PRKAG3
gene geneOn this page
Summary
PRKAG3 (protein kinase AMP-activated non-catalytic subunit gamma 3, HGNC:9387) is a protein-coding gene on chromosome 2q35, encoding 5’-AMP-activated protein kinase subunit gamma-3 (Q9UGI9). AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism.
The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit is one of the gamma regulatory subunits of AMPK. It is dominantly expressed in skeletal muscle. Studies of the pig counterpart suggest that this subunit may play a key role in the regulation of energy metabolism in skeletal muscle.
Source: NCBI Gene 53632 — RefSeq curated summary.
At a glance
- Gene–disease (curated): skeletal muscle glycogen content and metabolism quantitative trait locus (Moderate, GenCC)
- GWAS associations: 9
- Clinical variants (ClinVar): 101 total
- Druggable target: yes — 1 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_017431
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:9387 |
| Approved symbol | PRKAG3 |
| Name | protein kinase AMP-activated non-catalytic subunit gamma 3 |
| Location | 2q35 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000115592 |
| Ensembl biotype | protein_coding |
| OMIM | 604976 |
| Entrez | 53632 |
Gene structure
Transcript identifiers
Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron
ENST00000430489, ENST00000439262, ENST00000470307, ENST00000490971, ENST00000529249
RefSeq mRNA: 1 — MANE Select: NM_017431
NM_017431
CCDS: CCDS2424
Canonical transcript exons
ENST00000439262 — 14 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000922334 | 218828004 | 218828062 |
| ENSE00002272237 | 218823646 | 218823878 |
| ENSE00002295777 | 218824222 | 218824368 |
| ENSE00002411049 | 218827833 | 218827878 |
| ENSE00003458286 | 218827247 | 218827373 |
| ENSE00003470790 | 218824539 | 218824576 |
| ENSE00003507913 | 218828519 | 218828600 |
| ENSE00003508220 | 218831336 | 218831375 |
| ENSE00003512383 | 218829978 | 218830381 |
| ENSE00003560316 | 218827575 | 218827629 |
| ENSE00003617063 | 218826928 | 218827093 |
| ENSE00003754062 | 218830746 | 218830901 |
| ENSE00003978138 | 218831738 | 218831803 |
| ENSE00003978139 | 218822308 | 218823076 |
Expression profiles
Bgee: expression breadth broad, 94 present calls, max score 93.61.
FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2191 / max 33.9672, expressed in 63 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 33991 | 0.1515 | 42 |
| 33992 | 0.0510 | 29 |
| 33990 | 0.0166 | 13 |
Top tissues by expression
215 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| hindlimb stylopod muscle | UBERON:0004252 | 93.61 | gold quality |
| gastrocnemius | UBERON:0001388 | 91.06 | gold quality |
| muscle of leg | UBERON:0001383 | 90.31 | gold quality |
| tibialis anterior | UBERON:0001385 | 88.96 | silver quality |
| skeletal muscle tissue | UBERON:0001134 | 88.67 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 87.71 | silver quality |
| quadriceps femoris | UBERON:0001377 | 87.16 | silver quality |
| vastus lateralis | UBERON:0001379 | 86.17 | silver quality |
| pancreatic ductal cell | CL:0002079 | 85.42 | silver quality |
| biceps brachii | UBERON:0001507 | 84.69 | silver quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 84.10 | silver quality |
| deltoid | UBERON:0001476 | 83.92 | silver quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 83.12 | gold quality |
| muscle tissue | UBERON:0002385 | 80.61 | gold quality |
| ileal mucosa | UBERON:0000331 | 70.92 | silver quality |
| epithelial cell of pancreas | CL:0000083 | 67.05 | gold quality |
| body of tongue | UBERON:0011876 | 63.84 | gold quality |
| cerebellar vermis | UBERON:0004720 | 61.75 | gold quality |
| apex of heart | UBERON:0002098 | 60.31 | gold quality |
| tongue | UBERON:0001723 | 58.77 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 58.44 | gold quality |
| pharyngeal mucosa | UBERON:0000355 | 56.49 | gold quality |
| kidney epithelium | UBERON:0004819 | 56.34 | gold quality |
| jejunum | UBERON:0002115 | 56.03 | silver quality |
| inferior vagus X ganglion | UBERON:0005363 | 55.80 | gold quality |
| thymus | UBERON:0002370 | 55.73 | silver quality |
| upper leg skin | UBERON:0004262 | 55.11 | silver quality |
| ventral tegmental area | UBERON:0002691 | 55.08 | gold quality |
| thoracic aorta | UBERON:0001515 | 55.01 | gold quality |
| layer of synovial tissue | UBERON:0007616 | 54.85 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 0.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 2.27 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): BHLHE40
miRNA regulators (miRDB)
47 targeting PRKAG3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-3064-3P | 100.00 | 70.09 | 1254 |
| HSA-MIR-4692 | 100.00 | 67.32 | 2066 |
| HSA-MIR-3185 | 99.99 | 68.12 | 1959 |
| HSA-MIR-4514 | 99.99 | 67.10 | 1870 |
| HSA-MIR-1184 | 99.99 | 68.19 | 1458 |
| HSA-MIR-103A-3P | 99.98 | 69.14 | 1595 |
| HSA-MIR-107 | 99.98 | 69.14 | 1595 |
| HSA-MIR-9902 | 99.89 | 69.15 | 2250 |
| HSA-MIR-6780A-5P | 99.88 | 66.69 | 2776 |
| HSA-MIR-4728-5P | 99.85 | 69.39 | 4718 |
| HSA-MIR-4447 | 99.85 | 67.81 | 2900 |
| HSA-MIR-6785-5P | 99.82 | 68.68 | 4428 |
| HSA-MIR-6842-5P | 99.80 | 67.54 | 1587 |
| HSA-MIR-7110-5P | 99.80 | 67.84 | 1712 |
| HSA-MIR-149-3P | 99.72 | 68.22 | 3963 |
| HSA-MIR-6883-5P | 99.69 | 68.05 | 3785 |
| HSA-MIR-7157-5P | 99.66 | 69.33 | 1829 |
| HSA-MIR-6752-5P | 99.59 | 67.32 | 1243 |
| HSA-MIR-4310 | 99.59 | 68.84 | 2527 |
| HSA-MIR-203A-3P | 99.49 | 70.56 | 2806 |
| HSA-MIR-1224-5P | 99.48 | 65.59 | 803 |
| HSA-MIR-1275 | 99.47 | 67.90 | 2749 |
| HSA-MIR-3915 | 99.45 | 68.49 | 1905 |
| HSA-MIR-4786-3P | 99.36 | 68.35 | 1390 |
| HSA-MIR-4293 | 99.22 | 65.46 | 1263 |
| HSA-MIR-4291 | 99.20 | 68.88 | 2969 |
| HSA-MIR-6815-3P | 99.13 | 68.98 | 1530 |
| HSA-MIR-4254 | 99.11 | 65.15 | 1315 |
| HSA-MIR-8070 | 99.07 | 69.30 | 1303 |
| HSA-MIR-4478 | 99.07 | 65.16 | 2320 |
Literature-anchored findings (GeneRIF, showing 15)
- Functional analysis of the pig counterpart. (PMID:10818001)
- the observation that the AMPKgamma3 isoform is expressed primarily in white skeletal muscle, in which it is the predominant gamma-isoform, strongly suggests that gamma3 has a key role in this tissue (PMID:14559719)
- role of the AMPKgamma3 isoform in exercise-induced metabolic and gene regulatory responses in skeletal muscle (PMID:16306365)
- data show that different mutations in gamma3 exert different effects on allosteric regulation of alpha2beta2gamma3 complex by AMP, whereas we find no evidence for their role in regulating the level of phosphorylation of alpha2 by upstream kinases. (PMID:17518971)
- Genetic variability in PRKAG3 does not seem to have a major effect on glucose metabolism, but play a role in lipoprotein metabolism in humans. (PMID:17701023)
- identified for the first time a mutation in the skeletal muscle-specific regulatory gamma(3) subunit of AMPK in humans (PMID:17878938)
- Variants in genes for AMPKalpha2 and AMPKgamma3 were not associated with PCOS or its component traits. (PMID:19574280)
- Purification and characterization of truncated human AMPK alpha 2 beta 2 gamma 3 heterotrimer from baculovirus-infected insect cells (PMID:19836452)
- Through the enhancement of skeletal muscle glucose uptake and increased mitochondrial content, the R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)gamma(3)may significantly enhance exercise performance. (PMID:20473479)
- Low PRKAA2 expression is associated with follicular lymphoma. (PMID:23396962)
- PRKAG3-230 may be associated with sporadic Wolff-Parkinson-White (WPW) syndrome in a Taiwanese population. (PMID:27866917)
- Data suggest different gamma-isoforms in AMPK can have different effects on enzyme activation; here, activation of AMPK by compound 991 is greater if AMPK contains PRKAG2 versus PRKAG1 or PRKAG3. (PMID:28302767)
- The mTOR pathway was significantly associated with overall and estrogen receptor-negative (ER-) breast cancer risk (P = 0.003 and 0.03, respectively). PRKAG3 (Padj = 0.0018) and RPS6KA3 (Padj = 0.061) were the leading genes for the associations with overall breast cancer risk and ER- breast cancer risk, respectively. (PMID:28582508)
- AMPKgamma3 Controls Muscle Glucose Uptake in Recovery From Exercise to Recapture Energy Stores. (PMID:37506328)
- The human AMPKgamma3 R225W mutation negatively impacts site-1 nucleotide binding and does not enhance basal AMPKgamma3-associated activity nor glycogen production in human or mouse skeletal muscle. (PMID:39171449)
Cross-species orthologs
6 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | prkag3b | ENSDARG00000000369 |
| danio_rerio | prkag3a | ENSDARG00000017537 |
| mus_musculus | Prkag3 | ENSMUSG00000006542 |
| rattus_norvegicus | Prkag3 | ENSRNOG00000017248 |
| caenorhabditis_elegans | WBGENE00020633 | |
| caenorhabditis_elegans | WBGENE00021527 |
Paralogs (2): PRKAG2 (ENSG00000106617), PRKAG1 (ENSG00000181929)
Protein
Protein identifiers
5’-AMP-activated protein kinase subunit gamma-3 — Q9UGI9 (reviewed: Q9UGI9)
All UniProt accessions (3): Q9UGI9, B4DUK8, C9JIC7
UniProt curated annotations — full annotation on UniProt →
Function. AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. AMPK also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. The AMPK gamma3 subunit is a non-catalytic subunit with a regulatory role in muscle energy metabolism. It mediates binding to AMP, ADP and ATP, leading to AMPK activation or inhibition: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.
Subunit / interactions. AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.
Tissue specificity. Skeletal muscle, with weak expression in heart and pancreas.
Post-translational modifications. Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated protein kinase (AMPK) activity.
Domain organisation. The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1. The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2’- and 3’-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.
Polymorphism. Genetic variation in PRKAG3 defines the skeletal muscle glycogen content and metabolism quantitative trait locus (SMGMQTL) [MIM:619030]. Muscle fibers from carriers of variant Trp-225 have approximately 90% more muscle glycogen content than controls and decreased levels of intramuscular triglyceride.
Similarity. Belongs to the 5’-AMP-activated protein kinase gamma subunit family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q9UGI9-1 | 1 | yes |
| Q9UGI9-2 | 2 |
RefSeq proteins (1): NP_059127* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000644 | CBS_dom | Domain |
| IPR046342 | CBS_dom_sf | Homologous_superfamily |
| IPR050511 | AMPK_gamma/SDS23_families | Family |
Pfam: PF00571
Enzyme classification (BRENDA):
- EC 2.7.11.31 — [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase (BRENDA: 25 organisms, 266 substrates, 134 inhibitors, 51 Km, 0 kcat entries)
Substrate kinetics (BRENDA)
19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| ATP | 0.02–0.4168 | 15 |
| BIOTIN-GGHMRSAMSGLHLVKRR-NH2 | 0.0267–0.1214 | 6 |
| ACETYL-COA CARBOXYLASE | — | 4 |
| HMGSAMSGLHLVKRR | 0.573–2.316 | 2 |
| HMHSAMSGLHLVKRR | 0.118–0.428 | 2 |
| HMKSAMSGLHLVKRR | 0.111–0.133 | 2 |
| HMRSAGSGLHLVKRR | 0.069–0.07 | 2 |
| HMRSAMSGLHGVKRR | 0.013–0.096 | 2 |
| HMRSAMSGLHLGKRR | 0.038–0.042 | 2 |
| HMRSAMSGLHLVKRR | 0.0498–0.091 | 2 |
| HMRSAMTGLHGVKRR | 0.034–0.065 | 2 |
| HGRSAMSGLHLVKRR | 0.0404 | 1 |
| HISTONE | 0.005 | 1 |
| HISTONE H1 | 0.0029 | 1 |
| HMRSAMSGLHGGKRR | 0.049 | 1 |
UniProt features (69 total): binding site 35, sequence variant 20, domain 4, sequence conflict 4, compositionally biased region 2, chain 1, splice variant 1, region of interest 1, short sequence motif 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9UGI9-F1 | 69.68 | 0.43 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Ligand- & substrate-binding residues (35): 225; 225; 225; 240–245; 240–245; 240–245; 285; 285; 285; 306–307; 306–307; 306–307 …
Function
Pathways and Gene Ontology
Reactome pathways
27 pathways
| ID | Pathway |
|---|---|
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane |
| R-HSA-1632852 | Macroautophagy |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation |
| R-HSA-9613354 | Lipophagy |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission |
| R-HSA-112315 | Transmission across Chemical Synapses |
| R-HSA-112316 | Neuronal System |
| R-HSA-1592230 | Mitochondrial biogenesis |
| R-HSA-162582 | Signal Transduction |
| R-HSA-165159 | MTOR signalling |
| R-HSA-1852241 | Organelle biogenesis and maintenance |
| R-HSA-199991 | Membrane Trafficking |
| R-HSA-212436 | Generic Transcription Pathway |
| R-HSA-3700989 | Transcriptional Regulation by TP53 |
| R-HSA-438064 | Post NMDA receptor activation events |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events |
| R-HSA-5633007 | Regulation of TP53 Activity |
| R-HSA-5653656 | Vesicle-mediated transport |
| R-HSA-73857 | RNA Polymerase II Transcription |
| R-HSA-74160 | Gene expression (Transcription) |
| R-HSA-9612973 | Autophagy |
| R-HSA-9663891 | Selective autophagy |
MSigDB gene sets: 185 (showing top):
GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, REACTOME_MEMBRANE_TRAFFICKING, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY
GO Biological Process (12): regulation of glycolytic process (GO:0006110), fatty acid biosynthetic process (GO:0006633), response to muscle activity involved in regulation of muscle adaptation (GO:0014873), cellular response to nutrient levels (GO:0031669), intracellular signal transduction (GO:0035556), cellular response to glucose starvation (GO:0042149), regulation of carbon utilization (GO:0043609), negative regulation of glycogen biosynthetic process (GO:0045719), positive regulation of gluconeogenesis (GO:0045722), regulation of cell cycle (GO:0051726), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)
GO Molecular Function (8): AMP-activated protein kinase activity (GO:0004679), ATP binding (GO:0005524), AMP binding (GO:0016208), protein kinase regulator activity (GO:0019887), protein kinase binding (GO:0019901), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301)
GO Cellular Component (6): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nucleotide-activated protein kinase complex (GO:0031588)
Reactome top-level categories
Rollup of top-17 pathways:
| Category | Pathways |
|---|---|
| Membrane Trafficking | 1 |
| Autophagy | 1 |
| Mitochondrial biogenesis | 1 |
| MTOR signalling | 1 |
| Transcriptional Regulation by TP53 | 1 |
| Regulation of TP53 Activity | 1 |
| Selective autophagy | 1 |
| Post NMDA receptor activation events | 1 |
| Regulation of PD-L1(CD274) Post-translational modification | 1 |
| Transmission across Chemical Synapses | 1 |
| Neuronal System | 1 |
| Organelle biogenesis and maintenance | 1 |
| Signal Transduction | 1 |
| Vesicle-mediated transport | 1 |
| RNA Polymerase II Transcription | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 3 |
| intracellular anatomical structure | 2 |
| adenyl ribonucleotide binding | 2 |
| glycolytic process | 1 |
| regulation of purine nucleotide catabolic process | 1 |
| regulation of generation of precursor metabolites and energy | 1 |
| regulation of carbohydrate catabolic process | 1 |
| regulation of ATP metabolic process | 1 |
| fatty acid metabolic process | 1 |
| lipid biosynthetic process | 1 |
| monocarboxylic acid biosynthetic process | 1 |
| response to muscle activity | 1 |
| regulation of muscle adaptation | 1 |
| response to nutrient levels | 1 |
| cellular response to stimulus | 1 |
| signal transduction | 1 |
| cellular response to starvation | 1 |
| carbon utilization | 1 |
| regulation of response to nutrient levels | 1 |
| glycogen biosynthetic process | 1 |
| regulation of glycogen biosynthetic process | 1 |
| negative regulation of macromolecule biosynthetic process | 1 |
| negative regulation of glycogen metabolic process | 1 |
| gluconeogenesis | 1 |
| regulation of gluconeogenesis | 1 |
| positive regulation of biosynthetic process | 1 |
| positive regulation of glucose metabolic process | 1 |
| cell cycle | 1 |
| regulation of cellular process | 1 |
| primary metabolic process | 1 |
| lipid metabolic process | 1 |
| monocarboxylic acid metabolic process | 1 |
| protein serine/threonine kinase activity | 1 |
| AMP binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| anion binding | 1 |
| cation binding | 1 |
| protein kinase activity | 1 |
| kinase regulator activity | 1 |
| protein kinase binding | 1 |
Protein interactions and networks
STRING
2542 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| PRKAG3 | PRKAB1 | Q9Y478 | 925 |
| PRKAG3 | PRKAB2 | O43741 | 887 |
| PRKAG3 | PRKAA1 | Q13131 | 860 |
| PRKAG3 | PHKB | Q93100 | 815 |
| PRKAG3 | PRKAA2 | P54646 | 802 |
| PRKAG3 | H7C2H4 | H7C2H4 | 787 |
| PRKAG3 | PHKA1 | P46020 | 759 |
| PRKAG3 | P0DN79 | P0DN79 | 758 |
| PRKAG3 | PYGM | P11217 | 645 |
| PRKAG3 | PHKG1 | Q16816 | 600 |
| PRKAG3 | PRKAG1 | P54619 | 582 |
| PRKAG3 | RYR1 | P21817 | 544 |
| PRKAG3 | PRKAG2 | Q9UGJ0 | 470 |
| PRKAG3 | OR3A2 | P47893 | 458 |
| PRKAG3 | TELO2 | Q9Y4R8 | 450 |
IntAct
13 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| PRKAG3 | PRKAB2 | psi-mi:“MI:0914”(association) | 0.800 |
| PRKAB2 | PRKAG3 | psi-mi:“MI:0915”(physical association) | 0.800 |
| KRTAP19-5 | PRKAG3 | psi-mi:“MI:0915”(physical association) | 0.560 |
| PRKAG3 | PFDN6 | psi-mi:“MI:0914”(association) | 0.530 |
| Klc1 | PRKAG3 | psi-mi:“MI:0915”(physical association) | 0.400 |
| Klc2 | PRKAG3 | psi-mi:“MI:0915”(physical association) | 0.400 |
| PRKAG3 | CNOT1 | psi-mi:“MI:0914”(association) | 0.350 |
| PRKAG3 | KRTAP19-5 | psi-mi:“MI:0915”(physical association) | 0.000 |
| PRKAG3 | PRKAB2 | psi-mi:“MI:0915”(physical association) | 0.000 |
BioGRID (103): BRCA1 (Two-hybrid), PRKAB2 (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), PRKAA1 (Affinity Capture-MS), PRKAA2 (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS), PRKAB2 (Two-hybrid), KRTAP19-5 (Two-hybrid), PRKAA2 (Affinity Capture-MS), PRKAA1 (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), PRKAB2 (Affinity Capture-MS), SPTLC2 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS)
ESM2 similar proteins: A0A0B7P9G0, A0A131MCZ8, A3QM97, I1MGE5, O14145, O23969, O54950, O59781, O74427, P00927, P0DH79, P12904, P15001, P30733, P34094, P39722, P54619, P55004, P58108, P80385, P93673, Q09138, Q09826, Q0WLC7, Q10343, Q5R4S0, Q623S8, Q6C2J1, Q6C5K4, Q6CUE1, Q6CY37, Q6FIR8, Q758X6, Q75EC0, Q7PL76, Q80YE7, Q8GXI9, Q91WG5, Q9CAR3, Q9FMV3
Diamond homologs: O54950, P12904, P54619, P58108, P80385, Q09138, Q10343, Q2LL38, Q54H97, Q5R4S0, Q8BGM7, Q8T277, Q91WG5, Q944A6, Q9MYP4, Q9P869, Q9UGI9, Q9UGJ0, Q58799, O67820
SIGNOR signaling
3 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| PRKAG3 | “form complex” | AMPK | binding |
| ULK1 | down-regulates | PRKAG3 | phosphorylation |
| ULK2 | down-regulates | PRKAG3 | phosphorylation |
Disease & clinical
Clinical variants and AI predictions
ClinVar
101 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 86 |
| Likely benign | 8 |
| Benign | 5 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
2075 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 2:218824250:T:TA | donor_gain | 1.0000 |
| 2:218824251:C:A | donor_gain | 1.0000 |
| 2:218824286:C:CA | donor_gain | 1.0000 |
| 2:218824363:CAGG:C | acceptor_gain | 1.0000 |
| 2:218824364:AGGTG:A | acceptor_gain | 1.0000 |
| 2:218824365:GGTG:G | acceptor_gain | 1.0000 |
| 2:218824366:GTG:G | acceptor_gain | 1.0000 |
| 2:218824367:TG:T | acceptor_gain | 1.0000 |
| 2:218824368:GC:G | acceptor_loss | 1.0000 |
| 2:218824369:C:CA | acceptor_loss | 1.0000 |
| 2:218824369:C:CC | acceptor_gain | 1.0000 |
| 2:218824375:C:CT | acceptor_gain | 1.0000 |
| 2:218824376:A:T | acceptor_gain | 1.0000 |
| 2:218826911:AT:A | donor_gain | 1.0000 |
| 2:218826912:T:TA | donor_gain | 1.0000 |
| 2:218827241:GCTTA:G | donor_loss | 1.0000 |
| 2:218827244:TAC:T | donor_loss | 1.0000 |
| 2:218827245:A:AC | donor_gain | 1.0000 |
| 2:218827245:A:T | donor_loss | 1.0000 |
| 2:218827246:C:CC | donor_gain | 1.0000 |
| 2:218827246:CA:C | donor_gain | 1.0000 |
| 2:218827246:CAAAG:C | donor_gain | 1.0000 |
| 2:218827369:ACAGG:A | acceptor_gain | 1.0000 |
| 2:218827370:CAGG:C | acceptor_gain | 1.0000 |
| 2:218827370:CAGGC:C | acceptor_gain | 1.0000 |
| 2:218827371:AGG:A | acceptor_gain | 1.0000 |
| 2:218827372:GG:G | acceptor_gain | 1.0000 |
| 2:218827374:C:CC | acceptor_gain | 1.0000 |
| 2:218827628:CT:C | acceptor_gain | 1.0000 |
| 2:218827630:C:CC | acceptor_gain | 1.0000 |
AlphaMissense
0 scored. Top likely-pathogenic:
dbSNP variants (sampled 300 via entrez): RS1000348946 (2:218832412 G>A,C), RS1000816849 (2:218833582 C>G), RS1000934 (2:218826799 T>A,G), RS1000935 (2:218826772 T>G), RS1000936 (2:218826667 A>G), RS1000958374 (2:218828393 C>G,T), RS1000959106 (2:218825259 C>G), RS1001083764 (2:218822308 T>C,G), RS1001196703 (2:218829865 A>G,T), RS1001322594 (2:218824144 G>A), RS1001334160 (2:218831129 C>A), RS1001416768 (2:218823941 G>A,T), RS1001731486 (2:218829542 G>A), RS1002985428 (2:218822222 A>G), RS1003135442 (2:218825287 G>T)
Disease associations
OMIM: gene MIM:604976 | disease phenotypes:
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| skeletal muscle glycogen content and metabolism quantitative trait locus | Moderate | Autosomal dominant |
Mondo (1): (MONDO:0033571)
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
9 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST002899_42 | HDL cholesterol | 6.000000e-12 |
| GCST006661_114 | Male-pattern baldness | 2.000000e-16 |
| GCST010241_110 | Apolipoprotein A1 levels | 3.000000e-39 |
| GCST010242_520 | HDL cholesterol levels | 2.000000e-57 |
| GCST010244_33 | Triglyceride levels | 3.000000e-57 |
| GCST011345_32 | Triglyceride levels | 4.000000e-08 |
| GCST011348_45 | High density lipoprotein cholesterol levels | 1.000000e-14 |
| GCST90002388_311 | Lymphocyte count | 5.000000e-19 |
| GCST90002389_3 | Lymphocyte percentage of white cells | 2.000000e-18 |
EFO canonical traits (5, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004612 | high density lipoprotein cholesterol measurement |
| EFO:0004614 | apolipoprotein A 1 measurement |
| EFO:0004530 | triglyceride measurement |
| EFO:0004587 | lymphocyte count |
| EFO:0007993 | lymphocyte percentage of leukocytes |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (5): CHEMBL2096907 (PROTEIN COMPLEX GROUP), CHEMBL3038452 (PROTEIN COMPLEX), CHEMBL3038457 (PROTEIN COMPLEX), CHEMBL4106159 (PROTEIN COMPLEX), CHEMBL4106162 (PROTEIN COMPLEX)
Molecules with ChEMBL bioactivity
1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 165,316 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL752 | ADENOSINE PHOSPHATE | 4 | 165,316 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — AMPK subfamily
ChEMBL bioactivities
376 potent at pChembl≥5 of 425 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
PubChem BioAssay actives
135 with measured affinity, of 1013 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[(4-fluorophenyl)methyl]piperazine-1-carbonyl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0010 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[fluoro-(4-fluorophenyl)methyl]piperidine-1-carbonyl]pyridine-2-carboxamide | 1855899: Activation of AMPK in human HepG2 cells assessed as reduction in mitochondrial ATP production incubated for 1 hr | ic50 | 0.0010 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[(4-fluorophenyl)methyl]-3,3-dimethylpiperazine-1-carbonyl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0010 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[(4-methoxyphenyl)methyl]piperidine-1-carbonyl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0010 | uM |
| (3R,3aR,6R,6aR)-6-[[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol | 1552802: Activation of recombinant human AMPK expressed in Sf9 cells using SAMS peptide as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence based assay | ec50 | 0.0010 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-fluoro-4-(4-fluorobenzoyl)piperidine-1-carbonyl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0020 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-(4-fluorobenzoyl)piperidine-1-carbonyl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0020 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide | 1855899: Activation of AMPK in human HepG2 cells assessed as reduction in mitochondrial ATP production incubated for 1 hr | ic50 | 0.0028 | uM |
| 5-[4-(4-cyanophenoxy)piperidine-1-carbonyl]-N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0030 | uM |
| 2-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]benzene-1,3-diol | 1320702: Activation of human recombinant AMPK alpha2/beta2/gamma3 expressed in African green monkey COS7 cells assessed as increase in biotinylated AAC (1 to 120 residues) peptide phosphorylation at Ser-79 residue measured after 60 mins by Alphascreen assay | ec50 | 0.0040 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-(2,4-difluorophenoxy)piperidine-1-carbonyl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0040 | uM |
| N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide | 1474638: Inhibition of AMPK (unknown origin) using SAMS peptide as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method | ki | 0.0042 | uM |
| [4-[5-[1-[(6-methoxy-3-pyridinyl)methyl]piperidin-4-yl]-1,3,4-oxadiazol-2-yl]phenyl]-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]methanone;bis(4-methylbenzenesulfonic acid) | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0045 | uM |
| 4-[(4-methoxyphenyl)methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperazine-1-carboxamide | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0047 | uM |
| 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxylic acid | 1474638: Inhibition of AMPK (unknown origin) using SAMS peptide as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method | ki | 0.0049 | uM |
| 5-[4-(4-cyanobenzoyl)piperidine-1-carbonyl]-N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0050 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[2-(4-fluorophenyl)propan-2-yl]piperazine-1-carbonyl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0060 | uM |
| bis(N-cyclohexylcyclohexanamine);[5-(5-oxo-2H-1,2-oxazol-3-yl)furan-2-yl]phosphonic acid | 580978: Activation of human AMPK after 15 mins | ec50 | 0.0063 | uM |
| 4-[[4-(trifluoromethyl)phenyl]methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperazine-1-carboxamide | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0079 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-(2,4-difluorobenzoyl)piperidine-1-carbonyl]pyridine-2-carboxamide | 1855899: Activation of AMPK in human HepG2 cells assessed as reduction in mitochondrial ATP production incubated for 1 hr | ic50 | 0.0080 | uM |
| 6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]-N-[1-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0090 | uM |
| 6-[4-(4-pyrrolidin-1-ylbenzoyl)piperidine-1-carbonyl]-N-[1-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0090 | uM |
| methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxylate | 1474638: Inhibition of AMPK (unknown origin) using SAMS peptide as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method | ki | 0.0092 | uM |
| 1-[(4-methoxyphenyl)methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperidine-4-carboxamide;dihydrochloride | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0110 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-(4-methoxyphenoxy)piperidine-1-carbonyl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0110 | uM |
| 1-[(6-methoxy-3-pyridinyl)methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperidine-4-carboxamide | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0120 | uM |
| N-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-6-[4-(4-pyrrolidin-1-ylbenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0120 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-6-[4-(2,4-difluorophenoxy)piperidine-1-carbonyl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0130 | uM |
| 5-[4-[(4-cyanophenyl)methyl]piperidine-1-carbonyl]-N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0140 | uM |
| 2-[[5-[1-[(4-fluorophenyl)methyl]-3,6-dihydro-2H-pyridin-4-yl]-6-methyl-2-pyridinyl]oxymethyl]-3,5-dimethyl-1H-pyridin-4-one | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0160 | uM |
| 5-(4-benzylpiperazine-1-carbonyl)-N-(1-benzylpiperidin-4-yl)pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0160 | uM |
| [6-[1-[(6-methoxy-3-pyridinyl)methyl]piperidin-4-yl]-1H-benzimidazol-2-yl]-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]methanone;bis(4-methylbenzenesulfonic acid) | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0180 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-6-[4-(2,4-difluorobenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0180 | uM |
| [6-[1-[(6-methoxy-3-pyridinyl)methyl]piperidin-4-yl]-1H-benzimidazol-2-yl]-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]methanone | 1866092: Activation of AMPK (unknown origin) | ec50 | 0.0180 | uM |
| 5-[[6-chloro-5-(4-phenylphenyl)-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid | 1471592: Agonist activity at human recombinant phosphorylated AMPK complex 3 alpha1/beta1/gamma3 expressed in baculovirus infected Sf21 cells assessed as phosphorylation of 5-FAM-labeled SAMS substrate preincubated for 30 mins in presence of AMPK activator followed by substrate addition measured after 60 mins | ec50 | 0.0190 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-6-[4-(4-pyrrolidin-1-ylbenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0200 | uM |
| N-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-6-[4-(4-pyrazol-1-ylbenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0210 | uM |
| 4-[(4-methoxyphenyl)methyl]-N-[3-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperazine-1-carboxamide;dihydrochloride | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0220 | uM |
| 4-[(4-fluorophenyl)methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperazine-1-carboxamide | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0220 | uM |
| 4-benzyl-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperazine-1-carboxamide | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0270 | uM |
| N-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0270 | uM |
| 6-(4-benzylpiperazine-1-carbonyl)-N-(1-benzylpiperidin-4-yl)pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0350 | uM |
| 6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine | 527863: Inhibition of human AMPK alpha-2/beta-1/gamma-1 by Hot Spot filtration binding assay | ic50 | 0.0410 | uM |
| 6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]-N-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0410 | uM |
| 4-[(4-methoxyphenyl)methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]-1,4-diazepane-1-carbonyl]phenyl]piperazine-1-carboxamide;dihydrochloride | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0420 | uM |
| 4-[(4-methoxyphenyl)methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]-1,4-diazepane-1-carboxamide;dihydrochloride | 1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA | ec50 | 0.0460 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[(4-fluorophenyl)-hydroxymethyl]piperidine-1-carbonyl]pyridine-2-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0550 | uM |
| N-[1-[(4-methoxyphenyl)methyl]piperidin-4-yl]-6-[4-(4-pyrrolidin-1-ylbenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0570 | uM |
| 5-[6-[4-(2-morpholin-4-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-1H-pyridin-2-one | 527863: Inhibition of human AMPK alpha-2/beta-1/gamma-1 by Hot Spot filtration binding assay | ic50 | 0.0600 | uM |
| N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-6-[4-(4-pyrazol-1-ylbenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide | 1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr | ec50 | 0.0860 | uM |
CTD chemical–gene interactions
8 total (human), top 8 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| CGP 52608 | affects binding, increases reaction | 1 |
| theaflavin-3,3’-digallate | affects expression | 1 |
| Resveratrol | affects cotreatment, decreases expression | 1 |
| Benzo(a)pyrene | affects methylation, increases methylation | 1 |
| Ivermectin | decreases expression | 1 |
| Ozone | increases abundance, increases expression | 1 |
| Plant Extracts | affects cotreatment, decreases expression | 1 |
| Soot | increases abundance, increases expression | 1 |
ChEMBL screening assays
272 unique, capped per target: 271 binding, 1 functional
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1053698 | Binding | Induction of AMPK phosphorylation in human HepG2 cells by Western blot analysis in presence of 33 mM glucose | Palbinone and triterpenes from Moutan Cortex (Paeonia suffruticosa, Paeoniaceae) stimulate glucose uptake and glycogen synthesis via activation of AMPK in insulin-resistant human HepG2 Cells. — Bioorg Med Chem Lett |
| CHEMBL4649950 | Functional | AMP-dependent Kinase enzyme assay. An in vitro enzyme assay that detects ADP turnover that is directly proportional to AMPK activity. This uses naive AMPK that is activated during the assay with MK-8722 | University of Dundee, Small-Polar-MMV Screening Library |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.