PRKAG2

Summary

PRKAG2 (protein kinase AMP-activated non-catalytic subunit gamma 2, HGNC:9386) is a protein-coding gene on chromosome 7q36.1, encoding 5’-AMP-activated protein kinase subunit gamma-2 (Q9UGJ0). 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.

AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family. Mutations in this gene have been associated with Wolff-Parkinson-White syndrome, familial hypertrophic cardiomyopathy, and glycogen storage disease of the heart. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 51422 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PRKAG2-related cardiomyopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 60
• Clinical variants (ClinVar): 1,429 total — 14 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 56
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_016203

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9386
Approved symbol	PRKAG2
Name	protein kinase AMP-activated non-catalytic subunit gamma 2
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	AAKG, AAKG2, H91620p, WPWS, CMH6
Ensembl gene	ENSG00000106617
Ensembl biotype	protein_coding
OMIM	602743
Entrez	51422

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 15 protein_coding, 12 retained_intron, 7 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000287878, ENST00000392801, ENST00000418337, ENST00000461529, ENST00000474383, ENST00000476632, ENST00000478989, ENST00000479461, ENST00000481434, ENST00000483775, ENST00000485183, ENST00000487375, ENST00000488258, ENST00000491938, ENST00000492843, ENST00000493872, ENST00000650664, ENST00000650851, ENST00000650858, ENST00000650948, ENST00000651188, ENST00000651290, ENST00000651303, ENST00000651378, ENST00000651764, ENST00000651836, ENST00000651954, ENST00000652047, ENST00000652136, ENST00000652159, ENST00000652321, ENST00000652397, ENST00000652572, ENST00000652707, ENST00000652714, ENST00000867883, ENST00000867884, ENST00000867885

RefSeq mRNA: 25 — MANE Select: NM_016203 NM_001040633, NM_001304527, NM_001304531, NM_001363698, NM_001407021, NM_001407022, NM_001407023, NM_001407024, NM_001407026, NM_001407027, NM_001407028, NM_001407029, NM_001407030, NM_001407031, NM_001407032, NM_001407033, NM_001407034, NM_001407035, NM_001407036, NM_001407037, NM_001407038, NM_001407039, NM_001407040, NM_016203, NM_024429

CCDS: CCDS43683, CCDS47752, CCDS5928, CCDS94236

Canonical transcript exons

ENST00000287878 — 16 exons

Exon	Start	End
ENSE00000730269	151564078	151564224
ENSE00000730281	151568716	151568842
ENSE00001139542	151675420	151675637
ENSE00001871898	151556127	151557232
ENSE00003474954	151632069	151632138
ENSE00003477662	151560524	151560617
ENSE00003480707	151572664	151572709
ENSE00003490630	151570171	151570225
ENSE00003517335	151565346	151565383
ENSE00003517433	151786470	151786541
ENSE00003552936	151876507	151877115
ENSE00003608615	151576371	151576452
ENSE00003620860	151781152	151781431
ENSE00003649492	151565720	151565885
ENSE00003687367	151574891	151574949
ENSE00004021517	151595345	151595454

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9542 / max 297.0188, expressed in 1760 samples.

FANTOM5 promoters (32 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86911	8.0479	1673
86917	1.8708	330
86912	1.6290	1047
86963	1.3258	435
86918	0.9881	366
86922	0.8932	220
86960	0.8076	377
86913	0.6679	446
86967	0.5673	271
86966	0.5399	275

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	98.17	gold quality
cardiac atrium	UBERON:0002081	98.07	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.01	gold quality
heart	UBERON:0000948	95.90	gold quality
right coronary artery	UBERON:0001625	95.62	gold quality
heart left ventricle	UBERON:0002084	95.25	gold quality
left coronary artery	UBERON:0001626	95.20	gold quality
cardiac ventricle	UBERON:0002082	95.14	gold quality
myocardium	UBERON:0002349	95.11	gold quality
popliteal artery	UBERON:0002250	95.07	gold quality
tibial artery	UBERON:0007610	95.07	gold quality
mucosa of stomach	UBERON:0001199	94.98	gold quality
nucleus accumbens	UBERON:0001882	94.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.54	gold quality
coronary artery	UBERON:0001621	94.50	gold quality
lower esophagus	UBERON:0013473	94.50	gold quality
apex of heart	UBERON:0002098	94.39	gold quality
monocyte	CL:0000576	94.17	gold quality
mononuclear cell	CL:0000842	94.03	gold quality
caudate nucleus	UBERON:0001873	94.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.01	gold quality
colonic epithelium	UBERON:0000397	93.95	gold quality
aorta	UBERON:0000947	93.83	gold quality
leukocyte	CL:0000738	93.79	gold quality
right lobe of liver	UBERON:0001114	93.02	gold quality
putamen	UBERON:0001874	92.85	gold quality
sural nerve	UBERON:0015488	92.54	gold quality
ascending aorta	UBERON:0001496	92.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.33	gold quality
thoracic aorta	UBERON:0001515	92.31	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	2742.12
E-GEOD-131882	yes	2543.99
E-HCAD-35	yes	61.21
E-ANND-3	yes	9.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting PRKAG2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Identified a novel mutation (Arg531Gly) in the PRKAG2 of AMP-activated protein kinase (AMPK) to be responsible for a syndrome associated with ventricular preexcitation and early onset of atrial fibrillation and conduction disease. (PMID:11748095)
• The role of the causative gene, gamma-2 regulatory subunit (PRKAG2) of AMP-activated protein kinase, in the regulation of the glucose metabolic pathway in muscle suggests that genetic defects in PRKAG2 may induce a cardiac glycogenosis syndrome. (PMID:12015471)
• Three of the mutations studied occur within the cystathionine beta-synthase (CBS) domains of gamma(2). Two of these mutations lead to a marked decrease in AMP dependence, whereas the third reduces AMP sensitivity. (PMID:12397075)
• unlike familial WPW syndrome, constitutional mutation of PRKAG2 is not commonly associated with sporadic WPW syndrome (PMID:12716108)
• mutations affecting PRKAG2 are likely to confer a specific alteration of AMPK function of particular importance in the myocardium (PMID:14519435)
• Transgenic mice expressing human mutant(TG(R302Q)) PRKAG2 gene with the cardiac-specific promoter alpha-myosin heavy chain have ventricular pre-excitation, prolonged QRS, excess cardiac glycogen and a distinct AV accessory pathway. (PMID:15611370)
• The glycogen-storage cardiomyopathy produced by LAMP2 or PRKAG2 mutations resembles hypertrophic cardiomyopathy but is distinguished by electrophysiological abnormalities (PMID:15673802)
• The AMP kinase disease is uncommon in HCM and is characterized by progressive conduction disease and cardiac hypertrophy and includes extracardiac manifestations such as a skeletal myopathy. (PMID:15766830)
• Biochemical characterization of the recombinant R531Q mutant protein showed >100-fold reduction of binding affinities for the regulatory nucleotides AMP and ATP but an enhanced basal activity and increased phosphorylation of the alpha -subunit. (PMID:15877279)
• The PRKAG2 N488I mutation causes inappropriate AMPK activation, which leads to glycogen accumulation and heart conduction system disease when transfected into mice. (PMID:16275868)
• The study describe a 38-year-old man with a new heterozygous PRKAG2 mutation (Ser548Pro) manifesting by hypertrophic cardiomyopathy, severe conduction system abnormalities, and skeletal muscle glycogenosis. (PMID:16487706)
• AMP-activated protein kinase is regulated by a pseudosubstrate sequence on the gamma subunit. (PMID:17255938)
• Altered AMPK gamma 2 subunit activity under normal energetic status remodels the cardiac metabolic network to cause a unique form of glycogen storage disease in transgenic mice. (PMID:17431505)
• four members of the same family with a very similar ECG pattern characterized by conduction defects and mutations in PRKAG2 gene (PMID:17483151)
• Human mutations which disrupt the nucleotide-binding affinity of the gamma2 subunit lead to loss of inhibition by ATP and inappropriate activate AMP-Kinase under resting conditions. (PMID:17990392)
• Gene analysis identified a R302Q mutation of the gamma2 subunit producing AMP protein kinase, coded by the gene PRKAG2, and associated with a heart conduction defect. (PMID:18033003)
• data provide insight into mechanisms of cardiac PRKAG2 disease and suggest that glycogen-storage cardiomyopathy can be modulated by lowering glycogen content in the heart (PMID:18158359)
• REVIEW. Compelling evidence exists that Prkag2 mutations cause a “gain of function” in basal AMPK activity, leading to excessive cellular glucose uptake and pathological glycogen storage in the heart, resulting in a potentially fatal cardiac phenotype. (PMID:18195183)
• Mutational analysis of PRKAG2, LAMP2, and NKX2-5 genes in a cohort of 125 patients with accessory atrioventricular connection. (PMID:19533775)
• Preexcitation associated with the R302Q mutation in PRKAG2 is associated with Mahaim fibers. (PMID:19808419)
• This protein, transfected into a transgenic mouse, activates and mediates cardiac hypertrphic signaling pathways. (PMID:20005292)
• Newly identified polymorphisms (amino acid substitutions) are likely associated with cardiac disease in type 2 diabetic patients. (PMID:20022652)
• PRKAG2 R302Q mutant induces AMPK activation and increases glycogen content in cardiomyocytes. (PMID:20031621)
• The mutation in the PRKAG2 gene was identified as responsible for the familial form of WPW syndrome in this Chinese family. (PMID:20381067)
• no mutations were detected within the coding region of PRKAG2 in Wolff-Parkinson-White syndrome patients (PMID:20561859)
• These two individuals may be considered to suffer from a combination of both a classical hypertrophic cardiomyopathy (due to the two mutations in MYBPC3) and a glycogen storage cardiomyopathy (due to the mutation in PRKAG2). (PMID:21409595)
• found a significant association between the -26C/T polymorphism and cognitive impairment. Moreover, this polymorphism was also related to the presence of diabetes. (PMID:21813245)
• Data indicate that except AMPK-alpha1, expressions of the other five AMPK subunits -alpha2, -beta1, -beta2, -gamma1 and -gamma2 are significantly higher in ovarian carcinomas. (PMID:22897928)
• Single nucleotide polymorphisms in PRKAG2 is associated with drug response in breast cancer. (PMID:23034890)
• The authors found that the gene encoding the gamma2 subunit of AMP-activated protein kinase (AMPK) strongly correlated with Zaire Ebolavirus transduction in the tumor cell panel. (PMID:23115293)
• Its mutation causes AMPK signaling abnormality which leads to cardiac syndrome. (PMID:23778007)
• The PRKAG2 autosomal dominant cardiac syndrome may be commonly characterized by Left Ventricular Hypertrophy, an accessory pathway, and progression to conduction disease requiring implantation of a pacemaker. (PMID:23810891)
• Overexpression of G100S mutation in PRKAG2 causes Wolff-Parkinson-White syndrome in transgenic zebrafish. (PMID:23992123)
• PRKAG2 cardiac syndrome may present with eccentric distribution of LVH, involving focal mid-infero-lateral pattern in the early disease stage, and more diffuse pattern but focusing on interventricular septum in advanced cases. (PMID:26496977)
• mice with chronic AMPK activation, resulting from mutation of the AMPK gamma2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. (PMID:27133129)
• PRKAG2 polymorphism maybe important factor treating hypertensive patients with hydrochlorothiazide. (PMID:27381900)
• Case Report: PRKAG2 missense mutation causing glycogen storage disease and severe biventricular hypertrophy and high-grade atrio-ventricular block. (PMID:27496753)
• As in patients with PRKAG2 cardiomyopathy, iPS cell and mouse models are protected from cardiac fibrosis, and we define a crosstalk between AMPK and post-transcriptional regulation of TGFbeta isoform signaling that has implications in fibrotic forms of cardiomyopathy. (PMID:28009297)
• 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)
• This study of patients with PRKAG2 mutations provides a more comprehensive view of the natural history of this disease and demonstrates a high risk of cardiac complications. Early recognition of this disease appears important to allow an appropriate management. (PMID:28431061)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkag2a	ENSDARG00000012625
mus_musculus	Prkag2	ENSMUSG00000028944
rattus_norvegicus	Prkag2	ENSRNOG00000009085
caenorhabditis_elegans		WBGENE00020633
caenorhabditis_elegans		WBGENE00021527

Paralogs (2): PRKAG3 (ENSG00000115592), PRKAG1 (ENSG00000181929)

Protein

Protein identifiers

5’-AMP-activated protein kinase subunit gamma-2 — Q9UGJ0 (reviewed: Q9UGJ0)

Alternative names: H91620p

All UniProt accessions (15): Q9UGJ0, A0A090N8Q6, A0A384MDZ2, A0A494C026, A0A494C068, A0A494C094, A0A494C0H7, A0A494C155, A0A494C188, A0A494C1K7, A0A494C1R6, E9PGP6, F8WAY3, F8WDA1, F8WDB5

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. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: 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. Isoform B is ubiquitously expressed except in liver and thymus. The highest level is detected in heart with abundant expression in placenta and testis.

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.

Disease relevance. Wolff-Parkinson-White syndrome (WPW) [MIM:194200] A supernormal conduction disorder characterized by the presence of one or several accessory atrioventricular connections, which can lead to episodes of sporadic tachycardia. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, familial hypertrophic, 6 (CMH6) [MIM:600858] A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH6 patients present Wolff-Parkinson-White ventricular preexcitation, enlarged myocytes without myofiber disarray, and glycogen-containing cytosolic vacuoles within cardiomyocytes. The disease is caused by variants affecting the gene represented in this entry. Glycogen storage disease of heart lethal congenital (GSDH) [MIM:261740] Rare disease which leads to death within a few weeks to a few months after birth, through heart failure and respiratory compromise. The disease is caused by variants affecting the gene represented in this entry.

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.

Similarity. Belongs to the 5’-AMP-activated protein kinase gamma subunit family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UGJ0-1	A	yes
Q9UGJ0-2	B
Q9UGJ0-3	C

RefSeq proteins (25): NP_001035723, NP_001291456, NP_001291460, NP_001350627, NP_001393950, NP_001393951, NP_001393952, NP_001393953, NP_001393955, NP_001393956, NP_001393957, NP_001393958, NP_001393959, NP_001393960, NP_001393961, NP_001393962, NP_001393963, NP_001393964, NP_001393965, NP_001393966, NP_001393967, NP_001393968, NP_001393969, NP_057287, NP_077747 (=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

UniProt features (64 total): binding site 32, modified residue 10, sequence variant 9, domain 4, compositionally biased region 3, splice variant 2, chain 1, region of interest 1, short sequence motif 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGJ0-F1	67.24	0.42

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 (32): 302; 302; 302; 302; 317–322; 317–322; 317–322; 362; 362; 362; 383–384; 383–384 …

Post-translational modifications (10): 65, 71, 73, 90, 138, 143, 161, 162, 165, 196

Mutagenesis-validated functional residues (1):

Position	Phenotype
387	induces phosphorylation by ampk.

Function

Pathways and Gene Ontology

Reactome pathways

33 pathways

ID	Pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-1632852	Macroautophagy
R-HSA-163680	AMPK inhibits chREBP transcriptional activation activity
R-HSA-200425	Carnitine shuttle
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-1430728	Metabolism
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-162582	Signal Transduction
R-HSA-163685	Integration of energy metabolism
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-556833	Metabolism of lipids
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)

MSigDB gene sets: 500 (showing top): GOBP_LIPID_MODIFICATION, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GCANCTGNY_MYOD_Q6, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, REACTOME_MEMBRANE_TRAFFICKING, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS

GO Biological Process (16): glycogen metabolic process (GO:0005977), regulation of glycolytic process (GO:0006110), fatty acid biosynthetic process (GO:0006633), ATP biosynthetic process (GO:0006754), sterol biosynthetic process (GO:0016126), regulation of fatty acid metabolic process (GO:0019217), 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), positive regulation of gluconeogenesis (GO:0045722), regulation of fatty acid oxidation (GO:0046320), regulation of D-glucose import across plasma membrane (GO:0046324), regulation of cell cycle (GO:0051726), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (13): AMP-activated protein kinase activity (GO:0004679), cAMP-dependent protein kinase inhibitor activity (GO:0004862), ATP binding (GO:0005524), cAMP-dependent protein kinase regulator activity (GO:0008603), phosphorylase kinase regulator activity (GO:0008607), AMP binding (GO:0016208), protein kinase regulator activity (GO:0019887), protein kinase binding (GO:0019901), protein kinase activator activity (GO:0030295), ADP binding (GO:0043531), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nucleotide-activated protein kinase complex (GO:0031588), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Membrane Trafficking	1
Autophagy	1
Integration of energy metabolism	1
Fatty acid metabolism	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
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
adenyl ribonucleotide binding	3
protein kinase regulator activity	3
fatty acid metabolic process	2
intracellular anatomical structure	2
cAMP-dependent protein kinase activity	2
anion binding	2
protein kinase activity	2
energy reserve metabolic process	1
glucan metabolic process	1
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
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
steroid biosynthetic process	1
sterol metabolic process	1
regulation of ketone metabolic process	1
regulation of lipid metabolic process	1
regulation of small molecule metabolic process	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
gluconeogenesis	1
regulation of gluconeogenesis	1
positive regulation of biosynthetic process	1
positive regulation of glucose metabolic process	1
regulation of fatty acid metabolic process	1
fatty acid oxidation	1
regulation of D-glucose transmembrane transport	1
D-glucose import across plasma membrane	1
cell cycle	1

Protein interactions and networks

STRING

3049 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKAG2	PRKAB2	O43741	926
PRKAG2	PRKAB1	Q9Y478	894
PRKAG2	PRKAA1	Q13131	884
PRKAG2	MYL3	P08590	870
PRKAG2	MYBPC3	Q14896	867
PRKAG2	PRKAA2	P54646	854
PRKAG2	LAMP2	P13473	817
PRKAG2	H7C2H4	H7C2H4	797
PRKAG2	P0DN79	P0DN79	796
PRKAG2	ACTC1	P04270	795
PRKAG2	TNNI3	P19429	793
PRKAG2	CSRP3	P50461	776
PRKAG2	MYH7	P12883	773
PRKAG2	MYL2	P10916	766
PRKAG2	TNNT2	P45379	765

IntAct

45 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
PRKAB2	PRKAG1	psi-mi:“MI:0914”(association)	0.940
PRKAA1	PRKAG1	psi-mi:“MI:0914”(association)	0.940
PRKAB1	PRKAG1	psi-mi:“MI:0914”(association)	0.920
PRKAG2	PRKAB2	psi-mi:“MI:0914”(association)	0.730
PRKAB2	GYS1	psi-mi:“MI:0914”(association)	0.730
STIM2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
PRKAG2	PRKAA2	psi-mi:“MI:0914”(association)	0.640
POLR3K	POLR3A	psi-mi:“MI:0914”(association)	0.640
NEFL	PRKAG2	psi-mi:“MI:0915”(physical association)	0.560
PRKAG2	SQSTM1	psi-mi:“MI:0915”(physical association)	0.560
PRKAG2	COL25A1	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	PRKAB2	psi-mi:“MI:0914”(association)	0.550
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
PRKAG2	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
PRKAG2	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
PRKAG2	PDIA6	psi-mi:“MI:0915”(physical association)	0.400
PRKAG2	rep	psi-mi:“MI:0915”(physical association)	0.370
ECE1	PRKAG2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (118): PRKAG2 (Affinity Capture-MS), PRKAA1 (Affinity Capture-MS), PRKAA2 (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), PRKAB2 (Affinity Capture-MS), PRKAG2 (Affinity Capture-MS), PRKAG2 (Affinity Capture-MS), PRKAB2 (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), PRKAA2 (Affinity Capture-MS), PRKAA1 (Affinity Capture-MS), PRKAG2 (Affinity Capture-MS), PRKAG2 (Affinity Capture-MS), PRKAG2 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS)

ESM2 similar proteins: A3GFE3, A3LQC5, A3LWY2, A5DNL9, A6ZLF4, A6ZUC0, A7F3V4, A7TL18, C4YLK8, P07834, P0CY25, P11433, P17442, P36102, P38129, P38314, P38713, P39923, P40433, P47135, P53172, P53735, Q03177, Q08817, Q09826, Q0U194, Q12221, Q12276, Q2HHB4, Q550L8, Q59UY7, Q5A506, Q5A649, Q5A6T5, Q5A744, Q5ABA6, Q5R4S0, Q6BIL4, Q6BMN7, Q6BS08

Diamond homologs: O54950, P12904, P54619, P58108, P80385, Q09138, Q10343, Q2LL38, Q54H97, Q5R4S0, Q8BGM7, Q8T277, Q91WG5, Q944A6, Q9MYP4, Q9P869, Q9UGI9, Q9UGJ0, Q58799, F4J117, O43741, P34164, P78789, P80386, P80387, Q04739, Q5BIS9, Q5R801, Q6PAM0, Q9FEB5, Q9QZH4, Q9R078, Q9SCY5, Q9Y478, O67820

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKAG2	“form complex”	AMPK	binding
PRKAG2	“down-regulates activity”	STIM1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Energy dependent regulation of mTOR by LKB1-AMPK	5	70.3×	4e-07
Activation of AMPK downstream of NMDARs	5	68.0×	4e-07
Selective autophagy	5	49.7×	2e-06
MTOR signalling	5	47.4×	2e-06
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	6	41.5×	4e-07
Post NMDA receptor activation events	5	36.4×	5e-06
Activation of NMDA receptors and postsynaptic events	5	32.9×	8e-06
Autophagy	6	31.8×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to nutrient levels	5	73.1×	2e-06
fatty acid biosynthetic process	5	54.9×	4e-06
positive regulation of apoptotic process	5	8.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1429 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	11
Uncertain significance	652
Likely benign	497
Benign	95

Top pathogenic / likely-pathogenic (25)

Variant ID	HGVS	Classification
1452050	NM_016203.4(PRKAG2):c.1007T>C (p.Val336Ala)	Pathogenic
183142	NM_016203.4(PRKAG2):c.1151G>C (p.Arg384Thr)	Pathogenic
2136632	NM_016203.4(PRKAG2):c.1453A>G (p.Lys485Glu)	Pathogenic
2735109	NM_016203.4(PRKAG2):c.1516G>A (p.Glu506Lys)	Pathogenic
3384174	NM_016203.4(PRKAG2):c.1026G>C (p.Glu342Asp)	Pathogenic
3720795	NM_016203.4(PRKAG2):c.997T>C (p.Ser333Pro)	Pathogenic
6846	NM_016203.4(PRKAG2):c.905G>A (p.Arg302Gln)	Pathogenic
6848	NM_016203.4(PRKAG2):c.1050_1051insTTA (p.Arg350_Glu351insLeu)	Pathogenic
6850	NM_016203.4(PRKAG2):c.1463A>T (p.Asn488Ile)	Pathogenic
6851	NM_016203.4(PRKAG2):c.1591C>G (p.Arg531Gly)	Pathogenic
6852	NM_016203.4(PRKAG2):c.1592G>A (p.Arg531Gln)	Pathogenic
6854	NM_016203.4(PRKAG2):c.1589A>G (p.His530Arg)	Pathogenic
855977	NM_016203.4(PRKAG2):c.1588C>G (p.His530Asp)	Pathogenic
943169	NM_016203.4(PRKAG2):c.869A>T (p.Lys290Ile)	Pathogenic
177903	NM_016203.4(PRKAG2):c.1030C>T (p.His344Tyr)	Likely pathogenic
2030739	NM_016203.4(PRKAG2):c.1642T>G (p.Ser548Ala)	Likely pathogenic
241091	NM_016203.4(PRKAG2):c.1201C>G (p.His401Asp)	Likely pathogenic
3355423	NM_016203.4(PRKAG2):c.1150A>G (p.Arg384Gly)	Likely pathogenic
3544408	NM_016203.4(PRKAG2):c.466+45171G>T	Likely pathogenic
3894683	NM_016203.4(PRKAG2):c.1149C>G (p.His383Gln)	Likely pathogenic
45739	NM_016203.4(PRKAG2):c.967T>A (p.Phe323Ile)	Likely pathogenic
619265	NM_016203.4(PRKAG2):c.1022T>C (p.Leu341Ser)	Likely pathogenic
6849	NM_016203.4(PRKAG2):c.1199C>A (p.Thr400Asn)	Likely pathogenic
6855	NM_016203.4(PRKAG2):c.1516G>C (p.Glu506Gln)	Likely pathogenic
949886	NM_016203.4(PRKAG2):c.1591C>T (p.Arg531Trp)	Likely pathogenic

SpliceAI

5176 predictions. Top by Δscore:

Variant	Effect	Δscore
7:151560518:TTTTA:T	donor_loss	1.0000
7:151560519:TTTA:T	donor_loss	1.0000
7:151560520:TTA:T	donor_loss	1.0000
7:151560521:TACC:T	donor_loss	1.0000
7:151560522:ACCTG:A	donor_loss	1.0000
7:151560523:C:CG	donor_loss	1.0000
7:151560523:CCTG:C	donor_gain	1.0000
7:151560613:TGGAC:T	acceptor_gain	1.0000
7:151560614:GGAC:G	acceptor_gain	1.0000
7:151560614:GGACC:G	acceptor_loss	1.0000
7:151560615:GAC:G	acceptor_gain	1.0000
7:151560615:GACCT:G	acceptor_loss	1.0000
7:151560616:AC:A	acceptor_gain	1.0000
7:151560616:ACC:A	acceptor_loss	1.0000
7:151560617:CC:C	acceptor_gain	1.0000
7:151560617:CCT:C	acceptor_loss	1.0000
7:151560618:C:CC	acceptor_gain	1.0000
7:151560619:T:G	acceptor_loss	1.0000
7:151564088:A:AC	donor_gain	1.0000
7:151564089:C:CC	donor_gain	1.0000
7:151564089:CTATT:C	donor_gain	1.0000
7:151564220:AGATT:A	acceptor_gain	1.0000
7:151564221:GATT:G	acceptor_gain	1.0000
7:151564222:ATT:A	acceptor_gain	1.0000
7:151564223:TT:T	acceptor_gain	1.0000
7:151564224:TCTG:T	acceptor_loss	1.0000
7:151564225:C:CC	acceptor_gain	1.0000
7:151564225:CTGTA:C	acceptor_loss	1.0000
7:151564226:T:G	acceptor_loss	1.0000
7:151564230:A:AC	acceptor_gain	1.0000

AlphaMissense

3721 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:151560550:A:G	L551P	1.000
7:151560560:A:G	S548P	1.000
7:151560562:A:G	L547P	1.000
7:151560574:C:A	G543V	1.000
7:151560574:C:T	G543D	1.000
7:151560575:C:G	G543R	1.000
7:151560607:A:G	L532P	1.000
7:151560610:C:G	R531P	1.000
7:151560612:A:C	H530Q	1.000
7:151560612:A:T	H530Q	1.000
7:151560614:G:C	H530D	1.000
7:151560614:G:T	H530N	1.000
7:151564129:G:C	C511W	1.000
7:151564169:A:G	L498P	1.000
7:151564193:A:G	L490P	1.000
7:151564193:A:T	L490Q	1.000
7:151564203:A:C	Y487D	1.000
7:151564203:A:G	Y487H	1.000
7:151564217:G:T	A482D	1.000
7:151564220:A:G	L481P	1.000
7:151564220:A:T	L481H	1.000
7:151565347:A:T	I479N	1.000
7:151565353:T:A	D477V	1.000
7:151565353:T:C	D477G	1.000
7:151565353:T:G	D477A	1.000
7:151565354:C:G	D477H	1.000
7:151565355:A:C	F476L	1.000
7:151565355:A:T	F476L	1.000
7:151565356:A:C	F476C	1.000
7:151565356:A:G	F476S	1.000

dbSNP variants (sampled 300 via entrez): RS1000007480 (7:151607249 A>G), RS1000012750 (7:151656514 C>T), RS1000014664 (7:151687892 G>A), RS1000018436 (7:151575116 T>C), RS1000032011 (7:151607719 T>C,G), RS1000037994 (7:151800533 C>T), RS1000040839 (7:151757458 G>A), RS1000049155 (7:151569139 TC>T), RS1000049873 (7:151693134 T>C), RS1000051561 (7:151833183 CTT>C), RS1000066126 (7:151864485 TA>T), RS1000095280 (7:151868824 T>A), RS1000101512 (7:151761192 C>T), RS1000109319 (7:151805615 C>G,T), RS1000117073 (7:151613350 A>C,G)

Disease associations

OMIM: gene MIM:602743 | disease phenotypes: MIM:194200, MIM:261740, MIM:600858, MIM:192600, MIM:137920, MIM:609040

GenCC curated gene-disease

Disease	Classification	Inheritance
hypertrophic cardiomyopathy 6	Definitive	Autosomal dominant
Wolff-Parkinson-White syndrome	Strong	Autosomal dominant
lethal congenital glycogen storage disease of heart	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
PRKAG2-related cardiomyopathy	Definitive	AD

Mondo (17): cardiomyopathy (MONDO:0004994), Wolff-Parkinson-White syndrome (MONDO:0008685), lethal congenital glycogen storage disease of heart (MONDO:0009867), hypertrophic cardiomyopathy 6 (MONDO:0010946), hypertrophic cardiomyopathy (MONDO:0005045), congestive heart failure (MONDO:0005009), familial hypertrophic cardiomyopathy (MONDO:0024573), PRKAG2-related cardiomyopathy (MONDO:0800484), renal cysts and diabetes syndrome (MONDO:0007669), coronary artery disorder (MONDO:0005010), hypertensive disorder (MONDO:0005044), stroke disorder (MONDO:0005098), ventricular tachycardia (MONDO:0005477), dilated cardiomyopathy (MONDO:0005021), heart failure (MONDO:0005252)

Orphanet (8): Rare cardiomyopathy (Orphanet:167848), Fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease (Orphanet:439854), Rare hypertrophic cardiomyopathy (Orphanet:217569), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), HNF1B-related autosomal dominant tubulointerstitial kidney disease (Orphanet:93111), Dilated cardiomyopathy (Orphanet:217604), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000105	Enlarged kidney
HP:0000158	Macroglossia
HP:0000238	Hydrocephalus
HP:0000518	Cataract
HP:0000961	Cyanosis
HP:0001250	Seizure
HP:0001279	Syncope
HP:0001541	Ascites
HP:0001623	Breech presentation
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001645	Sudden cardiac death
HP:0001662	Bradycardia
HP:0001663	Ventricular fibrillation
HP:0001670	Asymmetric septal hypertrophy
HP:0001678	Atrioventricular block
HP:0001688	Sinus bradycardia
HP:0001698	Pericardial effusion
HP:0001716	Wolff-Parkinson-White syndrome
HP:0001962	Palpitations
HP:0001998	Neonatal hypoglycemia
HP:0002098	Respiratory distress
HP:0002104	Apnea
HP:0002202	Pleural effusion
HP:0002615	Hypotension
HP:0003198	Myopathy
HP:0003577	Congenital onset

GWAS associations

60 associations (top):

Study	Trait	p-value
GCST000499_4	Hemoglobin	3.000000e-15
GCST000502_3	Hematocrit	6.000000e-15
GCST000649_12	Chronic kidney disease	4.000000e-12
GCST000969_2	Bipolar disorder (age of onset and psychotic symptoms)	2.000000e-06
GCST001765_5	Red blood cell traits	8.000000e-15
GCST001791_25	Urate levels	4.000000e-09
GCST003372_20	Glomerular filtration rate (creatinine)	8.000000e-29
GCST003374_6	Chronic kidney disease	2.000000e-14
GCST003401_35	Glomerular filtration rate in non diabetics (creatinine)	2.000000e-29
GCST003790_1	Glomerular filtration rate	4.000000e-06
GCST003790_19	Glomerular filtration rate	7.000000e-11
GCST003876_6	Gut microbiota (beta diversity)	5.000000e-08
GCST004003_13	Hematocrit	1.000000e-08
GCST004005_3	Hemoglobin levels	3.000000e-12
GCST004215_5	Urea levels	6.000000e-09
GCST004292_47	Glomerular filtration rate (creatinine)	6.000000e-20
GCST004332_1	Red blood cell count	1.000000e-08
GCST004601_103	Red blood cell count	5.000000e-51
GCST004604_127	Hematocrit	3.000000e-69
GCST004615_53	Hemoglobin concentration	3.000000e-59
GCST005891_1	Glomerular filtration rate in diabetes	3.000000e-08
GCST005891_4	Glomerular filtration rate in diabetes	3.000000e-07
GCST005892_1	Glomerular filtration rate in type 2 diabetes	5.000000e-08
GCST005892_4	Glomerular filtration rate in type 2 diabetes	8.000000e-07
GCST006021_25	Systolic blood pressure	3.000000e-07
GCST006065_31	Glaucoma (primary open-angle)	3.000000e-08
GCST006412_72	Intraocular pressure	1.000000e-10
GCST007094_170	Diastolic blood pressure	2.000000e-11
GCST007095_12	Systolic blood pressure	4.000000e-07
GCST007096_45	Pulse pressure	4.000000e-09

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0005940	psychotic symptoms
EFO:0004531	urate measurement
EFO:0007874	gut microbiome measurement
EFO:0004305	erythrocyte count
EFO:0006335	systolic blood pressure
EFO:0004695	intraocular pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004285	albuminuria
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D003324	Coronary Artery Disease	C14.280.647.250.260; C14.907.137.126.339; C14.907.585.250.260
D006333	Heart Failure	C14.280.434
D006973	Hypertension	C14.907.489
D020521	Stroke	C10.228.140.300.775; C14.907.253.855
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C563808	Arrhythmogenic Right Ventricular Dysplasia, Familial, 9 (supp.)
C563436	Cardiomyopathy, Familial Hypertrophic, 6 (supp.)
C564888	Glycogen Storage Disease of Heart, Lethal Congenital (supp.)
C535520	Renal cysts and diabetes syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2096907 (PROTEIN COMPLEX GROUP), CHEMBL2453 (SINGLE PROTEIN), CHEMBL3038451 (PROTEIN COMPLEX), CHEMBL3885504 (PROTEIN COMPLEX), CHEMBL4106158 (PROTEIN COMPLEX), CHEMBL4106163 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 275,634 (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
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1236682	REFAMETINIB	2	3,223
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL495727	AT-9283	2	1,376
CHEMBL574737	UCN-01	2	2,217
CHEMBL575448	BMS-754807	2	406
CHEMBL1952329	SGI-1776	1	400
CHEMBL2041933	AZD-7762	1	1,240
CHEMBL3128043	PF-03758309	1	233
CHEMBL3544932	TAK-901	1	557
CHEMBL4289017	PF-03814735	1	537
CHEMBL494089	GSK-690693	1	2,061

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10224002	Efficacy	3	hydrochlorothiazide	Hypertension

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10224002	PRKAG2	3	3.00	1	hydrochlorothiazide
rs12703159	PRKAG2		0.00	0
rs13224758	PRKAG2		0.00	0
rs4725434	PRKAG2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — AMPK subfamily

ChEMBL bioactivities

389 potent at pChembl≥5 of 440 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	EC50	0.5	nM	CHEMBL3986249
9.15	EC50	0.7	nM	CHEMBL3979403
9.00	EC50	1	nM	CHEMBL4167177
9.00	EC50	1	nM	CHEMBL5179319
9.00	EC50	1	nM	CHEMBL5181529
9.00	EC50	1	nM	CHEMBL5183763
9.00	IC50	1	nM	CHEMBL5183579
8.77	EC50	1.7	nM	CHEMBL3975011
8.74	EC50	1.8	nM	CHEMBL3923669
8.70	EC50	2	nM	CHEMBL4111692
8.70	EC50	2	nM	CHEMBL5194054
8.70	EC50	2	nM	CHEMBL5180431
8.64	EC50	2.3	nM	CHEMBL3953722
8.62	EC50	2.4	nM	CHEMBL3893781
8.59	EC50	2.602	nM	CHEMBL3970868
8.55	IC50	2.82	nM	CHEMBL3393137
8.54	EC50	2.9	nM	CHEMBL4107500
8.52	EC50	3	nM	CHEMBL5174868
8.40	EC50	4	nM	CHEMBL5203262
8.38	EC50	4.2	nM	CHEMBL3891221
8.38	Ki	4.2	nM	CHEMBL1908392
8.37	EC50	4.3	nM	CHEMBL3979636
8.37	EC50	4.3	nM	CHEMBL3959268
8.35	EC50	4.5	nM	CHEMBL4648182
8.33	EC50	4.7	nM	CHEMBL4645351
8.31	Ki	4.9	nM	CHEMBL4089284
8.30	Kd	5	nM	PF-03758309
8.30	EC50	5	nM	CHEMBL5186795
8.25	EC50	5.6	nM	CHEMBL4111958
8.22	EC50	6	nM	CHEMBL5190451
8.22	EC50	6	nM	CHEMBL5183579
8.21	EC50	6.2	nM	CHEMBL3908241
8.20	EC50	6.3	nM	CHEMBL1688230
8.19	EC50	6.5	nM	CHEMBL3915611
8.18	EC50	6.56	nM	CHEMBL3980011
8.16	EC50	6.9	nM	CHEMBL3918798
8.15	EC50	7.1	nM	CHEMBL3894523
8.15	EC50	7.063	nM	CHEMBL3898048
8.15	IC50	7	nM	CHEMBL5179319
8.11	EC50	7.8	nM	CHEMBL3953722
8.10	EC50	7.9	nM	CHEMBL4636831
8.10	IC50	8	nM	CHEMBL5203450
8.08	EC50	8.3	nM	CHEMBL3936111
8.08	EC50	8.328	nM	CHEMBL3975761
8.05	EC50	9	nM	CHEMBL5205646
8.05	EC50	9	nM	CHEMBL5202027
8.04	Ki	9.2	nM	CHEMBL4062168
8.03	EC50	9.3	nM	CHEMBL4109075
8.03	EC50	9.33	nM	CHEMBL4109075
8.02	EC50	9.6	nM	CHEMBL3960657

PubChem BioAssay actives

161 with measured affinity, of 1240 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-chloro-2-hydroxy-5-(1-methylindol-5-yl)-1H-indol-3-yl]-(3-methoxy-1,2-oxazol-5-yl)methanone	1320676: Activation of recombinant human His-tagged AMPK alpha2 (2 to 552 residues)/beta1 (2 to 270 residues)/gamma2 (2 to 569 residues) expressed in baculovirus infected sf21 cells preincubated for 30 mins followed by biotinylated ACC-CREBp peptide substrate addition measured after 45 mins by HTRF assay	ec50	0.0007	uM
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
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
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1425127: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0050	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
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
5-[[6-chloro-5-(4-phenylphenyl)-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid	1471591: Agonist activity at human recombinant phosphorylated AMPK complex 2 alpha1/beta1/gamma2 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	0.0210	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
N-[(1-methylpiperidin-4-yl)methyl]-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazin-6-amine	1425127: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0230	uM
(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1425127: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0250	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149074: Binding affinity to human PRKAG2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0263	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
Aflatoxin B1	affects expression, decreases expression, increases expression, increases methylation	4
bisphenol A	decreases expression, affects methylation, affects cotreatment, increases methylation	3
sodium arsenite	decreases reaction, increases phosphorylation, decreases expression, increases abundance	3
Methotrexate	decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
dorsomorphin	decreases reaction, increases phosphorylation, affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Cyclosporine	increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
moringin	affects cotreatment, increases expression	1
OSMI-1	decreases reaction, increases phosphorylation	1
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases methylation	1
diethyl maleate	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
2-tert-butylhydroquinone	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1

ChEMBL screening assays

266 unique, capped per target: 265 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

Cellosaurus cell lines

16 cell lines: 10 induced pluripotent stem cell, 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4GZ	ZW-hiPSC 6	Induced pluripotent stem cell	Male
CVCL_A4HA	ZW-hiPSC 9	Induced pluripotent stem cell	Male
CVCL_A4HB	ZW-hiPSC 12	Induced pluripotent stem cell	Male
CVCL_A4HC	ZJ-hiPSC 3	Induced pluripotent stem cell	Male
CVCL_A4HD	ZJ-hiPSC 6	Induced pluripotent stem cell	Male
CVCL_A4HE	ZJ-hiPSC 11	Induced pluripotent stem cell	Male
CVCL_A4HI	ZW-C-hiPSC	Induced pluripotent stem cell	Male
CVCL_A4HJ	ZJ-C-hiPSC	Induced pluripotent stem cell	Male
CVCL_B6ZY	SCVIi036-A	Induced pluripotent stem cell	Male
CVCL_B7A1	SCVIi037-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

308 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	PHASE3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT00185250	PHASE2	COMPLETED	Betaferon/ Betaseron (Interferon Beta-1b) in Patients With Chronic Viral Cardiomyopathy
NCT00490347	PHASE2	COMPLETED	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Feasibility Trial
NCT00694161	PHASE2	COMPLETED	The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy