PRKAB2

Summary

PRKAB2 (protein kinase AMP-activated non-catalytic subunit beta 2, HGNC:9379) is a protein-coding gene on chromosome 1q21.1, encoding 5’-AMP-activated protein kinase subunit beta-2 (O43741). Non-catalytic 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 may be a positive regulator of AMPK activity. It is highly expressed in skeletal muscle and thus may have tissue-specific roles. Multiple alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 5565 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Disputed, ClinGen)
• Clinical variants (ClinVar): 27 total — 4 pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005399

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9379
Approved symbol	PRKAB2
Name	protein kinase AMP-activated non-catalytic subunit beta 2
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000131791
Ensembl biotype	protein_coding
OMIM	602741
Entrez	5565

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000254101, ENST00000474939, ENST00000496858, ENST00000896001, ENST00000896002, ENST00000911676

RefSeq mRNA: 1 — MANE Select: NM_005399 NM_005399

CCDS: CCDS925

Canonical transcript exons

ENST00000254101 — 8 exons

Exon	Start	End
ENSE00000903087	147167767	147167933
ENSE00001706527	147162440	147162573
ENSE00001858470	147172429	147172470
ENSE00001949097	147155106	147159642
ENSE00003584114	147166846	147166939
ENSE00003620866	147171989	147172167
ENSE00003627429	147166498	147166618
ENSE00003664558	147161712	147161780

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1245 / max 375.2191, expressed in 1779 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14206	5.9229	1615
14203	3.3017	1304
14207	2.5291	1241
14205	0.2828	122
14202	0.0881	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	97.24	gold quality
biceps brachii	UBERON:0001507	96.91	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.02	gold quality
jejunum	UBERON:0002115	95.42	gold quality
gastrocnemius	UBERON:0001388	95.32	gold quality
body of tongue	UBERON:0011876	95.25	gold quality
muscle of leg	UBERON:0001383	94.81	gold quality
saphenous vein	UBERON:0007318	93.36	gold quality
adrenal tissue	UBERON:0018303	92.32	gold quality
skeletal muscle organ	UBERON:0014892	92.29	gold quality
muscle organ	UBERON:0001630	92.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.65	gold quality
buccal mucosa cell	CL:0002336	91.17	gold quality
tibial artery	UBERON:0007610	90.83	gold quality
popliteal artery	UBERON:0002250	90.82	gold quality
duodenum	UBERON:0002114	90.63	gold quality
cortical plate	UBERON:0005343	90.62	gold quality
tibia	UBERON:0000979	90.48	gold quality
body of pancreas	UBERON:0001150	90.35	gold quality
middle temporal gyrus	UBERON:0002771	89.56	gold quality
right lobe of liver	UBERON:0001114	89.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.33	gold quality
right coronary artery	UBERON:0001625	89.24	gold quality
tongue	UBERON:0001723	89.20	gold quality
skin of hip	UBERON:0001554	89.09	gold quality
aorta	UBERON:0000947	88.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.15	gold quality
lower esophagus	UBERON:0013473	88.14	gold quality
urethra	UBERON:0000057	87.94	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	1246.03
E-ANND-3	no	4.49
E-CURD-112	no	2.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

162 targeting PRKAB2, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197

Literature-anchored findings (GeneRIF, showing 12)

• variants in PRKAB2 are unlikely to contribute to the type 2 diabetes mellitus susceptibility in Pima Indians (PMID:12490143)
• Purification and characterization of truncated human AMPK alpha 2 beta 2 gamma 3 heterotrimer from baculovirus-infected insect cells (PMID:19836452)
• These results suggest that the modification introduced by the laforin-malin complex could affect the subcellular distribution of AMPK beta subunits. (PMID:20534808)
• results of this study demonistrated that the novel findings that intronic SNPs in the genes coding for the regulatory beta2(PRKAB2) of AMPK are associated with antipsychotic-induced weight gain in schizophrenia or schizoaffective disorder patients (PMID:22305490)
• 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)
• Studies suggest insights into the regulation of AMPK, its diverse biological actions, and therapeutic potential in the heart. (PMID:22935535)
• Sumoylation of AMPKbeta2 subunit enhances AMP-activated protein kinase activity. (PMID:23552691)
• AMP-activated protein kinase can be modulated by diverse ligands and by phosphorylation. (PMID:30206123)
• Sleep disturbances are one of the most common problems affecting individuals with psychiatric disorders. We show that AMPK is required for maintenance of proper sleep architecture and for sleep recovery following sleep deprivation. Neuronal AMPKbeta loss specifically leads to sleep fragmentation and causes dysregulation of genes believed to play a role in sleep homeostasis. (PMID:30566533)
• these data indicate that increased expression of AMPKbeta2 is an important feature of efficient adipogenesis. (PMID:31189568)
• AMPKbeta1 and AMPKbeta2 define an isoform-specific gene signature in human pluripotent stem cells, differentially mediating cardiac lineage specification. (PMID:33454005)
• MiR-29b Alleviates High Glucose-induced Inflammation and Apoptosis in Podocytes by Down-regulating PRKAB2. (PMID:38204237)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000067817
mus_musculus	Prkab2	ENSMUSG00000038205
rattus_norvegicus	Prkab2	ENSRNOG00000018166
caenorhabditis_elegans		WBGENE00007222
caenorhabditis_elegans		WBGENE00010115
caenorhabditis_elegans		WBGENE00012928

Paralogs (1): PRKAB1 (ENSG00000111725)

Protein

Protein identifiers

5’-AMP-activated protein kinase subunit beta-2 — O43741 (reviewed: O43741)

All UniProt accessions (1): O43741

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic 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. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).

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).

Post-translational modifications. Phosphorylated when associated with the catalytic subunit (PRKAA1 or PRKAA2). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O43741-1	1	yes
O43741-2	2

RefSeq proteins (1): NP_005390* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006828	ASC_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR032640	AMPK1_CBM	Domain
IPR037256	ASC_dom_sf	Homologous_superfamily
IPR050827	CRP1_MDG1_kinase	Family

Pfam: PF04739, PF16561

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 (31 total): strand 12, modified residue 10, splice variant 2, helix 2, turn 2, chain 1, region of interest 1, mutagenesis site 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
2F15	X-RAY DIFFRACTION	2
2V8Q	X-RAY DIFFRACTION	2.1
4EAI	X-RAY DIFFRACTION	2.29
2V92	X-RAY DIFFRACTION	2.4
2Y8L	X-RAY DIFFRACTION	2.5
2YA3	X-RAY DIFFRACTION	2.51
2V9J	X-RAY DIFFRACTION	2.53
4EAJ	X-RAY DIFFRACTION	2.61
2Y8Q	X-RAY DIFFRACTION	2.8
4CFH	X-RAY DIFFRACTION	3.24
7JHG	ELECTRON MICROSCOPY	3.47
6B2E	X-RAY DIFFRACTION	3.8
7JHH	ELECTRON MICROSCOPY	3.92
7M74	ELECTRON MICROSCOPY	3.93
4RER	X-RAY DIFFRACTION	4.05
4REW	X-RAY DIFFRACTION	4.58
7JIJ	X-RAY DIFFRACTION	5.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43741-F1	78.62	0.59

Antibody-complex structures (SAbDab): 3 — 7JHG, 7JHH, 7M74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 174, 184, 39, 40, 69, 95, 108, 148, 158, 170

Mutagenesis-validated functional residues (1):

Position	Phenotype
235	results in an ampk enzyme that is activable by phosphorylation but has significantly increased rate of dephosphorylation

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: 281 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, KYNG_DNA_DAMAGE_DN, REACTOME_MEMBRANE_TRAFFICKING, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, SRF_Q5_01, PATIL_LIVER_CANCER, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, SRF_C, BROWNE_HCMV_INFECTION_14HR_DN, WTGAAAT_UNKNOWN

GO Biological Process (6): fatty acid biosynthetic process (GO:0006633), signal transduction (GO:0007165), cellular response to nutrient levels (GO:0031669), positive regulation of cold-induced thermogenesis (GO:0120162), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (3): protein kinase binding (GO:0019901), AMP-activated protein kinase activity (GO:0004679), protein binding (GO:0005515)

GO Cellular Component (5): 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-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	3
cellular response to stimulus	2
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
response to nutrient levels	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
kinase binding	1
protein serine/threonine kinase activity	1
AMP binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular protein-containing complex	1
protein kinase complex	1

Protein interactions and networks

STRING

1634 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKAB2	PRKAG1	P54619	996
PRKAB2	PRKAA2	P54646	971
PRKAB2	PRKAA1	Q13131	937
PRKAB2	PRKAG2	Q9UGJ0	926
PRKAB2	PRKAG3	Q9UGI9	887
PRKAB2	PRKAB1	Q9Y478	831
PRKAB2	ACP6	Q9NPH0	744
PRKAB2	CHD1L	Q86WJ1	719
PRKAB2	CAMKK2	Q96RR4	697
PRKAB2	STK11	Q15831	688
PRKAB2	GJA5	P36382	607
PRKAB2	GJA8	P48165	600
PRKAB2	GPHRA	B7ZAQ6	595
PRKAB2	FMO5	P49326	593
PRKAB2	NBPF11	Q86T75	575

IntAct

762 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
PRKAA1	PRKAB2	psi-mi:“MI:0915”(physical association)	0.950
PRKAB2	PRKAA1	psi-mi:“MI:0915”(physical association)	0.950
PRKAA2	PRKAB2	psi-mi:“MI:0915”(physical association)	0.940
PRKAB2	PRKAG1	psi-mi:“MI:0915”(physical association)	0.940
PRKAB2	PRKAA2	psi-mi:“MI:0915”(physical association)	0.940
PRKAG1	PRKAB2	psi-mi:“MI:0915”(physical association)	0.940
IKZF3	PRKAB2	psi-mi:“MI:0915”(physical association)	0.910
PRKAB2	IKZF3	psi-mi:“MI:0915”(physical association)	0.910
GOLGA2	PRKAB2	psi-mi:“MI:0915”(physical association)	0.880
PRKAB2	MDFI	psi-mi:“MI:0915”(physical association)	0.880
MDFI	PRKAB2	psi-mi:“MI:0915”(physical association)	0.880
PRKAB2	GOLGA2	psi-mi:“MI:0915”(physical association)	0.880

BioGRID (397): PRKAB2 (Two-hybrid), PRKAB2 (Two-hybrid), PRKAB2 (Two-hybrid), PRKAB2 (Two-hybrid), PRKAB2 (Two-hybrid), PRKAB2 (Two-hybrid), PRKAB2 (Two-hybrid), PRKAB2 (Two-hybrid), PRKAB2 (Two-hybrid), PRKAB2 (Two-hybrid), PRKAG1 (Two-hybrid), PYGM (Two-hybrid), TRAF2 (Two-hybrid), BLZF1 (Two-hybrid), STX11 (Two-hybrid)

ESM2 similar proteins: A0JN27, A0PJN4, A1L167, A1L3K1, A2ADY9, B5DFI8, C1C3R6, D3Z7P3, G3MWR8, O43741, O88508, O94925, P13264, Q07G17, Q12800, Q13888, Q16763, Q1LZ53, Q1RML1, Q28D01, Q28F89, Q2KJ29, Q2TBV5, Q3MHJ2, Q4R9A8, Q4W5Z4, Q5NVP9, Q5R532, Q5RBN9, Q5SP67, Q5TDH0, Q66H54, Q6AYU1, Q6P1K8, Q6PAM0, Q76EZ2, Q7L5Y9, Q7RTP6, Q86TJ2, Q8AVU2

Diamond homologs: F4KFB3, O43741, P80387, Q10F03, Q94AX2, Q9LFY0, P34164, P78789, P80386, Q5BIS9, Q5R801, Q6PAM0, Q84VQ1, Q944A6, Q9FEB5, Q9QZH4, Q9R078, Q9SCY5, Q9Y478, Q9ZUU8, A6ZT54, B3LSR0, C7GJZ2, C8Z9U3, E7KDM2, E7KPJ0, E7LVH4, E7NIP0, E7Q4T7, P38845, Q04739, G4LTX4, F4J117, O54950, P54619, Q09138, Q5R4S0, Q8T277, Q91WG5, Q9UGJ0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKAB2	“form complex”	AMPK	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
Regulation of TP53 Activity	5	18.4×	2e-04
TP53 Regulates Metabolic Genes	5	18.0×	2e-04
Regulation of TP53 Activity through Phosphorylation	5	16.4×	2e-04
Keratinization	10	15.5×	9e-08
Transcriptional Regulation by TP53	5	8.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1708187	GRCh37/hg19 1q21.1-21.2(chr1:146105170-147830830)x1	Pathogenic
1708199	GRCh37/hg19 1q21.1-21.2(chr1:145157447-148016122)x1	Pathogenic
3062789	GRCh37/hg19 1q21.1-21.2(chr1:146470887-147856007)x3	Pathogenic
565175	GRCh37/hg19 1q21.1-21.2(chr1:146470887-147845170)x1	Pathogenic

SpliceAI

1302 predictions. Top by Δscore:

Variant	Effect	Δscore
1:147159458:ATCAG:A	donor_gain	1.0000
1:147159482:T:TA	donor_gain	1.0000
1:147159597:A:AC	donor_gain	1.0000
1:147159598:C:CC	donor_gain	1.0000
1:147161707:CTTA:C	donor_loss	1.0000
1:147161708:TTA:T	donor_loss	1.0000
1:147161710:A:AG	donor_loss	1.0000
1:147161776:TCACA:T	acceptor_gain	1.0000
1:147161777:CACA:C	acceptor_gain	1.0000
1:147161777:CACAC:C	acceptor_gain	1.0000
1:147161778:ACA:A	acceptor_gain	1.0000
1:147161779:CA:C	acceptor_gain	1.0000
1:147161779:CAC:C	acceptor_gain	1.0000
1:147161779:CACTA:C	acceptor_loss	1.0000
1:147161780:ACTA:A	acceptor_loss	1.0000
1:147161781:C:CC	acceptor_gain	1.0000
1:147161781:C:T	acceptor_loss	1.0000
1:147161782:T:C	acceptor_loss	1.0000
1:147162438:A:AC	donor_gain	1.0000
1:147162439:C:CC	donor_gain	1.0000
1:147166845:CCT:C	donor_gain	1.0000
1:147166935:TATGG:T	acceptor_gain	1.0000
1:147166937:TGG:T	acceptor_gain	1.0000
1:147166938:GG:G	acceptor_gain	1.0000
1:147166939:GCTA:G	acceptor_loss	1.0000
1:147166940:C:CC	acceptor_gain	1.0000
1:147166940:CT:C	acceptor_loss	1.0000
1:147166941:T:C	acceptor_loss	1.0000
1:147171199:T:TA	donor_gain	1.0000
1:147171984:CTTA:C	donor_loss	1.0000

AlphaMissense

1805 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:147159579:A:C	Y269D	1.000
1:147159581:A:G	L268P	1.000
1:147159584:A:G	L267P	1.000
1:147159590:G:A	T265I	1.000
1:147159591:T:G	T265P	1.000
1:147159593:A:T	V264D	1.000
1:147159611:C:G	R258P	1.000
1:147159612:G:C	R258G	1.000
1:147159612:G:T	R258S	1.000
1:147159621:C:G	A255P	1.000
1:147159622:G:C	S254R	1.000
1:147159622:G:T	S254R	1.000
1:147159624:T:G	S254R	1.000
1:147159626:A:G	L253P	1.000
1:147159626:A:T	L253H	1.000
1:147159629:A:T	V252D	1.000
1:147161716:A:G	I246T	1.000
1:147161716:A:T	I246N	1.000
1:147161725:G:T	A243E	1.000
1:147161726:C:G	A243P	1.000
1:147161729:A:C	Y242D	1.000
1:147161729:A:G	Y242H	1.000
1:147161731:A:G	L241P	1.000
1:147161733:A:C	H240Q	1.000
1:147161733:A:T	H240Q	1.000
1:147161734:T:A	H240L	1.000
1:147161734:T:C	H240R	1.000
1:147161734:T:G	H240P	1.000
1:147161735:G:A	H240Y	1.000
1:147161735:G:C	H240D	1.000

dbSNP variants (sampled 300 via entrez): RS1000393777 (1:147171624 C>A), RS1000442268 (1:147171903 G>A,T), RS1000773945 (1:147170399 A>T), RS1001790194 (1:147164457 T>C), RS1002207930 (1:147157444 T>C), RS1002796530 (1:147169371 A>G), RS1002848682 (1:147169743 G>A), RS1003050379 (1:147162976 T>C,G), RS1003183717 (1:147168123 G>A), RS1003331987 (1:147160865 G>A,T), RS1003409374 (1:147162700 G>A), RS1003741938 (1:147173803 G>T), RS1003793717 (1:147161229 G>A,C), RS1004629079 (1:147170772 G>A), RS1004701327 (1:147172182 G>A,C,T)

Disease associations

OMIM: gene MIM:602741 | disease phenotypes: MIM:612474

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Disputed Evidence	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Disputed	UD

Mondo (2): chromosome 1q21.1 deletion syndrome (MONDO:0012914), congenital heart disease (MONDO:0005453)

Orphanet (1): 1q21.1 microdeletion syndrome (Orphanet:250989)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
C567291	Chromosome 1q21.1 Deletion Syndrome, 1.35-Mb (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL2096907 (PROTEIN COMPLEX GROUP), CHEMBL2117 (SINGLE PROTEIN), CHEMBL3038453 (PROTEIN COMPLEX), CHEMBL3038456 (PROTEIN COMPLEX), CHEMBL3038457 (PROTEIN COMPLEX), CHEMBL4106158 (PROTEIN COMPLEX), CHEMBL4106162 (PROTEIN COMPLEX), CHEMBL4106163 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 165,603 (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
CHEMBL3115681	NARAZACICLIB	2	287

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3766522	PRKAB2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — AMPK subfamily

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

Ligand	Action	Affinity	Parameter
MT47-100	Negative	4.61	pKi

ChEMBL bioactivities

407 potent at pChembl≥5 of 457 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
9.00	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	CHEMBL3957286
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	CHEMBL3957286
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	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

158 with measured affinity, of 1157 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
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	1320700: Activation of human recombinant AMPK alpha2/beta2/gamma1 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	0.0020	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
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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149069: Binding affinity to human PRKAB2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0101	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
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
5-[[6-chloro-5-(4-phenylphenyl)-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid	1471599: Agonist activity at human recombinant phosphorylated AMPK complex 11 alpha2/beta2/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	0.0230	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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149069: Binding affinity to human PRKAB2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0317	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
4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxybenzamide	1992753: Inhibition of AMPK alpha1/beta2/gamma1 (unknown origin) using SAMStide as substrate incubated for 45 to 60 mins in presence of 5’AMP and ATP by [33P]-gammaATP based Topcount scintillation counting analysis	ic50	0.0356	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	5
Benzo(a)pyrene	decreases expression, increases methylation	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression	2
FR900359	increases phosphorylation	1
testosterone enanthate	affects expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
nickel sulfate	decreases expression	1
coumarin	affects phosphorylation	1
phenethyl isothiocyanate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
adefovir dipivoxil	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Leflunomide	decreases expression	1
Cidofovir	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1

ChEMBL screening assays

322 unique, capped per target: 321 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

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7YC	Ubigene A-549 PRKAB2 KO	Cancer cell line	Male
CVCL_D8TT	Ubigene HCT 116 PRKAB2 KO	Cancer cell line	Male
CVCL_D9PF	Ubigene HEK293 PRKAB2 KO	Transformed cell line	Female
CVCL_E0LR	Ubigene HeLa PRKAB2 KO	Cancer cell line	Female
CVCL_TG68	HAP1 PRKAB2 (-) 1	Cancer cell line	Male
CVCL_TG69	HAP1 PRKAB2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE