glycogen storage disease IXb

Summary

glycogen storage disease IXb (MONDO:0009868) is a disease caused by PHKB (GenCC Strong), with 2 cohort genes and 2 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: PHKB (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 1,048
• Phenotypes (HPO): 43
• Clinical trials: 2

Clinical features

Signs & symptoms

Clinical features (HPO)

43 HPO clinical features (Orphanet curated; top 43 by frequency):

HPO ID	Term	Frequency
HP:0002155	Hypertriglyceridemia	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0008897	Postnatal growth retardation	Very frequent (80-99%)
HP:0012379	Abnormal enzyme/coenzyme activity	Very frequent (80-99%)
HP:0001395	Hepatic fibrosis	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0003124	Hypercholesterolemia	Frequent (30-79%)
HP:0003162	Fasting hypoglycemia	Frequent (30-79%)
HP:0000147	Polycystic ovaries	Occasional (5-29%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0000858	Irregular menstruation	Occasional (5-29%)
HP:0000876	Oligomenorrhea	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001394	Cirrhosis	Occasional (5-29%)
HP:0001744	Splenomegaly	Occasional (5-29%)
HP:0001947	Renal tubular acidosis	Occasional (5-29%)
HP:0001988	Recurrent hypoglycemia	Occasional (5-29%)
HP:0002194	Delayed gross motor development	Occasional (5-29%)
HP:0002719	Recurrent infections	Occasional (5-29%)
HP:0003202	Skeletal muscle atrophy	Occasional (5-29%)
HP:0003236	Elevated circulating creatine kinase concentration	Occasional (5-29%)
HP:0003323	Progressive muscle weakness	Occasional (5-29%)
HP:0003325	Limb-girdle muscle weakness	Occasional (5-29%)
HP:0003326	Myalgia	Occasional (5-29%)
HP:0003394	Muscle spasm	Occasional (5-29%)
HP:0003546	Exercise intolerance	Occasional (5-29%)
HP:0003749	Pelvic girdle muscle weakness	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0011342	Mild global developmental delay	Occasional (5-29%)
HP:0012378	Fatigue	Occasional (5-29%)
HP:0012734	Ketotic hypoglycemia	Occasional (5-29%)
HP:0100607	Dysmenorrhea	Occasional (5-29%)
HP:0000939	Osteoporosis	Very rare (<1-4%)
HP:0001402	Hepatocellular carcinoma	Very rare (<1-4%)
HP:0001903	Anemia	Very rare (<1-4%)
HP:0002013	Vomiting	Very rare (<1-4%)
HP:0002014	Diarrhea	Very rare (<1-4%)
HP:0002018	Nausea	Very rare (<1-4%)
HP:0002913	Myoglobinuria	Very rare (<1-4%)
HP:0003128	Lactic acidosis	Very rare (<1-4%)
HP:0003201	Rhabdomyolysis	Very rare (<1-4%)
HP:0004324	Increased body weight	Very rare (<1-4%)
HP:0012028	Hepatocellular adenoma	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease IXb
Mondo ID	MONDO:0009868
MeSH	C563008
OMIM	261750
Orphanet	79240
DOID	DOID:0111041
UMLS	C0543514
MedGen	107772
GARD	0016711
Is cancer (heuristic)	no

Also known as: glycogen storage disease 9B · glycogen storage disease caused by mutation in PHKB · glycogen storage disease IXb · glycogen storage disease type 9B · glycogen storage disease type IXb · glycogenosis due to liver and muscle phosphorylase kinase deficiency · glycogenosis type 9B · glycogenosis type IXb · GSD due to liver and muscle phosphorylase kinase deficiency · GSD IXb · GSD type 9B · GSD type IXb · GSD9B · PHKB glycogen storage disease · PHKB-related glycogen storage disease type IX

Data availability: 1,048 ClinVar variants · 4 GenCC gene-disease records.

Disease family

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 › glycogen storage disease IXb

Related subtypes (3): 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

600 retrieved; paginated sample, class counts are floors:

338 likely benign, 172 uncertain significance, 39 pathogenic, 21 likely pathogenic, 11 benign, 8 conflicting classifications of pathogenicity, 7 pathogenic/likely pathogenic, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13621	NM_000293.2(PHKB):c.[2923T>C;2926G>T]		Pathogenic	no assertion criteria provided
1070588	NM_000293.3(PHKB):c.2427+1045del	PHKB	Pathogenic	criteria provided, single submitter
1070610	NC_000016.9:g.(?47545556)(47581479_?)del	PHKB	Pathogenic	criteria provided, single submitter
1186084	NM_000293.3(PHKB):c.570_576delinsAC (p.Gln191fs)	PHKB	Pathogenic/Likely 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
13617	NM_000293.3(PHKB):c.1265dup (p.Asn422fs)	PHKB	Pathogenic	criteria provided, single submitter
13618	NM_000293.3(PHKB):c.1969C>T (p.Gln657Ter)	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
1433722	NC_000016.9:g.(?47495262)(47644851_?)del	PHKB	Pathogenic	criteria provided, single submitter
1455940	NM_000293.3(PHKB):c.2048dup (p.Ser684fs)	PHKB	Pathogenic	criteria provided, single submitter
1457393	NC_000016.9:g.(?47614186)(47644851_?)del	PHKB	Pathogenic	criteria provided, single submitter
1683502	NM_000293.3(PHKB):c.573_577del (p.Gln191fs)	PHKB	Pathogenic	criteria provided, multiple submitters, no conflicts
1686061	NM_000293.3(PHKB):c.1688C>A (p.Ser563Ter)	PHKB	Pathogenic	criteria provided, single submitter
1690697	NM_000293.3(PHKB):c.1972-2A>G	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
2035718	NM_000293.3(PHKB):c.341dup (p.Glu115fs)	PHKB	Pathogenic	criteria provided, single submitter
2078619	NM_000293.3(PHKB):c.1805_1808dup (p.Gln603fs)	PHKB	Pathogenic	criteria provided, single submitter
2422824	NC_000016.9:g.(?47531290)(47581479_?)del	PHKB	Pathogenic	criteria provided, single submitter
242718	NM_000293.3(PHKB):c.2926G>T (p.Glu976Ter)	PHKB	Pathogenic	criteria provided, single submitter
2501064	NM_000293.3(PHKB):c.2839C>T (p.Gln947Ter)	PHKB	Pathogenic	criteria provided, multiple submitters, no conflicts
2637056	NM_000293.3(PHKB):c.2896-1G>T	PHKB	Pathogenic	criteria provided, multiple submitters, no conflicts
2692944	NM_000293.3(PHKB):c.369_370del (p.Gly124fs)	PHKB	Pathogenic	criteria provided, single submitter
2693660	NM_000293.3(PHKB):c.1622dup (p.Ile543fs)	PHKB	Pathogenic	criteria provided, single submitter
2694652	NM_000293.3(PHKB):c.127G>T (p.Glu43Ter)	PHKB	Pathogenic	criteria provided, single submitter
2697311	NM_000293.3(PHKB):c.80C>G (p.Ser27Ter)	PHKB	Pathogenic	criteria provided, single submitter
2709953	NM_000293.3(PHKB):c.1320del (p.Leu442fs)	PHKB	Pathogenic	criteria provided, single submitter
2713914	NM_000293.3(PHKB):c.3038del (p.Asn1013fs)	PHKB	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PHKB	Strong	Autosomal recessive	glycogen storage disease IXb	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PHKB	Orphanet:79240	Glycogen storage disease due to liver and muscle phosphorylase kinase deficiency
GPT2	Orphanet:477673	Postnatal microcephaly-infantile hypotonia-spastic diplegia-dysarthria-intellectual disability syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PHKB	HGNC:8927	ENSG00000102893	Q93100	Phosphorylase b kinase regulatory subunit beta	gencc,clinvar
GPT2	HGNC:18062	ENSG00000166123	Q8TD30	Alanine aminotransferase 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PHKB	Phosphorylase b kinase regulatory subunit beta	Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.
GPT2	Alanine aminotransferase 2	Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PHKB	Enzyme (other)	yes	2.7.11.19	PHK_A/B_su, 6-hairpin_glycosidase_sf, GH15-like
GPT2	Other/Unknown	no		Aminotransferase_I/II_large, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
quadriceps femoris	1
vastus lateralis	1
body of pancreas	1
hindlimb stylopod muscle	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PHKB	299	ubiquitous	marker	adrenal tissue, vastus lateralis, quadriceps femoris
GPT2	237	ubiquitous	marker	lower esophagus mucosa, body of pancreas, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GPT2	2,823
PHKB	1,035

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHKB	Q93100	6
GPT2	Q8TD30	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Alanine metabolism	1	2855.0×	0.002	GPT2
Glycogen metabolism	1	951.7×	0.003	PHKB
Glycogen breakdown (glycogenolysis)	1	380.7×	0.004	PHKB
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.021	PHKB
Metabolism	1	5.8×	0.165	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete L-alanine metabolic process	1	8426.0×	6e-04	GPT2
L-alanine catabolic process	1	2106.5×	0.001	GPT2
2-oxoglutarate metabolic process	1	468.1×	0.004	GPT2
glycogen metabolic process	1	263.3×	0.005	PHKB
generation of precursor metabolites and energy	1	172.0×	0.006	PHKB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PHKB	0	0
GPT2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PHKB	21	Binding:21

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PHKB	2.7.11.19	phosphorylase kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PHKB
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GPT2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PHKB	21	—
GPT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04454216	Not specified	RECRUITING	GSD VI and GSD IX Natural History