GLA

Chr XX-linked

galactosidase alpha

Also known as: GALA

NCBI Gene: 2717 ENSG00000102393 UniProt: Q9UHE5

Alpha-galactosidase A is a lysosomal enzyme that hydrolyzes terminal alpha-galactosyl moieties from glycolipids and glycoproteins, predominantly ceramide trihexoside. Mutations cause Fabry disease, a lysosomal storage disorder that can present as a classic multisystem form or a cardiac variant form. This gene follows X-linked inheritance and is highly constrained against loss-of-function variants.

Summary from RefSeq, OMIM, UniProt

Research Assistant →

Primary Disease Associations & Inheritance

Fabry diseaseMIM #301500

X-linked

Fabry disease, cardiac variantMIM #301500

X-linked

Active trials

416

Pubs (1 yr)

183

P/LP submissions

94%

P/LP missense

0.18

LOEUF· LoF intol.

LOF

Mechanism· G2P

Clinical Summary— GLA

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Gene-Disease Validity (ClinGen)

Fabry disease · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

177 unique Pathogenic / Likely Pathogenic· 59 VUS of 297 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — GLA

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint

0.18LOEUF

pLI 0.997

Z-score 3.80

OE 0.00 (0.00–0.18)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint

1.88Z-score

OE missense 0.58 (0.49–0.69)

93 obs / 159.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.00 (0.00–0.18)

0≤0.351.4

Missense OE0.58 (0.49–0.69)

0≤0.61.4

Synonymous OE0.90

0≤1.21.6

LoF obs/exp: 0 / 16.9Missense obs/exp: 93 / 159.7Syn Z: 0.56

ClinVar Variant Classifications

297 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic76

Likely Pathogenic101

VUS59

Likely Benign17

Conflicting4

Pathogenic

101

Likely Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	68	5	0	76
Likely Pathogenic	1	99	1	0	101
VUS	1	55	3	0	59
Likely Benign	0	3	5	9	17
Benign	0	0	0	0	0
Conflicting	—				4
Total	5	225	14	9	257

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GLA · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

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GeneReview available — GLA

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Metastatic Non-small Cell Lung Cancer

A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

RECRUITING

NCT06417814Phase PHASE3AstraZenecaStarted 2024-10-04

Dato-DXdOsimertinibPemetrexed

Pulmonary Disease Due to Mycobacteria (Diagnosis)

Finding the Optimal Regimen for Mycobacterium Abscessus Treatment

RECRUITING

NCT04310930Phase PHASE2, PHASE3The University of QueenslandStarted 2020-03-02

AmikacinTigecyclineImipenem

Fabry DiseaseFabry Disease, Cardiac VariantLysosomal Storage Diseases

Fabry Disease in High-risk Patients With Left Ventricular Hypertrophy: Prevalence and Implementation of a Clinical Score

ACTIVE NOT RECRUITING

NCT04943991Phase NAWuerzburg University HospitalStarted 2021-07-01

blood sampling (alpha-Galactosidase & LysoGb3)

Advanced Solid TumorOvarian CancerOvarian Clear Cell Carcinoma

A Phase 1 Clinical Study of NXP800 in Subjects With Advanced Cancers and Expansion in Subjects With Ovarian Cancer

ACTIVE NOT RECRUITING

NCT05226507Phase PHASE1Nuvectis Pharma, Inc.Started 2021-12-31

NXP800

Arrhythmogenic Right Ventricular Cardiomyopathy

Non-interventional Study of Seroprevalence of Pre-existing Antibodies Against Adenovirus-associated Virus Vector (AAV9) and the Progression of Disease in Patients With Plakophilin 2 (PKP2)-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

RECRUITING

NCT06311708Tenaya TherapeuticsStarted 2023-01-31

Fabry Disease

Agalsidase Beta Long-Term Treatment Outcome for Fabry Disease Patients With IVS4 Mutation in Taiwan

ACTIVE NOT RECRUITING

NCT06052800SanofiStarted 2023-09-13

Fabry DiseaseEndothelial DysfunctionMicrovasculature

Characterizing the Retinal Microvasculature in Patients with Fabry Disease: a Prospective Observational Study

RECRUITING

NCT06758648Technical University of MunichStarted 2020-06-25

Dynamic retinal vessel analysis (DVA)Biochemistry and immune phenotypingQuestionnaires (Patient reported outcomes)

Muscle Invasive Bladder Cancer