PHKG2

Chr 16AR

phosphorylase kinase catalytic subunit gamma 2

NCBI Gene: 5261ENSG00000156873UniProt: P15735

Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. May regulate glycogeneolysis in the testis. In vitro, phosphorylates PYGM (PubMed:35549678)

Primary Disease Associations & Inheritance

Glycogen storage disease IXcMIM #613027
AR
525
ClinVar variants
41
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PHKG2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 129 VUS of 525 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.
0.66LOEUF
pLI 0.004
Z-score 2.76
OE 0.36 (0.21–0.66)
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.
0.45Z-score
OE missense 0.92 (0.82–1.03)
228 obs / 247.9 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.0.36 (0.21–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.82–1.03)
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.1.15
0≤1.21.6
LoF obs/exp: 8 / 22.0Missense obs/exp: 228 / 247.9Syn Z: -1.13

ClinVar Variant Classifications

525 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic12
VUS129
Likely Benign209
Benign10
Conflicting7
29
Pathogenic
12
Likely Pathogenic
129
VUS
209
Likely Benign
10
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
4
15
0
29
Likely Pathogenic
8
4
0
0
12
VUS
1
115
13
0
129
Likely Benign
0
7
77
125
209
Benign
0
1
8
1
10
Conflicting
—7
Total19131113126396

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glycogen storage disease IXc

MIM #613027

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).
Kishnani PS et al.·Genet Med
2019
Novel PHKG2 mutation causing GSD IX with prominent liver disease: report of three cases and review of literature.
Albash B et al.·Eur J Pediatr
2014Review
Integrative Analysis of Novel Ferroptosis-Related Genes Signatures as Prognostic Biomarkers in Ovarian Cancer.
Cao L et al.·Cancer Rep (Hoboken)
2025
Variability of clinical and biochemical phenotype in liver phosphorylase kinase deficiency with variants in the phosphorylase kinase (PHKG2) gene.
Waheed N et al.·J Pediatr Endocrinol Metab
2020Case report
A very rare case report of glycogen storage disease type IXc with novel PHKG2 variants.
Shao Y et al.·BMC Pediatr
2022Case report
Novel Multitarget Therapies for Lung Cancer and Respiratory Disease.
Yumura M et al.·Molecules
2020Review
A novel sequence of the PHKG2 mutation associated with the first case of glycogen storage diseases type IXc in Syria: a case report and review of literature.
Harh S et al.·J Med Case Rep
2025Review
Clinical, pathological and molecular spectrum of patients with glycogen storage diseases in Pakistan.
Ahmed S et al.·J Pediatr Endocrinol Metab
2022Cohort
Severe phenotype of phosphorylase kinase-deficient liver glycogenosis with mutations in the PHKG2 gene.
Burwinkel B et al.·Pediatr Res
2003Case report
Liver glycogenosis due to phosphorylase kinase deficiency: PHKG2 gene structure and mutations associated with cirrhosis.
Burwinkel B et al.·Hum Mol Genet
1998
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