GUSB

glucuronidase beta, the group of Glycoside hydrolases

Basic information

Region (hg38): 7:65960684-65982215

Links

ENSG00000169919 ∙ NCBI:2990 ∙ OMIM:611499 ∙ HGNC:4696 ∙ Uniprot:P08236 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mucopolysaccharidosis type 7 (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 7 (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 7 (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 7 (Supportive), mode of inheritance: AR
• mucopolysaccharidosis type 7 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis type VII	AR	Biochemical	Enzyme replacement therapy is available, and has been approved for both pediatric and adult patients; BMT has been described	Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	4265197; 144057; 101485; 6813001; 1702266; 7680524; 9099834; 9543069; 12403825; 12522561; 12748853; 19224584; 26908836; 28595941; 29478819
The condition can include cardiac manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GUSB gene.

• Mucopolysaccharidosis_type_7 (639 variants)
• Inborn_genetic_diseases (69 variants)
• not_provided (62 variants)
• not_specified (33 variants)
• GUSB-related_disorder (19 variants)
• Non-immune_hydrops_fetalis (5 variants)
• Mucopolysaccharidosis_type_6 (2 variants)
• Intellectual_disability (2 variants)
• Prostate_cancer (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GUSB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000181.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	2	231	5	239
missense	5	37	185	11		238
nonsense	15	11	1			27
start loss	1	1				2
frameshift	27	9	3	1		40
splice donor/acceptor (+/-2bp)	1	12	5			18
Total	49	71	196	243	5

Highest pathogenic variant AF is 0.00007251587

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GUSB	protein_coding	protein_coding	ENST00000304895	12	21631

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125648	0	100	125748	0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	315	375	0.840	0.0000239	4208
Missense in Polyphen		104	153.55	0.67732		1771
Synonymous	-0.798	173	160	1.08	0.0000110	1282
Loss of Function	2.71	18	35.4	0.508	0.00000202	358

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00108	0.00106
Ashkenazi Jewish	0.000331	0.000298
East Asian	0.000114	0.000109
Finnish	0.000201	0.000185
European (Non-Finnish)	0.000481	0.000431
Middle Eastern	0.000114	0.000109
South Asian	0.000449	0.000425
Other	0.000574	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in the degradation of dermatan and keratan sulfates.
• Disease: DISEASE: Mucopolysaccharidosis 7 (MPS7) [MIM:253220]: An autosomal recessive lysosomal storage disease characterized by inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment. {ECO:0000269|PubMed:12522561, ECO:0000269|PubMed:12859417, ECO:0000269|PubMed:1702266, ECO:0000269|PubMed:7573038, ECO:0000269|PubMed:7633414, ECO:0000269|PubMed:7680524, ECO:0000269|PubMed:8089138, ECO:0000269|PubMed:8111412, ECO:0000269|PubMed:8111413, ECO:0000269|PubMed:8644704, ECO:0000269|PubMed:8707294, ECO:0000269|PubMed:9099834, ECO:0000269|PubMed:9490302}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Porphyrin and chlorophyll metabolism - Homo sapiens (human);Pentose and glucuronate interconversions - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Glycogen synthetase deficiency;Glycogenosis, Type III. Cori disease, Debrancher glycogenosis;Mucopolysaccharidosis VI. Sly syndrome;Sucrase-isomaltase deficiency;Glycogenosis, Type IV. Amylopectinosis, Anderson disease;Glycogenosis, Type VI. Hers disease;Hereditary Coproporphyria (HCP);Porphyria Variegata (PV);Congenital Erythropoietic Porphyria (CEP) or Gunther Disease;Acute Intermittent Porphyria;Starch and Sucrose Metabolism;Porphyrin Metabolism;Neutrophil degranulation;Hyaluronan uptake and degradation;Hyaluronan metabolism;Metabolism of carbohydrates;HS-GAG degradation;Heparan sulfate/heparin (HS-GAG) metabolism;Glycosaminoglycan metabolism;Innate Immune System;Immune System;Metabolism (Consensus)

Intolerance Scores

• loftool: 0.0891
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.88

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: carbohydrate metabolic process;glycosaminoglycan catabolic process;glucuronoside catabolic process;hyaluronan catabolic process;neutrophil degranulation
• Cellular component: extracellular region;extracellular space;membrane;azurophil granule lumen;lysosomal lumen;intracellular membrane-bounded organelle;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: beta-glucuronidase activity;signaling receptor binding;protein domain specific binding;carbohydrate binding