ARSH

Summary

ARSH (arylsulfatase family member H, HGNC:32488) is a protein-coding gene on chromosome Xp22.33, encoding Arylsulfatase H (Q5FYA8).

Sulfatases, such as ARSH, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).

Source: NCBI Gene 347527 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 122 total
• MANE Select transcript: NM_001011719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32488
Approved symbol	ARSH
Name	arylsulfatase family member H
Location	Xp22.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205667
Ensembl biotype	protein_coding
OMIM	300586
Entrez	347527

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000381130

RefSeq mRNA: 1 — MANE Select: NM_001011719 NM_001011719

CCDS: CCDS35198

Canonical transcript exons

ENST00000381130 — 9 exons

Exon	Start	End
ENSE00001487595	3033018	3034111
ENSE00001487597	3029247	3029368
ENSE00001487599	3027313	3027475
ENSE00001487600	3024021	3024155
ENSE00001487602	3018534	3018670
ENSE00001487603	3014970	3015393
ENSE00001487606	3013047	3013172
ENSE00001487608	3010030	3010151
ENSE00001487610	3006546	3006704

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 75.21.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.21	gold quality
gall bladder	UBERON:0002110	47.79	gold quality
lower esophagus mucosa	UBERON:0035834	47.09	silver quality
ganglionic eminence	UBERON:0004023	47.02	gold quality
islet of Langerhans	UBERON:0000006	47.01	gold quality
esophagus mucosa	UBERON:0002469	46.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	41.86	gold quality
endometrium	UBERON:0001295	40.95	silver quality
tonsil	UBERON:0002372	40.20	gold quality
ventricular zone	UBERON:0003053	39.95	gold quality
pancreas	UBERON:0001264	39.39	gold quality
saliva-secreting gland	UBERON:0001044	38.07	gold quality
minor salivary gland	UBERON:0001830	37.21	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
urinary bladder	UBERON:0001255	36.84	silver quality
cortical plate	UBERON:0005343	36.47	gold quality
mucosa of transverse colon	UBERON:0004991	36.42	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
sural nerve	UBERON:0015488	35.55	gold quality
placenta	UBERON:0001987	35.17	silver quality
body of pancreas	UBERON:0001150	34.82	gold quality
skin of abdomen	UBERON:0001416	34.67	gold quality
vagina	UBERON:0000996	34.39	gold quality
esophagus	UBERON:0001043	33.94	gold quality
bone marrow	UBERON:0002371	33.89	gold quality
zone of skin	UBERON:0000014	33.68	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
muscle tissue	UBERON:0002385	33.23	gold quality
thoracic mammary gland	UBERON:0005200	32.77	silver quality
skin of leg	UBERON:0001511	32.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.78

Regulation

Is transcription factor: no

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	sulf2a	ENSDARG00000018423
danio_rerio	arsib	ENSDARG00000117075
drosophila_melanogaster	CG18278	FBGN0033836
drosophila_melanogaster	CG7408	FBGN0036765
drosophila_melanogaster	CG7402	FBGN0036768
drosophila_melanogaster	Sulf1	FBGN0040271
drosophila_melanogaster	CG32191	FBGN0052191
drosophila_melanogaster	CG30059	FBGN0260475
caenorhabditis_elegans		WBGENE00006308
caenorhabditis_elegans		WBGENE00006309
caenorhabditis_elegans		WBGENE00006310

Paralogs (16): ARSD (ENSG00000006756), IDS (ENSG00000010404), ARSF (ENSG00000062096), ARSA (ENSG00000100299), STS (ENSG00000101846), ARSB (ENSG00000113273), GNS (ENSG00000135677), SULF1 (ENSG00000137573), GALNS (ENSG00000141012), ARSG (ENSG00000141337), ARSL (ENSG00000157399), ARSK (ENSG00000164291), ARSJ (ENSG00000180801), SGSH (ENSG00000181523), ARSI (ENSG00000183876), SULF2 (ENSG00000196562)

Protein

Protein identifiers

Arylsulfatase H — Q5FYA8 (reviewed: Q5FYA8)

All UniProt accessions (1): Q5FYA8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

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.

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

Similarity. Belongs to the sulfatase family.

RefSeq proteins (1): NP_001011719* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000917	Sulfatase_N	Domain
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily
IPR024607	Sulfatase_CS	Conserved_site
IPR050738	Sulfatase	Family

Pfam: PF00884, PF14707

UniProt features (14 total): binding site 8, transmembrane region 2, active site 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5FYA8-F1	94.15	0.87

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): 55 (nucleophile); 117

Ligand- & substrate-binding residues (8): 323; 324; 348; 15; 16; 55 (via 3-oxoalanine); 115; 271

Post-translational modifications (1): 55

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1663150	The activation of arylsulfatases
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 15 (showing top): REACTOME_SPHINGOLIPID_METABOLISM, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_SULFURIC_ESTER_HYDROLASE_ACTIVITY, GOMF_ARYLSULFATASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, chrXp22, PEDRIOLI_MIR31_TARGETS_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_GAMMA_CARBOXYLATION_HYPUSINYLATION_HYDROXYLATION_AND_ARYLSULFATASE_ACTIVATION, REACTOME_METABOLISM_OF_LIPIDS, DESCARTES_MAIN_FETAL_BIPOLAR_CELLS, REACTOME_GLYCOSPHINGOLIPID_CATABOLISM, REACTOME_GLYCOSPHINGOLIPID_METABOLISM, REACTOME_THE_ACTIVATION_OF_ARYLSULFATASES

GO Biological Process (0):

GO Molecular Function (3): arylsulfatase activity (GO:0004065), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (2): endoplasmic reticulum lumen (GO:0005788), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Glycosphingolipid metabolism	1
Post-translational protein modification	1
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sulfuric ester hydrolase activity	1
cation binding	1
catalytic activity	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARSH	AS3MT	Q9HBK9	613
ARSH	GET3	O43681	573
ARSH	ARSK	Q6UWY0	532
ARSH	CUTC	Q9NTM9	510
ARSH	SLURP1	P55000	418
ARSH	COPB1	P53618	397
ARSH	PRR32	B1ATL7	395
ARSH	ARSI	Q5FYB1	383
ARSH	COPG1	Q9Y678	376
ARSH	ARSJ	Q5FYB0	363
ARSH	GNS	P15586	347
ARSH	CTPS2	Q9NRF8	315
ARSH	APEH	P13798	313
ARSH	SRRT	Q9BXP5	303
ARSH	AQP9	O43315	302

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ARSH	HERC4	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): ITCH (Affinity Capture-MS), GPHN (Affinity Capture-MS), HERC4 (Affinity Capture-MS)

ESM2 similar proteins: A0A2D0TC04, A1A4K5, A2VDP5, A8K7I4, J3SBP3, J3SEZ3, O14638, P06802, P0DQQ4, P15396, P18563, P18564, P22413, P54793, P97259, P97675, Q08834, Q09328, Q13822, Q14CN2, Q1RPR6, Q29444, Q2TU62, Q32KH8, Q3SZI1, Q4FZV0, Q5FYA8, Q5GF25, Q5R5M5, Q64610, Q6AYF4, Q6DDW2, Q6DYE8, Q6NXH2, Q6PT52, Q6Q473, Q863C4, Q8BTJ4, Q8K1B9, Q8K2I4

Diamond homologs: P08842, P14000, P15289, P15589, P20713, P34059, P50427, P50428, P50473, P51689, P51690, P54793, Q08DD1, Q32KH5, Q32KH8, Q32KH9, Q32KJ6, Q32KJ9, Q3TYD4, Q571E4, Q5FYA8, Q5FYB0, Q60HH5, Q8BM89, Q8WNQ7, Q9X759, T2KMG4, T2KN90, P22304, P31447, Q08890, Q32KI9, Q32KJ8, Q5FYB1, Q96EG1, P33727, P50430, Q32KH7, Q8A2F6, Q8A2H2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	8
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

1606 predictions. Top by Δscore:

Variant	Effect	Δscore
X:3006700:GTGAG:G	donor_gain	1.0000
X:3010020:T:TA	acceptor_gain	1.0000
X:3010021:G:A	acceptor_gain	1.0000
X:3010025:TGCA:T	acceptor_loss	1.0000
X:3010026:GCAG:G	acceptor_loss	1.0000
X:3010028:A:AG	acceptor_gain	1.0000
X:3010029:G:GA	acceptor_gain	1.0000
X:3010029:GC:G	acceptor_gain	1.0000
X:3010029:GCA:G	acceptor_gain	1.0000
X:3010029:GCAC:G	acceptor_gain	1.0000
X:3010029:GCACA:G	acceptor_gain	1.0000
X:3010149:CAGG:C	donor_loss	1.0000
X:3010150:AGGTG:A	donor_loss	1.0000
X:3010151:GGTG:G	donor_loss	1.0000
X:3010152:G:GA	donor_loss	1.0000
X:3013045:AG:A	acceptor_gain	1.0000
X:3013045:AGG:A	acceptor_gain	1.0000
X:3013046:GG:G	acceptor_gain	1.0000
X:3013046:GGG:G	acceptor_gain	1.0000
X:3013046:GGGAT:G	acceptor_gain	1.0000
X:3024015:CTCCA:C	acceptor_loss	1.0000
X:3024017:CCAG:C	acceptor_loss	1.0000
X:3024020:GGTA:G	acceptor_gain	1.0000
X:3024020:GGTAA:G	acceptor_gain	1.0000
X:3024128:C:G	donor_gain	1.0000
X:3024152:AAAGG:A	donor_loss	1.0000
X:3024154:AG:A	donor_loss	1.0000
X:3024155:GG:G	donor_loss	1.0000
X:3024156:G:T	donor_loss	1.0000
X:3024157:T:G	donor_loss	1.0000

AlphaMissense

3685 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:3014975:T:A	W116R	0.991
X:3014975:T:C	W116R	0.991
X:3014977:G:C	W116C	0.985
X:3014977:G:T	W116C	0.985
X:3015038:T:C	F137L	0.985
X:3015040:T:A	F137L	0.985
X:3015040:T:G	F137L	0.985
X:3006641:T:A	V10D	0.984
X:3027414:A:C	S380R	0.982
X:3027416:C:A	S380R	0.982
X:3027416:C:G	S380R	0.982
X:3033299:T:A	W535R	0.982
X:3033299:T:C	W535R	0.982
X:3010109:A:C	S58R	0.978
X:3010111:T:A	S58R	0.978
X:3010111:T:G	S58R	0.978
X:3018658:G:C	D297H	0.978
X:3027349:G:C	R358P	0.976
X:3027361:T:A	I362K	0.975
X:3027423:G:C	D383H	0.975
X:3033034:A:C	K446N	0.974
X:3033034:A:T	K446N	0.974
X:3015039:T:C	F137S	0.973
X:3015047:T:C	F140L	0.972
X:3015049:T:A	F140L	0.972
X:3015049:T:G	F140L	0.972
X:3010134:G:C	R66P	0.971
X:3015039:T:G	F137C	0.969
X:3015260:T:A	W211R	0.969
X:3015260:T:C	W211R	0.969

dbSNP variants (sampled 300 via entrez): RS1000257165 (X:3020958 A>G), RS1000263790 (X:3009893 T>G), RS1000347558 (X:3032857 A>G), RS1000380164 (X:3033484 T>C), RS1000416330 (X:3021205 T>C), RS1000519144 (X:3023271 T>G), RS1000628176 (X:3031196 G>A), RS1000838701 (X:3007671 T>G), RS1000891136 (X:3007507 A>G), RS1001046604 (X:3014655 A>T), RS1001189288 (X:3018954 T>C,G), RS1001299970 (X:3027891 C>A), RS1001500552 (X:3004832 C>A), RS1001504296 (X:3011595 T>C), RS1001712760 (X:3010809 A>G)

Disease associations

OMIM: gene MIM:300586 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
propionaldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
2-palmitoylglycerol	increases expression	1
bisphenol S	decreases methylation	1
Methapyrilene	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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