Glycoprotein storage disease

Summary

Glycoprotein storage disease (MONDO:0009296) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glycoprotein storage disease
Mondo ID	MONDO:0009296
MeSH	C565538
OMIM	232900
SNOMED CT	7810004
UMLS	C1856275
MedGen	343516
GARD	0024655
Is cancer (heuristic)	no

Also known as: glycoprotein storage disease · glycoprotein storage disorder

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › lysosomal storage disease › glycoprotein storage disease

Related subtypes (10): lysosomal acid phosphatase deficiency, pycnodysostosis, hereditary spastic paraplegia 48, late infantile neuronal ceroid lipofuscinosis, glycoproteinosis, disorder of sialic acid metabolism, lysosomal glycogen storage disease, lysosomal lipid storage disorder, inborn disorder of lysosomal amino acid transport, mucopolysaccharidosis

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
972747	NM_000152.5(GAA):c.1781G>A (p.Arg594His)	GAA	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GAA	Orphanet:308552	Glycogen storage disease due to acid maltase deficiency, infantile onset
GAA	Orphanet:420429	Glycogen storage disease due to acid maltase deficiency, late-onset

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
GAA	HGNC:4065	ENSG00000171298	P10253	Lysosomal alpha-glucosidase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GAA	Lysosomal alpha-glucosidase	Essential for the degradation of glycogen in lysosomes.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GAA	Enzyme (other)	yes	3.2.1.20	Glyco_hydro_31_TIM, P_trefoil_dom, Gal_mutarotase_sf_dom

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
GAA	261	ubiquitous	marker	granulocyte, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GAA	2,116

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GAA	P10253	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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 storage diseases	1	5710.0×	0.001	GAA
Glycogen storage disease type II (GAA)	1	5710.0×	0.001	GAA
Glycogen metabolism	1	1903.3×	0.002	GAA
Diseases of carbohydrate metabolism	1	815.7×	0.003	GAA
Glycogen breakdown (glycogenolysis)	1	761.3×	0.003	GAA
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.017	GAA
Diseases of metabolism	1	80.4×	0.021	GAA
Innate Immune System	1	25.5×	0.058	GAA
Neutrophil degranulation	1	23.1×	0.058	GAA
Disease	1	13.1×	0.084	GAA
Immune System	1	13.0×	0.084	GAA
Metabolism	1	11.6×	0.086	GAA

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
maltose metabolic process	1	16852.0×	3e-04	GAA
sucrose metabolic process	1	16852.0×	3e-04	GAA
obsolete vacuolar sequestering	1	16852.0×	3e-04	GAA
diaphragm contraction	1	4213.0×	0.001	GAA
tissue development	1	1872.4×	0.002	GAA
glycophagy	1	1404.3×	0.002	GAA
glycogen catabolic process	1	1203.7×	0.002	GAA
neuromuscular process controlling posture	1	1053.2×	0.002	GAA
regulation of the force of heart contraction	1	991.3×	0.002	GAA
muscle cell cellular homeostasis	1	648.1×	0.003	GAA
aorta development	1	561.7×	0.003	GAA
cardiac muscle contraction	1	401.2×	0.003	GAA
heart morphogenesis	1	374.5×	0.003	GAA
neuromuscular process controlling balance	1	330.4×	0.004	GAA
lysosome organization	1	306.4×	0.004	GAA
glucose metabolic process	1	255.3×	0.004	GAA
locomotory behavior	1	179.3×	0.006	GAA

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
GAA	DIENESTROL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GAA	112	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DIENESTROL	4	GAA
MIGLUSTAT	4	GAA
DICLOFENAC SODIUM	4	GAA
DIBUCAINE	4	GAA
AMLEXANOX	4	GAA
MIGALASTAT	4	GAA
ARIPIPRAZOLE	4	GAA
DULOXETINE	4	GAA
LABETALOL HYDROCHLORIDE	4	GAA
MORICIZINE HYDROCHLORIDE	4	GAA
PHENYLEPHRINE HYDROCHLORIDE	4	GAA
DEMECLOCYCLINE HYDROCHLORIDE	4	GAA
DOXAZOSIN MESYLATE	4	GAA
PRILOCAINE HYDROCHLORIDE	4	GAA
FLUOROMETHOLONE	4	GAA
PHENELZINE SULFATE	4	GAA
RABEPRAZOLE SODIUM	4	GAA
METHYSERGIDE MALEATE	4	GAA
ACRISORCIN	4	GAA
ECONAZOLE NITRATE	4	GAA
ISOETHARINE MESYLATE	4	GAA
QUINESTROL	4	GAA
DEFEROXAMINE MESYLATE	4	GAA
MAPROTILINE HYDROCHLORIDE	4	GAA
EPINEPHRINE BITARTRATE	4	GAA
PROCHLORPERAZINE MALEATE	4	GAA
IRBESARTAN	4	GAA
OXYTETRACYCLINE	4	GAA
DOPAMINE HYDROCHLORIDE	4	GAA
PRAZOSIN HYDROCHLORIDE	4	GAA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GAA	280	Binding:267, Functional:13

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GAA	3.2.1.20	alpha-glucosidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GAA	280

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)
DIENESTROL	4	GAA
MIGLUSTAT	4	GAA
DICLOFENAC SODIUM	4	GAA
DIBUCAINE	4	GAA
AMLEXANOX	4	GAA
MIGALASTAT	4	GAA
ARIPIPRAZOLE	4	GAA
DULOXETINE	4	GAA
LABETALOL HYDROCHLORIDE	4	GAA
MORICIZINE HYDROCHLORIDE	4	GAA
PHENYLEPHRINE HYDROCHLORIDE	4	GAA
DEMECLOCYCLINE HYDROCHLORIDE	4	GAA
DOXAZOSIN MESYLATE	4	GAA
PRILOCAINE HYDROCHLORIDE	4	GAA
FLUOROMETHOLONE	4	GAA
PHENELZINE SULFATE	4	GAA
RABEPRAZOLE SODIUM	4	GAA
METHYSERGIDE MALEATE	4	GAA
ACRISORCIN	4	GAA
ECONAZOLE NITRATE	4	GAA
ISOETHARINE MESYLATE	4	GAA
QUINESTROL	4	GAA
DEFEROXAMINE MESYLATE	4	GAA
MAPROTILINE HYDROCHLORIDE	4	GAA
EPINEPHRINE BITARTRATE	4	GAA
PROCHLORPERAZINE MALEATE	4	GAA
IRBESARTAN	4	GAA
OXYTETRACYCLINE	4	GAA
DOPAMINE HYDROCHLORIDE	4	GAA
PRAZOSIN HYDROCHLORIDE	4	GAA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GAA
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: 0.