GLB1
galactosidase beta 1, the group of Galactosidases beta
Basic information
Region (hg38): 3:32996609-33097202
Previous symbols: [ "ELNR1" ]
Links
Phenotypes
GenCC
Source:
- GM1 gangliosidosis (Definitive), mode of inheritance: AR
- GM1 gangliosidosis type 3 (Definitive), mode of inheritance: AR
- mucopolysaccharidosis type 4B (Strong), mode of inheritance: AR
- GM1 gangliosidosis type 3 (Strong), mode of inheritance: AR
- GM1 gangliosidosis type 1 (Strong), mode of inheritance: AR
- GM1 gangliosidosis type 2 (Strong), mode of inheritance: AR
- GM1 gangliosidosis type 1 (Supportive), mode of inheritance: AR
- GM1 gangliosidosis type 2 (Supportive), mode of inheritance: AR
- GM1 gangliosidosis type 3 (Supportive), mode of inheritance: AR
- mucopolysaccharidosis type 4B (Supportive), mode of inheritance: AR
- GM1 gangliosidosis type 3 (Strong), mode of inheritance: AR
- mucopolysaccharidosis type 4B (Strong), mode of inheritance: AR
- GM1 gangliosidosis (Definitive), mode of inheritance: AR
- mucopolysaccharidosis type 4B (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Mucopolysaccharidosis type IVB (Morquio syndrome B); GM1-gangliosidosis, type I; GM1-gangliosidosis, type II; GM1-gangliosidosis, type III | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic | 14209687; 14261015; 4227214; 4173446; 4231206; 4243740; 5541675; 4650864; 5031983; 4143049; 4420522; 4139552; 131309; 62026; 404231; 416929; 99363; 121869; 6777095; 6791574; 6791575; 7173264; 3926630; 3917501; 1909089; 1928092; 1907800; 1336295; 1353343; 8198123; 7586649; 10841810; 10737981; 11511921; 12644936; 15986423; 16466959; 16941474; 17309651; 18524657; 19472408; 20175788; 21204790; 21497194; 22234367; 23046582 |
ClinVar
This is a list of variants' phenotypes submitted to
- Mucopolysaccharidosis,_MPS-IV-B (942 variants)
- GM1_gangliosidosis (906 variants)
- Infantile_GM1_gangliosidosis (207 variants)
- GM1_gangliosidosis_type_2 (166 variants)
- GM1_gangliosidosis_type_3 (162 variants)
- not_provided (158 variants)
- not_specified (108 variants)
- Inborn_genetic_diseases (57 variants)
- GLB1-related_disorder (35 variants)
- GM1-gangliosidosis,_type_I,_with_cardiac_involvement (5 variants)
- Intellectual_disability (3 variants)
- Morquio_syndrome (2 variants)
- See_cases (2 variants)
- Spondyloepiphyseal_dysplasia (1 variants)
- Progressive_familial_intrahepatic_cholestasis (1 variants)
- Schizophrenia (1 variants)
- Spastic_ataxia (1 variants)
- Ependymoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLB1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000404.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 298 | 303 | ||||
| missense | 40 | 119 | 207 | 25 | 391 | |
| nonsense | 26 | 16 | 44 | |||
| start loss | 2 | 2 | ||||
| frameshift | 46 | 33 | 83 | |||
| splice donor/acceptor (+/-2bp) | 18 | 18 | 37 | |||
| Total | 130 | 188 | 218 | 323 | 1 |
Highest pathogenic variant AF is 0.00014953953
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GLB1 | protein_coding | protein_coding | ENST00000307363 | 16 | 100623 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 7.92e-10 | 0.972 | 124737 | 0 | 61 | 124798 | 0.000244 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.794 | 333 | 376 | 0.885 | 0.0000210 | 4388 |
| Missense in Polyphen | 131 | 167.71 | 0.7811 | 1962 | ||
| Synonymous | 0.433 | 140 | 147 | 0.955 | 0.00000825 | 1354 |
| Loss of Function | 2.20 | 20 | 33.8 | 0.592 | 0.00000180 | 371 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000399 | 0.000396 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000111 | 0.000111 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000288 | 0.000282 |
| Middle Eastern | 0.000111 | 0.000111 |
| South Asian | 0.000491 | 0.000490 |
| Other | 0.000330 | 0.000330 |
dbNSFP
Source:
- Function
- FUNCTION: Isoform 1: Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans. {ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:2511208, ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:8200356}.;
- Disease
- DISEASE: GM1-gangliosidosis 2 (GM1G2) [MIM:230600]: A gangliosidosis characterized by onset between ages 1 and 5. The main symptom is locomotor ataxia, ultimately leading to a state of decerebration with epileptic seizures. Patients do not display the skeletal changes associated with the infantile form, but they nonetheless excrete elevated amounts of beta-linked galactose- terminal oligosaccharides. Inheritance is autosomal recessive. {ECO:0000269|PubMed:10737981, ECO:0000269|PubMed:12644936, ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651, ECO:0000269|PubMed:1907800, ECO:0000269|PubMed:1909089, ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:24737316, ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:8213816}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: GM1-gangliosidosis 3 (GM1G3) [MIM:230650]: A gangliosidosis with a variable phenotype. Patients show mild skeletal abnormalities, dysarthria, gait disturbance, dystonia and visual impairment. Visceromegaly is absent. Intellectual deficit can initially be mild or absent but progresses over time. Inheritance is autosomal recessive. {ECO:0000269|PubMed:11511921, ECO:0000269|PubMed:15986423, ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651, ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:1907800, ECO:0000269|PubMed:1909089, ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:24737316, ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:8198123, ECO:0000269|Ref.28, ECO:0000269|Ref.30}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mucopolysaccharidosis 4B (MPS4B) [MIM:253010]: A form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life. {ECO:0000269|PubMed:11511921, ECO:0000269|PubMed:12393180, ECO:0000269|PubMed:16538002, ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:1928092, ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:7586649}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Glycosphingolipid biosynthesis - ganglio series - Homo sapiens (human);Lysosome - Homo sapiens (human);Other glycan degradation - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Galactose metabolism - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Ectoderm Differentiation;Degradation pathway of sphingolipids, including diseases;lactose degradation III;Neutrophil degranulation;Metabolism of carbohydrates;Keratan sulfate degradation;Keratan sulfate/keratin metabolism;Metabolism of lipids;HS-GAG degradation;Heparan sulfate/heparin (HS-GAG) metabolism;Glycosaminoglycan metabolism;Post-translational protein modification;Metabolism of proteins;Glycolysis Gluconeogenesis;Glycosphingolipid biosynthesis - ganglioseries;Innate Immune System;Immune System;Metabolism;Glycosphingolipid metabolism;Galactose metabolism;Glycerophospholipid metabolism;Sialic acid metabolism;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;Glycosphingolipid metabolism;Sphingolipid metabolism;TNFalpha;Galactose metabolism
(Consensus)
Recessive Scores
- pRec
- 0.0987
Intolerance Scores
- loftool
- 0.0464
- rvis_EVS
- 0.58
- rvis_percentile_EVS
- 82.25
Haploinsufficiency Scores
- pHI
- 0.138
- hipred
- N
- hipred_score
- 0.253
- ghis
- 0.451
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.939
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Glb1
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype; renal/urinary system phenotype; 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); hematopoietic 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); reproductive system phenotype;
Gene ontology
- Biological process
- glycosaminoglycan catabolic process;glycosphingolipid metabolic process;galactose catabolic process;keratan sulfate catabolic process;neutrophil degranulation;cellular carbohydrate metabolic process;response to cortisone;response to Thyroglobulin triiodothyronine
- Cellular component
- extracellular region;cytoplasm;vacuole;Golgi apparatus;azurophil granule lumen;lysosomal lumen;intracellular membrane-bounded organelle;perinuclear region of cytoplasm;extracellular exosome;ficolin-1-rich granule lumen
- Molecular function
- exo-alpha-sialidase activity;beta-galactosidase activity;protein binding;galactoside binding;protein homodimerization activity