PRKAB2
Chr 1protein kinase AMP-activated non-catalytic subunit beta 2
The protein serves as a non-catalytic regulatory subunit of AMP-activated protein kinase (AMPK), an energy sensor that monitors cellular energy status and regulates metabolic pathways by phosphorylating key enzymes involved in fatty acid and cholesterol biosynthesis. Mutations cause Wolff-Parkinson-White syndrome with intellectual disability and other abnormalities, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.485), indicating that complete protein loss is poorly tolerated.
Disputed — evidence questions this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
325 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools