ARSJ

Summary

ARSJ (arylsulfatase family member J, HGNC:26286) is a protein-coding gene on chromosome 4q26, encoding Arylsulfatase J (Q5FYB0).

Sulfatases (EC 3.1.5.6), such as ARSJ, 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 79642 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 68 total — 1 pathogenic
• MANE Select transcript: NM_024590

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26286
Approved symbol	ARSJ
Name	arylsulfatase family member J
Location	4q26
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23548
Ensembl gene	ENSG00000180801
Ensembl biotype	protein_coding
OMIM	610010
Entrez	79642

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding_CDS_not_defined, 1 protein_coding, 1 nonsense_mediated_decay

ENST00000315366, ENST00000503013, ENST00000509829, ENST00000636527

RefSeq mRNA: 2 — MANE Select: NM_024590 NM_001354210, NM_024590

CCDS: CCDS43264

Canonical transcript exons

ENST00000315366 — 2 exons

Exon	Start	End
ENSE00001368167	113900284	113903675
ENSE00002075002	113978437	113979647

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 90.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2710 / max 189.7082, expressed in 1160 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53698	4.8766	1025
53697	1.0587	648
53699	0.5831	344
53695	0.2584	121
53693	0.1878	81
53700	0.1271	36
53696	0.0894	39
53694	0.0516	14
53701	0.0382	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	90.10	gold quality
cartilage tissue	UBERON:0002418	87.83	gold quality
calcaneal tendon	UBERON:0003701	80.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.93	gold quality
ascending aorta	UBERON:0001496	79.32	gold quality
thoracic aorta	UBERON:0001515	79.29	gold quality
aorta	UBERON:0000947	78.45	gold quality
right coronary artery	UBERON:0001625	78.23	gold quality
popliteal artery	UBERON:0002250	78.07	gold quality
tibial artery	UBERON:0007610	78.04	gold quality
descending thoracic aorta	UBERON:0002345	77.93	gold quality
left coronary artery	UBERON:0001626	76.81	gold quality
rectum	UBERON:0001052	75.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	75.67	gold quality
lower esophagus	UBERON:0013473	75.64	gold quality
gall bladder	UBERON:0002110	75.13	gold quality
islet of Langerhans	UBERON:0000006	75.01	gold quality
coronary artery	UBERON:0001621	74.95	gold quality
upper lobe of left lung	UBERON:0008952	74.60	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	74.11	gold quality
upper lobe of lung	UBERON:0008948	73.76	gold quality
metanephros cortex	UBERON:0010533	72.74	gold quality
minor salivary gland	UBERON:0001830	72.64	gold quality
esophagus	UBERON:0001043	72.23	gold quality
epithelial cell of pancreas	CL:0000083	71.81	silver quality
endometrium	UBERON:0001295	71.71	gold quality
muscle layer of sigmoid colon	UBERON:0035805	71.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	70.61	gold quality
prostate gland	UBERON:0002367	70.58	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.50
E-MTAB-6678	no	3.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

136 targeting ARSJ, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
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
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 1)

• The identification, molecular cloning and initial characterization of three new members of this human gene family is reported. (PMID:16500042)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	arsj	ENSDARG00000077590
mus_musculus	Arsj	ENSMUSG00000046561
rattus_norvegicus	Arsj	ENSRNOG00000000001
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

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), SGSH (ENSG00000181523), ARSI (ENSG00000183876), SULF2 (ENSG00000196562), ARSH (ENSG00000205667)

Protein

Protein identifiers

Arylsulfatase J — Q5FYB0 (reviewed: Q5FYB0)

All UniProt accessions (2): D6RGC1, Q5FYB0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

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 (2): NP_001341139, NP_078866* (*=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

UniProt features (28 total): binding site 8, glycosylation site 6, sequence conflict 5, compositionally biased region 2, active site 2, signal peptide 1, chain 1, modified residue 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5FYB0-F1	87.34	0.74

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): 122 (nucleophile); 178

Ligand- & substrate-binding residues (8): 176; 269; 327; 328; 345; 84; 85; 122 (via 3-oxoalanine)

Post-translational modifications (1): 122

Glycosylation sites (6): 157, 306, 318, 431, 497, 527

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: 101 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, AACTTT_UNKNOWN, REACTOME_SPHINGOLIPID_METABOLISM, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, NUYTTEN_NIPP1_TARGETS_DN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_SULFURIC_ESTER_HYDROLASE_ACTIVITY, GOMF_ARYLSULFATASE_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, REN_ALVEOLAR_RHABDOMYOSARCOMA_DN, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, VERHAAK_GLIOBLASTOMA_MESENCHYMAL, PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_4

GO Biological Process (0):

GO Molecular Function (4): arylsulfatase activity (GO:0004065), sulfuric ester hydrolase activity (GO:0008484), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (4): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), actin cytoskeleton (GO:0015629), 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
cellular anatomical structure	2
sulfuric ester hydrolase activity	1
hydrolase activity, acting on ester bonds	1
cation binding	1
catalytic activity	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cytoskeleton	1

Protein interactions and networks

STRING

956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARSJ	ARSK	Q6UWY0	696
ARSJ	ENPP1	P22413	624
ARSJ	ABCC6	P78420	519
ARSJ	PALMD	Q9NP74	454
ARSJ	COL20A1	Q9P218	448
ARSJ	RIC3	Q7Z5B4	443
ARSJ	IFT38	Q96AJ1	442
ARSJ	KLHL31	Q9H511	438
ARSJ	ACAD10	Q6JQN1	432
ARSJ	TDRD7	Q8NHU6	417
ARSJ	UBE2H	P37286	410
ARSJ	AUTS2	Q8WXX7	394
ARSJ	MKNK1	Q9BUB5	393
ARSJ	ARSH	Q5FYA8	363
ARSJ	ZCCHC24	Q8N2G6	358

IntAct

2 interactions, top by confidence:

A	B	Type	Score
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): ARSJ (Two-hybrid), ARSJ (Two-hybrid), ARSJ (Two-hybrid), ZMIZ2 (Two-hybrid), ARSJ (Affinity Capture-RNA), ARSJ (Protein-peptide)

ESM2 similar proteins: A1A5C7, A5D7H1, A6H7A0, A6NJW4, A6QLN9, A8MUP2, A8MXK1, B0BMW8, B0BNL6, O35393, O62657, O75078, P52875, P55244, P56880, P57791, Q08334, Q0V881, Q15768, Q16557, Q2M1K6, Q3SZQ2, Q3UHH2, Q4V899, Q5E9H2, Q5FYB0, Q5M7U7, Q5R6I6, Q5RCI5, Q5SQ64, Q642A6, Q6PCB0, Q7TPB4, Q8BM89, Q8BZH0, Q8N431, Q8N5I2, Q8R2R5, Q8R2Z5, Q8VE98

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, P15586, P50426, Q32KJ8, Q5FYB1, Q8A2F6, Q8A2H2, Q8BFR4, Q8IWU6, Q8K007, Q8VI60, Q90XB6, P15848

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	65
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
426095	t(4;14)(q26;q12)	Pathogenic

SpliceAI

1227 predictions. Top by Δscore:

Variant	Effect	Δscore
4:113903675:CC:C	acceptor_loss	1.0000
4:113903675:CCT:C	acceptor_gain	1.0000
4:113903677:T:C	acceptor_gain	1.0000
4:113903677:T:TC	acceptor_gain	1.0000
4:113903672:ATAC:A	acceptor_gain	0.9900
4:113903673:TAC:T	acceptor_gain	0.9900
4:113903674:AC:A	acceptor_gain	0.9900
4:113903676:C:CC	acceptor_gain	0.9900
4:113903676:C:T	acceptor_gain	0.9900
4:113917199:A:AC	donor_gain	0.9900
4:113917200:C:CC	donor_gain	0.9900
4:113917216:AGTG:A	donor_gain	0.9900
4:113917234:T:A	donor_gain	0.9900
4:113977434:TGGC:T	donor_gain	0.9900
4:113903671:GATAC:G	acceptor_gain	0.9800
4:113953396:CA:C	acceptor_gain	0.9800
4:113978439:T:A	donor_gain	0.9700
4:113979447:GACAC:G	donor_loss	0.9700
4:113979448:ACACT:A	donor_loss	0.9700
4:113979449:CACT:C	donor_loss	0.9700
4:113979450:ACTC:A	donor_loss	0.9700
4:113979451:CTCAC:C	donor_loss	0.9700
4:113979452:T:TC	donor_loss	0.9700
4:113979453:CACC:C	donor_loss	0.9700
4:113979454:ACC:A	donor_loss	0.9700
4:113979455:CCAGG:C	donor_gain	0.9700
4:113978435:ACTTT:A	donor_gain	0.9600
4:113978436:CTTTC:C	donor_gain	0.9600
4:113979454:A:AC	donor_gain	0.9600
4:113979455:C:CC	donor_gain	0.9600

AlphaMissense

3905 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:113903039:T:A	K345N	1.000
4:113903039:T:G	K345N	1.000
4:113903040:T:A	K345I	1.000
4:113903094:T:A	D327V	1.000
4:113903545:A:G	W177R	1.000
4:113903545:A:T	W177R	1.000
4:113903547:T:A	K176I	1.000
4:113978581:T:A	D85V	1.000
4:113978584:T:A	D84V	1.000
4:113902423:A:G	W551R	0.999
4:113902423:A:T	W551R	0.999
4:113902590:A:G	L495P	0.999
4:113902678:A:G	W466R	0.999
4:113902678:A:T	W466R	0.999
4:113902936:A:G	W380R	0.999
4:113902936:A:T	W380R	0.999
4:113902939:C:G	D379H	0.999
4:113903020:C:A	G352W	0.999
4:113903022:C:A	G351V	0.999
4:113903022:C:T	G351E	0.999
4:113903023:C:G	G351R	0.999
4:113903023:C:T	G351R	0.999
4:113903041:T:C	K345E	0.999
4:113903041:T:G	K345Q	0.999
4:113903046:C:A	G343V	0.999
4:113903048:T:A	R342S	0.999
4:113903048:T:G	R342S	0.999
4:113903049:C:G	R342T	0.999
4:113903060:G:C	N338K	0.999
4:113903060:G:T	N338K	0.999

dbSNP variants (sampled 300 via entrez): RS1000002387 (4:113922737 C>T), RS1000118461 (4:113922485 A>G), RS1000125629 (4:113970005 C>T), RS10001850 (4:113912494 T>A,C), RS1000215898 (4:113945079 G>A), RS1000217209 (4:113962469 G>A), RS1000232700 (4:113981036 C>T), RS1000266558 (4:113931902 A>G), RS1000284084 (4:113938842 G>C), RS1000336802 (4:113949961 G>A,T), RS1000378910 (4:113903875 A>C), RS1000439830 (4:113926490 G>C), RS1000442203 (4:113944904 G>A,T), RS1000458380 (4:113915949 A>G), RS1000550309 (4:113946233 A>C)

Disease associations

OMIM: gene MIM:610010 | disease phenotypes: MIM:613454

GenCC curated gene-disease

Mondo (1): FOXG1 disorder (MONDO:0100040)

Orphanet (3): Atypical Rett syndrome (Orphanet:3095), FOXG1 syndrome (Orphanet:561854), FOXG1 syndrome due to intragenic alteration (Orphanet:598164)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002249_11	Blood pressure measurement (high sodium intervention)	3.000000e-07
GCST002252_13	Blood pressure measurement (high sodium and potassium intervention)	2.000000e-07
GCST002252_9	Blood pressure measurement (high sodium and potassium intervention)	3.000000e-06
GCST007628_3	Impulsivity (motor)	9.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005401	response to high sodium diet
EFO:0006335	systolic blood pressure
EFO:0005403	response to dietary potassium supplementation
EFO:0006340	mean arterial pressure
EFO:0006946	behavioural disinhibition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	2
Arsenic	increases methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	increases methylation, affects expression	2
Valproic Acid	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Rifampin	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Vanadates	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07293546	PHASE1/PHASE2	NOT_YET_RECRUITING	Phase 1/2 Study of FRF-001, an AAV-9 Gene Therapy, in Patients With FOXG1 Syndrome (FS)
NCT02705677	Not specified	COMPLETED	Biobanking of Rett Syndrome and Related Disorders
NCT02738281	Not specified	COMPLETED	Natural History of Rett Syndrome & Related Disorders
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families