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 (Supportive), mode of inheritance: AR
• mucopolysaccharidosis type 7 (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 7 (Strong), 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 (39 variants)
• not provided (4 variants)
• Mucopolysaccharidosis type 6 (2 variants)
• GUSB-related disorder (1 variants)
• Inborn genetic diseases (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.

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		1	1	197	9	208
missense	2	12	154	3	1	172
nonsense	17	1	1			19
start loss	1	1				2
frameshift	21	2	2			25
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)	1	7	1			9
splice region			11	21	2	34
non coding		1	10	104	9	124
Total	42	25	172	305	19

Highest pathogenic variant AF is 0.0000657

Variants in GUSB

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

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

Position	Type	Phenotype	Significance	ClinVar
7-65960689-A-C		Mucopolysaccharidosis type 7	Uncertain significance (Jan 12, 2018)
7-65960689-A-G		Mucopolysaccharidosis type 7	Uncertain significance (Jan 13, 2018)
7-65960725-T-C		Mucopolysaccharidosis type 7	Benign (Jan 12, 2018)
7-65960743-C-T		Mucopolysaccharidosis type 7	Uncertain significance (Jan 12, 2018)
7-65960749-T-C		Mucopolysaccharidosis type 7	Uncertain significance (Jan 12, 2018)
7-65960803-T-C		Mucopolysaccharidosis type 7	Uncertain significance (Jan 13, 2018)
7-65960842-G-A		Mucopolysaccharidosis type 7	Benign (Jan 12, 2018)
7-65960874-C-A			Likely benign (Oct 26, 2017)
7-65960885-T-C		Mucopolysaccharidosis type 7	Uncertain significance (Jan 13, 2018)
7-65960906-CA-TG		Mucopolysaccharidosis type 7	Likely benign (Jan 19, 2024)
7-65960907-A-G		not specified • Mucopolysaccharidosis type 7	Benign (Feb 01, 2024)
7-65960908-G-A		Mucopolysaccharidosis type 7	Likely benign (May 05, 2022)
7-65960911-T-G		Mucopolysaccharidosis type 7	Uncertain significance (Aug 24, 2021)
7-65960924-T-C		Mucopolysaccharidosis type 7 • GUSB-related disorder	Likely benign (Jan 19, 2024)
7-65960926-G-A		Mucopolysaccharidosis type 7	Uncertain significance (May 13, 2022)
7-65960927-T-C		Mucopolysaccharidosis type 7	Likely benign (Jul 10, 2023)
7-65960934-G-GCTA		Mucopolysaccharidosis type 7 • GUSB-related disorder	Likely benign (Jan 16, 2024)
7-65960941-A-G		Mucopolysaccharidosis type 7	Uncertain significance (Jan 13, 2018)
7-65960942-G-A		Mucopolysaccharidosis type 7	Likely benign (Jun 27, 2023)
7-65960948-A-G		Mucopolysaccharidosis type 7	Likely benign (Mar 04, 2022)
7-65960952-C-G		Inborn genetic diseases	Uncertain significance (Feb 11, 2022)
7-65960957-T-C		Mucopolysaccharidosis type 7	Likely benign (Jan 01, 2024)
7-65960966-A-C		Mucopolysaccharidosis type 7	Uncertain significance (Feb 03, 2022)
7-65960967-A-G		Mucopolysaccharidosis type 7	Uncertain significance (Mar 13, 2022)
7-65960966-A-AATC		GUSB-related disorder	Uncertain significance (Feb 15, 2024)

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
4.04e-8	0.997	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

Haploinsufficiency Scores

• pHI: 0.173
• hipred: Y
• hipred_score: 0.531
• ghis: 0.598

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

Mouse Genome Informatics

• Gene name: Gusb
• Phenotype: hematopoietic system phenotype; normal 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype

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