PRKAA2

Chr 1

protein kinase AMP-activated catalytic subunit alpha 2

Also known as: AMPK, AMPK2, AMPKa2, PRKAA

NCBI Gene: 5563ENSG00000162409UniProt: P54646

The protein encoded by this gene is a catalytic 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. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. [provided by RefSeq, Jul 2008]

78
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PRKAA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 60 VUS of 78 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.92LOEUF
pLI 0.000
Z-score 1.88
OE 0.61 (0.41–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.99Z-score
OE missense 0.68 (0.61–0.76)
207 obs / 304.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.61 (0.41–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.61–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 16 / 26.4Missense obs/exp: 207 / 304.5Syn Z: 0.59

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS60
Likely Benign4
Benign5
7
Pathogenic
2
Likely Pathogenic
60
VUS
4
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
54
6
0
60
Likely Benign
0
2
0
2
4
Benign
0
0
2
3
5
Total05617578

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRKAA2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human.
Niskanen JE et al.·Genome Med
2023
SIRT5-mediated PRKAA2 succinylation ameliorates apoptosis of human placental trophoblasts in hypertensive disorder complicating pregnancy.
Ren F et al.·Clin Exp Hypertens
2024
Deubiquitinase USP18 mediates cell migration, apoptosis and ferroptosis in lung adenocarcinoma by depending on POU4F1/PRKAA2 axis.
Pan X et al.·BMC Cancer
2025
Targeting USP9X-AMPK Axis in ARID1A-Deficient Hepatocellular Carcinoma.
Zhang FK et al.·Cell Mol Gastroenterol Hepatol
2022
Systems Pharmacology to Explore the Potential Mechanism of Ginseng Against Heart Failure.
Gao K et al.·Rejuvenation Res
2025Functional
Identification of lipid metabolism-related signature in nonalcoholic fatty liver: evidences from transcriptomics and single cell RNA-sequencing analysis.
Sun Y et al.·Eur J Med Res
2025
Influence of Single-Nucleotide Polymorphisms in PPAR-δ, PPAR-γ, and PRKAA2 on the Changes in Anthropometric Indices and Blood Measurements through Exercise-Centered Lifestyle Intervention in Japanese Middle-Aged Men.
Nishida Y et al.·Int J Mol Sci
2018
AMPKα2 promotes tumor immune escape by inducing CD8+ T-cell exhaustion and CD4+ Treg cell formation in liver hepatocellular carcinoma.
Ouyang Y et al.·BMC Cancer
2024
Role of autophagy-related genes in liver cancer prognosis.
Zhou Y et al.·Genomics
2024
Network pharmacology and molecular docking approaches to elucidate the potential compounds and targets of Saeng-Ji-Hwang-Ko for treatment of type 2 diabetes mellitus.
Ko M et al.·Comput Biol Med
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools