GAA
Chr 17ARalpha glucosidase
Also known as: IOPD, LOPD, LYAG
This gene encodes lysosomal alpha-glucosidase, which is essential for the degradation of glycogen to glucose in lysosomes. The encoded preproprotein is proteolytically processed to generate multiple intermediate forms and the mature form of the enzyme. Defects in this gene are the cause of glycogen storage disease II, also known as Pompe's disease, which is an autosomal recessive disorder with a broad clinical spectrum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
ClinVar Variant Classifications
587 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 35 | 6 | 19 | 1 | 61 |
Likely Pathogenic | 29 | 43 | 11 | 0 | 83 |
VUS | 0 | 150 | 24 | 10 | 184 |
Likely Benign | 0 | 1 | 140 | 112 | 253 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 4 | |||
| Total | 64 | 200 | 196 | 123 | 587 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View 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.
Gene2Phenotype Curations
GAA-related Pompe disease
definitiveGAA-related glycogen storage disease
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases
RECRUITINGClinical and Functional Assessment of Patients With Inherited Non-Duchenne Myopathies in Sohag University Hospital
RECRUITINGA Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)
ACTIVE NOT RECRUITINGCharacterisation of the Cognitive Profile of Patients Suffering From Friedreich's Ataxia
RECRUITINGNatural History of Pompe Disease
RECRUITINGA 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)
RECRUITINGA 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
RECRUITINGA Study About Antibody Levels and Biomarkers in the Blood in People With Late-onset Pompe Disease
ACTIVE NOT RECRUITINGEvaluation of the Safety, Tolerability and Efficacy of Gene Therapy Drug for Late Onset Pompe Disease (LOPD)
NOT YET RECRUITINGA Natural History Study to TRACK Brain and Spinal Cord Changes in Individuals with Friedreich Ataxia (TRACK-FA)
ACTIVE NOT RECRUITINGAtaxia GAA-FGF14 - Descriptive Genetic and Clinical Study
ACTIVE NOT RECRUITINGEvaluation of the Safety and Efficacy of Late-onset Pompe Disease Gene Therapy Drug
RECRUITINGExternal Resources
Links to major genomics databases and tools