosphatase measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL3885507 (PROTEIN FAMILY), CHEMBL4829 (SINGLE PROTEIN)
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 ACACB — 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 (7 total), top 7:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| compound 2e [PMID: 31900320] | Inhibition | 8.72 | pIC50 |
| compound 21 [PMID: 23981033] | Inhibition | 8.4 | pIC50 |
| firsocostat | Negative | 8.21 | pIC50 |
| A-908292 | Inhibition | 7.64 | pIC50 |
| clesacostat | Inhibition | 7.6 | pIC50 |
| CP-640186 | Inhibition | 7.42 | pIC50 |
| TOFA | Inhibition | 4.91 | pIC50 |
Binding affinities (BindingDB)
3704 measured of 4061 human assays (4141 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 |
| 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 |
| 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-(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 |
| CHEMBL6168887 | IC50 | 0.95 nM | |
| CHEMBL4085633 | IC50 | 0.96 nM | |
| CHEMBL4086127 | IC50 | 0.96 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 |
| 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 |
| 2-[1-[2-[[(3aR,6aS)-5,5-difluoro-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 | 1.43 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 2-[1-[2-[[(3aR,6aS)-5-cyano-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 | 1.43 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 2-fluoro-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]benzoic acid | IC50 | 1.48 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| CHEMBL4528475 | IC50 | 1.5 nM | |
| CHEMBL6169460 | IC50 | 1.5 nM | |
| 2-[1-[2-[[(2S,3aS,6aR)-4,5-dihydroxy-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 | 1.55 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 2-[1-[2-[[(3aS,6aR)-5-(cyanomethyl)-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 | 1.56 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 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]benzoic acid | IC50 | 1.57 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| 2-[1-[2-[(5-cyano-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 | 1.64 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 3-[1-(1H-imidazole-2-carbonyl)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 | 1.69 nM | US-11186587: Compound as ACC inhibitor and use thereof |
| 2-[1-[2-(3,3a,4,5,6,6a-hexahydro-1H-cyclopenteno[c]furan5-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 | 1.76 nM | US-10759812: Thienopyrimidine derivative and use thereof in medicine |
| 2-tert-butyl-1’-[2-(propylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | IC50 | 1.8 nM | US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors |
| N-[(2S)-1-[4-(6-cyclobutyloxy-4,7-difluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide | IC50 | 2 nM | US-10150728: Alkylene derivatives |
ChEMBL bioactivities
4258 potent at pChembl≥5 of 4326 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 9.68 | IC50 | 0.21 | nM | CHEMBL1089882 |
| 9.52 | IC50 | 0.3 | nM | CHEMBL1089883 |
| 9.51 | IC50 | 0.31 | nM | CHEMBL1091996 |
| 9.00 | IC50 | 1 | nM | CHEMBL3699916 |
| 8.96 | IC50 | 1.1 | nM | CHEMBL2419600 |
| 8.95 | IC50 | 1.13 | nM | CHEMBL5768893 |
| 8.89 | IC50 | 1.3 | nM | CHEMBL2323626 |
| 8.82 | IC50 | 1.5 | nM | CHEMBL2419589 |
| 8.77 | IC50 | 1.7 | nM | CHEMBL2419600 |
| 8.77 | IC50 | 1.7 | nM | FIRSOCOSTAT |
| 8.77 | IC50 | 1.7 | nM | CHEMBL2419598 |
| 8.77 | IC50 | 1.7 | nM | CHEMBL3699930 |
| 8.76 | IC50 | 1.72 | nM | CHEMBL3699929 |
| 8.75 | IC50 | 1.76 | nM | CHEMBL5788250 |
| 8.74 | IC50 | 1.8 | nM | CHEMBL3699918 |
| 8.72 | IC50 | 1.9 | nM | CHEMBL3699881 |
| 8.72 | IC50 | 1.9 | nM | CHEMBL4225405 |
| 8.70 | IC50 | 2 | nM | CHEMBL5825494 |
| 8.70 | IC50 | 2 | nM | CHEMBL6059087 |
| 8.68 | IC50 | 2.1 | nM | CHEMBL2323628 |
| 8.68 | IC50 | 2.1 | nM | CHEMBL3699871 |
| 8.68 | IC50 | 2.1 | nM | CHEMBL3699886 |
| 8.68 | IC50 | 2.1 | nM | CHEMBL3699903 |
| 8.68 | IC50 | 2.1 | nM | CHEMBL4229067 |
| 8.66 | IC50 | 2.2 | nM | CHEMBL3699914 |
| 8.66 | IC50 | 2.19 | nM | CHEMBL5918349 |
| 8.64 | IC50 | 2.3 | nM | CHEMBL2419589 |
| 8.62 | IC50 | 2.4 | nM | CHEMBL3699889 |
| 8.62 | IC50 | 2.4 | nM | CHEMBL3699893 |
| 8.62 | IC50 | 2.4 | nM | CHEMBL3699915 |
| 8.60 | IC50 | 2.5 | nM | CHEMBL3699925 |
| 8.59 | IC50 | 2.6 | nM | CHEMBL2419597 |
| 8.59 | IC50 | 2.6 | nM | CHEMBL3699913 |
| 8.59 | IC50 | 2.6 | nM | FIRSOCOSTAT |
| 8.57 | IC50 | 2.7 | nM | CHEMBL3699873 |
| 8.57 | IC50 | 2.7 | nM | CHEMBL3699924 |
| 8.57 | IC50 | 2.7 | nM | CHEMBL3699927 |
| 8.56 | IC50 | 2.74 | nM | CHEMBL5791009 |
| 8.55 | IC50 | 2.81 | nM | CHEMBL6149358 |
| 8.54 | IC50 | 2.9 | nM | CHEMBL2323629 |
| 8.54 | IC50 | 2.9 | nM | CHEMBL3699921 |
| 8.52 | IC50 | 3 | nM | CHEMBL2419593 |
| 8.52 | IC50 | 3 | nM | CHEMBL221169 |
| 8.52 | IC50 | 3 | nM | CHEMBL4557289 |
| 8.52 | Kd | 3 | nM | CHEMBL540678 |
| 8.52 | IC50 | 3 | nM | CHEMBL5923446 |
| 8.52 | IC50 | 3 | nM | CHEMBL5835621 |
| 8.52 | IC50 | 3 | nM | CHEMBL5744755 |
| 8.52 | IC50 | 3 | nM | CHEMBL6031375 |
| 8.52 | IC50 | 3 | nM | CHEMBL6034807 |
PubChem BioAssay actives
640 with measured affinity, of 763 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 |
|---|---|---|---|---|
| 6-(1-methylpyrazol-4-yl)-1’-[2-(1-methylpyrazol-3-yl)-3H-benzimidazole-5-carbonyl]spiro[3H-pyrano[2,3-c]pyridine-2,4’-piperidine]-4-one | 476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader | ic50 | 0.0002 | uM |
| 1’-(7-methyl-1H-indazole-5-carbonyl)-6-(1-methylpyrazol-4-yl)spiro[3H-pyrano[2,3-c]pyridine-2,4’-piperidine]-4-one | 476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader | ic50 | 0.0003 | uM |
| 6-methoxy-1’-(7-methyl-1H-indazole-5-carbonyl)spiro[3H-pyrano[2,3-c]pyridine-2,4’-piperidine]-4-one | 476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader | ic50 | 0.0003 | uM |
| 2-tert-butyl-1’-[2-(methylamino)quinoline-7-carbonyl]spiro[4,6-dihydroindazole-5,4’-piperidine]-7-one | 725836: Inhibition of human recombinant ACC2 | ic50 | 0.0013 | 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 | 1195663: In vitro inhibition of human recombinant His-tagged ACC2 assessed as malonyl-CoA level | ic50 | 0.0017 | uM |
| 2-tert-butyl-1’-[2-(propylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 | 0.0017 | uM |
| N-[(E,2S)-4-[6-[(7-chloro-2-ethoxy-1,3-benzothiazol-6-yl)oxy]-3-pyridinyl]but-3-en-2-yl]acetamide | 1393080: Inhibition of recombinant human ACC2 assessed as reduction in conversion of acetyl-CoA to malonyl-CoA incubated for 1 to 3 hrs with substrate by MALDI-TOF-MS analysis | ic50 | 0.0019 | uM |
| N-[(E,2S)-4-[6-[(7-fluoro-2-propan-2-yl-1,3-benzothiazol-6-yl)oxy]-3-pyridinyl]but-3-en-2-yl]acetamide | 1393080: Inhibition of recombinant human ACC2 assessed as reduction in conversion of acetyl-CoA to malonyl-CoA incubated for 1 to 3 hrs with substrate by MALDI-TOF-MS analysis | ic50 | 0.0021 | uM |
| 1’-(6-methoxyquinoline-3-carbonyl)-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-7-one | 725836: Inhibition of human recombinant ACC2 | ic50 | 0.0021 | uM |
| 2-tert-butyl-1’-[2-(dimethylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 | 0.0023 | 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0028 | uM |
| 5-(7-oxo-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-1’-carbonyl)-1H-indole-2-carboxamide | 725836: Inhibition of human recombinant ACC2 | ic50 | 0.0029 | uM |
| N-[(1S)-1-[3-[2-(4-propan-2-yloxyphenoxy)-1,3-thiazol-5-yl]-1,2-oxazol-5-yl]ethyl]acetamide | 280225: Inhibition of human recombinant ACC2 expressed in SF9 cells | ic50 | 0.0030 | uM |
| 5-[1’-(1-cyclopropyl-4-methoxy-3-methylindole-6-carbonyl)-4-oxospiro[3H-chromene-2,4’-piperidine]-6-yl]pyridine-3-carboxylic acid | 1546894: Inhibition of ACC2 (unknown origin) | ic50 | 0.0030 | uM |
| [(1R,2S,5S,10S,11R,12E,14S,15S,16S,17S,18R)-1,17-dihydroxy-10,18-dimethoxy-2,14,16-trimethyl-3-oxo-5-phenyl-4,19-dioxabicyclo[13.3.1]nonadec-12-en-11-yl] 3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)propanoate | 426474: Binding affinity to human His-tagged acetyl-CoA-carboxylase biotin carboxylase domain | kd | 0.0030 | uM |
| 2-tert-butyl-1’-(3-chloro-1H-indole-6-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 | 0.0030 | 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0037 | uM |
| N-[4-[2-(4-propoxyphenoxy)-1,3-thiazol-5-yl]but-3-yn-2-yl]acetamide | 276641: Inhibition of human recombinant ACC2 | ic50 | 0.0040 | uM |
| 2-tert-butyl-1’-(2-methoxyquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 | 0.0040 | 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0041 | uM |
| 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0041 | 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0042 | uM |
| 2-tert-butyl-1’-[2-(methylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 | 0.0042 | uM |
| 2-tert-butyl-1’-(1-methoxyisoquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 | 0.0042 | uM |
| N-[(E,2S)-4-[6-[(7-chloro-2-propan-2-yl-1,3-benzothiazol-6-yl)oxy]-3-pyridinyl]but-3-en-2-yl]acetamide | 1393080: Inhibition of recombinant human ACC2 assessed as reduction in conversion of acetyl-CoA to malonyl-CoA incubated for 1 to 3 hrs with substrate by MALDI-TOF-MS analysis | ic50 | 0.0043 | uM |
| 1-[3-[4-[(5S)-3,3-dimethyl-1-oxo-2-oxa-9-azaspiro[4.5]decan-9-yl]piperidine-1-carbonyl]-6-methylthieno[2,3-b]pyridin-2-yl]-3-methylurea | 662187: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay | ic50 | 0.0044 | 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0044 | uM |
| 1’-(7-methyl-1H-indazole-5-carbonyl)-5-propan-2-yloxyspiro[3H-pyrano[3,2-c]pyridine-2,4’-piperidine]-4-one | 476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader | ic50 | 0.0045 | uM |
| 1’-(7-methyl-1H-indazole-5-carbonyl)-6-(1H-pyrazol-5-yl)spiro[3H-chromene-2,4’-piperidine]-4-one | 476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader | ic50 | 0.0045 | uM |
| 1’-(3,7-dimethyl-2H-indazole-5-carbonyl)-2-(2-methylbutan-2-yl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 | 0.0045 | uM |
| 1-[3-[4-(1,3-dioxospiro[5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazine-2,3’-piperidine]-1’-yl)piperidine-1-carbonyl]-7-methoxy-1-benzothiophen-2-yl]-3-ethylurea | 672140: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay | ic50 | 0.0049 | uM |
| N-[4-[2-[4-(cyclopentylmethoxy)phenoxy]-1,3-thiazol-5-yl]but-3-yn-2-yl]acetamide | 276641: Inhibition of human recombinant ACC2 | ic50 | 0.0050 | uM |
| 4-[6-(dimethylamino)-4-(7-oxo-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-1’-carbonyl)-2-pyridinyl]benzoic acid | 1675564: Inhibition of recombinant human ACC2 using acetyl coA as substrate incubated for 1 hr by transcreener fluorescence polarization assay | ic50 | 0.0050 | uM |
| 2-tert-butyl-1’-(3-chloro-1H-pyrrolo[3,2-b]pyridine-6-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 |
| 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0051 | uM |
| 1-[3-[4-(1,3-dioxospiro[5,6,7,8,9,10-hexahydropyrazolo[1,2-a]diazocine-2,3’-piperidine]-1’-yl)piperidine-1-carbonyl]-1-benzothiophen-2-yl]-3-ethylurea | 672140: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay | ic50 | 0.0051 | uM |
| 1-[3-[4-[(5S)-3,3-dimethyl-1-oxo-2-oxa-9-azaspiro[4.5]decan-9-yl]piperidine-1-carbonyl]-1-benzothiophen-2-yl]-3-ethylurea | 626469: Inhibition of human ACC2 | ic50 | 0.0054 | uM |
| N-[(1S)-1-[3-[(2S)-4-(4-ethoxy-2-methylphenyl)-2-methylpiperazin-1-yl]-1,2,4-oxadiazol-5-yl]ethyl]acetamide | 1065780: Inhibition of human ACC2 expressed in CHOK1 cells assessed as acetylCoA to malonylCoA conversion after 1 hr by LC-MS/MS analysis | ic50 | 0.0054 | uM |
| [3-[4-(1,3-dioxospiro[5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazine-2,3’-piperidine]-1’-yl)piperidine-1-carbonyl]-7-methoxy-1-benzothiophen-2-yl]urea | 672140: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay | ic50 | 0.0059 | uM |
| N-[4-[4-(4-propan-2-yloxyphenoxy)phenyl]but-3-yn-2-yl]acetamide | 267164: Inhibition of human recombinant ACC2 expressed in baculovirus/sf9 system | ic50 | 0.0060 | uM |
| 2-tert-butyl-1’-[1-(methylamino)isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 |
| 2-tert-butyl-1’-(3,7-dimethyl-2H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one | 767839: Inhibition of human ACC2 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 |
| 1-[3-[4-(1,3-dioxospiro[5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazine-2,3’-piperidine]-1’-yl)piperidine-1-carbonyl]-7-methoxy-1-benzothiophen-2-yl]-3-methylurea | 672140: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay | ic50 | 0.0061 | uM |
| 1’-(7-methyl-1H-indazole-5-carbonyl)-6-(1-methylpyrazol-3-yl)spiro[3H-chromene-2,4’-piperidine]-4-one | 476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader | ic50 | 0.0061 | 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0062 | 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0062 | 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 | 2262886: Inhibition of recombinant human ACC2 using acetyl-Co A as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay | ic50 | 0.0064 | uM |
| 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1’-(7-methyl-1H-indazole-5-carbonyl)spiro[3H-chromene-2,4’-piperidine]-4-one | 476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader | ic50 | 0.0064 | uM |
| 5-methoxy-1’-(7-methyl-1H-indazole-5-carbonyl)spiro[3H-chromene-2,4’-piperidine]-4-one | 476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader | ic50 | 0.0065 | uM |
| 2-tert-butyl-1’-(2,7-dimethyl-3H-benzimidazole-5-carbonyl)spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one | 648875: Inhibition of human Acetyl-CoA carboxylase 2 expressed in CHO cells after 1 hr by fluorescence assay | ic50 | 0.0066 | uM |
CTD chemical–gene interactions
78 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Benzo(a)pyrene | affects methylation, decreases expression | 3 |
| sodium arsenite | decreases expression, affects cotreatment, increases abundance | 2 |
| Acetaminophen | decreases expression | 2 |
| Arsenic | affects methylation, affects cotreatment, decreases expression, increases abundance | 2 |
| Cisplatin | increases expression, decreases expression | 2 |
| Dexamethasone | increases expression, affects cotreatment | 2 |
| Lead | affects methylation, decreases expression | 2 |
| Nickel | decreases expression | 2 |
| Phenylmercuric Acetate | affects cotreatment, decreases expression | 2 |
| Tobacco Smoke Pollution | decreases expression | 2 |
| Tretinoin | increases expression, decreases expression, affects cotreatment | 2 |
| Valproic Acid | affects expression, affects methylation, decreases expression | 2 |
| Cyclosporine | decreases expression, increases expression | 2 |
| Aflatoxin B1 | affects expression, decreases expression | 2 |
| GSK-J4 | decreases expression | 1 |
| bisphenol F | increases expression | 1 |
| dicrotophos | increases expression | 1 |
| methylmercuric chloride | decreases expression | 1 |
| methyleugenol | decreases expression | 1 |
| beta-thujone | affects cotreatment, increases expression | 1 |
| bisphenol A | increases expression | 1 |
| spathulenol | affects cotreatment, increases expression | 1 |
| arsenite | affects binding, decreases reaction | 1 |
| mono-(2-ethylhexyl)phthalate | increases expression | 1 |
| tris(1,3-dichloro-2-propyl)phosphate | decreases expression | 1 |
| linalool | increases expression, affects cotreatment | 1 |
| perfluorooctanoic acid | decreases expression | 1 |
| caryophyllene | affects cotreatment, increases expression | 1 |
| ferrous chloride | decreases expression | 1 |
| AICA ribonucleotide | increases phosphorylation | 1 |
ChEMBL screening assays
81 unique, capped per target: 81 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1110301 | Binding | Inhibition of human recombinant ACC1/2 | (4-Piperidinyl)-piperazine: a new platform for acetyl-CoA carboxylase inhibitors. — *Bioorg Med Chem Lett* |
Clinical trials (associated diseases)
Via MONDO — disease-level, not drug-specific.
showing 60 of 300 trials:
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00417066 | Phase 4 | COMPLETED | Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders |
| NCT00732693 | Phase 4 | COMPLETED | Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure |
| NCT00837616 | Phase 4 | COMPLETED | Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism |
| NCT01853501 | Phase 4 | UNKNOWN | Effects of ADSC Therapy in Women With POF |
| NCT02783937 | Phase 4 | COMPLETED | Filgrastim for Premature Ovarian Insufficiency |
| NCT03535480 | Phase 4 | UNKNOWN | Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure |
| NCT00391261 | Phase 4 | COMPLETED | An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications. |
| NCT01028820 | Phase 4 | COMPLETED | FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders |
| NCT01333865 | Phase 4 | COMPLETED | A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders |
| NCT01337700 | Phase 4 | COMPLETED | Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism |
| NCT01695200 | Phase 4 | COMPLETED | Omega-3 Fatty Acids in Autism Spectrum Disorders |
| NCT02096952 | Phase 4 | COMPLETED | Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD |
| NCT02235467 | Phase 4 | COMPLETED | Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism |
| NCT02940574 | Phase 4 | COMPLETED | Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders |
| NCT03333629 | Phase 4 | COMPLETED | Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes |
| NCT03337646 | Phase 4 | COMPLETED | Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism |
| NCT03538431 | Phase 4 | COMPLETED | Improving Driving in Young People With Autism Spectrum Disorders |
| NCT03757585 | Phase 4 | COMPLETED | Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD) |
| NCT04903353 | Phase 4 | COMPLETED | Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole |
| NCT05063656 | Phase 4 | COMPLETED | Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin |
| NCT05146245 | Phase 4 | UNKNOWN | Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT |
| NCT05916339 | Phase 4 | RECRUITING | AWARE: Management of ADHD in Autism Spectrum Disorder |
| NCT05954052 | Phase 4 | TERMINATED | A Study of Glutathione in Children With Autism Spectrum Disorder |
| NCT06853665 | Phase 4 | RECRUITING | The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine |
| NCT07054697 | Phase 4 | COMPLETED | Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder |
| NCT07161804 | Phase 4 | COMPLETED | Pilot RCT Using Homeopathic Medicines in ASD |
| NCT07439042 | Phase 4 | RECRUITING | Buspirone for Anxiety in Autistic Youth |
| NCT07770152 | Phase 4 | NOT_YET_RECRUITING | Semaglutide in Youth With Autism Spectrum Disorder |
| NCT00140998 | Phase 3 | COMPLETED | Estrogen Treatment (Oral vs. Patches) in Turner Syndrome |
| NCT01302964 | Phase 3 | COMPLETED | Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders |
| NCT01706523 | Phase 3 | TERMINATED | Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders |
| NCT01825798 | Phase 3 | COMPLETED | Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD) |
| NCT01972074 | Phase 3 | COMPLETED | Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder |
| NCT02985749 | Phase 3 | COMPLETED | A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder |
| NCT03197922 | Phase 3 | COMPLETED | Treatment of Encopresis in Children With Autism Spectrum Disorders |
| NCT03504917 | Phase 3 | TERMINATED | A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension |
| NCT03553875 | Phase 3 | TERMINATED | Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions |
| NCT03640156 | Phase 3 | COMPLETED | Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin |
| NCT03715153 | Phase 3 | TERMINATED | Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder. |
| NCT03715166 | Phase 3 | TERMINATED | Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder |
| NCT04233502 | Phase 3 | WITHDRAWN | Efficacy and Safety of Slenyto for Insomnia in Children With ASD |
| NCT04578756 | Phase 3 | COMPLETED | Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder |
| NCT04623398 | Phase 3 | COMPLETED | Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency) |
| NCT04725383 | Phase 3 | TERMINATED | Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders |
| NCT05212493 | Phase 3 | COMPLETED | The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder |
| NCT05361707 | Phase 3 | UNKNOWN | Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances |
| NCT05439616 | Phase 3 | COMPLETED | Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD |
| NCT06229210 | Phase 3 | RECRUITING | Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder |
| NCT06333964 | Phase 3 | COMPLETED | A Study to Evaluate the Efficacy and Safety of AST-001 in ASD Children |
| NCT07257939 | Phase 3 | NOT_YET_RECRUITING | NTI164 in Autism Spectrum Disorder |
| NCT07655115 | Phase 3 | RECRUITING | Single Dose Double-blind, Placebo-controlled Cross-over (SDDBPCCO) Shiftability Study, Will be Followed by a 10-week Open-label Study With Arbaclofen (4 Weeks of Titration and Then 6 Weeks of Active/Stable Treatment). The Effects of Arbaclofen on Target EEG and ERG Metrics Will be Associated With th |
| NCT00001951 | Phase 2 | COMPLETED | Hormone Replacement in Young Women With Premature Ovarian Failure |
| NCT00370019 | Phase 2 | WITHDRAWN | Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure |
| NCT00429494 | Phase 2 | COMPLETED | GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients |
| NCT03816852 | Phase 2 | SUSPENDED | The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency |
| NCT04536467 | Phase 2 | UNKNOWN | Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients |
| NCT06117982 | Phase 2 | COMPLETED | The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency |
| NCT00251303 | Phase 2 | COMPLETED | Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders |
| NCT00614198 | Phase 2 | COMPLETED | ScanBrit Dietary Intervention in Autism |
| NCT00619190 | Phase 2 | COMPLETED | Study of Aripiprazole to Treat Children and Adolescents With Autism |
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for ACACB across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
- Associated diseases: isolated cleft palate
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): cervical carcinoma, hyper-IgM syndrome type 5, isolated cleft palate