GAA

Chr 17AR

alpha glucosidase

The encoded lysosomal alpha-glucosidase degrades glycogen to glucose in lysosomes by hydrolyzing alpha-1,4-linked and alpha-1,6-linked glucosidic bonds. Mutations cause Pompe disease, an autosomal recessive glycogen storage disorder that presents as either infantile-onset or late-onset forms. The pathogenic mechanism involves loss of enzyme function leading to pathological glycogen accumulation in lysosomes.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.982 OMIM phenotypes
VCEP Guidelines: Lysosomal DiseasesReleased
ClinGen Panel
Clinical SummaryGAA
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Gene-Disease Validity (ClinGen)
glycogen storage disease II · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.66
OE 0.74 (0.560.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.63Z-score
OE missense 1.07 (1.001.15)
646 obs / 602.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.74 (0.560.98)
00.351.4
Missense OE1.07 (1.001.15)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 34 / 46.1Missense obs/exp: 646 / 602.3Syn Z: -0.90
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGAA-related Pompe diseaseLOFAR
definitiveGAA-related glycogen storage diseaseLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5869th %ile
GOF
0.6541th %ile
LOF
0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GAA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Friedreich Ataxia

A Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)

ACTIVE NOT RECRUITING
NCT04349514Monash UniversityStarted 2021-02-10
Natural history
Ataxia, Gait

Ataxia GAA-FGF14 - Descriptive Genetic and Clinical Study

ACTIVE NOT RECRUITING
NCT05884086Central Hospital, Nancy, FranceStarted 2023-05-01
Pompe Disease (Late-onset)Pompe Disease Late-OnsetLOPD

A Study to Evaluate Safety, Tolerability, and Efficacy of AB-1009 Gene Therapy (GAA Gene) in Adult Participants With Late Onset Pompe Disease (PROGRESS-GT LOPD)

RECRUITING
NCT07282847Phase PHASE1, PHASE2AskBio IncStarted 2026-04-15
AB-1009 (GAA Gene)
Pompe Disease (Late-onset)

A Study About Antibody Levels and Biomarkers in the Blood in People With Late-onset Pompe Disease

ACTIVE NOT RECRUITING
NCT06150820Phase NAAstellas Gene TherapiesStarted 2024-02-01
No Intervention
Spinocerebellar Ataxia 27B (SCA27B)

A Randomized, Parallel-arm, Double Blind, Placebo-controlled Study to Assess the Efficacy of Fampridine for Patients With Spinocerebellar Ataxia SCA27B Caused by a GAA Expansion in the FGF14 Gene

RECRUITING
NCT07185347Phase PHASE3Assistance Publique - Hôpitaux de ParisStarted 2025-10-21
Fampridine 10 mg prolonged-release tablet (per os)Placebo (tablets per os)
Glycogen Storage Disease Type II, Adult

Natural History of Pompe Disease

RECRUITING
NCT03564561Assistance Publique - Hôpitaux de ParisStarted 2019-06-07
Friedreich Ataxia

Characterisation of the Cognitive Profile of Patients Suffering From Friedreich's Ataxia

RECRUITING
NCT05874388Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2023-06-19
Inherited Non-Duchenne Myopathies

Clinical and Functional Assessment of Patients With Inherited Non-Duchenne Myopathies in Sohag University Hospital

RECRUITING
NCT06574919Sohag UniversityStarted 2024-08-01
Pompe Disease (Late-onset)

Evaluation of the Safety and Efficacy of Late-onset Pompe Disease Gene Therapy Drug

RECRUITING
NCT06391736Phase PHASE1, PHASE2GeneCradle IncStarted 2024-04-19
GC301
Pompe Disease Infantile-Onset

Evaluation of the Safety and Efficacy of Infantile-onset Pompe Disease Gene Therapy Drug

ACTIVE NOT RECRUITING
NCT05793307Phase PHASE1, PHASE2GeneCradle IncStarted 2023-06-02
GC301
Pompe DiseasePompe Disease (Late-onset)Glycogen Storage Disease Type 2

A Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)

ACTIVE NOT RECRUITING
NCT04093349Phase PHASE1, PHASE2Spark Therapeutics, Inc.Started 2020-10-01
SPK-3006
Rare Genetic Muscle DiseasesMuscular Dystrophy, DuchenneMuscular Dystrophy, Becker

Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases

RECRUITING
NCT06833489Phase NAAssistance Publique Hopitaux De MarseilleStarted 2025-03-01
ARN extraction from muscle biopsies
Clinical Literature
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