SULF1

Summary

SULF1 (sulfatase 1, HGNC:20391) is a protein-coding gene on chromosome 8q13.2-q13.3, encoding Extracellular sulfatase Sulf-1 (Q8IWU6). Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity.

This gene encodes an extracellular heparan sulfate endosulfatase. The encoded enzyme selectively removes 6-O-sulfate groups from heparan sulfate chains of heparan sulfate proteoglycans (HSPGs). The enzyme is secreted through the Golgi and is subsequently localized to the cell surface. The expression of this gene may be down-regulated in several types of cancer, including hepatocellular (HCC), ovarian and breast cancers. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23213 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 487 total
• MANE Select transcript: NM_001128205

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20391
Approved symbol	SULF1
Name	sulfatase 1
Location	8q13.2-q13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1077, SULF-1, hSulf-1
Ensembl gene	ENSG00000137573
Ensembl biotype	protein_coding
OMIM	610012
Entrez	23213

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 16 protein_coding, 7 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000260128, ENST00000402687, ENST00000419716, ENST00000458141, ENST00000521946, ENST00000524731, ENST00000525061, ENST00000525112, ENST00000525999, ENST00000526654, ENST00000526808, ENST00000528146, ENST00000528286, ENST00000528783, ENST00000529041, ENST00000529134, ENST00000530674, ENST00000531064, ENST00000531512, ENST00000532015, ENST00000534088, ENST00000534179, ENST00000616868, ENST00000889120, ENST00000889121, ENST00000889122, ENST00000889123, ENST00000925206, ENST00000955413

RefSeq mRNA: 24 — MANE Select: NM_001128205 NM_001128204, NM_001128205, NM_001128206, NM_001412828, NM_001412829, NM_001412830, NM_001412831, NM_001412832, NM_001412833, NM_001412834, NM_001412835, NM_001412836, NM_001412837, NM_001412838, NM_001412839, NM_001412840, NM_001412841, NM_001412842, NM_001412844, NM_001412845, NM_001412846, NM_001412850, NM_001412851, NM_015170

CCDS: CCDS6204

Canonical transcript exons

ENST00000402687 — 23 exons

Exon	Start	End
ENSE00001191942	69658505	69660912
ENSE00001549770	69495765	69495926
ENSE00001618968	69501874	69501968
ENSE00001625698	69588972	69589141
ENSE00001653078	69563539	69563611
ENSE00001737840	69563916	69564147
ENSE00002158951	69492847	69493125
ENSE00003487134	69575970	69576209
ENSE00003497653	69628171	69628236
ENSE00003506695	69638735	69638858
ENSE00003517973	69640808	69640841
ENSE00003523687	69604803	69604932
ENSE00003528982	69627210	69627306
ENSE00003533204	69638502	69638644
ENSE00003541787	69621035	69621251
ENSE00003560272	69627772	69627866
ENSE00003563091	69586357	69586508
ENSE00003588952	69600603	69600753
ENSE00003594497	69629504	69629679
ENSE00003663176	69623942	69624197
ENSE00003673138	69603192	69603320
ENSE00003679429	69601654	69601829
ENSE00003684902	69603600	69603656

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.0629 / max 4235.7219, expressed in 1199 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89272	44.2136	1018
89269	15.9582	735
89268	2.8392	402
89266	2.3136	416
89271	1.9229	381
89270	0.9738	305
89267	0.7982	264
89281	0.6536	267
89279	0.5077	223
89292	0.2597	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parietal pleura	UBERON:0002400	99.24	gold quality
stromal cell of endometrium	CL:0002255	99.05	gold quality
pigmented layer of retina	UBERON:0001782	98.92	gold quality
retina	UBERON:0000966	98.90	gold quality
germinal epithelium of ovary	UBERON:0001304	98.84	gold quality
right coronary artery	UBERON:0001625	98.52	gold quality
pleura	UBERON:0000977	98.42	gold quality
descending thoracic aorta	UBERON:0002345	98.30	gold quality
thoracic aorta	UBERON:0001515	98.14	gold quality
ascending aorta	UBERON:0001496	98.11	gold quality
saphenous vein	UBERON:0007318	97.50	gold quality
aorta	UBERON:0000947	97.29	gold quality
choroid plexus epithelium	UBERON:0003911	97.03	gold quality
visceral pleura	UBERON:0002401	96.96	gold quality
popliteal artery	UBERON:0002250	96.68	gold quality
tibial artery	UBERON:0007610	96.68	gold quality
urethra	UBERON:0000057	96.62	gold quality
renal glomerulus	UBERON:0000074	96.62	gold quality
metanephric glomerulus	UBERON:0004736	96.55	gold quality
colonic epithelium	UBERON:0000397	96.53	gold quality
smooth muscle tissue	UBERON:0001135	96.48	gold quality
blood vessel layer	UBERON:0004797	96.36	gold quality
cauda epididymis	UBERON:0004360	96.19	gold quality
tendon of biceps brachii	UBERON:0008188	96.07	gold quality
left coronary artery	UBERON:0001626	95.91	gold quality
coronary artery	UBERON:0001621	95.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.08	gold quality
calcaneal tendon	UBERON:0003701	94.57	gold quality
cartilage tissue	UBERON:0002418	94.50	gold quality
tendon	UBERON:0000043	94.11	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	1189.53
E-MTAB-9154	yes	998.95
E-GEOD-84465	yes	674.82
E-MTAB-11121	yes	320.58
E-MTAB-6108	yes	138.62
E-MTAB-8410	yes	44.47
E-CURD-119	yes	27.62
E-MTAB-6678	yes	11.58
E-CURD-112	yes	6.55
E-HCAD-30	no	355.96
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NKX2-2, NR5A2, PAX6, WT1

miRNA regulators (miRDB)

122 targeting SULF1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-548D-3P	99.87	70.67	4362

Literature-anchored findings (GeneRIF, showing 40)

• Sulfs are extracellular endosulfatases with strong potential for modulating the interactions of heparan sulfate proteoglycans in the extracellular microenvironment (PMID:12368295)
• modulates signaling by heparin-binding growth factors, and HSulf-1 down-regulation represents a novel mechanism by which cancer cells can enhance growth factor signaling (PMID:12686563)
• Down-regulation of hSulf1 contributes to hepatocarcinogenesis by enhancing heparin-binding growth factor signaling and resistance to apoptosis. (PMID:14699503)
• High expression of Hsulf-1 occurs in the stromal elements as well as in the tumor cells in pancreatic cancer and interferes with heparin-binding growth factor signaling (PMID:15817123)
• HSulf-1 (SULF1) and HSulf-2 (SULF2) are potent inhibitors of myeloma tumor growth in vivo. (PMID:16192265)
• HSulf-1 and HSulf-2 have roles in inhibiting myeloma tumor growth (PMID:16192265)
• Loss of HSulf-1 expression is associated with breast cancer (PMID:17363371)
• The combined effects of heparanase and HSULF could account for the lack of biologically active HS in tumour cells rather than deficiencies in the biosynthetic enzymes. (PMID:17437011)
• Sulf1 is a TGF-beta1-responsive gene both in vitro and in vivo and may function as a negative regulator of TGF-beta1-induced fibrogenesis (PMID:18503048)
• Increased sulf-1 expression may change the sulfation patterns of heparan sulfate proteoglycans and growth factor activities and thus contribute to abnormal chondrocyte activation and cartilage degradation in osteoarthritis. (PMID:18507859)
• Sulf1 and Sulf2 are two heparan sulfate 6-O-endosulfatases that regulate the activity of multiple growth factors, such as fibroblast growth factor and Wnt, and are essential for mammalian development and survival (PMID:18687675)
• detection of the HSulf-1 promoter methylation in serum samples may have clinical implications in early detection and diagnosis of human breast and gastric cancers. (PMID:19006069)
• Strategies targeting sulfatase 1(SULF1) or the interaction between SULF1 and the related sulfatase 2 will potentially be important in developing novel cancer therapies. (PMID:19373441)
• vHNF1 acts as a repressor of HSulf-1 expression and might be a molecular target for ovarian cancer therapy. (PMID:19487294)
• analysis of the subdomain organization of sulf-1 and sulf-2 (PMID:19520866)
• Data show that specific regions of the Sulf1 hydrophilic domain (HD) influence different aspects of heparan sulfate binding, cellular localization, and enzyme function. (PMID:19666466)
• The expression levels of four of the up-regulated genes, CXCL1, SPARC, SPP1 and SULF, were significantly higher in the cancerous tissue compared with the normal tissue (fold change 3.4-8.9). (PMID:19780053)
• Haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS. (PMID:20602915)
• Genetic variations in SULF1 may play a role in ovarian cancer onset and prognosis. (PMID:21214932)
• Phage microarrays containing colorectal cancer cDNA libraries were prepared to identify phage-expressed peptides recognized by tumor-specific autoantibodies from patient sera. (PMID:21228115)
• Data show that HSulf-1 depletion in breast cancer cells resulted in an increased and sustained bFGF2 (basic fibroblast growth factor) signaling and promoted cell migration and invasion under hypoxic conditions. (PMID:21266348)
• SULF1 and SULF2 are overexpressed in various human cancer types and can be associated to progression and prognosis. (PMID:21599997)
• extracellular HSulf-1 may function as a negative regulator of proliferation and invasion in gastric cancer by suppressing Wnt/beta-catenin signaling at the cell surface. (PMID:21722266)
• Sulf-1 protein expression is down-regulated in gastric cancer. (PMID:22524839)
• SULF1 may serve as a promising biomarker for patients with gastric carcinoma. (PMID:22653794)
• these observations provide evidence that HPEI nanogels delivering HSulf-1 combined with DDP may have a promising application in the therapy of human ovarian cancer. (PMID:22825572)
• HSULF-1 is expressed at lower levels in H292 lung cancer cells than in normal human alveolar cells and that its over-expression reduced cell viability in H292 cells by inducing apoptotic pathways, at least in part by inhibiting ERK/Akt signaling (PMID:22873647)
• inhibits proliferation and invasion of esophageal squamous cell carcinoma by decreasing heparin-binding growth factor signaling (PMID:23053899)
• HSulf-1 and HSulf-2 share the same desulfation processs but with a different rate (PMID:23457216)
• Ectopic expression of SULF1 or SULF2 in HeLa cells, which decreases cell surface heparan sulfate proteoglycan sulfation, diminished Chlamydia muridarum binding and decreased vacuole formation. (PMID:23480519)
• miR-21-mediated suppression of both hSulf-1 and PTEN led to activation of AKT/ERK pathways and epithelial-mesenchymal transition in hepatocellular carcinoma, promoting tumor growth. (PMID:23684551)
• Strong interaction depends on the presence of Sulf1-substrate groups. (PMID:23891937)
• Knockdown of SULF2 in human corneal epithelial cell line slowed migration, which was restored by overexpression of either mouse SULF2 or human SULF1. (PMID:23950901)
• rs6990375 polymorphism of SULF1 gene could be one of the factors related to recurrent miscarriage in Iranian women. (PMID:24322345)
• Loss of HSulf-1 expression promotes tumorigenicity in ovarian cancer through regulating Bim expression. (PMID:24596063)
• SULF1/SULF2 splice variants regulate pancreatic tumor progression. (PMID:24726914)
• identification of markers including SULF1 may improve detection of this disease at its earliest stages improving patient treatment and prognosis (PMID:24911625)
• Data suggest that Sulfatase 1 (hSulf-1) may be a suitable target for cancer therapy. (PMID:24970807)
• findings show an upregulation of SULF1 in degenerative discs for the first time, and suggest that there is a link between SULF1 and disc degeneration (PMID:25469740)
• Results show that SULF1 or SULF2 overexpression contributes to colorectal cancer cell proliferation, migration, and invasion. (PMID:25477293)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	sulf1	ENSDARG00000038428
mus_musculus	Sulf1	ENSMUSG00000016918
rattus_norvegicus	Sulf1	ENSRNOG00000009037
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), GALNS (ENSG00000141012), ARSG (ENSG00000141337), ARSL (ENSG00000157399), ARSK (ENSG00000164291), ARSJ (ENSG00000180801), SGSH (ENSG00000181523), ARSI (ENSG00000183876), SULF2 (ENSG00000196562), ARSH (ENSG00000205667)

Protein

Protein identifiers

Extracellular sulfatase Sulf-1 — Q8IWU6 (reviewed: Q8IWU6)

Alternative names: Arylsulfatase, N-acetylglucosamine-6-sulfatase

All UniProt accessions (8): Q8IWU6, A0A087WWR8, E9PI06, E9PJL8, E9PLS5, E9PPQ3, E9PS14, H0YDR1

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin. Diminishes HSPG (heparan sulfate proteoglycans) sulfation, inhibits signaling by heparin-dependent growth factors, diminishes proliferation, and facilitates apoptosis in response to exogenous stimulation.

Subcellular location. Endoplasmic reticulum. Golgi apparatus. Golgi stack. Cell surface Secreted.

Tissue specificity. Expressed at highest levels in testis, stomach, skeletal muscle, lung, kidney, pancreas, small intestine and colon. It is also detected in normal ovarian surface epithelial cells. Down-regulation seen in ovarian carcinoma cell lines, ovarian cancers, breast, pancreatic, renal and hepatocellular carcinoma cell lines.

Post-translational modifications. Processing by furin produces a secreted form. 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 (24): NP_001121676, NP_001121677, NP_001121678, NP_001399757, NP_001399758, NP_001399759, NP_001399760, NP_001399761, NP_001399762, NP_001399763, NP_001399764, NP_001399765, NP_001399766, NP_001399767, NP_001399768, NP_001399769, NP_001399770, NP_001399771, NP_001399773, NP_001399774, NP_001399775, NP_001399779, NP_001399780, NP_055985 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000917	Sulfatase_N	Domain
IPR014615	Extracellular_sulfatase	Family
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily
IPR024607	Sulfatase_CS	Conserved_site
IPR024609	Extracellular_sulfatase_C	Domain

Pfam: PF00884, PF12548

Catalyzed reactions (Rhea), 1 shown:

• an aryl sulfate + H2O = a phenol + sulfate + H(+) (RHEA:17261)

UniProt features (29 total): glycosylation site 10, binding site 5, region of interest 4, chain 2, sequence conflict 2, signal peptide 1, site 1, modified residue 1, mutagenesis site 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWU6-F1	74.27	0.45

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): 544–545 (cleavage; by furin); 87 (nucleophile)

Ligand- & substrate-binding residues (5): 52; 87 (via 3-oxoalanine); 316; 317; 51

Post-translational modifications (1): 87

Glycosylation sites (10): 64, 111, 131, 148, 170, 197, 240, 623, 773, 783

Mutagenesis-validated functional residues (1):

Position	Phenotype
87–88	loss of arylsulfatase activity and loss of ability to modulate apoptosis.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 394 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, YAATNRNNNYNATT_UNKNOWN, GOBP_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_PROSTATE_GLAND_MORPHOGENESIS, GAANYNYGACNY_UNKNOWN

GO Biological Process (22): kidney development (GO:0001822), negative regulation of endothelial cell proliferation (GO:0001937), chondrocyte development (GO:0002063), glomerular filtration (GO:0003094), apoptotic process (GO:0006915), positive regulation of vascular endothelial growth factor production (GO:0010575), esophagus smooth muscle contraction (GO:0014846), negative regulation of angiogenesis (GO:0016525), positive regulation of Wnt signaling pathway (GO:0030177), heparan sulfate proteoglycan metabolic process (GO:0030201), negative regulation of cell migration (GO:0030336), positive regulation of BMP signaling pathway (GO:0030513), glomerular basement membrane development (GO:0032836), glial cell-derived neurotrophic factor receptor signaling pathway (GO:0035860), regulation of fibroblast growth factor receptor signaling pathway (GO:0040036), negative regulation of fibroblast growth factor receptor signaling pathway (GO:0040037), vascular endothelial growth factor receptor signaling pathway (GO:0048010), embryonic skeletal system development (GO:0048706), cartilage development (GO:0051216), bone development (GO:0060348), innervation (GO:0060384), negative regulation of prostatic bud formation (GO:0060686)

GO Molecular Function (7): arylsulfatase activity (GO:0004065), calcium ion binding (GO:0005509), glycosaminoglycan binding (GO:0005539), N-acetylglucosamine-6-sulfatase activity (GO:0008449), sulfuric ester hydrolase activity (GO:0008484), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), Golgi stack (GO:0005795), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane raft (GO:0045121), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
skeletal system development	3
cell surface receptor protein tyrosine kinase signaling pathway	2
fibroblast growth factor receptor signaling pathway	2
sulfuric ester hydrolase activity	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
renal system development	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
chondrocyte differentiation	1
cell development	1
renal filtration	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
positive regulation of cytokine production	1
vascular endothelial growth factor production	1
regulation of vascular endothelial growth factor production	1
gastro-intestinal system smooth muscle contraction	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
proteoglycan metabolic process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
extracellular matrix organization	1
glomerulus development	1
anatomical structure development	1
regulation of signal transduction	1

Protein interactions and networks

STRING

1786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SULF1	SLCO5A1	Q9H2Y9	925
SULF1	SCEL	O95171	752
SULF1	HS6ST1	O60243	666
SULF1	HS2ST1	Q7LGA3	664
SULF1	YIPF3	Q9GZM5	649
SULF1	SYNPO	Q8N3V7	648
SULF1	CYP26A1	O43174	647
SULF1	FGF13	Q92913	637
SULF1	SDC3	O75056	628
SULF1	FGF2	P09038	618
SULF1	GLCE	O94923	614
SULF1	HBEGF	Q99075	590
SULF1	HS3ST1	O14792	586
SULF1	NPHS1	O60500	583
SULF1	EXT1	Q16394	579

IntAct

36 interactions, top by confidence:

A	B	Type	Score
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
LRRC4C	DVL2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530
SYCN	AIP	psi-mi:“MI:0914”(association)	0.500
APP	ZNF724	psi-mi:“MI:0914”(association)	0.350
INSL5	LAMA5	psi-mi:“MI:0914”(association)	0.350
SDC2	METTL8	psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
OS9	GXYLT2	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	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
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
SULF2	CCDC85C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
NOG	TCAF2	psi-mi:“MI:0914”(association)	0.350
MFAP5	MANBA	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
INS	LAMA5	psi-mi:“MI:0914”(association)	0.350
LYZL2	ZZEF1	psi-mi:“MI:0914”(association)	0.350
PMCH	B4GALT5	psi-mi:“MI:0914”(association)	0.350
RETNLB	PLXNA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (43): SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS), SULF1 (Affinity Capture-MS)

ESM2 similar proteins: A2VDP5, B0BND0, F1N5C8, O19015, O70362, P06802, P14000, P15589, P50428, P50473, P51689, P51690, P54793, P80108, P80109, P84039, P97675, Q08CJ7, Q14703, Q32KH8, Q32KJ9, Q3TYD4, Q566N0, Q58D68, Q5BKW7, Q5FYA8, Q5RAC0, Q5RB45, Q5ZK90, Q60HH5, Q6DDP3, Q6UWR7, Q8BGN3, Q8BTJ4, Q8C255, Q8CFG0, Q8IW92, Q8IWU5, Q8IWU6, Q8K007

Diamond homologs: A0A455ZJM4, P14217, Q10723, Q21376, Q797B3, Q8A2F6, Q8CFG0, Q8IWU5, Q8IWU6, Q8K007, Q8VI60, Q9VEX0, P15586, P50426, Q1LZH9, Q8BFR4, Q90XB6, P08842, P14000, P15289, P15589, P34059, P50427, P50428, P50473, P51689, P51690, P54793, Q08DD1, Q32KH5, Q32KH8, Q32KH9, Q32KJ6, Q32KJ8, Q3TYD4, Q571E4, Q5FYA8, Q5FYB0, Q5FYB1, Q60HH5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	267
Likely benign	148
Benign	32

Top pathogenic / likely-pathogenic (0)

SpliceAI

3931 predictions. Top by Δscore:

Variant	Effect	Δscore
8:69487122:G:GT	donor_gain	1.0000
8:69501868:TCGTA:T	acceptor_loss	1.0000
8:69501869:CGTAG:C	acceptor_loss	1.0000
8:69501870:GTA:G	acceptor_loss	1.0000
8:69501871:TAGG:T	acceptor_loss	1.0000
8:69501872:A:C	acceptor_loss	1.0000
8:69501964:CAAAG:C	donor_loss	1.0000
8:69501965:AAAGG:A	donor_loss	1.0000
8:69501966:AAGG:A	donor_loss	1.0000
8:69501967:AGG:A	donor_loss	1.0000
8:69501968:GGT:G	donor_loss	1.0000
8:69501969:GT:G	donor_loss	1.0000
8:69501970:T:A	donor_loss	1.0000
8:69562943:G:GT	donor_gain	1.0000
8:69586351:CTGCA:C	acceptor_loss	1.0000
8:69586352:T:A	acceptor_gain	1.0000
8:69586352:TGCAG:T	acceptor_loss	1.0000
8:69586353:GCAGC:G	acceptor_loss	1.0000
8:69586354:CAGCC:C	acceptor_loss	1.0000
8:69586355:A:AG	acceptor_gain	1.0000
8:69586355:AGCCT:A	acceptor_loss	1.0000
8:69586356:G:GA	acceptor_gain	1.0000
8:69586356:G:GT	acceptor_loss	1.0000
8:69586356:GCCT:G	acceptor_gain	1.0000
8:69586504:CAAAG:C	donor_loss	1.0000
8:69586505:AAAGG:A	donor_loss	1.0000
8:69586506:AAGG:A	donor_loss	1.0000
8:69586507:AGGT:A	donor_loss	1.0000
8:69586508:GGT:G	donor_loss	1.0000
8:69586510:T:A	donor_loss	1.0000

AlphaMissense

5816 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:69564126:G:C	D51H	1.000
8:69564127:A:T	D51V	1.000
8:69564130:A:C	D52A	1.000
8:69564130:A:T	D52V	1.000
8:69576056:T:C	C87R	1.000
8:69576057:G:A	C87Y	1.000
8:69576058:C:G	C87W	1.000
8:69576059:T:C	C88R	1.000
8:69576060:G:A	C88Y	1.000
8:69576061:C:G	C88W	1.000
8:69576121:C:A	N108K	1.000
8:69576121:C:G	N108K	1.000
8:69576131:T:A	C112S	1.000
8:69576131:T:C	C112R	1.000
8:69576132:G:A	C112Y	1.000
8:69576132:G:C	C112S	1.000
8:69576133:C:G	C112W	1.000
8:69576146:T:A	W117R	1.000
8:69576146:T:C	W117R	1.000
8:69576148:G:C	W117C	1.000
8:69576148:G:T	W117C	1.000
8:69586366:G:A	G141E	1.000
8:69586410:T:A	W156R	1.000
8:69586410:T:C	W156R	1.000
8:69586419:T:A	W159R	1.000
8:69586419:T:C	W159R	1.000
8:69600638:A:T	K257I	1.000
8:69600639:A:C	K257N	1.000
8:69600639:A:T	K257N	1.000
8:69600643:T:A	W259R	1.000

dbSNP variants (sampled 300 via entrez): RS1000001713 (8:69530205 A>T), RS1000020140 (8:69526639 A>G,T), RS1000037517 (8:69529993 C>T), RS1000040256 (8:69608747 A>C,G), RS1000050218 (8:69654021 G>A), RS1000055748 (8:69568417 A>G), RS1000060094 (8:69594144 C>G,T), RS1000067588 (8:69523655 G>A,T), RS1000072705 (8:69526370 T>C), RS1000098331 (8:69523848 G>A), RS1000109279 (8:69582222 G>A), RS1000129046 (8:69541835 T>G), RS1000167070 (8:69503150 A>G), RS1000174177 (8:69626671 C>G,T), RS1000193987 (8:69635239 C>G)

Disease associations

OMIM: gene MIM:610012 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Microphthalmia-anophthalmia-coloboma (Orphanet:98555)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001144_6	Dupuytren’s disease	2.000000e-13
GCST001263_11	Height	1.000000e-06
GCST001526_16	Fasting blood insulin (BMI interaction)	7.000000e-07
GCST004833_5	Cervical cancer	7.000000e-06
GCST004862_8	Itch intensity from mosquito bite adjusted by bite size	4.000000e-06
GCST006899_14	Thyroid stimulating hormone levels	4.000000e-09
GCST010575_5	Evening vs. morning chronotype (sMEQ score)	5.000000e-06
GCST010577_2	Crohn’s disease	7.000000e-06
GCST010653_33	Thyroid stimulating hormone levels	7.000000e-10
GCST012490_245	Femur bone mineral density x serum urate levels interaction	7.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture
EFO:0004340	body mass index
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008328	chronotype measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	6
sodium arsenite	affects cotreatment, increases abundance, decreases expression	5
Estradiol	affects cotreatment, decreases expression, increases expression	4
Silicon Dioxide	increases expression, decreases expression, increases reaction, increases response to substance	4
methylmercuric chloride	decreases expression	3
trichostatin A	affects cotreatment, decreases expression, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
bisphenol S	increases methylation, affects cotreatment, decreases expression	2
Arsenic Trioxide	decreases expression	2
Arsenic	decreases expression, increases abundance, affects methylation, affects cotreatment	2
Benzo(a)pyrene	affects methylation	2
Dexamethasone	decreases expression, affects cotreatment	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
cupric chloride	decreases expression	1
nickel sulfate	increases expression	1
triadimefon	decreases expression	1
octa-2,4,6-trienoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
3-nitrobenzanthrone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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