PRKAB2

Chr 1

protein kinase AMP-activated non-catalytic subunit beta 2

NCBI Gene: 5565ENSG00000131791UniProt: O43741

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. [provided by RefSeq, Jul 2013]

315
ClinVar variants
285
Pathogenic / LP
0.73
pLI score
0
Active trials
Clinical Summary— PRKAB2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.73) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
285 Pathogenic / Likely Pathogenic· 30 VUS of 315 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.48LOEUF
pLI 0.726
Z-score 2.82
OE 0.15 (0.06–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.50Z-score
OE missense 0.65 (0.55–0.77)
97 obs / 148.4 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.0.15 (0.06–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.55–0.77)
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.0.94
0≤1.21.6
LoF obs/exp: 2 / 13.0Missense obs/exp: 97 / 148.4Syn Z: 0.38

ClinVar Variant Classifications

315 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic247
Likely Pathogenic38
VUS30
247
Pathogenic
38
Likely Pathogenic
30
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————247
Likely Pathogenic
————38
VUS
————30
Likely Benign
————0
Benign
————0
Total—315

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRKAB2 · 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
📖
GeneReview available — PRKAB2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Variant screening of PRKAB2, a type 2 diabetes mellitus susceptibility candidate gene on 1q in Pima Indians.
Prochazka M et al.·Mol Cell Probes
2002
Understanding the impact of 1q21.1 copy number variant.
Harvard C et al.·Orphanet J Rare Dis
2011
The codon 72 polymorphism of p53 influences cell fate following nutrient deprivation.
Kung CP et al.·Cancer Biol Ther
2017
Identifying prognostic hub genes and key pathways in pediatric adrenocortical tumors through RNA sequencing and Co-expression analysis.
Veronez LC et al.·Mol Cell Endocrinol
2024
miR-1227-3p participates in the development of fetal growth restriction via regulating trophoblast cell proliferation and apoptosis.
Cui J et al.·Sci Rep
2022
Human gene copy number spectra analysis in congenital heart malformations.
Tomita-Mitchell A et al.·Physiol Genomics
2012
Methyl-β-cyclodextrin restores impaired autophagy flux in Niemann-Pick C1-deficient cells through activation of AMPK.
Dai S et al.·Autophagy
2017
Identification of new classes among acute myelogenous leukaemias with normal karyotype using gene expression profiling.
Vey N et al.·Oncogene
2004
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PRKAB2 as a tumor suppressor in renal cell carcinoma: inhibiting mitophagy via the LRPPRC-PRKN/parkin interaction and cardiolipin biosynthesis.
Chen K et al.·Autophagy
2026
Chromosome 1 variants associated with decreased HIV set-point viral load correlate with PRKAB2 expression changes.
Tough RH et al.·Front Genet
2025🔓 Open Access
Low PRKAB2 Expression Is Associated with Poor Outcomes in Pediatric Adrenocortical Tumors, and Treatment with Rottlerin Increases the PRKAB2 Level and Inhibits Tumorigenic Aspects in the NCI-H295R Adrenocortical Cancer Cell Line.
Xavier AET et al.·Cancers (Basel)
2024🔓 Open Access
MiR-29b Alleviates High Glucose-induced Inflammation and Apoptosis in Podocytes by Down-regulating PRKAB2.
Du H et al.·Endocr Metab Immune Disord Drug Targets
2024🔓 Open Access
The study of copy number variations in the regions of PRKAB2 and PPM1K among congenital heart defects patients.
Dong HQ et al.·Rev Assoc Med Bras (1992)
2019Cohort
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