STS

Summary

STS (steroid sulfatase, HGNC:11425) is a protein-coding gene on chromosome Xp22.31, encoding Steryl-sulfatase (P08842). Catalyzes the conversion of sulfated steroid precursors, such as dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate to the free steroid. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a multi-pass membrane protein that is localized to the endoplasmic reticulum. It belongs to the sulfatase family and hydrolyzes several 3-beta-hydroxysteroid sulfates, which serve as metabolic precursors for estrogens, androgens, and cholesterol. Mutations in this gene are associated with X-linked ichthyosis (XLI). Alternatively spliced transcript variants resulting from the use of different promoters have been described for this gene (PMID:17601726).

Source: NCBI Gene 412 — RefSeq curated summary.

At a glance

• Gene–disease (curated): recessive X-linked ichthyosis (Definitive, GenCC)
• Clinical variants (ClinVar): 270 total — 15 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 35
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001320752

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11425
Approved symbol	STS
Name	steroid sulfatase
Location	Xp22.31
Locus type	gene with protein product
Status	Approved
Aliases	ARSC
Ensembl gene	ENSG00000101846
Ensembl biotype	protein_coding
OMIM	300747
Entrez	412

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000217961, ENST00000658154, ENST00000660000, ENST00000664306, ENST00000666110, ENST00000674429, ENST00000870798, ENST00000870799, ENST00000870800, ENST00000934599, ENST00000962860, ENST00000962861

RefSeq mRNA: 6 — MANE Select: NM_001320752 NM_000351, NM_001320750, NM_001320751, NM_001320752, NM_001320753, NM_001320754

CCDS: CCDS14127

Canonical transcript exons

ENST00000674429 — 11 exons

Exon	Start	End
ENSE00000664669	7257242	7257363
ENSE00000664671	7257466	7257588
ENSE00001136339	7333986	7334107
ENSE00001136363	7259349	7259772
ENSE00001203198	7325339	7325498
ENSE00001203204	7305046	7305183
ENSE00001203210	7275951	7276087
ENSE00003898250	7349888	7354641
ENSE00003898442	7147712	7148083
ENSE00003898699	7253196	7253336
ENSE00003898862	7190880	7191008

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 94.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0820 / max 504.7255, expressed in 1586 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195417	3.3812	1449
195416	1.6535	510
195423	0.3592	42
195424	0.2241	33
209591	0.1088	37
195425	0.0757	18
195426	0.0618	16
195432	0.0528	18
195430	0.0417	18
195429	0.0347	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	94.64	gold quality
endothelial cell	CL:0000115	92.07	gold quality
palpebral conjunctiva	UBERON:0001812	88.64	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.30	gold quality
pancreatic ductal cell	CL:0002079	87.02	gold quality
decidua	UBERON:0002450	85.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	85.48	gold quality
middle temporal gyrus	UBERON:0002771	85.40	gold quality
primary visual cortex	UBERON:0002436	85.36	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.04	gold quality
stromal cell of endometrium	CL:0002255	84.43	gold quality
popliteal artery	UBERON:0002250	83.92	gold quality
tibial artery	UBERON:0007610	83.91	gold quality
eye	UBERON:0000970	83.66	gold quality
artery	UBERON:0001637	83.29	gold quality
occipital lobe	UBERON:0002021	82.96	gold quality
prefrontal cortex	UBERON:0000451	82.22	gold quality
right coronary artery	UBERON:0001625	82.07	gold quality
orbitofrontal cortex	UBERON:0004167	82.02	gold quality
dorsal root ganglion	UBERON:0000044	81.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.48	gold quality
adipose tissue	UBERON:0001013	81.41	gold quality
calcaneal tendon	UBERON:0003701	81.31	gold quality
aorta	UBERON:0000947	81.13	gold quality
nasal cavity epithelium	UBERON:0005384	81.08	gold quality
postcentral gyrus	UBERON:0002581	81.05	gold quality
superior frontal gyrus	UBERON:0002661	81.02	gold quality
connective tissue	UBERON:0002384	80.70	gold quality
parietal lobe	UBERON:0001872	80.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AR, ARNT, DNMT3B, ESR1, ESR2, MYB, SOX17, STAT3, STAT5B

miRNA regulators (miRDB)

152 targeting STS, 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-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-186-5P	99.99	70.83	3707
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-6077	99.99	68.04	2299
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-605-3P	99.88	69.22	1833

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Analysis of deletions indicates complex origin, apart from homologous recombination, of deletion mutants. (PMID:11844872)
• in the human hair follicle, concentrates in the dermal papilla. (PMID:11886493)
• Regulation of estrogen activity in human endometrium: effect of IL-1beta on steroid sulfatase activity in human endometrial stromal cells. (PMID:11996939)
• data demonstrate that LNCaP prostate cancer cells contain a steryl sulfatase with properties similar to that found in human breast cancer cells (PMID:12231117)
• The structure of this enzyme, purified from the microsomal fraction of human placentas, determined by x-ray crystallography. (PMID:12657638)
• Levels of STS and estrogen sulfotransferase mRNA and activity may be significantly associated with degree of atherosclerotic changes in female aorta, which may be related to cytokines produced in situ, such as IL-1beta, in human atherosclerotic lesions. (PMID:14507642)
• estrogen-dependent cell growth of the estrogen sulfatase-transfected cell clones was found to be abolished, due to the enhanced sulfoconjugation of estrogen (PMID:14556660)
• Steroid sulfatase increases steroid acute regulatory protein expression level and stimulates steroid production. (PMID:14969586)
• SSase is concentrated in lamellar bodies (LB), and secreted into the SC interstices, along with other LB-derived lipid hydrolases. There, it degrades CSO4, generating some cholesterol for the barrier (PMID:15009711)
• Strong activity and mRNA expression of DHEAS desulfating STS was found, twice as high in cerebral neocortex than in subcortical white matter. Cerebral STS resembled the characteristics of the known placental enzyme (PMID:15056284)
• Dehydroepiandrosterone blood levels are influenced by a steroid sulfatase polymorphism following acute resistance exercise. (PMID:15152080)
• Gonadotropin-releasing hormone agonist (leuprolide)inhibits estrone sulfatase expression in cystic endometriosis in the ovary. (PMID:15302278)
• Increased steroid sulfatase expression is associated with estrogen-dependent endometrial carcinomas (PMID:15355916)
• Findings of steroid sulfatase localized in the cytoplasm of the cumulus cells and expression of STS mRNA suggest a local steroidal regulation mechanism in cumulus cells. (PMID:16084891)
• Studies on the localization of steroid sulfatase were performed. (PMID:16399357)
• Corticotrophin-releasing hormone (CRH) increased whereas alpha-helical CRH decreased the mRNA levels of STS, CYP19A1, and HSD17B1, the key enzymes for estrogen synthesis. (PMID:16467490)
• Steroid sulfatase mRNA level was significantly higher in soft tissue metastases than in primary tumors. (PMID:16556483)
• Activity of this enzyme in endometrial cancer obtained by tritium-labeled steroids. (PMID:17415442)
• genetic evidence suggesting a potential role of SULT2A1, but not STS, in the inherited adrenal androgen excess of polycystic ovary syndrome (PMID:17426092)
• Sulfatase was significantly upregulated in ovarian tissue of patients with ovarian endometriosis. (PMID:17454161)
• Estradiol inhibits the estrone sulfatase activity in normal and cancerous human breast tissues. (PMID:17481887)
• the regulation of STS transcription appears to be more complex than previously thought, suggesting that this enzyme plays a substantial role in intercellular integration. (PMID:17601726)
• Analysis of the mutated STS protein showed that N- and C-terminal truncated STS constructs are inactive. (PMID:18180093)
• differences in STS and SULT activity in brain tumors (glioblastomas, pituitary adenomas, meningiomas, astrocytomas) (PMID:18249534)
• Cholesterol sulphate sulphohydrolase was isolated from placenta lysosomal membrane, with a high specificity to cholesterol sulphate, pI at 5.7, molecular weight 38 kDa, and pH preference at 3. (PMID:18343103)
• STS deficiency may be a risk factor for ADHD with predominantly inattentive symptoms; Boys with XLI and large deletions encompassing STS and NLGN4 are at increased risk of developing autism and related disorders. (PMID:18413370)
• Sata showed lower levels of STS mRNA for polycystic ovarian syndrome endometria without treatment and with endometrial hyperplasia compared to control. (PMID:18467089)
• The activity levels of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD/3-KSR) and estrone sulfatase in ovarian epithelial carcinomas, were assayed. (PMID:18723074)
• The involvement of aromatase, steroid sulfatase (STS) and reductive 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) in the production of estrogens was determined in four cell lines of endometrial cancer and one cell line of cervix cancer. (PMID:18817841)
• Association of STS gene with ADHD is reported. (PMID:18937300)
• Clinical manifestations of XLI are due to a great variety of environmental, genetic and individual factors (PMID:19200188)
• An association between menopausal status - but not BMI - and the intra-tumoral expression of steroid sulfatase and ERalpha. (PMID:19347708)
• two new splicing patterns found in prostate and ovary cells; report gene expression analysis for the simultaneous detection, in qualitative and/or semi-quantitative terms, of the transcription patterns of STS in different tissues (PMID:19429462)
• Both steroid sulfatase and filaggrin mutations are found in X-linked ichthyosis. (PMID:20149601)
• A significant increment of STS followed exemestane neoadjuvant therapy of postmenopausal ER-positive breast carcinoma. This may represent the compensatory response of breast carcinoma tissues to estrogen depletion. (PMID:20151319)
• Recessive X-linked ichthyosis is caused by a deficiency in steroid sulphatase (STS), whose gene has been located on the X chromosome. (PMID:20236202)
• Six novel single nucleotide polymorphisms of the steroid sulfatase gene in a Japanese population. (PMID:20814163)
• Genetic variation in the STS gene may be implicated in ADHD susceptibility and one polymorphism may be associated with lower STS mRNA expression as well as being more prevalent in female ADHD homozygotes. (PMID:20862695)
• Recent results of STS and EST in several estrogen-dependent carcinomas, are summarised. (PMID:21073915)
• Genetic variants affecting steroid sulfatase expression and/or activity could influence the function of brain regions perturbed in attention deficit hyperactivity disorder (ADHD). (PMID:21255266)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	sts	ENSDARG00000053241
mus_musculus	Sts	ENSMUSG00000121914
rattus_norvegicus	Sts	ENSRNOG00000032487
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), ARSB (ENSG00000113273), 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

Steryl-sulfatase — P08842 (reviewed: P08842)

Alternative names: Arylsulfatase C, Estrone sulfatase, Steroid sulfatase, Steryl-sulfate sulfohydrolase

All UniProt accessions (3): A0A590UJL0, A0A590UJT4, A0A590UJY9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of sulfated steroid precursors, such as dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate to the free steroid.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Microneme membrane. Endoplasmic reticulum 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.

Disease relevance. Ichthyosis, X-linked (IXL) [MIM:308100] A keratinization disorder manifesting with mild erythroderma and generalized exfoliation of the skin within a few weeks after birth. Affected boys later develop large, polygonal, dark brown scales, especially on the neck, extremities, trunk, and buttocks. The disease is caused by variants affecting the gene represented in this entry.

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

Similarity. Belongs to the sulfatase family.

RefSeq proteins (6): NP_000342, NP_001307679, NP_001307680, NP_001307681, NP_001307682, NP_001307683 (=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

Enzyme classification (BRENDA):

• EC 3.1.6.2 — steryl-sulfatase (BRENDA: 16 organisms, 80 substrates, 453 inhibitors, 75 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
DEHYDROEPIANDROSTERONE 3-SULFATE	0.0029–0.113	12
TESTOSTERONE 3-SULFATE	0.0045–0.088	10
DEHYDROEPIANDROSTERONE SULFATE	0.0017–0.013	8
ESTRONE 3-SULFATE	0.0034–0.035	6
METHYLUMBELLIFERYL SULFATE	0.1–2.5	5
4-NITROPHENYL SULFATE	0.007–10.2	4
CHOLESTEROL 3-SULFATE	0.0006–0.0057	4
ESTRONE SULFATE	0.0022–0.0727	4
P-NITROPHENYL SULFATE	0.007–1600	4
PREGNENOLONE 3-SULFATE	0.0002–0.0018	4
17BETA-ESTRADIOL SULFATE	0.0019–0.0043	3
ESTERONE 3-SULFATE	0.005–0.0506	2
16ALPHA-HYDROXYDEHYDROEPIANDROSTERONE 3-SULFATE	0.02	1
4-METHYLUMBELLIFERYLSULFATE	0.217	1
ANDROSTENEDIOL 3-SULFATE	0.0031	1

Catalyzed reactions (Rhea), 2 shown:

• dehydroepiandrosterone 3-sulfate + H2O = 3beta-hydroxyandrost-5-en-17-one + sulfate + H(+) (RHEA:19873)
• estrone 3-sulfate + H2O = estrone + sulfate + H(+) (RHEA:31055)

UniProt features (88 total): strand 27, helix 22, sequence variant 8, disulfide bond 6, binding site 5, turn 5, topological domain 3, site 2, glycosylation site 2, transmembrane region 2, active site 2, signal peptide 1, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8EG3	X-RAY DIFFRACTION	2.04
1P49	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08842-F1	94.31	0.91

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 (4): 333 (not glycosylated); 459 (not glycosylated); 75 (nucleophile); 136

Ligand- & substrate-binding residues (5): 36; 75 (via 3-oxoalanine); 342; 343; 35

Post-translational modifications (1): 75

Disulfide bonds (6): 141–148, 170–242, 446–489, 481–487, 562–570, 563–572

Glycosylation sites (2): 47, 259

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1663150	The activation of arylsulfatases
R-HSA-196071	Metabolism of steroid hormones
R-HSA-9840310	Glycosphingolipid catabolism

MSigDB gene sets: 221 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, ONKEN_UVEAL_MELANOMA_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, GOZGIT_ESR1_TARGETS_UP, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_LIPID_METABOLIC_PROCESS, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, VALK_AML_CLUSTER_5, REACTOME_SPHINGOLIPID_METABOLISM, KEGG_STEROID_HORMONE_BIOSYNTHESIS, GOBP_LIPID_CATABOLIC_PROCESS

GO Biological Process (3): steroid catabolic process (GO:0006706), female pregnancy (GO:0007565), epidermis development (GO:0008544)

GO Molecular Function (5): arylsulfatase activity (GO:0004065), steryl-sulfatase activity (GO:0004773), sulfuric ester hydrolase activity (GO:0008484), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (9): lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), intracellular membrane-bounded organelle (GO:0043231)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Metabolism of steroids	1
Glycosphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
sulfuric ester hydrolase activity	2
cytoplasm	2
intracellular membrane-bounded organelle	2
steroid metabolic process	1
lipid catabolic process	1
multi-organism reproductive process	1
multi-multicellular organism process	1
tissue development	1
hydrolase activity, acting on ester bonds	1
cation binding	1
catalytic activity	1
lytic vacuole	1
cytoplasmic vesicle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1
intracellular anatomical structure	1
membrane-bounded organelle	1
intracellular organelle	1

Protein interactions and networks

STRING

1184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STS	SULT1E1	P49888	864
STS	PUDP	Q08623	842
STS	VCX	Q9H320	776
STS	VCX2	Q9H322	776
STS	VCX3A	Q9NNX9	776
STS	CD99	P14209	775
STS	SHOX	O15266	762
STS	SLC25A6	P12236	761
STS	SULT1A1	P50225	747
STS	ANOS1	P23352	746
STS	CYP19A1	P11511	736
STS	HSD17B1	P14061	736
STS	SULT1A3	P0DMM9	700
STS	DHRS11	Q6UWP2	677
STS	PNPLA4	P41247	671

IntAct

18 interactions, top by confidence:

A	B	Type	Score
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
STS	GJA1	psi-mi:“MI:0914”(association)	0.530
STS	CBL	psi-mi:“MI:0915”(physical association)	0.400
LYZL1	MANBA	psi-mi:“MI:0914”(association)	0.350
FUT8	ITGAV	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLRN2	FAM234B	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
ASCL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
LYZL1	ZZEF1	psi-mi:“MI:0914”(association)	0.350
TSPAN16	ENDOD1	psi-mi:“MI:0914”(association)	0.350
WNT8A	STS	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
A2M	TPP1	psi-mi:“MI:0403”(colocalization)	0.350

BioGRID (51): FAM134A (Affinity Capture-MS), SUMF1 (Affinity Capture-MS), JAG2 (Affinity Capture-MS), STS (Affinity Capture-MS), STS (Affinity Capture-MS), STS (Affinity Capture-MS), ALG9 (Affinity Capture-MS), ZDHHC6 (Affinity Capture-MS), SLC30A1 (Affinity Capture-MS), LRRC8A (Affinity Capture-MS), CISD2 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), ATP11C (Affinity Capture-MS), GJA1 (Affinity Capture-MS), TMEM214 (Affinity Capture-MS)

ESM2 similar proteins: A1A4K5, O14638, P06802, P08842, P15396, P15586, P15589, P15848, P22304, P22413, P33727, P50426, P50429, P51689, P51690, P54793, P97535, P97675, Q08890, Q08C93, Q13219, Q13822, Q1LZH9, Q32KH8, Q32KH9, Q32KJ9, Q3TYD4, Q5E9H0, Q5FYA8, Q5M900, Q5NDE3, Q5R5M5, Q5ZK90, Q60HH5, Q64610, Q66PG4, Q6DYE8, Q6NRQ1, Q6P9A2, Q6UWY0

Diamond homologs: A0A455ZJM4, O69787, P08842, P14217, P50426, Q0IHJ2, Q10723, Q148F3, Q1LZH9, Q21376, Q32KH0, Q32KJ2, Q6UWY0, Q8BFR4, Q8CFG0, Q8IWU5, Q8K007, Q8VI60, Q90XB6, Q9D2L1, Q9VEX0, P14000, P15289, P15589, P20713, P34059, P50427, P50428, P50473, P51689, P51690, P54793, Q08DD1, Q32KH5, Q32KH8, Q32KH9, Q32KJ6, Q32KJ9, Q3TYD4, Q571E4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	8
Uncertain significance	99
Likely benign	25
Benign	34

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1012900	GRCh37/hg19 Xp22.31(chrX:7137497-7272667)x0	Pathogenic
1012901	GRCh37/hg19 Xp22.31(chrX:7137717-7268302)x0	Pathogenic
10552	NM_001320752.2(STS):c.1099T>A (p.Trp367Arg)	Pathogenic
10553	NM_001320752.2(STS):c.1322G>A (p.Cys441Tyr)	Pathogenic
10556	NM_001320752.2(STS):c.1316A>G (p.His439Arg)	Pathogenic
10557	NM_001320752.2(STS):c.1241+1G>T	Pathogenic
1452376	NC_000023.10:g.(?7137717)(7268302_?)del	Pathogenic
1677277	NM_000351.4:g.(?6551155)(8032120_?)del	Pathogenic
3245789	NC_000023.10:g.(?7137717)(7252168_?)del	Pathogenic
3383027	NM_001320752.2(STS):c.806+1G>A	Pathogenic
453154	NM_001320752.2(STS):c.169G>T (p.Gly57Ter)	Pathogenic
564693	GRCh37/hg19 Xp22.33-22.13(chrX:168546-18601364)x1	Pathogenic
564762	GRCh37/hg19 Xp22.31(chrX:6598868-7966755)x1	Pathogenic
564770	GRCh37/hg19 Xp22.31(chrX:7143912-7185127)x0	Pathogenic
625856	NM_001320752.2(STS):c.272G>A (p.Trp91Ter)	Pathogenic
1325152	NM_001320752.2(STS):c.437del (p.Pro146fs)	Likely pathogenic
1803158	NM_001320752.2(STS):c.1108G>T (p.Gly370Cys)	Likely pathogenic
2422953	NC_000023.10:g.(?7171217)(7177833_?)del	Likely pathogenic
2634838	NM_001320752.2(STS):c.1346G>A (p.Arg449His)	Likely pathogenic
2737074	NM_001320752.2(STS):c.1060G>A (p.Gly354Arg)	Likely pathogenic
3256558	NM_001320752.2(STS):c.382G>A (p.Gly128Arg)	Likely pathogenic
3382684	NM_001320752.2(STS):c.1241+1G>C	Likely pathogenic
450562	NM_001320752.2(STS):c.1109G>C (p.Gly370Ala)	Likely pathogenic

SpliceAI

1752 predictions. Top by Δscore:

Variant	Effect	Δscore
X:7219683:TAAGG:T	donor_loss	1.0000
X:7219685:AGGT:A	donor_loss	1.0000
X:7219687:GTAA:G	donor_loss	1.0000
X:7253190:TTACA:T	acceptor_loss	1.0000
X:7253191:TACA:T	acceptor_loss	1.0000
X:7253194:A:AT	acceptor_loss	1.0000
X:7253195:GGAA:G	acceptor_gain	1.0000
X:7253333:TCAG:T	donor_loss	1.0000
X:7253334:CAGG:C	donor_loss	1.0000
X:7253335:AGG:A	donor_loss	1.0000
X:7253337:G:GA	donor_loss	1.0000
X:7257236:TTCTA:T	acceptor_loss	1.0000
X:7257237:TCTA:T	acceptor_loss	1.0000
X:7257238:CTA:C	acceptor_loss	1.0000
X:7257240:A:AG	acceptor_gain	1.0000
X:7257240:A:G	acceptor_loss	1.0000
X:7257240:AG:A	acceptor_gain	1.0000
X:7257241:G:GT	acceptor_gain	1.0000
X:7257241:GG:G	acceptor_gain	1.0000
X:7257585:ATAGG:A	donor_loss	1.0000
X:7257587:AGGTA:A	donor_loss	1.0000
X:7257588:GG:G	donor_loss	1.0000
X:7257589:GTAT:G	donor_loss	1.0000
X:7257590:T:G	donor_loss	1.0000
X:7275950:GGAAC:G	acceptor_gain	1.0000
X:7276070:A:T	donor_gain	1.0000
X:7305042:CCA:C	acceptor_loss	1.0000
X:7305043:CA:C	acceptor_loss	1.0000
X:7305044:A:AG	acceptor_gain	1.0000
X:7305045:G:GG	acceptor_gain	1.0000

AlphaMissense

3813 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:7257321:A:C	S78R	0.997
X:7257323:C:A	S78R	0.997
X:7257323:C:G	S78R	0.997
X:7259354:T:A	W135R	0.996
X:7259354:T:C	W135R	0.996
X:7253291:A:T	D36V	0.995
X:7257346:G:C	R86P	0.995
X:7259356:G:C	W135C	0.995
X:7259356:G:T	W135C	0.995
X:7253288:A:T	D35V	0.993
X:7257314:C:G	C75W	0.993
X:7259352:A:T	K134I	0.993
X:7305112:A:T	D342V	0.993
X:7259417:T:C	F156L	0.992
X:7259419:C:A	F156L	0.992
X:7259419:C:G	F156L	0.992
X:7253291:A:C	D36A	0.991
X:7305109:C:G	S341W	0.991
X:7325345:A:T	K368I	0.991
X:7325437:A:C	S399R	0.991
X:7325439:C:A	S399R	0.991
X:7325439:C:G	S399R	0.991
X:7334083:G:C	A452P	0.991
X:7253292:C:A	D36E	0.990
X:7253292:C:G	D36E	0.990
X:7349904:G:C	K465N	0.990
X:7349904:G:T	K465N	0.990
X:7349970:C:G	C487W	0.990
X:7349976:T:G	C489W	0.990
X:7257312:T:C	C75R	0.989

dbSNP variants (sampled 300 via entrez): RS1000021335 (X:7308831 T>C), RS1000035492 (X:7248624 A>G), RS1000081482 (X:7311027 G>C), RS1000095260 (X:7186172 A>G), RS1000145071 (X:7240479 A>T), RS1000146242 (X:7185699 A>G), RS1000214771 (X:7206754 A>G), RS1000216647 (X:7328885 G>A), RS1000225589 (X:7188009 T>C), RS1000229125 (X:7161644 T>C), RS1000259667 (X:7257761 T>G), RS1000278872 (X:7274939 A>G), RS1000281227 (X:7145324 C>T), RS1000291457 (X:7215142 T>C), RS1000316010 (X:7265991 T>A)

Disease associations

OMIM: gene MIM:300747 | disease phenotypes: MIM:308100

GenCC curated gene-disease

Disease	Classification	Inheritance
recessive X-linked ichthyosis	Definitive	X-linked

Mondo (1): recessive X-linked ichthyosis (MONDO:0010622)

Orphanet (1): Recessive X-linked ichthyosis (Orphanet:461)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000083	Renal insufficiency
HP:0000122	Unilateral renal agenesis
HP:0000135	Hypogonadism
HP:0000717	Autism
HP:0000958	Dry skin
HP:0000962	Hyperkeratosis
HP:0000966	Hypohidrosis
HP:0000982	Palmoplantar keratoderma
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001339	Lissencephaly
HP:0001419	X-linked recessive inheritance
HP:0002167	Abnormal speech pattern
HP:0002381	Aphasia
HP:0002488	Acute leukemia
HP:0002577	Abnormal stomach morphology
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004298	Abnormal abdominal wall morphology
HP:0004322	Short stature
HP:0007018	Attention deficit hyperactivity disorder
HP:0007431	Congenital ichthyosiform erythroderma
HP:0007549	Desquamation of skin soon after birth
HP:0007759	Opacification of the corneal stroma
HP:0007957	Corneal opacity
HP:0008064	Ichthyosis

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3559 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 163,319 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL135	ESTRADIOL	4	123,080
CHEMBL1405	ESTRONE	4	36,722
CHEMBL494753	ESTRONE SULFURIC ACID	4	3,380
CHEMBL286738	IROSUSTAT	2	137

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

Binding affinities (BindingDB)

53 measured of 71 human assays (72 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Sulfamic acid 2-adamantan-1-yl-4-oxo-4H-thiochromen-6-yl ester	IC50	0.34 nM
(5-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}-2-fluorophenyl) sulfamate	IC50	0.77 nM
Sulfamic acid 2-adamantan-2-ylidenemethyl-benzooxazol-6-yl ester	IC50	0.77 nM
YM511-based dual aromatase-sulfatase inhibitor (DASI) 7	IC50	0.82 nM
(2-chloro-5-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl) sulfamate	IC50	0.92 nM
(4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}-2-iodophenyl) sulfamate	IC50	1.5 nM
(2-chloro-4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl) sulfamate	IC50	2.3 nM
(2-chloro-4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}-6-methoxyphenyl) sulfamate	IC50	2.9 nM
{2-bromo-4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]phenyl} sulfamate	IC50	3 nM
{2-bromo-4-[(R)-(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]phenyl} sulfamate	IC50	3.2 nM
(2-bromo-5-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl) sulfamate	IC50	3.9 nM
Sulfamic acid 2-adamantan-2-yl-4-oxo-4H-chromen-6-yl ester	IC50	5.6 nM
Sulfamic acid 2-adamantan-1-yl-4-oxo-4H-chromen-6-yl ester	IC50	5.6 nM
Sulfamic acid 2-(octahydro-2,5-methano-pentalen-7-yl)-4-oxo-4H-chromen-6-yl ester	IC50	11 nM
YM511-based dual aromatase-sulfatase inhibitor (DASI) 5	IC50	12 nM
{2-chloro-4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]phenyl} sulfamate	IC50	12 nM
(5-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}-2-methoxyphenyl) sulfamate	IC50	12 nM
{4-[(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]phenyl} sulfamate	IC50	13 nM
{2-bromo-4-[(S)-(4-cyanophenyl)(1H-1,2,4-triazol-1-yl)methyl]phenyl} sulfamate	IC50	14.3 nM
(15S)-15-methyl-14-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-5-yl sulfamate	IC50	23 nM
CHEMBL4637433	IC50	26 nM
(2-cyano-4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl) sulfamate	IC50	27 nM
YM511-based dual aromatase-sulfatase inhibitor (DASI) 8	IC50	39 nM
(4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}-2-methoxyphenyl) sulfamate	IC50	42 nM
(2-bromo-4-{3-bromo-4-(sulfamoyloxy)phenylmethyl}phenyl) sulfamate	IC50	43 nM
[3-(2-cyclohexylethyl)-4-methyl-2-oxo-2H-chromen-7-yl] sulfamate	IC50	59 nM
CHEMBL4646243	IC50	68 nM
CHEMBL4636936	IC50	74 nM
Phenyl-acetic acid (1S,3R,5R)-8-(3,5-bis-trifluoromethyl-benzenesulfonylaminocarbonyl)-8-aza-bicyclo[3.2.1]oct-3-yl ester	IC50	84 nM
(15S)-15-methyl-14-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-triene-5-sulfonamide	IC50	92 nM
(3-{3-(sulfamoyloxy)phenylmethyl}phenyl) sulfamate	IC50	99 nM
YM511 Analog 4	IC50	100 nM
CHEMBL4635151	IC50	110 nM
Sulfamic acid 2-adamantan-1-yl-4-oxo-chroman-6-yl ester	IC50	140 nM
2-Adamantan-1-yl-4-oxo-4H-thiochromene-6-carboxylic acid	IC50	180 nM
2-Adamantan-2-ylidenemethyl-benzooxazol-6-ol	IC50	260 nM
(15S)-4-ethyl-15-methyl-5-(sulfamoyloxy)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-yl sulfamate	IC50	290 nM
Sulfamic acid 2-adamantan-1-yl-4-hydroxy-chroman-6-yl ester	IC50	291 nM
6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate	IC50	300 nM
(15S)-4-ethyl-15-methyl-14-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-5-yl sulfamate	IC50	332 nM
(15S)-14-hydroxy-4-methoxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-5-yl sulfamate	IC50	376 nM
(15S)-4-methoxy-15-methyl-5-(sulfamoyloxy)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-yl sulfamate	IC50	379 nM
(15S)-5-hydroxy-4-methoxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-yl sulfamate	IC50	526 nM
Phenyl-acetic acid (1R,3R,5S)-8-(4-trifluoromethyl-benzenesulfonylaminocarbonyl)-8-aza-bicyclo[3.2.1]oct-3-yl ester	KI	530 nM
8-[N-(4-chlorophenylsulfonamido)-carbonyl amino]-8-azabicyclo[3.2.1]oct-3-yl 2-phenylacetate	KI	890 nM
Formic acid 2-adamantan-2-ylidenemethyl-benzooxazol-6-yl ester	IC50	1500 nM
Phenyl-acetic acid (1R,3R,5S)-8-(4-bromo-benzenesulfonylaminocarbonyl)-8-aza-bicyclo[3.2.1]oct-3-yl ester	KI	1850 nM
Phenyl-acetic acid (1R,3R,5S)-8-(4-chloro-benzenesulfonylaminocarbonyl)-8-aza-bicyclo[3.2.1]oct-3-yl ester	KI	2400 nM
JMC514226 Compound 3	IC50	3040 nM
Phenyl-acetic acid (1R,3R,5S)-8-[2-(4-chloro-benzenesulfonyl)-acetyl]-8-aza-bicyclo[3.2.1]oct-3-yl ester	IC50	4320 nM

ChEMBL bioactivities

729 potent at pChembl≥5 of 832 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL2011408
10.62	IC50	0.024	nM	CHEMBL3805209
10.46	IC50	0.035	nM	CHEMBL3622029
10.40	IC50	0.04	nM	CHEMBL3806018
10.40	IC50	0.04	nM	CHEMBL4643348
10.33	IC50	0.047	nM	CHEMBL137392
10.30	IC50	0.05	nM	CHEMBL3805209
10.19	IC50	0.065	nM	EMATE
10.19	IC50	0.065	nM	CHEMBL5202760
10.05	IC50	0.089	nM	CHEMBL137692
10.00	IC50	0.1	nM	CHEMBL2011422
9.96	IC50	0.11	nM	CHEMBL364332
9.89	IC50	0.13	nM	CHEMBL1672979
9.82	IC50	0.15	nM	CHEMBL1627465
9.82	IC50	0.15	nM	CHEMBL136112
9.68	IC50	0.21	nM	CHEMBL5199004
9.47	IC50	0.34	nM	CHEMBL262050
9.41	IC50	0.39	nM	CHEMBL1627878
9.40	IC50	0.4	nM	CHEMBL3806300
9.40	IC50	0.4	nM	CHEMBL4456330
9.36	IC50	0.44	nM	CHEMBL2011415
9.21	IC50	0.62	nM	CHEMBL2011414
9.17	IC50	0.68	nM	CHEMBL4520442
9.12	IC50	0.75	nM	CHEMBL136112
9.11	IC50	0.77	nM	CHEMBL136112
9.10	IC50	0.8	nM	CHEMBL2011408
9.10	IC50	0.8	nM	CHEMBL1627465
9.09	IC50	0.81	nM	CHEMBL364745
9.08	IC50	0.83	nM	EMATE
9.08	IC50	0.83	nM	CHEMBL1672978
9.05	IC50	0.9	nM	EMATE
9.00	Ki	1	nM	CHEMBL3600587
9.00	IC50	1	nM	CHEMBL3622012
9.00	IC50	1	nM	CHEMBL3622021
9.00	IC50	1	nM	CHEMBL1235380
9.00	IC50	1	nM	CHEMBL3622028
9.00	IC50	1	nM	CHEMBL3622026
9.00	IC50	1	nM	CHEMBL3622027
9.00	IC50	1	nM	CHEMBL3622024
9.00	IC50	1	nM	CHEMBL3622023
9.00	IC50	1	nM	CHEMBL3621214
9.00	IC50	1	nM	CHEMBL3622022
9.00	IC50	1	nM	CHEMBL3622018
9.00	IC50	1	nM	CHEMBL3827021
9.00	IC50	1	nM	CHEMBL3622010
9.00	IC50	1	nM	CHEMBL4436186
9.00	IC50	1	nM	CHEMBL4517286
9.00	IC50	1	nM	CHEMBL4459312
8.97	IC50	1.06	nM	IROSUSTAT
8.92	IC50	1.2	nM	CHEMBL2011416

PubChem BioAssay actives

735 with measured affinity, of 1775 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(8R,9S,13S,14S,17R)-17-[(4-tert-butylphenyl)methyl]-17-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	1667487: Irreversible inhibition of human steroid sulfatase expressed in HEK293 cells using [3H] E1S as substrate after 2 hrs by liquid scintillation counting method	ic50	<0.0001	uM
(2-tert-butyl-4-oxochromen-6-yl) sulfamate	1599441: Inhibition of human sulfatase using 4-methylumbelliferyl sulfate as substrate after 60 mins	ic50	<0.0001	uM
[(8R,9S,13S,14S,17R)-17-benzyl-17-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	1299649: Inhibition of estrone sulfatase (unknown origin) transfected in HEK293 cells using E1S as substrate	ic50	<0.0001	uM
[(8R,9S,13S,14S,17R)-17-[(4-tert-butylphenyl)methyl]-17-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	1299649: Inhibition of estrone sulfatase (unknown origin) transfected in HEK293 cells using E1S as substrate	ic50	<0.0001	uM
[(8R,9S,14S,17R)-17-[(4-tert-butylphenyl)methyl]-17-hydroxy-2-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	1667487: Irreversible inhibition of human steroid sulfatase expressed in HEK293 cells using [3H] E1S as substrate after 2 hrs by liquid scintillation counting method	ic50	<0.0001	uM
[(4aS,4bR,10bS,12aS)-12a-methyl-1,3-dioxo-2-(3,3,3-trifluoropropyl)-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1249527: Inhibition of STS activity in human JEG-3 cells by liquid scintillation spectrometry in presence of [6,7-3H]estrone3-sulfate	ic50	<0.0001	uM
[(8R,9S,13S,14S)-13-methyl-4-nitro-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	654845: Inhibition of steroid sulfatase in human MCF7 cells using [3H]E1S as substrate after 20 hrs by scintillation spectrometry	ic50	<0.0001	uM
[(8R,9S,13S,14S)-2-bromo-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	654845: Inhibition of steroid sulfatase in human MCF7 cells using [3H]E1S as substrate after 20 hrs by scintillation spectrometry	ic50	0.0001	uM
[(8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	1243900: Inhibition of STS in human MCF7 cells	ic50	0.0001	uM
[(8S,9S,13S,14S)-9,13-dimethyl-17-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-yl] sulfamate	1855806: Inhibition of estrone sulfatase in human MCF7 cells assessed as inhibition of [3H]estrone and [3H]estradiol formation using [3H]estrone sulfate as substrate incubated for 20 hrs	ic50	0.0001	uM
[2-bromo-4-[[4-cyano-3-phenyl-N-(1,2,4-triazol-4-yl)anilino]methyl]phenyl] sulfamate	570241: Inhibition of steroid sulfatase in human JEG-3 cells using [6,7-3H]E1S after 1 hr by scintillation spectrometry	ic50	0.0001	uM
[(8R,9S,13S,14S)-2-(difluoromethyl)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	1299642: Inhibition of placental microsomal estrone sulfatase (unknown origin) using [6,7-3H]E1S as substrate incubated for 1 hr by scintillation spectrometric analysis	ic50	0.0001	uM
[2-(2-adamantylidenemethyl)-1,3-benzoxazol-6-yl] sulfamate	1299658: Inhibition of estrone sulfatase in human sebocytes using DHEAS as substrate	ic50	0.0001	uM
(2-nonyl-4-oxochromen-6-yl) sulfamate	1599441: Inhibition of human sulfatase using 4-methylumbelliferyl sulfate as substrate after 60 mins	ic50	0.0001	uM
[4-[1-(3,5-difluorophenyl)triazol-4-yl]phenyl] sulfamate	1903904: Inhibition of STS in human MCF7 cells using [3H]E1S as substrate incubated for 20 hrs by radioisotope cellular assay	ic50	0.0002	uM
[2-(1-adamantyl)-4-oxothiochromen-6-yl] sulfamate	1299664: Inhibition of recombinant human estrone sulfatase using 4-methylumbelliferyl sulfate as substrate by colorimetric assay	ic50	0.0003	uM
[(8R,9S,13S,14S,17R)-17-benzyl-17-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	1599439: Inhibition of sulfatase (unknown origin) using [3H]E1S as substrate after 18 hrs	ic50	0.0004	uM
[4-[5-(4-tert-butylphenyl)-5-hydroxyundecyl]phenyl] sulfamate	1600037: Inhibition of human placental steroid sulfatase expressed in HEK293 cells using [3H] E1S as substrate after 2 hrs by liquid scintillation counting method	ic50	0.0004	uM
[4-[5-[(4-tert-butylphenyl)methyl]-5-hydroxyundecyl]phenyl] sulfamate	1299666: Inhibition of human placental estrone sulfatase expressed in HEK293 cells using [3H]E1S as substrate incubated for 2 hrs by liquid scintillation counting method	ic50	0.0004	uM
[(8R,9S,13S,14S)-2-chloro-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	654845: Inhibition of steroid sulfatase in human MCF7 cells using [3H]E1S as substrate after 20 hrs by scintillation spectrometry	ic50	0.0004	uM
[(8R,9S,13S,14S)-2-fluoro-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	654845: Inhibition of steroid sulfatase in human MCF7 cells using [3H]E1S as substrate after 20 hrs by scintillation spectrometry	ic50	0.0006	uM
(3-hexyl-4-methyl-2-oxochromen-7-yl) sulfamate	1600017: Inhibition of steroid sulfatase in human MCF7 cells	ic50	0.0007	uM
[2-chloro-4-[[4-cyano-3-phenyl-N-(1,2,4-triazol-4-yl)anilino]methyl]phenyl] sulfamate	570241: Inhibition of steroid sulfatase in human JEG-3 cells using [6,7-3H]E1S after 1 hr by scintillation spectrometry	ic50	0.0008	uM
[(8R,9S,13S,14S)-2-iodo-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	654845: Inhibition of steroid sulfatase in human MCF7 cells using [3H]E1S as substrate after 20 hrs by scintillation spectrometry	ic50	0.0008	uM
[(4aS,4bR,10bS,12aS)-12a-methyl-1,3-dioxo-2-prop-2-enyl-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1299644: Inhibition of human placental microsomal estrone sulfatase using [3H]E1S as substrate incubated for 30 mins	ic50	0.0010	uM
[(4aS,4bR,10bS,12aS)-2-butyl-12a-methyl-1,3-dioxo-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1299644: Inhibition of human placental microsomal estrone sulfatase using [3H]E1S as substrate incubated for 30 mins	ic50	0.0010	uM
[(4aS,4bR,10bS,12aS)-2-hexyl-12a-methyl-1,3-dioxo-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1299644: Inhibition of human placental microsomal estrone sulfatase using [3H]E1S as substrate incubated for 30 mins	ic50	0.0010	uM
[(4aS,4bR,10bS,12aS)-2-benzyl-12a-methyl-1,3-dioxo-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1299644: Inhibition of human placental microsomal estrone sulfatase using [3H]E1S as substrate incubated for 30 mins	ic50	0.0010	uM
[(4aS,4bR,10bS,12aS)-2-[(4-tert-butylphenyl)methyl]-12a-methyl-1,3-dioxo-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1299644: Inhibition of human placental microsomal estrone sulfatase using [3H]E1S as substrate incubated for 30 mins	ic50	0.0010	uM
[(4aS,4bR,10bS,12aS)-12a-methyl-1,3-dioxo-2-propyl-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1249521: Inhibition of STS activity in human placental microsome in presence of [3H]-estrone sulfate	ic50	0.0010	uM
[(4aS,4bR,10bS,12aS)-12a-methyl-1,3-dioxo-2-pentyl-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1299644: Inhibition of human placental microsomal estrone sulfatase using [3H]E1S as substrate incubated for 30 mins	ic50	0.0010	uM
(9-oxo-8-oxatricyclo[8.8.0.02,7]octadeca-1(10),2(7),3,5-tetraen-5-yl) sulfamate	1249492: Inhibition of STS activity in human placental microsome	ic50	0.0010	uM
N-[(8R,9S,13S,14S,17S)-3-hydroxy-13-methyl-4-nitro-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]-4-phenylbenzenesulfonamide	1238967: Reversible inhibition of STS (unknown origin) using 4-MUS as substrate measured over 10 mins by fluorescence assay	ki	0.0010	uM
[(4aS,4bR,10bS,12aS)-12a-methyl-1,3-dioxo-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1299644: Inhibition of human placental microsomal estrone sulfatase using [3H]E1S as substrate incubated for 30 mins	ic50	0.0010	uM
[(4aS,4bR,10bS,12aS)-2-(4-bromobutyl)-12a-methyl-1,3-dioxo-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1299644: Inhibition of human placental microsomal estrone sulfatase using [3H]E1S as substrate incubated for 30 mins	ic50	0.0010	uM
(20-oxo-19-oxatricyclo[10.8.0.013,18]icosa-13(18),14,16-trien-16-yl) sulfamate	1312619: Inhibition of placental sulphatase (unknown origin)	ic50	0.0010	uM
[(3aS,3bR,9bS,11aS)-11a-methyl-1,3-dioxo-2-propyl-3b,4,5,9b,10,11-hexahydro-3aH-naphtho[2,1-e]isoindol-7-yl] sulfamate	1600012: Inhibition of steroid sulfatase (unknown origin)	ic50	0.0010	uM
(3-benzyl-4-methyl-2-oxochromen-7-yl) sulfamate	1600017: Inhibition of steroid sulfatase in human MCF7 cells	ic50	0.0010	uM
[(3aS,3bR,9bS,11aS)-11a-methyl-1,3-dioxo-2-(pyridin-3-ylmethyl)-3b,4,5,9b,10,11-hexahydro-3aH-naphtho[2,1-e]isoindol-7-yl] sulfamate	1600012: Inhibition of steroid sulfatase (unknown origin)	ic50	0.0010	uM
(9-oxo-8-oxatricyclo[8.6.0.02,7]hexadeca-1(10),2(7),3,5-tetraen-5-yl) sulfamate	1600012: Inhibition of steroid sulfatase (unknown origin)	ic50	0.0010	uM
[(4aS,4bR,10bS,12aS)-12a-methyl-1,3-dioxo-2-(pyridin-3-ylmethyl)-4,4a,4b,5,6,10b,11,12-octahydronaphtho[2,1-f]isoquinolin-8-yl] sulfamate	1249521: Inhibition of STS activity in human placental microsome in presence of [3H]-estrone sulfate	ic50	0.0010	uM
(6-oxo-8,9,10,11-tetrahydro-7H-cyclohepta[c]chromen-3-yl) sulfamate	1903904: Inhibition of STS in human MCF7 cells using [3H]E1S as substrate incubated for 20 hrs by radioisotope cellular assay	ic50	0.0011	uM
[(8R,9S,13S,14S)-2-cyano-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	654845: Inhibition of steroid sulfatase in human MCF7 cells using [3H]E1S as substrate after 20 hrs by scintillation spectrometry	ic50	0.0012	uM
[4-(cyclohexanecarbonylamino)phenyl] sulfamate	1298865: Inhibition of steroid sulfatase in human JEG-3 cells assessed as [14C]-Estrone formation using [3H]E1S as substrate	ic50	0.0017	uM
[4-[1-(3,5-dichlorophenyl)triazol-4-yl]phenyl] sulfamate	1903904: Inhibition of STS in human MCF7 cells using [3H]E1S as substrate incubated for 20 hrs by radioisotope cellular assay	ic50	0.0017	uM
[4-[1-(3-fluorophenyl)triazol-4-yl]phenyl] sulfamate	1903904: Inhibition of STS in human MCF7 cells using [3H]E1S as substrate incubated for 20 hrs by radioisotope cellular assay	ic50	0.0017	uM
[4-[1-(3-chlorophenyl)triazol-4-yl]phenyl] sulfamate	1903904: Inhibition of STS in human MCF7 cells using [3H]E1S as substrate incubated for 20 hrs by radioisotope cellular assay	ic50	0.0019	uM
[4-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]-3-fluorophenyl] sulfamate	1482692: Inhibition of STS in human T47D cells preincubated for 1 hr followed by addition of [3H]-E1S/E1S as substrate measured after 24 hrs by HPLC based radio-detection method	ic50	0.0021	uM
[(8R,9S,13S,14S,17S)-17-[[[5-(dimethylamino)naphthalen-1-yl]sulfonylamino]methyl]-17-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate	1667489: Irreversible inhibition of steroid sulfatase (unknown origin) expressed in HEK293 cells using [3H] E1S as substrate after 2 hrs by scintillation counting method	ic50	0.0021	uM
[4-[[4-cyano-3-phenyl-N-(1,2,4-triazol-4-yl)anilino]methyl]-2-fluorophenyl] sulfamate	570241: Inhibition of steroid sulfatase in human JEG-3 cells using [6,7-3H]E1S after 1 hr by scintillation spectrometry	ic50	0.0023	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	9
estrone-3-O-sulfamate	decreases activity	3
2-methoxyestradiol-3,17-bis-O,O-sulfamate	decreases activity	3
irosustat	decreases activity	3
estrone sulfate	affects metabolic processing, decreases sulfation	2
mercuric bromide	affects cotreatment, increases expression	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, increases expression, increases activity, decreases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases activity	2
(+)-JQ1 compound	decreases expression	2
Bortezomib	decreases reaction, increases expression, decreases expression	2
Wortmannin	decreases reaction, increases activity, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetradecanoylphorbol Acetate	increases secretion, increases activity, decreases reaction, increases expression, affects reaction (+1 more)	2
Tretinoin	decreases reaction, increases activity, increases reaction, affects reaction, affects cotreatment (+1 more)	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
parthenolide	decreases reaction, increases activity	1
sulfamic acid	decreases activity	1
5-pregnene-3,20-diol	decreases activity	1
sodium borate	decreases activity	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
afimoxifene	decreases expression	1
4-nitrocatechol sulfate	decreases activity	1
4-nitrophenyl sulfate	decreases activity	1
nickel sulfate	decreases expression	1
4,17 beta-dihydroxy-4-androstene-3-one	decreases activity	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	increases activity, decreases reaction	1

ChEMBL screening assays

331 unique, capped per target: 330 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1067559	Binding	Inhibition of steroid sulfatase in human JEG3 cells by scintillation spectrometry	Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template. — J Med Chem
CHEMBL834494	Functional	Inhibitory activity against human steroid sulfatase over-expressed in CHO cells	2-(1-adamantyl)-4-(thio)chromenone-6-carboxylic acids: potent reversible inhibitors of human steroid sulfatase. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2HT	Abcam HeLa STS KO	Cancer cell line	Female
CVCL_R955	MCS-2 [Human breast carcinoma]	Cancer cell line	Female
CVCL_TR07	HAP1 STS (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00074685	Not specified	COMPLETED	National Registry for Ichthyosis and Related Disorders