PHKB

Chr 16AR

phosphorylase kinase regulatory subunit beta

NCBI Gene: 5257 ENSG00000102893 UniProt: Q93100 OMIM: 172490

The PHKB protein serves as the regulatory beta subunit of phosphorylase kinase, a 16-subunit enzyme that controls glycogen breakdown through phosphorylation-mediated regulation. Mutations in PHKB cause glycogen storage disease type 9B (phosphorylase kinase deficiency of liver and muscle) with autosomal recessive inheritance. The pathogenic mechanism involves gain-of-function effects that disrupt normal glycogen metabolism regulation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, encoded by two different genes. The beta subunit is the same in both the muscle and hepatic isoforms, encoded by this gene, which is a member of the phosphorylase b kinase regulatory subunit family. The gamma subunit also includes the skeletal muscle and hepatic isoforms, encoded by two different genes. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9B, also known as phosphorylase kinase deficiency of liver and muscle. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. Two pseudogenes have been found on chromosomes 14 and 20, respectively.[provided by RefSeq, Feb 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

GOFmechanismARLOEUF 0.841 OMIM phenotype

Clinical Summary— PHKB

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Gene-Disease Validity (ClinGen)

glycogen storage disease IXb · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

162 unique Pathogenic / Likely Pathogenic· 391 VUS of 1256 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PHKB

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.66

OE 0.65 (0.51–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.30Z-score

OE missense 0.97 (0.90–1.03)

568 obs / 588.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.51–0.84)

0≤0.351.4

Missense OE?0.97 (0.90–1.03)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 44 / 67.6Missense obs/exp: 568 / 588.4Syn Z: 0.74

This gene — mechanism propensity

0.6065th %ile

GOF

0.6639th %ile

LOF

0.3746th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

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

1256 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic90

Likely Pathogenic72

VUS391

Likely Benign596

Benign35

Conflicting40

Pathogenic

Likely Pathogenic

391

VUS

596

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	67	0	23	0	90
Likely Pathogenic	61	0	11	0	72
VUS	4	334	48	5	391
Likely Benign	4	21	300	271	596
Benign	0	3	29	3	35
Conflicting	—				40
Total	136	358	411	279	1,224

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap PHKB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →