glycogen storage disease IXa2

Summary

glycogen storage disease IXa2 (MONDO:0100439) is a disease with 2 cohort genes and 1 clinical trial.

At a glance

• Cohort genes: 2
• ClinVar variants: 8
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease IXa2
Mondo ID	MONDO:0100439
UMLS	C2748941
MedGen	411335
GARD	0026215
Is cancer (heuristic)	no

Also known as: GSD IXa2 · GSD9A2 · liver glycogenosis, X-linked, type 2

Data availability: 8 ClinVar variants.

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 IXa2

Related subtypes (3): glycogen storage disease IXb, glycogen storage disease IXa1, glycogen storage disease IXc

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

8 retrieved; paginated sample, class counts are floors:

4 pathogenic, 3 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
10536	NM_000292.3(PHKA2):c.395A>C (p.His132Pro)	PHKA2	Pathogenic	criteria provided, single submitter
10537	NM_000292.3(PHKA2):c.394C>T (p.His132Tyr)	PHKA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10539	NM_000292.3(PHKA2):c.750_752del (p.Thr251del)	PHKA2	Pathogenic	no assertion criteria provided
10540	NM_000292.3(PHKA2):c.3327_3332dup (p.Arg1111_Glu1112insThrArg)	PHKA2	Pathogenic	no assertion criteria provided
10533	NM_000292.3(PHKA2):c.3341C>T (p.Thr1114Ile)	PHKA2-AS1	Pathogenic	criteria provided, single submitter
10535	NM_000292.3(PHKA2):c.557G>A (p.Arg186His)	PHKA2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
10538	NM_000292.3(PHKA2):c.556C>T (p.Arg186Cys)	PHKA2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
10541	NM_000292.3(PHKA2):c.565A>G (p.Lys189Glu)	PHKA2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PHKA2	Orphanet:264580	Glycogen storage disease due to liver phosphorylase kinase deficiency

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PHKA2-AS1	HGNC:44110	ENSG00000237836		PHKA2 antisense RNA 1	clinvar
PHKA2	HGNC:8926	ENSG00000044446	P46019	Phosphorylase b kinase regulatory subunit alpha, liver isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PHKA2	Phosphorylase b kinase regulatory subunit alpha, liver isoform	Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.

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)
PHKA2-AS1	Other/Unknown	no
PHKA2	Enzyme (other)	yes	2.7.11.19	PHK_A/B_su, 6-hairpin_glycosidase_sf, GH15-like

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
right adrenal gland	1
right adrenal gland cortex	1
apex of heart	1
right lobe of liver	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PHKA2-AS1	131		yes	male germ line stem cell (sensu Vertebrata) in testis, right adrenal gland, right adrenal gland cortex
PHKA2	266	ubiquitous	marker	right lobe of liver, right uterine tube, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHKA2	1,070
PHKA2-AS1	0

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 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 2 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 metabolism	1	1903.3×	0.002	PHKA2
Glycogen breakdown (glycogenolysis)	1	761.3×	0.003	PHKA2
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.011	PHKA2
Metabolism	1	11.6×	0.086	PHKA2

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
glycogen metabolic process	1	526.6×	0.005	PHKA2
generation of precursor metabolites and energy	1	343.9×	0.005	PHKA2
protein modification process	1	244.2×	0.005	PHKA2
carbohydrate metabolic process	1	135.9×	0.007	PHKA2

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
PHKA2-AS1	0	0
PHKA2	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
PHKA2	48	Binding:48

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PHKA2	2.7.11.19	phosphorylase kinase

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

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	0
D	Druggable family + AlphaFold only, no drug	1	PHKA2
E	Difficult family or no structure, no drug	1	PHKA2-AS1

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)
PHKA2-AS1	0	—
PHKA2	48	—

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
NCT04454216	Not specified	RECRUITING	GSD VI and GSD IX Natural History