glycogen storage disease IX

Summary

glycogen storage disease IX (MONDO:0700291) is a disease with 4 cohort genes and 1 clinical trial. The dominant Reactome pathway is Glycogen breakdown (glycogenolysis) (4 cohort genes).

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 4
• ClinVar variants: 30
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1	Europe	Validated
Prevalence at birth	1-9 / 1 000 000	0.3	Israel	Validated
Prevalence at birth	1-9 / 1 000 000	0.5	Specific population	Validated
Point prevalence	1-9 / 100 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease IX
Mondo ID	MONDO:0700291
MeSH	C580130
Orphanet	370
DOID	DOID:0050594
NCIT	C122662
SNOMED CT	235908005
UMLS	C0268147
MedGen	468559
GARD	0027381
Is cancer (heuristic)	no

Also known as: glycogen storage disease 9 · glycogen storage disease IX · glycogen storage disease type 9 · glycogen storage disease type IX · glycogenosis due to phosphorylase kinase deficiency · glycogenosis type 9 · glycogenosis type IX · GSD IX · GSD type 9 · GSD type IX · GSD9 · GSDIX · phosphorylase kinase deficiency

Data availability: 30 ClinVar variants · 11 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorder of glycogen metabolism › glycogen storage disease IX

Related subtypes (23): glycogen storage disease I, glycogen storage disease due to GLUT2 deficiency, glycogen storage disease II, glycogen storage disease III, glycogen storage disease due to glycogen branching enzyme deficiency, glycogen storage disease V, glycogen storage disease VI, glycogen storage disease VII, glycogen storage disorder due to hepatic glycogen synthase deficiency, Lafora disease, glycogen storage disease due to phosphoglycerate mutase deficiency, lethal congenital glycogen storage disease of heart, Danon disease, glycogen storage disease IXd, glycogen storage disease due to phosphoglycerate kinase 1 deficiency, glycogen storage disease due to muscle and heart glycogen synthase deficiency, glycogen storage disease due to muscle beta-enolase deficiency, glycogen storage disease due to lactate dehydrogenase M-subunit deficiency, polyglucosan body myopathy 1 with or without immunodeficiency, glycogen storage disease due to lactate dehydrogenase deficiency, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, glycogen storage disease due to liver phosphorylase kinase deficiency, GYG1-related disorder of glycogen metabolism

Subtypes (4): glycogen storage disease IXb, glycogen storage disease IXa1, glycogen storage disease IXc, glycogen storage disease IXa2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

30 retrieved; paginated sample, class counts are floors:

10 pathogenic/likely pathogenic, 9 likely pathogenic, 8 pathogenic, 2 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3056727	NM_002637.4(PHKA1):c.2911C>T (p.Arg971Ter)	PHKA1	Pathogenic	criteria provided, single submitter
452732	NM_002637.4(PHKA1):c.2606+1G>A	PHKA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4849096	NM_002637.4(PHKA1):c.1571_1572dup (p.Ile525fs)	PHKA1	Pathogenic	criteria provided, single submitter
578746	NM_002637.4(PHKA1):c.892C>T (p.Arg298Ter)	PHKA1	Pathogenic	criteria provided, multiple submitters, no conflicts
1013871	NM_000292.3(PHKA2):c.4C>G (p.Arg2Gly)	PHKA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208493	NM_000292.3(PHKA2):c.883C>T (p.Arg295Cys)	PHKA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1333370	NM_000293.3(PHKB):c.1127-2A>G	PHKB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13619	NM_000293.3(PHKB):c.306-2A>G	PHKB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13620	NM_000293.3(PHKB):c.1257T>A (p.Tyr419Ter)	PHKB	Pathogenic	criteria provided, multiple submitters, no conflicts
1424135	NM_000293.3(PHKB):c.2427+965A>C	PHKB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1699565	NM_000293.3(PHKB):c.1285C>T (p.Arg429Ter)	PHKB	Pathogenic	criteria provided, multiple submitters, no conflicts
1804671	NM_000293.3(PHKB):c.2623C>T (p.Arg875Ter)	PHKB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2501064	NM_000293.3(PHKB):c.2839C>T (p.Gln947Ter)	PHKB	Pathogenic	criteria provided, multiple submitters, no conflicts
426940	NM_000293.3(PHKB):c.307C>T (p.Arg103Ter)	PHKB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
620526	NM_000293.3(PHKB):c.2326C>T (p.Gln776Ter)	PHKB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685403	NM_000294.3(PHKG2):c.835C>T (p.Arg279Cys)	PHKG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
623365	NM_000294.3(PHKG2):c.469G>A (p.Glu157Lys)	PHKG2	Pathogenic	criteria provided, multiple submitters, no conflicts
998119	NM_000294.3(PHKG2):c.643G>A (p.Asp215Asn)	PHKG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804673	NM_000293.3(PHKB):c.76+1G>C	LOC130058947	Likely pathogenic	criteria provided, single submitter
1804872	NM_002637.4(PHKA1):c.3244-155_3618del	PHKA1	Likely pathogenic	criteria provided, single submitter
2691280	NC_000023.10:g.71800926_(71804153_71812953)del	PHKA1	Likely pathogenic	criteria provided, single submitter
653856	NM_002637.4(PHKA1):c.2527-1G>T	PHKA1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1698539	NM_000292.3(PHKA2):c.2606C>G (p.Pro869Arg)	PHKA2	Likely pathogenic	criteria provided, single submitter
1328986	NC_000016.9:g.(47495338_47531309)_(47581460_47614205)del	PHKB	Likely pathogenic	criteria provided, single submitter
1723385	NC_000016.9:g.(47495338_47531309)_(47545684_47549431)del	PHKB	Likely pathogenic	criteria provided, single submitter
2429139	NC_000016.9:g.(47623014_47627410)_(47630443_47644736)del	PHKB	Likely pathogenic	criteria provided, single submitter
2445869	NM_000294.3(PHKG2):c.925C>T (p.Arg309Trp)	PHKG2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1321456	NM_000292.3(PHKA2):c.3058-1G>A	PHKA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3041477	NM_000294.3(PHKG2):c.698T>C (p.Phe233Ser)	PHKG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
440944	NM_000292.3(PHKA2):c.2137+5G>A	PHKA2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PHKA1	Orphanet:715	Glycogen storage disease due to muscle phosphorylase kinase deficiency
PHKA2	Orphanet:264580	Glycogen storage disease due to liver phosphorylase kinase deficiency
PHKB	Orphanet:79240	Glycogen storage disease due to liver and muscle phosphorylase kinase deficiency
PHKG2	Orphanet:264580	Glycogen storage disease due to liver phosphorylase kinase deficiency

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PHKA1	HGNC:8925	ENSG00000067177	P46020	Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform	clinvar
PHKA2	HGNC:8926	ENSG00000044446	P46019	Phosphorylase b kinase regulatory subunit alpha, liver isoform	clinvar
PHKB	HGNC:8927	ENSG00000102893	Q93100	Phosphorylase b kinase regulatory subunit beta	clinvar
PHKG2	HGNC:8931	ENSG00000156873	P15735	Phosphorylase b kinase gamma catalytic chain, liver/testis isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PHKA1	Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform	Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.
PHKA2	Phosphorylase b kinase regulatory subunit alpha, liver isoform	Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.
PHKB	Phosphorylase b kinase regulatory subunit beta	Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.
PHKG2	Phosphorylase b kinase gamma catalytic chain, liver/testis isoform	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.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	3	9.0×	0.004
Kinase	1	6.9×	0.137

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PHKA1	Enzyme (other)	yes	2.7.11.19	PHK_A/B_su, 6-hairpin_glycosidase_sf, GH15-like
PHKA2	Enzyme (other)	yes	2.7.11.19	PHK_A/B_su, 6-hairpin_glycosidase_sf, GH15-like
PHKB	Enzyme (other)	yes	2.7.11.19	PHK_A/B_su, 6-hairpin_glycosidase_sf, GH15-like
PHKG2	Kinase	yes	2.7.11.19	Prot_kinase_dom, Phosph_kin_gamma, Ser/Thr_kinase_AS

Expression context

Cohort genes with no expression data: 0.

4 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
gastrocnemius	1
skeletal muscle tissue of rectus abdominis	1
apex of heart	1
right lobe of liver	1
right uterine tube	1
adrenal tissue	1
quadriceps femoris	1
vastus lateralis	1
granulocyte	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PHKA1	227	ubiquitous	marker	gastrocnemius, skeletal muscle tissue of rectus abdominis, biceps brachii
PHKA2	266	ubiquitous	marker	right lobe of liver, right uterine tube, apex of heart
PHKB	299	ubiquitous	marker	adrenal tissue, vastus lateralis, quadriceps femoris
PHKG2	204	ubiquitous	marker	left testis, right testis, granulocyte

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHKA2	1,070
PHKB	1,035
PHKA1	973
PHKG2	190

Intra-cohort edges

A	B	Sources
PHKA1	PHKA2	intact
PHKA1	PHKB	string_interaction
PHKA1	PHKG2	biogrid_interaction, intact
PHKA2	PHKB	biogrid_interaction, intact
PHKA2	PHKG2	biogrid_interaction, intact
PHKB	PHKG2	biogrid_interaction, intact

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHKA1	P46020	10
PHKB	Q93100	6
PHKG2	P15735	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PHKA2	P46019	81.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 4 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glycogen breakdown (glycogenolysis)	4	761.3×	8e-12	PHKA1, PHKA2, PHKB, PHKG2
Glycogen metabolism	3	1427.5×	6e-10	PHKA1, PHKA2, PHKB
Metabolism of carbohydrates and carbohydrate derivatives	3	90.2×	3e-06	PHKA1, PHKA2, PHKB
Metabolism	3	8.7×	0.002	PHKA1, PHKA2, PHKB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glycogen metabolic process	4	526.6×	9e-11	PHKA1, PHKA2, PHKB, PHKG2
generation of precursor metabolites and energy	4	343.9×	3e-10	PHKA1, PHKA2, PHKB, PHKG2
positive regulation of glycogen catabolic process	2	2106.5×	7e-07	PHKA1, PHKG2
glycogen catabolic process	1	300.9×	0.007	PHKG2
protein modification process	1	61.1×	0.026	PHKA2
carbohydrate metabolic process	1	34.0×	0.039	PHKA2
protein phosphorylation	1	17.0×	0.066	PHKG2
signal transduction	1	4.0×	0.227	PHKG2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 3

Druggability breadth: 4 of 4 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PHKG2	AFATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PHKG2	36	4
PHKA1	0	0
PHKA2	0	0
PHKB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AFATINIB	4	PHKG2
FEDRATINIB	4	PHKG2
ALECTINIB	4	PHKG2
RUXOLITINIB	4	PHKG2
AFATINIB DIMALEATE	4	PHKG2
VANDETANIB	4	PHKG2
NILOTINIB	4	PHKG2
BOSUTINIB	4	PHKG2
GILTERITINIB	4	PHKG2
BRIGATINIB	4	PHKG2
NINTEDANIB	4	PHKG2
SUNITINIB	4	PHKG2
MIDOSTAURIN	4	PHKG2
GEFITINIB	4	PHKG2
CRENOLANIB	3	PHKG2
ALVOCIDIB	3	PHKG2
DOVITINIB	3	PHKG2
LESTAURTINIB	3	PHKG2
SILMITASERTIB	2	PHKG2
SU-014813	2	PHKG2
OSI-632	2	PHKG2
BMS-690514	2	PHKG2
MIVAVOTINIB	2	PHKG2
DANUSERTIB	2	PHKG2
R-406	2	PHKG2
BI-2536	2	PHKG2
MILCICLIB	2	PHKG2
TOZASERTIB	2	PHKG2
PELITINIB	2	PHKG2
PHA-793887	1	PHKG2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PHKG2	278	Binding:277, Functional:1
PHKA2	48	Binding:48
PHKB	21	Binding:21
PHKA1	20	Binding:20

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PHKA1	2.7.11.19	phosphorylase kinase
PHKA2	2.7.11.19	phosphorylase kinase
PHKB	2.7.11.19	phosphorylase kinase
PHKG2	2.7.11.19	phosphorylase kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PHKG2	278

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
AFATINIB	4	PHKG2
FEDRATINIB	4	PHKG2
ALECTINIB	4	PHKG2
RUXOLITINIB	4	PHKG2
AFATINIB DIMALEATE	4	PHKG2
VANDETANIB	4	PHKG2
NILOTINIB	4	PHKG2
BOSUTINIB	4	PHKG2
GILTERITINIB	4	PHKG2
BRIGATINIB	4	PHKG2
NINTEDANIB	4	PHKG2
SUNITINIB	4	PHKG2
MIDOSTAURIN	4	PHKG2
GEFITINIB	4	PHKG2
CRENOLANIB	3	PHKG2
ALVOCIDIB	3	PHKG2
DOVITINIB	3	PHKG2
LESTAURTINIB	3	PHKG2
SILMITASERTIB	2	PHKG2
SU-014813	2	PHKG2
OSI-632	2	PHKG2
BMS-690514	2	PHKG2
MIVAVOTINIB	2	PHKG2
DANUSERTIB	2	PHKG2
R-406	2	PHKG2
BI-2536	2	PHKG2
MILCICLIB	2	PHKG2
TOZASERTIB	2	PHKG2
PELITINIB	2	PHKG2
PHA-793887	1	PHKG2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PHKG2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	PHKA1, PHKB
D	Druggable family + AlphaFold only, no drug	1	PHKA2
E	Difficult family or no structure, no drug	0

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PHKA1	20	—
PHKA2	48	—
PHKB	21	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy