AGA

Chr 4AR

aspartylglucosaminidase

Also known as: AGU, ASRG, GA

This gene encodes a member of the N-terminal nucleophile (Ntn) hydrolase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta chains that comprise the mature enzyme. This enzyme is involved in the catabolism of N-linked oligosaccharides of glycoproteins. It cleaves asparagine from N-acetylglucosamines as one of the final steps in the lysosomal breakdown of glycoproteins. Mutations in this gene are associated with the lysosomal storage disease aspartylglycosaminuria that results in progressive neurodegeneration. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is subject to proteolytic processing. [provided by RefSeq, Nov 2015]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 1.041 OMIM phenotype
Clinical SummaryAGA
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Gene-Disease Validity (ClinGen)
aspartylglucosaminuria · 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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.04LOEUF
pLI 0.000
Z-score 1.43
OE 0.63 (0.401.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.45Z-score
OE missense 1.09 (0.971.22)
214 obs / 196.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.63 (0.401.04)
00.351.4
Missense OE?1.09 (0.971.22)
00.61.4
Synonymous OE?0.92
01.21.6
LoF obs/exp: 11 / 17.4Missense obs/exp: 214 / 196.4Syn Z: 0.50
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveAGA-related aspartylglucosaminuriaLOFAR

This gene — mechanism propensity

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

DN
0.6937th %ile
GOF
0.6443th %ile
LOF
0.3260th %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

AGA · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Lung Adenocarcinoma

PHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC

NOT YET RECRUITING
NCT07416058Phase PHASE2Guangdong Association of Clinical TrialsStarted 2026-01-31
QL1706 (bispecific antibody targeting PD-1 and CLTA-4)
Malnutrition (Calorie)Infant Nutrition DisorderGrowth Flatering

Goat Milk-Derived Formula vs. Undiluted Goat Milk in Infants Unable to Exclusively Breastfeed: Growth and Biomarker Analysis

RECRUITING
NCT07225153Phase NAAga Khan UniversityStarted 2025-08-30
GMDFAUndiluted Goat Milk
Heat StressPregnancyWomen of Reproductive Age

Indigenous Nutritional Supplements for Pregnancy to Improve Resilience in Environmental Heat

NOT YET RECRUITING
NCT07489664Phase NAAga Khan UniversityStarted 2026-03
Indigenous Balanced Diet Arm
Environmental Enteric Dysfunction (EED)Stunting

Maternal Probiotic Intervention to Improve Gut Health-Trial II-Pakistan

RECRUITING
NCT07207434Phase PHASE2Aga Khan UniversityStarted 2025-08-30
Oral VancomycinVE818Placebo
Pregnancy RelatedPregnancy LossPregnancy Complications

Microbiome and Malnutrition in Pregnancy

ACTIVE NOT RECRUITING
NCT04992104The Hospital for Sick ChildrenStarted 2023-02-22
Venezuelan Equine EncephalitisVenezuelan Equine Encephalitis Virus Infection

A Phase 1 Study Evaluating the Safety, Tolerability, and Immunogenicity of V4020 Vaccine in Healthy Volunteers

NOT YET RECRUITING
NCT07088822Phase PHASE1Medigen, Inc.Started 2025-08-15
V4020
Fabry Disease

An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease

ACTIVE NOT RECRUITING
NCT04519749Phase PHASE1, PHASE24D Molecular TherapeuticsStarted 2020-09-01
4D-310
Recurrent Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

Treatment for Advanced Non-small Cell Lung Cancer With Actionable Genomic Alterations After Targeted Treatment and Chemotherapy (An Expanded Lung-MAP Treatment Trial)

NOT YET RECRUITING
NCT07393555Phase PHASE2SWOG Cancer Research NetworkStarted 2026-08-07
Biospecimen CollectionComputed TomographyIvonescimab
AspartylglucosaminuriaAspartylglucosamidase (AGA) Deficiency

Safety and Efficacy of scAAV9/AGA Gene Therapy in Participants With Aspartylglucosaminuria (AGU)

NOT YET RECRUITING
NCT07530796Phase PHASE1, PHASE2Rare Trait HopeStarted 2026-05-01
scAAV9/AGA
Non-Small Cell Lung Cancer

Study of MCLA-129 in the Treatment of Advanced Non-small Cell Lung Cancer with AGA and MET Amplification.

NOT YET RECRUITING
NCT06885840Phase PHASE2Betta Pharmaceuticals Co., Ltd.Started 2025-03-31
MCLA-129
Fabry Disease

Evaluate the Safety and Preliminary Efficacy of EXG110 in Subjects With Fabry Disease

RECRUITING
NCT06539624Phase NAThe Children's Hospital of Zhejiang University School of MedicineStarted 2024-10-16
EXG110 injection
SchizophreniaSchizo Affective DisorderHealthy

Clinical Trial of an IL-23 Inhibitor for Immune Activation in Clinical Trial of an IL-23 Inhibitor for Immune Activation in People With Schizophrenia

NOT YET RECRUITING
NCT07615075Phase PHASE4University of Maryland, BaltimoreStarted 2026-09-01
PlaceboIL-23