GLA

Protein identityUniProt · HPA

UniProt accession

P06280

Gene

GLA

Ensembl

ENSG00000102393

Chromosome

X

Canonical length

429 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. This enzyme predominantly hydrolyzes ceramide trihexoside, and it can catalyze the hydrolysis of melibiose into galactose and glucose. A variety of mutations in this gene affect the synthesis, processing, and stability of this enzyme, which causes Fabry disease, a rare lysosomal storage disorder that results from a failure to catabolize alpha-D-galactosyl glycolipid moieties. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

429 residues, UniProt reviewed canonical sequence.

>P06280|GLA
     1  MQLRNPELHL GCALALRFLA LVSWDIPGAR ALDNGLARTP TMGWLHWERF MCNLDCQEEP
    61  DSCISEKLFM EMAELMVSEG WKDAGYEYLC IDDCWMAPQR DSEGRLQADP QRFPHGIRQL
   121  ANYVHSKGLK LGIYADVGNK TCAGFPGSFG YYDIDAQTFA DWGVDLLKFD GCYCDSLENL
   181  ADGYKHMSLA LNRTGRSIVY SCEWPLYMWP FQKPNYTEIR QYCNHWRNFA DIDDSWKSIK
   241  SILDWTSFNQ ERIVDVAGPG GWNDPDMLVI GNFGLSWNQQ VTQMALWAIM AAPLFMSNDL
   301  RHISPQAKAL LQDKDVIAIN QDPLGKQGYQ LRQGDNFEVW ERPLSGLAWA VAMINRQEIG
   361  GPRSYTIAVA SLGKGVACNP ACFITQLLPV KRKLGFYEWT SRLRSHINPT GTVLLQLENT
   421  MQMSLKDLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GLA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

37 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GLA.

Disease | AllUniProt

Conditions GLA is implicated in, by any mechanism.

• Fabry disease (FD) MIM:301500

Disease | GeneticClinVar

1,124 pathogenic / likely-pathogenic of 2,028 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Fabry disease
• Cardiovascular phenotype
• Migalastat response
• GLA-related disorder
• Nonpapillary renal cell carcinoma

Disease | ImmuneIEDB

Conditions an epitope on GLA was assayed in.

• colonic benign neoplasm T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.18

gnomAD pLI

1

gnomAD missense Z

1.88

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• glycoside catabolic process
• glycosphingolipid catabolic process
• glycosylceramide catabolic process
• negative regulation of nitric oxide biosynthetic process
• negative regulation of nitric-oxide synthase activity
• oligosaccharide metabolic process

Molecular functions

• alpha-galactosidase activity
• catalytic activity
• hydrolase activity
• protein homodimerization activity
• signaling receptor binding

Cellular components

• azurophil granule lumen
• cytoplasm
• extracellular exosome
• extracellular region
• Golgi apparatus
• lysosomal lumen
• lysosome
• membrane

Protein domainsUniProt · Pfam · InterPro

• Glycoside hydrolase family 27/36, conserved site
• Glycoside hydrolase, family 27
• Glycosyl hydrolase, all-beta
• Aldolase-type TIM barrel
• Glycoside hydrolase superfamily
• Alpha galactosidase A, C-terminal domain
• Alpha galactosidase A
• Alpha galactosidase A C-terminal beta sandwich domain

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Glycosidase
• Hydrolase
• Lipid metabolism
• Lysosome
• Pharmaceutical
• RNA editing
• Signal

InteractionsUniProt · HPA

Protein binding partners of GLA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CANX