PHKG2
Chr 16ARphosphorylase kinase catalytic subunit gamma 2
Also known as: GSD9C
The phosphorylase kinase gamma regulatory subunit catalyzes the phosphorylation and activation of glycogen phosphorylase, which is essential for glycogen breakdown in the liver. Biallelic mutations cause glycogen storage disease type IXc, characterized by hepatomegaly and growth retardation typically presenting in infancy or early childhood with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.657), primarily affecting hepatic glycogen metabolism.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
329 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 15 | 5 | 6 | 0 | 26 |
Likely Pathogenic | 7 | 4 | 0 | 0 | 11 |
VUS | 3 | 116 | 10 | 0 | 129 |
Likely Benign | 0 | 9 | 40 | 70 | 119 |
Benign | 0 | 1 | 3 | 1 | 5 |
Conflicting | — | 10 | |||
| Total | 25 | 135 | 59 | 71 | 300 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PHKG2 · 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