ARSB
arylsulfatase B, the group of Sulfatases
Basic information
Region (hg38): 5:78777208-78986087
Links
Phenotypes
GenCC
Source:
- mucopolysaccharidosis type 6 (Definitive), mode of inheritance: AR
- mucopolysaccharidosis type 6 (Definitive), mode of inheritance: AR
- mucopolysaccharidosis type 6 (Strong), mode of inheritance: AR
- mucopolysaccharidosis type 6 (Strong), mode of inheritance: AR
- mucopolysaccharidosis type 6 (Strong), mode of inheritance: AR
- mucopolysaccharidosis type 6 (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Mucopolysaccharidosis type VI (Maroteaux-Lamy) | AR | Biochemical; Cardiovascular | Enzyme replacement therapy is available; The condition can include cardiovascular manifestations, and awareness may allow surveillance and early detection, which may lead to improved management; BMT has been reported | Biochemical; Cardiovascular; Musculoskeletal; Ophthalmologic | 14091597; 6767429; 6776877; 6225949; 6150438; 1832719; 1718978; 1550123; 1301949; 1728449; 8651289; 10070618; 10036316; 11668612; 15324318; 15823680; 15690405; 17643332; 17671068; 21637564; 21930407; 21744090; 22127392; 22669363; 22278137; 22704873; 22864057; 21917494; 22938833; 22133300; 22336888; 22971959; 22495825; 22976768; 23023219; 22405600; 22395531; 25864794; 28595941; 33775523; 33678523 |
ClinVar
This is a list of variants' phenotypes submitted to
- Mucopolysaccharidosis type 6 (747 variants)
- not provided (93 variants)
- not specified (26 variants)
- Inborn genetic diseases (16 variants)
- Metachromatic leukodystrophy (4 variants)
- Mucopolysaccharidosis, type vi, severe (4 variants)
- ARSB-related condition (2 variants)
- See cases (2 variants)
- Mucopolysaccharidosis, type vi, mild (1 variants)
- Mucopolysaccharidosis, type vi, intermediate (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARSB 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 | 175 | 186 | ||||
| missense | 12 | 58 | 148 | 230 | ||
| nonsense | 23 | 14 | 38 | |||
| start loss | 0 | |||||
| frameshift | 29 | 34 | 63 | |||
| inframe indel | 10 | |||||
| splice donor/acceptor (+/-2bp) | 13 | 17 | ||||
| splice region ? | 2 | 6 | 25 | 33 | ||
| non coding ? | 82 | 38 | 41 | 162 | ||
| Total | 69 | 121 | 239 | 222 | 55 |
Highest pathogenic variant AF is 0.000158
Variants in ARSB
This is a list of pathogenic ClinVar variants found in the ARSB region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-78777216-A-C | Mucopolysaccharidosis type 6 | Benign (Jan 13, 2018) | ||
| 5-78777216-A-T | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 13, 2018) | ||
| 5-78777223-A-C | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) | ||
| 5-78777234-A-G | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) | ||
| 5-78777245-T-C | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) | ||
| 5-78777250-C-T | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 13, 2018) | ||
| 5-78777350-A-G | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 13, 2018) | ||
| 5-78777422-C-A | Mucopolysaccharidosis type 6 | Benign (Jan 12, 2018) | ||
| 5-78777538-A-G | Mucopolysaccharidosis type 6 | Benign (Jan 12, 2018) | ||
| 5-78777566-A-T | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 13, 2018) | ||
| 5-78777613-G-T | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) | ||
| 5-78777689-C-T | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 13, 2018) | ||
| 5-78777690-G-A | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 13, 2018) | ||
| 5-78777713-C-T | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) | ||
| 5-78777717-G-A | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) | ||
| 5-78777725-T-C | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 13, 2018) | ||
| 5-78777743-T-C | Mucopolysaccharidosis type 6 | Benign (Jan 13, 2018) | ||
| 5-78777757-C-CAGG | Mucopolysaccharidosis type 6 | Uncertain significance (Jun 14, 2016) | ||
| 5-78777789-C-T | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 13, 2018) | ||
| 5-78777804-A-C | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) | ||
| 5-78777819-T-A | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) | ||
| 5-78777826-T-C | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 13, 2018) | ||
| 5-78777838-C-T | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) | ||
| 5-78777851-C-CAAA | Mucopolysaccharidosis type 6 | Uncertain significance (Jun 14, 2016) | ||
| 5-78777871-A-T | Mucopolysaccharidosis type 6 | Uncertain significance (Jan 12, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ARSB | protein_coding | protein_coding | ENST00000264914 | 8 | 208879 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 7.00e-9 | 0.689 | 125709 | 0 | 39 | 125748 | 0.000155 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.631 | 254 | 284 | 0.895 | 0.0000159 | 3412 |
| Missense in Polyphen | 95 | 124.55 | 0.76272 | 1514 | ||
| Synonymous | 0.521 | 108 | 115 | 0.938 | 0.00000634 | 1105 |
| Loss of Function | 1.33 | 16 | 22.9 | 0.699 | 0.00000134 | 259 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000181 | 0.000181 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.000211 | 0.000211 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Removes sulfate groups from chondroitin-4-sulfate (C4S) and regulates its degradation (PubMed:19306108). Involved in the regulation of cell adhesion, cell migration and invasion in colonic epithelium (PubMed:19306108). In the central nervous system, is a regulator of neurite outgrowth and neuronal plasticity, acting through the control of sulfate glycosaminoglycans and neurocan levels (By similarity). {ECO:0000250|UniProtKB:P50430, ECO:0000269|PubMed:19306108}.;
- Disease
- DISEASE: Mucopolysaccharidosis 6 (MPS6) [MIM:253200]: An autosomal recessive lysosomal storage disease characterized by intracellular accumulation of dermatan sulfate. Clinical features can include abnormal growth, short stature, stiff joints, skeletal malformations, corneal clouding, hepatosplenomegaly, and cardiac abnormalities. A wide variation in clinical severity is observed. {ECO:0000269|PubMed:10036316, ECO:0000269|PubMed:10738004, ECO:0000269|PubMed:11802522, ECO:0000269|PubMed:14974081, ECO:0000269|PubMed:1550123, ECO:0000269|PubMed:1718978, ECO:0000269|PubMed:19259130, ECO:0000269|PubMed:8116615, ECO:0000269|PubMed:8125475, ECO:0000269|PubMed:8541342, ECO:0000269|PubMed:8651289}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multiple sulfatase deficiency (MSD) [MIM:272200]: A clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post- translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay. {ECO:0000269|PubMed:15146462}. Note=The protein represented in this entry is involved in disease pathogenesis. Arylsulfatase B activity is impaired in multiple sulfatase deficiency due to mutations in SUMF1. SUMF1 mutations result in defective post-translational modification of ARSB at residue Cys-91 that is not converted to 3-oxoalanine.;
- Pathway
- Lysosome - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Neutrophil degranulation;Metabolism of carbohydrates;Metabolism of lipids;CS/DS degradation;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;chondroitin sulfate degradation (metazoa);Post-translational protein modification;Metabolism of proteins;The activation of arylsulfatases;Gamma carboxylation, hypusine formation and arylsulfatase activation;Androgen and estrogen biosynthesis and metabolism;Innate Immune System;Immune System;Metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism
(Consensus)
Recessive Scores
- pRec
- 0.256
Intolerance Scores
- loftool
- 0.0956
- rvis_EVS
- 0.02
- rvis_percentile_EVS
- 55.61
Haploinsufficiency Scores
- pHI
- 0.0623
- hipred
- Y
- hipred_score
- 0.601
- ghis
- 0.463
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.835
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | Medium |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Arsb
- Phenotype
- vision/eye 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; renal/urinary system phenotype; skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); 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); hematopoietic system phenotype; growth/size/body region phenotype; reproductive system phenotype; craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype;
Gene ontology
- Biological process
- autophagy;lysosome organization;lysosomal transport;central nervous system development;response to nutrient;response to pH;regulation of epithelial cell migration;positive regulation of neuron projection development;chondroitin sulfate catabolic process;neutrophil degranulation;response to estrogen;response to methylmercury;colon epithelial cell migration
- Cellular component
- extracellular region;mitochondrion;lysosome;endoplasmic reticulum lumen;rough endoplasmic reticulum;Golgi apparatus;cell surface;azurophil granule lumen;lysosomal lumen;extracellular exosome;ficolin-1-rich granule lumen
- Molecular function
- N-acetylgalactosamine-4-sulfatase activity;arylsulfatase activity;metal ion binding