GLB1

galactosidase beta 1, the group of Galactosidases beta

Basic information

Region (hg38): 3:32996609-33097202

Previous symbols: [ "ELNR1" ]

Links

ENSG00000170266 ∙ NCBI:2720 ∙ OMIM:611458 ∙ HGNC:4298 ∙ Uniprot:P16278 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the GLB1 gene.

• Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis (49 variants)
• GM1 gangliosidosis;Mucopolysaccharidosis, MPS-IV-B (48 variants)
• not provided (23 variants)
• Infantile GM1 gangliosidosis (23 variants)
• Mucopolysaccharidosis, MPS-IV-B (16 variants)
• GM1 gangliosidosis (15 variants)
• GM1 gangliosidosis type 2 (7 variants)
• GM1 gangliosidosis type 3 (4 variants)
• GM1 gangliosidosis type 2;Mucopolysaccharidosis, MPS-IV-B;Infantile GM1 gangliosidosis;GM1 gangliosidosis type 3 (3 variants)
• GLB1-related disorder (3 variants)
• GM1-gangliosidosis, type I, with cardiac involvement (2 variants)
• Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis type 3;GM1 gangliosidosis type 2;Infantile GM1 gangliosidosis (2 variants)
• Infantile GM1 gangliosidosis;GM1 gangliosidosis type 2;Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis type 3 (2 variants)
• GM1 gangliosidosis type 3;GM1 gangliosidosis type 2;Mucopolysaccharidosis, MPS-IV-B;Infantile GM1 gangliosidosis (1 variants)
• GM1 gangliosidosis type 2;GM1 gangliosidosis type 3;Mucopolysaccharidosis, MPS-IV-B;Infantile GM1 gangliosidosis (1 variants)
• GM1 gangliosidosis type 3;Mucopolysaccharidosis, MPS-IV-B;Infantile GM1 gangliosidosis;GM1 gangliosidosis type 2 (1 variants)
• Inborn genetic diseases (1 variants)
• Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis type 2;GM1 gangliosidosis type 3;Infantile GM1 gangliosidosis (1 variants)
• Spastic ataxia (1 variants)
• GM1 gangliosidosis type 2;Infantile GM1 gangliosidosis;GM1 gangliosidosis type 3;Mucopolysaccharidosis, MPS-IV-B (1 variants)
• Spondyloepiphyseal dysplasia (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.

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				267	3	270
missense	32	74	169	21	2	298
nonsense	22	11	3			36
start loss		2				2
frameshift	39	24	5			68
inframe indel	1	2	2			5
splice donor/acceptor (+/-2bp)	9	22	1			32
splice region	3	1	15	42	2	63
non coding			36	159	54	249
Total	103	135	216	447	59

Highest pathogenic variant AF is 0.000197

Variants in GLB1

This is a list of pathogenic ClinVar variants found in the GLB1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-32996622-T-C		GM1 gangliosidosis • Mucopolysaccharidosis, MPS-IV-B	Uncertain significance (Jan 13, 2018)
3-32996669-G-C		Mucopolysaccharidosis, MPS-IV-B • GM1 gangliosidosis	Likely benign (Jan 13, 2018)
3-32996691-A-G		GM1 gangliosidosis • Mucopolysaccharidosis, MPS-IV-B	Benign (Jan 12, 2018)
3-32996726-C-T		Mucopolysaccharidosis, MPS-IV-B • GM1 gangliosidosis	Conflicting classifications of pathogenicity (Mar 01, 2023)
3-32996821-C-A		GM1 gangliosidosis • Mucopolysaccharidosis, MPS-IV-B	Uncertain significance (Jan 13, 2018)
3-32996851-G-T		Mucopolysaccharidosis, MPS-IV-B • GM1 gangliosidosis	Uncertain significance (Jan 13, 2018)
3-32996861-C-T		Mucopolysaccharidosis, MPS-IV-B • GM1 gangliosidosis	Likely benign (Jan 13, 2018)
3-32996863-T-C		GM1 gangliosidosis • Mucopolysaccharidosis, MPS-IV-B	Benign (Jan 13, 2018)
3-32997001-G-A		Mucopolysaccharidosis, MPS-IV-B • GM1 gangliosidosis	Uncertain significance (Jan 13, 2018)
3-32997006-G-A		Mucopolysaccharidosis, MPS-IV-B • GM1 gangliosidosis	Uncertain significance (Jan 12, 2018)
3-32997045-T-G		GM1 gangliosidosis type 2;Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis type 3;Infantile GM1 gangliosidosis	Uncertain significance (Mar 28, 2018)
3-32997047-A-G		GM1 gangliosidosis type 2;Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis type 3;Infantile GM1 gangliosidosis	Uncertain significance (Jun 06, 2018)
3-32997048-T-C		GM1 gangliosidosis;Mucopolysaccharidosis, MPS-IV-B	Likely benign (May 21, 2021)
3-32997049-A-C		Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis • Mucopolysaccharidosis, MPS-IV-B	Uncertain significance (Aug 16, 2022)
3-32997051-A-G		GM1 gangliosidosis;Mucopolysaccharidosis, MPS-IV-B	Likely benign (Jan 05, 2023)
3-32997057-C-T		Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis	Likely benign (Jan 03, 2024)
3-32997063-T-A		GM1 gangliosidosis;Mucopolysaccharidosis, MPS-IV-B	Likely benign (Nov 10, 2022)
3-32997063-T-C		Infantile GM1 gangliosidosis • GM1 gangliosidosis type 3 • Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis • GM1 gangliosidosis type 2 • GM1 gangliosidosis • Mucopolysaccharidosis, MPS-IV-B	Conflicting classifications of pathogenicity (Jan 18, 2024)
3-32997067-T-C		GM1 gangliosidosis;Mucopolysaccharidosis, MPS-IV-B • Infantile GM1 gangliosidosis;GM1 gangliosidosis type 2;Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis type 3	Conflicting classifications of pathogenicity (Sep 20, 2024)
3-32997067-TC-T		GM1 gangliosidosis type 2;Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis type 3;Infantile GM1 gangliosidosis	Uncertain significance (Mar 12, 2018)
3-32997068-CTT-C		GM1 gangliosidosis;Mucopolysaccharidosis, MPS-IV-B • not specified	Conflicting classifications of pathogenicity (Jul 10, 2023)
3-32997068-CTTTG-C		GM1 gangliosidosis type 2;Mucopolysaccharidosis, MPS-IV-B;GM1 gangliosidosis type 3;Infantile GM1 gangliosidosis	Uncertain significance (Mar 20, 2017)
3-32997068-C-CT		Infantile GM1 gangliosidosis	Uncertain significance (Jun 24, 2022)
3-32997070-T-C		GM1 gangliosidosis;Mucopolysaccharidosis, MPS-IV-B	Uncertain significance (Feb 05, 2022)
3-32997071-T-C		GM1 gangliosidosis;Mucopolysaccharidosis, MPS-IV-B	Uncertain significance (Dec 02, 2021)

GnomAD

Source: gnomAD

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: dbNSFP

• 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