glycogen storage disease IXc

Summary

glycogen storage disease IXc (MONDO:0013091) is a disease caused by PHKG2 (GenCC Strong), with 1 cohort gene and 2 clinical trials.

At a glance

• Causal gene: PHKG2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 344
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease IXc
Mondo ID	MONDO:0013091
MeSH	C567809
OMIM	613027
DOID	DOID:0111043
UMLS	C2751643
MedGen	442778
GARD	0018387
Is cancer (heuristic)	no

Also known as: glycogen storage disease caused by mutation in PHKG2 · glycogen storage disease IXc · glycogen storage disease type IXc · GSD type 9C · GSD type IXc · GSD9C · PHKG2 glycogen storage disease · PHKG2-related glycogen storage disease type IX

Data availability: 344 ClinVar variants · 3 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 due to liver phosphorylase kinase deficiency › glycogen storage disease IXc

Related subtypes (1): glycogen storage disease IXa1

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

344 retrieved; paginated sample, class counts are floors:

203 likely benign, 59 uncertain significance, 36 pathogenic, 23 conflicting classifications of pathogenicity, 9 likely pathogenic, 7 pathogenic/likely pathogenic, 4 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066974	NM_000294.3(PHKG2):c.96-11G>A	PHKG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072144	NM_000294.3(PHKG2):c.557-1_557delinsAG	PHKG2	Pathogenic	criteria provided, single submitter
13625	NM_000294.3(PHKG2):c.265dup (p.His89fs)	PHKG2	Pathogenic	criteria provided, single submitter
13626	NM_000294.3(PHKG2):c.566G>A (p.Gly189Glu)	PHKG2	Pathogenic	no assertion criteria provided
13627	NM_000294.3(PHKG2):c.317T>A (p.Val106Glu)	PHKG2	Pathogenic	criteria provided, single submitter
13628	NM_000294.3(PHKG2):c.130C>T (p.Arg44Ter)	PHKG2	Pathogenic	criteria provided, multiple submitters, no conflicts
13629	NM_000294.3(PHKG2):c.277del (p.Leu93fs)	PHKG2	Pathogenic	no assertion criteria provided
13630	NM_000294.3(PHKG2):c.433C>T (p.His145Tyr)	PHKG2	Pathogenic	no assertion criteria provided
13631	NM_000294.3(PHKG2):c.677T>G (p.Leu226Arg)	PHKG2	Pathogenic	no assertion criteria provided
1453300	NM_000294.3(PHKG2):c.226C>T (p.Arg76Ter)	PHKG2	Pathogenic	criteria provided, single submitter
1459077	NM_000294.3(PHKG2):c.502C>T (p.Arg168Ter)	PHKG2	Pathogenic	criteria provided, single submitter
1685403	NM_000294.3(PHKG2):c.835C>T (p.Arg279Cys)	PHKG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686062	NM_000294.3(PHKG2):c.927+1G>A	PHKG2	Pathogenic	criteria provided, single submitter
1687518	NM_000294.3(PHKG2):c.800_801+34del	PHKG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705670	NM_000294.3(PHKG2):c.802-2A>C	PHKG2	Pathogenic	criteria provided, single submitter
2020749	NM_000294.3(PHKG2):c.334_337del (p.Lys112fs)	PHKG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2023569	NM_000294.3(PHKG2):c.648-2_648del	PHKG2	Pathogenic	criteria provided, single submitter
2023570	NM_000294.3(PHKG2):c.827del (p.Pro276fs)	PHKG2	Pathogenic	criteria provided, single submitter
2126568	NM_000294.3(PHKG2):c.767del (p.Glu256fs)	PHKG2	Pathogenic	criteria provided, single submitter
2736338	NM_000294.3(PHKG2):c.900G>A (p.Trp300Ter)	PHKG2	Pathogenic	criteria provided, single submitter
2752978	NM_000294.3(PHKG2):c.385G>T (p.Glu129Ter)	PHKG2	Pathogenic	criteria provided, single submitter
2769867	NM_000294.3(PHKG2):c.905_909del (p.Leu302fs)	PHKG2	Pathogenic	criteria provided, single submitter
2834443	NM_000294.3(PHKG2):c.53_54del (p.Lys18fs)	PHKG2	Pathogenic	criteria provided, single submitter
2862845	NM_000294.3(PHKG2):c.72C>A (p.Tyr24Ter)	PHKG2	Pathogenic	criteria provided, single submitter
3000582	NM_000294.3(PHKG2):c.850C>T (p.Gln284Ter)	PHKG2	Pathogenic	criteria provided, single submitter
3243489	NC_000016.9:g.(?30760142)(30768418_?)del	PHKG2	Pathogenic	criteria provided, single submitter
3243490	NC_000016.9:g.(?30762850)(30762944_?)del	PHKG2	Pathogenic	criteria provided, single submitter
3721908	NM_000294.3(PHKG2):c.679del (p.Leu227fs)	PHKG2	Pathogenic	criteria provided, single submitter
3722164	NM_000294.3(PHKG2):c.859C>T (p.Gln287Ter)	PHKG2	Pathogenic	criteria provided, single submitter
4813543	NM_000294.3(PHKG2):c.455G>A (p.Arg152Gln)	PHKG2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
PHKG2	Strong	Autosomal recessive	glycogen storage disease IXc	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PHKG2	Orphanet:264580	Glycogen storage disease due to liver phosphorylase kinase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PHKG2	HGNC:8931	ENSG00000156873	P15735	Phosphorylase b kinase gamma catalytic chain, liver/testis isoform	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 1 · 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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PHKG2	204	ubiquitous	marker	left testis, right testis, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHKG2	190

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHKG2	P15735	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 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 1 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)	1	761.3×	0.001	PHKG2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of glycogen catabolic process	1	4213.0×	0.001	PHKG2
glycogen catabolic process	1	1203.7×	0.002	PHKG2
glycogen metabolic process	1	526.6×	0.004	PHKG2
generation of precursor metabolites and energy	1	343.9×	0.004	PHKG2
protein phosphorylation	1	68.0×	0.018	PHKG2
signal transduction	1	16.1×	0.062	PHKG2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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

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): 1.

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

Symbol	Assays	Type breakdown
PHKG2	278	Binding:277, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
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: 1; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

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