Human Gene GLA (uc004ehl.1)
  Description: Homo sapiens galactosidase, alpha (GLA), mRNA.
RefSeq Summary (NM_000169): 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].
Transcript (Including UTRs)
   Position: hg19 chrX:100,652,779-100,663,001 Size: 10,223 Total Exon Count: 7 Strand: -
Coding Region
   Position: hg19 chrX:100,652,797-100,662,891 Size: 10,095 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:100,652,779-100,663,001)mRNA (may differ from genome)Protein (429 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: AGAL_HUMAN
DESCRIPTION: RecName: Full=Alpha-galactosidase A; EC=3.2.1.22; AltName: Full=Alpha-D-galactosidase A; AltName: Full=Alpha-D-galactoside galactohydrolase; AltName: Full=Melibiase; AltName: INN=Agalsidase; Flags: Precursor;
CATALYTIC ACTIVITY: Hydrolysis of terminal, non-reducing alpha-D- galactose residues in alpha-D-galactosides, including galactose oligosaccharides, galactomannans and galactolipids.
SUBUNIT: Homodimer.
SUBCELLULAR LOCATION: Lysosome.
RNA EDITING: Modified_positions=396; Note=Partially edited.
DISEASE: Defects in GLA are the cause of Fabry disease (FD) [MIM:301500]. FD is a rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaoslyceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities.
PHARMACEUTICAL: Available under the names Replagal (Transkaryotic Therapies) and Fabrazyme (Genzyme). Used as a long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease.
SIMILARITY: Belongs to the glycosyl hydrolase 27 family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GLA";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GLA
CDC HuGE Published Literature: GLA

-  MalaCards Disease Associations
  MalaCards Gene Search: GLA
Diseases sorted by gene-association score: fabry disease* (1764), classic fabry disease (18), cramp-fasciculation syndrome (18), angiokeratoma (15), chromosome 10q26 deletion syndrome (15), sphingolipidosis (14), mucopolysaccharidosis vii (12), skin hemangioma (12), keutel syndrome (10), anhidrosis (7), sweat gland disease (7), necrotizing ulcerative gingivitis (7), lipid storage disease (7), mucopolysaccharidosis is (6), inherited metabolic disorder (6), hypohidrosis (6), integumentary system benign neoplasm (6), lysosomal storage disease (4), cardiomyopathy, familial hypertrophic (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 15.29 RPKM in Whole Blood
Total median expression: 321.57 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -34.70110-0.315 Picture PostScript Text
3' UTR 0.00180.000 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013785 - Aldolase_TIM
IPR013780 - Glyco_hydro_13_b
IPR002241 - Glyco_hydro_27
IPR000111 - Glyco_hydro_GHD
IPR017853 - Glycoside_hydrolase_SF

Pfam Domains:
PF02065 - Melibiase
PF16499 - Alpha galactosidase A
PF17450 - Alpha galactosidase A C-terminal beta sandwich domain

SCOP Domains:
51011 - Glycosyl hydrolase domain
51445 - (Trans)glycosidases

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1R46 - X-ray MuPIT 1R47 - X-ray MuPIT 3GXN - X-ray MuPIT 3GXP - X-ray MuPIT 3GXT - X-ray MuPIT 3HG2 - X-ray MuPIT 3HG3 - X-ray MuPIT 3HG4 - X-ray MuPIT 3HG5 - X-ray MuPIT 3LX9 - X-ray MuPIT 3LXA - X-ray MuPIT 3LXB - X-ray MuPIT 3LXC - X-ray MuPIT 3S5Y - X-ray MuPIT 3S5Z - X-ray MuPIT 3TV8 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P06280
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003824 catalytic activity
GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds
GO:0004557 alpha-galactosidase activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0016787 hydrolase activity
GO:0016798 hydrolase activity, acting on glycosyl bonds
GO:0016936 galactoside binding
GO:0042803 protein homodimerization activity
GO:0052692 raffinose alpha-galactosidase activity

Biological Process:
GO:0005975 carbohydrate metabolic process
GO:0006687 glycosphingolipid metabolic process
GO:0008152 metabolic process
GO:0009311 oligosaccharide metabolic process
GO:0016139 glycoside catabolic process
GO:0043312 neutrophil degranulation
GO:0045019 negative regulation of nitric oxide biosynthetic process
GO:0046477 glycosylceramide catabolic process
GO:0046479 glycosphingolipid catabolic process
GO:0051001 negative regulation of nitric-oxide synthase activity

Cellular Component:
GO:0005576 extracellular region
GO:0005737 cytoplasm
GO:0005764 lysosome
GO:0005794 Golgi apparatus
GO:0035578 azurophil granule lumen
GO:0043202 lysosomal lumen
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK222627 - Homo sapiens mRNA for galactosidase, alpha variant, clone: CBL04521.
X05790 - Human mRNA for alpha-galactosidase A (EC 3.2.1-22).
AK291095 - Homo sapiens cDNA FLJ76285 complete cds, highly similar to Homo sapiens galactosidase, alpha (GLA), mRNA.
D00039 - Homo sapiens mRNA for alpha-galactosidase A, partial cds.
HW649496 - JP 2014523411-A/4: LIPID NANOPARTICLE COMPOSITIONS AND METHODS FOR MRNA DELIVERY.
HZ189939 - JP 2015519301-A/4: Ionizable Cationic Lipids.
JB074621 - Sequence 4 from Patent WO2012170930.
JC570530 - Sequence 4 from Patent WO2014089486.
LP056570 - Sequence 4 from Patent EP2830595.
MA155778 - JP 2017014278-A/4: LIPID NANOPARTICLE COMPOSITIONS AND METHODS FOR MRNA DELIVERY.
X16889 - Human alpha-galactosidase A (alpha-GalA) pseudogene mRNA from individual with Fabry disease.
BC002689 - Homo sapiens galactosidase, alpha, mRNA (cDNA clone MGC:4162 IMAGE:3609235), complete cds.
BT006864 - Homo sapiens galactosidase, alpha mRNA, complete cds.
DQ890721 - Synthetic construct clone IMAGE:100003351; FLH165457.01X; RZPDo839C07160D galactosidase, alpha (GLA) gene, encodes complete protein.
DQ893899 - Synthetic construct Homo sapiens clone IMAGE:100008359; FLH165453.01L; RZPDo839C07159D galactosidase, alpha (GLA) gene, encodes complete protein.
LF382223 - JP 2014500723-A/189726: Polycomb-Associated Non-Coding RNAs.
CU678122 - Synthetic construct Homo sapiens gateway clone IMAGE:100019352 5' read GLA mRNA.
AK297148 - Homo sapiens cDNA FLJ56739 complete cds, highly similar to Alpha-galactosidase A precursor (EC 3.2.1.22).
LF382224 - JP 2014500723-A/189727: Polycomb-Associated Non-Coding RNAs.
LF382225 - JP 2014500723-A/189728: Polycomb-Associated Non-Coding RNAs.
LF382231 - JP 2014500723-A/189734: Polycomb-Associated Non-Coding RNAs.
MA617800 - JP 2018138019-A/189726: Polycomb-Associated Non-Coding RNAs.
MA617801 - JP 2018138019-A/189727: Polycomb-Associated Non-Coding RNAs.
MA617802 - JP 2018138019-A/189728: Polycomb-Associated Non-Coding RNAs.
MA617808 - JP 2018138019-A/189734: Polycomb-Associated Non-Coding RNAs.
MA890447 - JP 2017203045-A/4: LIPID NANOPARTICLE COMPOSITIONS AND METHODS FOR MRNA DELIVERY.
MB437426 - JP 2018095653-A/4: Ionizable Cationic Lipids.
MP440717 - Sequence 4 from Patent EP3586861.
MP559898 - Sequence 4 from Patent EP3628335.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00052 - Galactose metabolism
hsa00561 - Glycerolipid metabolism
hsa00600 - Sphingolipid metabolism
hsa00603 - Glycosphingolipid biosynthesis - globo series
hsa04142 - Lysosome

BioCyc Knowledge Library
PWY0-1301 - melibiose degradation

Reactome (by CSHL, EBI, and GO)

Protein P06280 (Reactome details) participates in the following event(s):

R-HSA-6798751 Exocytosis of azurophil granule lumen proteins
R-HSA-1605736 Alpha-galactosidase A removes a terminal galactose from alpha-D-galactoside oligomers
R-HSA-6798695 Neutrophil degranulation
R-HSA-1660662 Glycosphingolipid metabolism
R-HSA-168249 Innate Immune System
R-HSA-428157 Sphingolipid metabolism
R-HSA-168256 Immune System
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: AGAL_HUMAN, NM_000169, NP_000160, P06280
UCSC ID: uc004ehl.1
RefSeq Accession: NM_000169
Protein: P06280 (aka AGAL_HUMAN)
CCDS: CCDS14484.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene GLA:
fabry (Fabry Disease)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000169.2
exon count: 7CDS single in 3' UTR: no RNA size: 1418
ORF size: 1290CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2769.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.