ARSB

Summary

ARSB (arylsulfatase B, HGNC:714) is a protein-coding gene on chromosome 5q14.1, encoding Arylsulfatase B (P15848). Removes sulfate groups from chondroitin-4-sulfate (C4S) and regulates its degradation.

Arylsulfatase B encoded by this gene belongs to the sulfatase family. The arylsulfatase B homodimer hydrolyzes sulfate groups of N-Acetyl-D-galactosamine, chondriotin sulfate, and dermatan sulfate. The protein is targeted to the lysozyme. Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 411 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mucopolysaccharidosis type 6 (Definitive, ClinGen)
• GWAS associations: 18
• Clinical variants (ClinVar): 944 total — 86 pathogenic, 107 likely-pathogenic
• Phenotypes (HPO): 64
• Druggable target: yes
• MANE Select transcript: NM_000046

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:714
Approved symbol	ARSB
Name	arylsulfatase B
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Aliases	ASB
Ensembl gene	ENSG00000113273
Ensembl biotype	protein_coding
OMIM	611542
Entrez	411

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000264914, ENST00000396151, ENST00000521011, ENST00000521117, ENST00000521800, ENST00000565165, ENST00000934338

RefSeq mRNA: 2 — MANE Select: NM_000046 NM_000046, NM_198709

CCDS: CCDS4043, CCDS43334

Canonical transcript exons

ENST00000264914 — 8 exons

Exon	Start	End
ENSE00001005072	78955295	78955502
ENSE00001005073	78964416	78964606
ENSE00001005074	78969006	78969192
ENSE00001083459	78885584	78885827
ENSE00001083461	78839356	78839426
ENSE00001216478	78777209	78780662
ENSE00001366770	78984937	78985310
ENSE00003624443	78781852	78781974

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 89.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.5040 / max 203.1126, expressed in 1745 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62246	9.8564	1503
62248	3.0110	1398
62247	2.5378	1276
62249	0.2658	158
62251	0.2252	76
62245	0.1584	51
62252	0.1335	46
62255	0.1086	47
62250	0.0926	29
62254	0.0840	29

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	89.13	gold quality
monocyte	CL:0000576	87.13	gold quality
mononuclear cell	CL:0000842	86.45	gold quality
leukocyte	CL:0000738	86.16	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.61	gold quality
lower esophagus	UBERON:0013473	85.49	gold quality
stromal cell of endometrium	CL:0002255	85.01	gold quality
cortical plate	UBERON:0005343	83.58	gold quality
tendon	UBERON:0000043	83.29	gold quality
ventricular zone	UBERON:0003053	81.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.90	gold quality
tendon of biceps brachii	UBERON:0008188	80.52	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	80.42	gold quality
right coronary artery	UBERON:0001625	80.26	gold quality
thoracic aorta	UBERON:0001515	80.22	gold quality
ascending aorta	UBERON:0001496	80.16	gold quality
islet of Langerhans	UBERON:0000006	79.83	gold quality
descending thoracic aorta	UBERON:0002345	79.83	gold quality
colonic epithelium	UBERON:0000397	79.71	gold quality
smooth muscle tissue	UBERON:0001135	79.67	gold quality
rectum	UBERON:0001052	79.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.43	gold quality
ganglionic eminence	UBERON:0004023	79.38	gold quality
gall bladder	UBERON:0002110	78.91	gold quality
aorta	UBERON:0000947	78.51	gold quality
left coronary artery	UBERON:0001626	78.18	gold quality
popliteal artery	UBERON:0002250	77.58	gold quality
tibial artery	UBERON:0007610	77.56	gold quality
granulocyte	CL:0000094	77.31	gold quality
coronary artery	UBERON:0001621	76.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.48
E-MTAB-9801	no	3.25
E-CURD-112	no	2.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

164 targeting ARSB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 40)

• Mucopolysaccharidosis type VI: Structural and clinical implications of mutations in N-acetylgalactosamine-4-sulfatase (PMID:11668612)
• Seven novel mutation were identified in ARSB in mucopolysaccharidosis type VI patients undergoing a Clinical trial of enzyme replacement therapy, 3 of these mutations resulted in truncated proteins. (PMID:14974081)
• analysis of novel mutations on the arylsulphatase B gene in South American Mucopolysaccharidosis type VI patients (PMID:16435196)
• Decreased arylsulfatase B activity is associated with cystic fibrosis (PMID:17324393)
• The identification of many novel mutations unique to individuals/their families highlighted the genetic heterogeneity of the mucopolysaccharidosis VI disorder. (PMID:17458871)
• Novel mutations in arylsulfatase B is associated with mucopolysaccharidosis VI (PMID:17643332)
• modification of expression of the lysosomal sulfatases ASB and GALNS regulates the content of CSs. (PMID:18285341)
• Reduced activity of arylsulfatase B enzymatic activity in children with cystic fibrosis (PMID:18299243)
• All the ARSB mutations studied had a significant effect on enzyme activity, protein processing and/or mRNA stability. (PMID:18406185)
• arylsulfatase B gene mutation profile in Taiwanese MPS VI patients may be different from MPS VI patients from other countries[mucopolysaccharidosis type VI ] (PMID:18486607)
• Arylsulfatase B regulates colonic epithelial cell migration by effects on MMP9 expression and RhoA activation. (PMID:19306108)
• IL-8 increases in bronchial epithelial cells after arylsulfatase B silencing due to sequestration with chondroitin-4-sulfate (PMID:19346317)
• Altered ARSB immunostaining and reduced activity may be useful indicators of malignant transformation in human colonic tissue. (PMID:21378286)
• 13 mucopolysaccharidosis type VI patients were found to be homozygous for the previously undescribed H178L ARSB mutation (PMID:21996138)
• investigation of substrate specificity of arylsulfatase B in colonic epithelial cells; competitive binding of complex polysaccharides/glycosaminoglycans with arylsulfatase B can affect generation of reactive oxygen species and inflammatory response (PMID:22079206)
• Hypoxia reduces arylsulfatase B activity and silencing arylsulfatase B replicates and mediates the effects of hypoxia. (PMID:22428001)
• Arylsulfatase B activity was significantly less in the polymorphonuclear leukocytes and mononuclear cells from the cystic fibrosis patients than controls. (PMID:22550062)
• PTC124 but not gentamicin, increases the level of ARSB activity. (PMID:22971959)
• Sequencing analysis revealed a novel homozygous missense mutation in the ARSB gene at c.1457A (PMID:23023219)
• results indicate that mammalian ARSB improves functional recovery after CNS injury. (PMID:23520469)
• ARSB activity was significantly higher in the normal tissues. (PMID:23835622)
• novel homozygous missense mutation, c.278 C>T, p.P93L, associated with mucopolysaccharidosis type VI (PMID:23855929)
• Arylsulfatase B regulates versican expression by galectin-3 and AP-1 mediated transcriptional effects. (PMID:24240681)
• Mutation analysis of the ARSB gene revealed seven missense and three frameshift mutations of which eight were novel. (PMID:24677745)
• These studies reveal how carrageenan exposure can lead to transcriptional events in colonic epithelial cells through decline in arylsulfatase B activity, with subsequent impact on C4S, galectin-3, Sp1, and Wnt9A (PMID:24778176)
• Silencing Wnt9A increased the expression of CHST11 in the colonic epithelial cells, and chromatin immunoprecipitation assay demonstrated enhancing effects of Wnt9A siRNA and exogenous BMP4 on the CHST11 promoter (PMID:25511584)
• Nine novel mutations of ARSB were identified in MPS VI cases from India in the present study. The study also provides some insights into the genotype-phenotype association in MPS VI (PMID:26609033)
• Three novel mutations in ARSB were detected, expanding the mutational spectrum of ARSB causing MPS VI. A compound heterozygous for the c.464G>A (p.C155Y) and c.1163G>C (p.R388T) mutations, a 13.8-kb deletion encompassing exons 2 and 3, mutation c.479G>A (p.R160Q), and novel c.464G>A (p.C155Y) mutation. (PMID:27797586)
• Mutation analysis of 19 Indian mucopolysaccharidosis VI patients revealed the presence of a total of 15 different mutations of which twelve were novel. (PMID:27826022)
• The outcome of this study highlight a potential role for arylsulfatase B in promoting atherosclerosis-related stroke and warrants its further investigation as a therapeutic target that could be of potential clinical benefit. (PMID:28659610)
• Of the 20 patients included in the study, molecular genetic analysis was performed on 17 patients… molecular analysis results of four patients who was excluded from the overall study (three of which were another adult male siblings who did not receive ERT and one patient whose ERT duration was shorter than 6 months) were were included in determination of allele frequency of ARSB. (PMID:28884960)
• Findings indicate that lower arylsulfatase B (ARSB) is associated with prostate cancer recurrence. (PMID:29081414)
• Decreased ARSB expression is associated with cystic fibrosis. (PMID:29703589)
• Low ARSB expression is associated with prostate cancer. (PMID:29794138)
• Data of this study confirms the existence of mutational heterogeneity in the ARSB between Iranian patients. (PMID:30982216)
• Sequencing analysis of ARSB gene revealed four pathogenic homozygote mutations, including a novel nonsense mutation c.281C>A (p.Ser94X) in 9 patients, as well as, a known nonsense mutation c.753C>G (p.Try251X) in 3 cases, and two missense mutations c.904G>A (p.Gly302Arg) and c.454C>T (p.Arg152Trp) in two cases. The type of mutations affected the severity patient’s phenotypes. (PMID:31009684)
• A Possible Role for Arylsulfatase G in Dermatan Sulfate Metabolism. (PMID:32664626)
• Deep intronic variant in the ARSB gene as the genetic cause for Maroteaux-Lamy syndrome (MPS VI). (PMID:34435740)
• Mucopolysaccharidosis Type VI, an Updated Overview of the Disease. (PMID:34948256)
• Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases. (PMID:36361933)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ARSB	ENSDARG00000108788
mus_musculus	Arsb	ENSMUSG00000042082
rattus_norvegicus	Arsb	ENSRNOG00000011150
drosophila_melanogaster	CG18278	FBGN0033836
drosophila_melanogaster	CG7408	FBGN0036765
drosophila_melanogaster	CG7402	FBGN0036768
drosophila_melanogaster	CG32191	FBGN0052191
drosophila_melanogaster	CG30059	FBGN0260475

Paralogs (16): ARSD (ENSG00000006756), IDS (ENSG00000010404), ARSF (ENSG00000062096), ARSA (ENSG00000100299), STS (ENSG00000101846), GNS (ENSG00000135677), SULF1 (ENSG00000137573), GALNS (ENSG00000141012), ARSG (ENSG00000141337), ARSL (ENSG00000157399), ARSK (ENSG00000164291), ARSJ (ENSG00000180801), SGSH (ENSG00000181523), ARSI (ENSG00000183876), SULF2 (ENSG00000196562), ARSH (ENSG00000205667)

Protein

Protein identifiers

Arylsulfatase B — P15848 (reviewed: P15848)

Alternative names: N-acetylgalactosamine-4-sulfatase

All UniProt accessions (3): P15848, A0A2U3U034, E5RHC4

UniProt curated annotations — full annotation on UniProt →

Function. Removes sulfate groups from chondroitin-4-sulfate (C4S) and regulates its degradation. Involved in the regulation of cell adhesion, cell migration and invasion in colonic epithelium. In the central nervous system, is a regulator of neurite outgrowth and neuronal plasticity, acting through the control of sulfate glycosaminoglycans and neurocan levels.

Subunit / interactions. Monomer.

Subcellular location. Lysosome. Cell surface.

Post-translational modifications. The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. This post-translational modification is severely defective in multiple sulfatase deficiency (MSD).

Disease relevance. Mucopolysaccharidosis 6 (MPS6) [MIM:253200] A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPS6 is an autosomal recessive form 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. The disease is caused by variants affecting the gene represented in this entry. 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. 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.

Activity regulation. Inhibited by ethanol.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Similarity. Belongs to the sulfatase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P15848-1	1	yes
P15848-2	2

RefSeq proteins (2): NP_000037, NP_942002 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000917	Sulfatase_N	Domain
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily
IPR024607	Sulfatase_CS	Conserved_site
IPR047115	ARSB	Family

Pfam: PF00884

Enzyme classification (BRENDA):

• EC 3.1.6.1 — arylsulfatase (type I) (BRENDA: 49 organisms, 138 substrates, 159 inhibitors, 117 Km, 35 kcat entries)
• EC 3.1.6.12 — N-acetylgalactosamine-4-sulfatase (BRENDA: 9 organisms, 42 substrates, 40 inhibitors, 19 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

44 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL SULFATE	0.0003–26	46
4-NITROCATECHOL SULFATE	0.105–20.6	20
P-NITROCATECHOL SULFATE	1.3–3.9	5
P-NITROPHENYL SULFATE	0.0549–8.7	4
2-HYDROXY-5-NITROPHENYL SULFATE	0.043–0.085	3
ESTRONE 3-SULFATE	0.014–0.351	3
4-METHYLUMBELLIFERYL SULFATE	0.06–5.6	3
NITROCATECHOL SULFATE	0.8–3.6	3
4-METHYLUMBELLIFERYL SULFATE	0.0066–0.175	2
4-NITROPHENYL PHOSPHATE	0.0291–0.0752	2
DOPAMINE 3-SULFATE	7.2–9.8	2
DOPAMINE 4-SULFATE	2.1–2.8	2
EPINEPHRINE 3-SULFATE	14.1–18	2
EPINEPHRINE 4-SULFATE	1.9–2.5	2
NOREPINEPHRINE 3-SULFATE	10.5–12.8	2

UniProt features (102 total): sequence variant 34, helix 19, strand 17, binding site 8, turn 6, glycosylation site 6, disulfide bond 4, active site 2, sequence conflict 2, signal peptide 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1FSU	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15848-F1	93.74	0.90

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 91 (nucleophile); 147

Ligand- & substrate-binding residues (8): 301; 318; 53; 54; 91 (via 3-oxoalanine); 145; 242; 300

Post-translational modifications (1): 91

Disulfide bonds (4): 117–521, 121–155, 181–192, 405–447

Glycosylation sites (6): 188, 279, 291, 366, 426, 458

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-1663150	The activation of arylsulfatases
R-HSA-2024101	CS/DS degradation
R-HSA-2206285	MPS VI - Maroteaux-Lamy syndrome
R-HSA-6798695	Neutrophil degranulation
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation
R-HSA-1643685	Disease
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-1793185	Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-2206281	Mucopolysaccharidoses
R-HSA-392499	Metabolism of proteins
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-5663084	Diseases of carbohydrate metabolism
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 410 (showing top): HORIUCHI_WTAP_TARGETS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_LYSOSOMAL_TRANSPORT, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_VACUOLE_ORGANIZATION, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME, GOBP_NEUROGENESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (11): autophagy (GO:0006914), lysosome organization (GO:0007040), lysosomal transport (GO:0007041), response to nutrient (GO:0007584), response to pH (GO:0009268), regulation of epithelial cell migration (GO:0010632), positive regulation of neuron projection development (GO:0010976), chondroitin sulfate proteoglycan catabolic process (GO:0030207), response to estrogen (GO:0043627), response to methylmercury (GO:0051597), colon epithelial cell migration (GO:0061580)

GO Molecular Function (5): N-acetylgalactosamine-4-sulfatase activity (GO:0003943), arylsulfatase activity (GO:0004065), sulfuric ester hydrolase activity (GO:0008484), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (8): extracellular region (GO:0005576), lysosome (GO:0005764), endoplasmic reticulum lumen (GO:0005788), cell surface (GO:0009986), azurophil granule lumen (GO:0035578), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Chondroitin sulfate/dermatan sulfate metabolism	1
Mucopolysaccharidoses	1
Innate Immune System	1
Glycosphingolipid metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Post-translational protein modification	1
Sphingolipid metabolism	1
Immune System	1
Glycosaminoglycan metabolism	1
Diseases of carbohydrate metabolism	1
Metabolism of lipids	1
Metabolism	1
Diseases of metabolism	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to chemical	2
sulfuric ester hydrolase activity	2
cellular anatomical structure	2
intracellular organelle lumen	2
vacuolar lumen	2
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
lytic vacuole organization	1
vacuolar transport	1
response to nutrient levels	1
response to abiotic stimulus	1
epithelial cell migration	1
regulation of cell migration	1
regulation of multicellular organismal process	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
proteoglycan catabolic process	1
chondroitin sulfate proteoglycan metabolic process	1
response to hormone	1
intestinal epithelial cell migration	1
hydrolase activity, acting on ester bonds	1
cation binding	1
catalytic activity	1
lytic vacuole	1
endoplasmic reticulum	1
secretory granule lumen	1
azurophil granule	1
lysosome	1
extracellular vesicle	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARSB	SUMF1	Q8NBK3	857
ARSB	OGA	O60502	761
ARSB	IDUA	P35475	736
ARSB	GUSB	P08236	729
ARSB	MMUT	P22033	714
ARSB	NAGLU	P54802	565
ARSB	FARSB	Q9NSD9	527
ARSB	SERPINA7	P05543	506
ARSB	GLA	P06280	500
ARSB	HGSNAT	Q68CP4	496
ARSB	GLB1	P16278	475
ARSB	ARSK	Q6UWY0	474
ARSB	AGA	P20933	471
ARSB	NTRK2	Q16620	426
ARSB	GBA1	P04062	423

IntAct

54 interactions, top by confidence:

A	B	Type	Score
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
AVP	ATE1	psi-mi:“MI:0914”(association)	0.530
ERP29	ARSB	psi-mi:“MI:0914”(association)	0.530
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SUSD4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
AVP	B4GALT5	psi-mi:“MI:0914”(association)	0.350
PTPRK	MANBA	psi-mi:“MI:0914”(association)	0.350
INSL5	LAMA5	psi-mi:“MI:0914”(association)	0.350
ERP29	EXOC5	psi-mi:“MI:0914”(association)	0.350
SIAE	COCH	psi-mi:“MI:0914”(association)	0.350
NAAA	NRP2	psi-mi:“MI:0914”(association)	0.350
ESR1		psi-mi:“MI:0914”(association)	0.350
STK3	MYO1C	psi-mi:“MI:0914”(association)	0.350
MYC	PDZD2	psi-mi:“MI:0914”(association)	0.350
POC5	PDHX	psi-mi:“MI:0914”(association)	0.350
CCP110	A2ML1	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
NAAA	POTEF	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
FBXO45	METTL15	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-MS), ARSB (Affinity Capture-RNA)

ESM2 similar proteins: A3KGW5, F8S0Z7, O00754, O14773, O46432, O89023, P04062, P05186, P05187, P08289, P09242, P09487, P09923, P10696, P15589, P15693, P15848, P16301, P17439, P18424, P19111, P24822, P24823, P33727, P50429, P50430, P51740, P58242, P83456, Q04519, Q0V8B6, Q0VD19, Q29451, Q29486, Q2KHZ8, Q3TIW9, Q5IS74, Q5R8E3, Q60HE9, Q60HH1

Diamond homologs: P15848, P25549, P33727, P34059, P50429, P50430, Q32KH7, Q32KI9, Q32KJ6, Q32KJ8, Q571E4, Q5FYB0, Q5FYB1, Q8BM89, Q8WNQ7, P20713, P50473, Q5ZK90, Q60HH5, Q9X759, P15289, Q08DD1, Q32KH5, P08842, P14000, P15589, P50427, P50428, P51689, P51690, P54793, Q32KH8, Q32KH9, Q32KJ9, Q3TYD4, Q5FYA8, Q8A7C8, Q96EG1, P51691, Q89YS5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

944 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	86
Likely pathogenic	107
Uncertain significance	285
Likely benign	286
Benign	57

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100718	NM_000046.3:c.384_386delCTC	Pathogenic
1068506	NM_000046.5(ARSB):c.1558del (p.Arg520fs)	Pathogenic
1073284	NC_000005.9:g.(?78111899)(78135259_?)del	Pathogenic
1073285	NC_000005.9:g.(?78260219)(78265035_?)del	Pathogenic
1074059	NM_000046.5(ARSB):c.468del (p.Pro157fs)	Pathogenic
1323935	NM_000046.5(ARSB):c.1208C>A (p.Ser403Ter)	Pathogenic
1352140	NM_000046.5(ARSB):c.430G>C (p.Gly144Arg)	Pathogenic
1384664	NM_000046.5(ARSB):c.1142+1G>A	Pathogenic
1400506	NM_000046.5(ARSB):c.866_867insTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAAGAGATCGAGACCATCCCGGCTAAAACGGTGAAACCCCGTCTCTACTAAAAATACAAAAAAATTAGCCGGGCGTAGTGGCGGGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAGCAGTGGGCT (p.Leu289_Trp290insGlyArgProArgArgAlaAspHisGluValLysArgSerArgProSerArgLeuLysArgTer)	Pathogenic
1427846	NC_000005.9:g.(?78076210)(78181660_?)del	Pathogenic
1454563	NM_000046.5(ARSB):c.1336+2T>C	Pathogenic
1460302	NC_000005.9:g.(?78251108)(78281081_?)del	Pathogenic
1685546	NM_000046.5(ARSB):c.959G>T (p.Ser320Ile)	Pathogenic
1985289	NM_000046.5(ARSB):c.1418G>A (p.Trp473Ter)	Pathogenic
2013910	NM_000046.5(ARSB):c.376G>T (p.Glu126Ter)	Pathogenic
2028132	NM_000046.5(ARSB):c.745G>T (p.Glu249Ter)	Pathogenic
2038420	NM_000046.5(ARSB):c.54del (p.Leu19fs)	Pathogenic
2089502	NM_000046.5(ARSB):c.956G>A (p.Trp319Ter)	Pathogenic
2102504	NM_000046.5(ARSB):c.680del (p.Pro227fs)	Pathogenic
2133456	NM_000046.5(ARSB):c.1143-1G>T	Pathogenic
2161808	NM_000046.5(ARSB):c.1539C>A (p.Tyr513Ter)	Pathogenic
2422191	NC_000005.9:g.(?78251108)(78251335_?)del	Pathogenic
2446055	NM_000046.5(ARSB):c.438del (p.Trp146fs)	Pathogenic
2722742	NM_000046.5(ARSB):c.1521dup (p.His508fs)	Pathogenic
2739484	NM_000046.5(ARSB):c.916_917del (p.Leu306fs)	Pathogenic
2754155	NM_000046.5(ARSB):c.1533del (p.Val512fs)	Pathogenic
2785521	NM_000046.5(ARSB):c.1433del (p.Asp478fs)	Pathogenic
2794737	NM_000046.5(ARSB):c.551T>C (p.Ile184Thr)	Pathogenic
2821364	NM_000046.5(ARSB):c.715C>T (p.Gln239Ter)	Pathogenic
3015401	NM_000046.5(ARSB):c.403G>T (p.Glu135Ter)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3437 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:78885773:T:A	K318I	0.999
5:78885827:T:A	D300V	0.998
5:78969069:A:G	W146R	0.998
5:78969069:A:T	W146R	0.998
5:78969071:T:A	K145I	0.998
5:78885772:T:A	K318N	0.997
5:78885772:T:G	K318N	0.997
5:78955295:C:G	D300H	0.997
5:78984976:G:C	C91W	0.997
5:78885669:A:G	W353R	0.996
5:78885669:A:T	W353R	0.996
5:78885827:T:G	D300A	0.996
5:78969019:A:C	F162L	0.996
5:78969019:A:T	F162L	0.996
5:78969021:A:G	F162L	0.996
5:78969067:C:A	W146C	0.996
5:78969067:C:G	W146C	0.996
5:78984968:G:C	S94W	0.996
5:78984977:C:T	C91Y	0.996
5:78984978:A:G	C91R	0.996
5:78985088:T:A	D54V	0.996
5:78781869:A:G	L440P	0.995
5:78885793:G:C	N311K	0.995
5:78885793:G:T	N311K	0.995
5:78885823:G:C	N301K	0.995
5:78885823:G:T	N301K	0.995
5:78885824:T:A	N301I	0.995
5:78969070:T:A	K145N	0.995
5:78969070:T:G	K145N	0.995
5:78780578:A:G	L474P	0.994

dbSNP variants (sampled 300 via entrez): RS1000011427 (5:78944917 G>C), RS1000012781 (5:78893669 A>G), RS1000048669 (5:78981388 C>T), RS1000068061 (5:78845506 G>C), RS1000080149 (5:78940119 T>C), RS1000090853 (5:78854502 C>A,T), RS1000100974 (5:78870975 T>C), RS1000112303 (5:78982241 C>T), RS1000112996 (5:78808150 A>G,T), RS1000117613 (5:78957645 C>A,T), RS1000124829 (5:78898245 G>A), RS1000126165 (5:78888240 C>A,T), RS1000127264 (5:78829428 T>G), RS1000190566 (5:78905252 A>G), RS1000202571 (5:78809470 C>G,T)

Disease associations

OMIM: gene MIM:611542 | disease phenotypes: MIM:253200, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
mucopolysaccharidosis type 6	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mucopolysaccharidosis type 6	Definitive	AR

Mondo (3): mucopolysaccharidosis type 6 (MONDO:0009661), schizophrenia (MONDO:0005090), metachromatic leukodystrophy (MONDO:0018868)

Orphanet (3): Mucopolysaccharidosis type 6 (Orphanet:583), Metachromatic leukodystrophy (Orphanet:512), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000158	Macroglossia
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000280	Coarse facial features
HP:0000365	Hearing impairment
HP:0000501	Glaucoma
HP:0000670	Carious teeth
HP:0000684	Delayed eruption of teeth
HP:0000768	Pectus carinatum
HP:0000884	Prominent sternum
HP:0000885	Broad ribs
HP:0000943	Dysostosis multiplex
HP:0001007	Hirsutism
HP:0001072	Thickened skin
HP:0001171	Split hand
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001371	Flexion contracture
HP:0001385	Hip dysplasia
HP:0001387	Joint stiffness
HP:0001537	Umbilical hernia
HP:0001638	Cardiomyopathy
HP:0001653	Mitral regurgitation
HP:0001718	Mitral stenosis
HP:0001744	Splenomegaly
HP:0002090	Pneumonia
HP:0002091	Restrictive ventilatory defect

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000301_15	Iron status biomarkers	8.000000e-06
GCST000461_12	Hippocampal atrophy	7.000000e-06
GCST002048_2	Attention deficit hyperactivity disorder	5.000000e-06
GCST002670_1	Blood and toenail selenium levels	2.000000e-39
GCST002670_5	Blood and toenail selenium levels	5.000000e-14
GCST002670_6	Blood and toenail selenium levels	5.000000e-10
GCST002670_7	Blood and toenail selenium levels	2.000000e-15
GCST002670_8	Blood and toenail selenium levels	2.000000e-11
GCST002671_15	Toenail selenium levels	3.000000e-13
GCST002671_5	Toenail selenium levels	1.000000e-16
GCST006976_41	Macular thickness	6.000000e-16
GCST006979_110	Heel bone mineral density	6.000000e-09
GCST006997_1	Cerebrospinal fluid t-tau levels in mild cognitive impairment	2.000000e-07
GCST007478_10	Non-word reading	6.000000e-06
GCST007666_10	Depressive symptom improvement	1.000000e-06
GCST008362_105	Birth weight	3.000000e-08
GCST009391_1632	Metabolite levels	1.000000e-07
GCST90002394_70	Monocyte percentage of white cells	2.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004461	iron biomarker measurement
EFO:0005039	hippocampal atrophy
EFO:0009270	heel bone mineral density
EFO:0004760	t-tau measurement
EFO:0005299	non-word reading
EFO:0007006	depressive symptom measurement
EFO:0004344	birth weight
EFO:0007787	plasma betaine measurement
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007966	Leukodystrophy, Metachromatic	C10.228.140.163.100.362.550; C10.228.140.163.100.435.825.850.500; C10.228.140.695.625.550; C10.314.400.550; C16.320.565.189.362.550; C16.320.565.189.435.825.850.500; C16.320.565.398.641.803.925.500; C16.320.565.595.554.825.850.500; C18.452.132.100.362.550; C18.452.132.100.435.825.850.500; C18.452.584.563.641.803.925.500; C18.452.648.189.362.550; C18.452.648.189.435.825.850.500; C18.452.648.398.641.803.925.500; C18.452.648.595.554.825.850.500
D009087	Mucopolysaccharidosis VI	C16.320.565.202.715.670; C16.320.565.595.600.670; C17.300.550.575.670; C18.452.648.202.715.670; C18.452.648.595.600.670

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2399 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	affects expression, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Nickel	increases expression	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
SR 11302	affects expression, decreases reaction	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
phenylhydrazonopyrazolone sulfonate 1	increases reaction, affects expression, affects activity	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL651171	Binding	Inhibitory activity against human aryl sulfatase B (ASB) isolated from human placenta at a concentration up to 10 uM	6-(2-adamantan-2-ylidene-hydroxybenzoxazole)-O-sulfamate: a potent non-steroidal irreversible inhibitor of human steroid sulfatase. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C9HD	RCMGi012-A	Induced pluripotent stem cell	Female
CVCL_D5EJ	HeLa::TMEM192-3xHA ARSB KO	Cancer cell line	Female
CVCL_E1R0	HAP1 ARSB (-) 2	Cancer cell line	Male
CVCL_XL56	HAP1 ARSB (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00299000	PHASE4	COMPLETED	A Phase 4 Two Dose Level Study of Naglazyme(TM) (Galsulfase) in Infants With MPS VI
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients