GLA
galactosidase alpha, the group of Galactosidases alpha
Basic information
Region (hg38): X:101393272-101408012
Links
Phenotypes
GenCC
Source:
- Fabry disease (Strong), mode of inheritance: XL
- Fabry disease (Strong), mode of inheritance: XL
- Fabry disease (Supportive), mode of inheritance: XL
- Fabry disease (Definitive), mode of inheritance: XL
- Fabry disease (Definitive), mode of inheritance: AD
- Fabry disease (Definitive), mode of inheritance: Mitochondrial
- Fabry disease (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Fabry disease; Fabry disease, cardiac variant | XL | Biochemical; Cardiovascular; Renal | In individuals with Fabry disease, enzyme therapy is available; Both males and females with variants can suffer from significant multisystemic disease manifestations (including cardiovascular, cerebrovascular, and renal disease) and require monitoring and treatment, which can reduce morbidity; Individuals with Cardiac variant Fabry disease can have adult-onset left ventricular hypertrophy with or without renal failure, and early diagnosis and medical management may be beneficial | Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Dermatologic; Neurologic; Ophthalmologic; Renal | 5411915; 4914726; 5466114; 6294821; 6283080; 3107860; 2539398; 2120125; 1645238; 1846223; 8395937; 7879606; 7817917; 7596372; 8807334; 8738659; 11105184; 10618424; 11694547; 11179018; 11732485; 11530143; 11386930; 11804208; 11889412; 12911529; 12519371; 15253767; 15162124; 15154115; 16298216; 16533976; 16926253; 16980809; 17371887; 17256799; 17362993; 17224688; 18023222; 19473999; 19318041; 19843486; 19853240; 19959221; 19965549; 19745746; 20301469; 21502868; 22431073; 22450713; 22498845; 22704481; 22731890; 22878429; 22880956; 22881192; 22880956; 22898981; 22963910; 22998007; 23040658; 23089251; 23094092; 23703683; 31860127 |
ClinVar
This is a list of variants' phenotypes submitted to
- Fabry disease (705 variants)
- not provided (378 variants)
- Cardiovascular phenotype (109 variants)
- not specified (85 variants)
- Cardiomyopathy (23 variants)
- Migalastat response (23 variants)
- GLA-related condition (12 variants)
- Hypertrophic cardiomyopathy (7 variants)
- Primary familial hypertrophic cardiomyopathy (6 variants)
- Fabry disease, cardiac variant (5 variants)
- - (3 variants)
- Hypertrophic cardiomyopathy;Fabry disease (2 variants)
- Hypertrophic cardiomyopathy 1 (2 variants)
- Sudden unexplained death (1 variants)
- Fabry disease;Hypertrophic cardiomyopathy (1 variants)
- Stroke disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLA gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 100 | 102 | ||||
| missense | 90 | 124 | 210 | 428 | ||
| nonsense | 52 | 60 | ||||
| start loss | 5 | |||||
| frameshift | 56 | 29 | 85 | |||
| inframe indel | 13 | |||||
| splice donor/acceptor (+/-2bp) | 17 | 24 | ||||
| splice region ? | 1 | 11 | 12 | 24 | ||
| non coding ? | 42 | 25 | 78 | |||
| Total | 220 | 178 | 225 | 146 | 26 |
Highest pathogenic variant AF is 0.00000894
Variants in GLA
This is a list of pathogenic ClinVar variants found in the GLA region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GLA | protein_coding | protein_coding | ENST00000218516 | 7 | 10123 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.997 | 0.00325 | 125704 | 0 | 1 | 125705 | 0.00000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.88 | 93 | 160 | 0.582 | 0.0000111 | 2846 |
| Missense in Polyphen | 23 | 67.511 | 0.34069 | 1238 | ||
| Synonymous | 0.559 | 50 | 55.3 | 0.904 | 0.00000373 | 794 |
| Loss of Function | 3.80 | 0 | 16.9 | 0.00 | 0.00000135 | 227 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000122 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Disease
- DISEASE: Fabry disease (FD) [MIM:301500]: 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 globotriaosylceramide (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. {ECO:0000269|PubMed:10090526, ECO:0000269|PubMed:10208848, ECO:0000269|PubMed:10666480, ECO:0000269|PubMed:10838196, ECO:0000269|PubMed:10916280, ECO:0000269|PubMed:11076046, ECO:0000269|PubMed:11295840, ECO:0000269|PubMed:11668641, ECO:0000269|PubMed:11889412, ECO:0000269|PubMed:12694230, ECO:0000269|PubMed:12786754, ECO:0000269|PubMed:1315715, ECO:0000269|PubMed:15162124, ECO:0000269|PubMed:15712228, ECO:0000269|PubMed:16533976, ECO:0000269|PubMed:1846223, ECO:0000269|PubMed:19621417, ECO:0000269|PubMed:2152885, ECO:0000269|PubMed:2171331, ECO:0000269|PubMed:2539398, ECO:0000269|PubMed:26415523, ECO:0000269|PubMed:27142856, ECO:0000269|PubMed:27211852, ECO:0000269|PubMed:7504405, ECO:0000269|PubMed:7531540, ECO:0000269|PubMed:7575533, ECO:0000269|PubMed:7596372, ECO:0000269|PubMed:7599642, ECO:0000269|PubMed:7759078, ECO:0000269|PubMed:8069316, ECO:0000269|PubMed:8395937, ECO:0000269|PubMed:8738659, ECO:0000269|PubMed:8807334, ECO:0000269|PubMed:8834244, ECO:0000269|PubMed:8863162, ECO:0000269|PubMed:8875188, ECO:0000269|PubMed:8931708, ECO:0000269|PubMed:9100224, ECO:0000269|PubMed:9105656, ECO:0000269|PubMed:9452068, ECO:0000269|PubMed:9452090, ECO:0000269|PubMed:9452111, ECO:0000269|PubMed:9554750}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Glycerolipid metabolism - Homo sapiens (human);Lysosome - Homo sapiens (human);Glycosphingolipid biosynthesis - globo and isoglobo series - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Galactose metabolism - Homo sapiens (human);Sphingolipid Metabolism;Galactose Metabolism;Gaucher Disease;Globoid Cell Leukodystrophy;Metachromatic Leukodystrophy (MLD);Fabry disease;Galactosemia;Krabbe disease;Degradation pathway of sphingolipids, including diseases;Neutrophil degranulation;Metabolism of lipids;Glycosphingolipid biosynthesis - globoseries;Innate Immune System;Immune System;Metabolism;Glycosphingolipid metabolism;Phosphatidylinositol phosphate metabolism;Galactose metabolism;Glycerophospholipid metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism
(Consensus)
Recessive Scores
- pRec
- 0.742
Intolerance Scores
- loftool
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 56.92
Haploinsufficiency Scores
- pHI
- 0.0939
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.516
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gla
- Phenotype
- growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype;
Gene ontology
- Biological process
- glycosphingolipid metabolic process;oligosaccharide metabolic process;glycoside catabolic process;neutrophil degranulation;negative regulation of nitric oxide biosynthetic process;glycosylceramide catabolic process;glycosphingolipid catabolic process;negative regulation of nitric-oxide synthase activity
- Cellular component
- extracellular region;cytoplasm;lysosome;Golgi apparatus;azurophil granule lumen;lysosomal lumen;extracellular exosome
- Molecular function
- catalytic activity;alpha-galactosidase activity;signaling receptor binding;protein binding;hydrolase activity;galactoside binding;protein homodimerization activity;raffinose alpha-galactosidase activity