PHKA2

Chr XXLR

phosphorylase kinase regulatory subunit alpha 2

Also known as: GSD9A, PHK, PYK, PYKL, XLG, XLG2

The PHKA2 gene encodes the hepatic alpha subunit of phosphorylase kinase, a regulatory enzyme in glycogen metabolism where the alpha subunit controls enzyme activity through phosphorylation while the gamma subunit contains the catalytic site. Mutations cause glycogen storage disease types IXa1 and IXa2 (X-linked liver glycogenosis) through loss of phosphorylase kinase regulation, leading to impaired glycogen breakdown in the liver. This follows X-linked recessive inheritance, primarily affecting males.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
XLRLOEUF 0.372 OMIM phenotypes
Clinical SummaryPHKA2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 37 VUS of 100 total submissions
📖
GeneReview available — PHKA2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.37LOEUF
pLI 0.384
Z-score 5.01
OE 0.23 (0.140.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.82Z-score
OE missense 0.78 (0.710.84)
404 obs / 521.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.140.37)
00.351.4
Missense OE0.78 (0.710.84)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 11 / 48.8Missense obs/exp: 404 / 521.2Syn Z: -2.04

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic5
VUS37
Likely Benign43
Benign4
4
Pathogenic
5
Likely Pathogenic
37
VUS
43
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
3
0
4
Likely Pathogenic
3
2
0
0
5
VUS
0
30
7
0
37
Likely Benign
0
4
18
21
43
Benign
0
0
2
2
4
Total436302393

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

View in ClinVar →

Protein Context — Lollipop Plot

PHKA2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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