SULF2

Summary

SULF2 (sulfatase 2, HGNC:20392) is a protein-coding gene on chromosome 20q13.12, encoding Extracellular sulfatase Sulf-2 (Q8IWU5). Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity.

Heparan sulfate proteoglycans (HSPGs) act as coreceptors for numerous heparin-binding growth factors and cytokines and are involved in cell signaling. Heparan sulfate 6-O-endosulfatases, such as SULF2, selectively remove 6-O-sulfate groups from heparan sulfate. This activity modulates the effects of heparan sulfate by altering binding sites for signaling molecules (Dai et al., 2005 [PubMed 16192265]).

Source: NCBI Gene 55959 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 175 total
• MANE Select transcript: NM_001387048

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20392
Approved symbol	SULF2
Name	sulfatase 2
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1247, HSULF-2, SULF-2
Ensembl gene	ENSG00000196562
Ensembl biotype	protein_coding
OMIM	610013
Entrez	55959

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 24 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000359930, ENST00000433632, ENST00000437955, ENST00000463221, ENST00000465769, ENST00000467815, ENST00000474450, ENST00000478766, ENST00000479472, ENST00000479970, ENST00000484875, ENST00000495544, ENST00000688720, ENST00000698128, ENST00000859450, ENST00000859451, ENST00000859452, ENST00000859453, ENST00000859454, ENST00000859455, ENST00000859456, ENST00000859457, ENST00000859458, ENST00000859459, ENST00000917826, ENST00000917827, ENST00000917828, ENST00000965272, ENST00000965273, ENST00000965274, ENST00000965275, ENST00000965276

RefSeq mRNA: 11 — MANE Select: NM_001387048 NM_001161841, NM_001387048, NM_001387049, NM_001387050, NM_001387051, NM_001387052, NM_001387053, NM_001387054, NM_001387055, NM_018837, NM_198596

CCDS: CCDS13408, CCDS13409

Canonical transcript exons

ENST00000688720 — 21 exons

Exon	Start	End
ENSE00003553626	47757189	47757463
ENSE00003617788	47736703	47736942
ENSE00003791098	47702519	47702670
ENSE00003927265	47785343	47785481
ENSE00003972778	47663453	47663622
ENSE00003972780	47663070	47663212
ENSE00003972781	47659697	47659730
ENSE00003972782	47664130	47664189
ENSE00003972783	47665199	47665293
ENSE00003972785	47676494	47676623
ENSE00003972786	47657406	47658392
ENSE00003972787	47661773	47661896
ENSE00003972788	47678676	47678804
ENSE00003972789	47672198	47672393
ENSE00003972790	47677078	47677134
ENSE00003972791	47665857	47665953
ENSE00003972792	47684431	47684581
ENSE00003972793	47682994	47683169
ENSE00003972794	47690126	47690295
ENSE00003972795	47659399	47659452
ENSE00003972796	47666260	47666488

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.7282 / max 516.7983, expressed in 1421 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187653	17.5474	1310
187656	5.3964	1052
187664	2.1588	440
187657	2.0822	665
187666	1.8303	362
187648	1.6912	418
187662	1.0357	183
187665	1.0134	201
187654	0.8779	196
187663	0.7522	252

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.58	gold quality
body of uterus	UBERON:0009853	98.85	gold quality
myometrium	UBERON:0001296	98.65	gold quality
left ovary	UBERON:0002119	98.62	gold quality
right ovary	UBERON:0002118	98.56	gold quality
ectocervix	UBERON:0012249	98.31	gold quality
left uterine tube	UBERON:0001303	98.09	gold quality
monocyte	CL:0000576	98.04	gold quality
tendon of biceps brachii	UBERON:0008188	98.00	gold quality
smooth muscle tissue	UBERON:0001135	97.97	gold quality
leukocyte	CL:0000738	97.96	gold quality
lower esophagus mucosa	UBERON:0035834	97.94	gold quality
endocervix	UBERON:0000458	97.79	gold quality
right uterine tube	UBERON:0001302	97.49	gold quality
uterine cervix	UBERON:0000002	97.45	gold quality
uterus	UBERON:0000995	97.15	gold quality
lower esophagus	UBERON:0013473	97.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.01	gold quality
gall bladder	UBERON:0002110	96.98	gold quality
layer of synovial tissue	UBERON:0007616	96.97	gold quality
calcaneal tendon	UBERON:0003701	96.93	gold quality
granulocyte	CL:0000094	96.67	gold quality
esophagus	UBERON:0001043	96.38	gold quality
ovary	UBERON:0000992	96.30	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.08	gold quality
tendon	UBERON:0000043	96.01	gold quality
pericardium	UBERON:0002407	95.94	gold quality
esophagus mucosa	UBERON:0002469	95.91	gold quality
peritoneum	UBERON:0002358	95.79	gold quality
omental fat pad	UBERON:0010414	95.79	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	112.97
E-GEOD-84465	yes	27.63
E-MTAB-9067	yes	14.05
E-CURD-112	yes	13.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53, WT1

miRNA regulators (miRDB)

76 targeting SULF2, 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-186-5P	99.99	70.83	3707
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-6722-3P	99.45	67.62	1919

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)
• 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)
• Purified recombinant Sulf-2 promoted angiogenesis in the chick chorioallantoic membrane assay. (PMID:16331886)
• Binding of VEGF, FGF-1, & certain chemokines (SDF-1 & SLC) to immobilized heparin was abolished or diminished by pre-treating the heparin with HSulf-2. Recombinant or native HSulf-2 released these soluble proteins from their association with heparin. (PMID:16417632)
• Increased sulf-2 mRNA and protein levels 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)
• Genetic and pharmacologic perturbation of p53 directly influences SULF2 expression in tumor cell lines. (PMID:19190338)
• analysis of the subdomain organization of sulf-1 and sulf-2 (PMID:19520866)
• Our findings support an essential role for Sulf-2 in lung cancer (PMID:19855436)
• Loss of SULF2 is associated with breast cancer. (PMID:20707913)
• Mechanism mediating the oncogenic function of SULF2 in human hepatoma that includes GPC3-mediated activation of Wnt signaling. (PMID:20725905)
• The prosurvival, anti-apoptotic effect of SULF2 in hepatocellular carcinoma is mediated through activation of the PI3K/Akt pathway. (PMID:21040406)
• enzymatic activity of HSulf2 (PMID:21347431)
• SULF1 and SULF2 are overexpressed in various human cancer types and can be associated to progression and prognosis. (PMID:21599997)
• This study demonstrates that unlike normal adult lung with little or no SULF2 expression, this enzyme is expressed at high levels in most lung tumours showing differential cellular distribution of full length and shorter SULF2 variants in such tumours. (PMID:21968018)
• genes and pathways modulated by epigenetic inactivation of SULF2 and the effects on sensitivity to chemotherapy were characterized in lung cancer in vitro and in vivo; silencing SULF2 primarily increased expression of interferon-inducible genes including ISG15 (PMID:22158045)
• Heparan sulfate sulfatase SULF2 regulates PDGFRalpha signaling and growth in human and mouse malignant glioma (PMID:22293178)
• Sulf-2 expression is be critical for human breast cancer progression. (PMID:22410125)
• Sulf2 is overexpressed in idiopathic pulmonary fibrosis and may play a role in regulating TGF-beta1 signaling in type II alveolar epithelial cells. (PMID:23418199)
• studied the functional consequences of HSulf-2 activity on fibroblast growth factor (FGF)-induced mitogenesis and found that the enzyme could differentially regulate FGF1 and FGF2 activities (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)
• 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)
• SULF2 methylation is negatively associated with cisplatin sensitivity in vitro. (PMID:24124496)
• Results indicate that the genetic variation rs2281279 in SULF2 associates with postprandial clearance of remnant TRLs and triglyceride levels in healthy subjects. (PMID:24278138)
• The SULF2 single nucleotide polymorphism was reproducibly associated with lower fasting plasma triglycerides levels in obese type 2 diabetic subjects. (PMID:24339435)
• SULF2 promoter methylation was associated with irinotecan sensitivity in gastric carcinoma. (PMID:24359226)
• SULF1/SULF2 splice variants regulate pancreatic tumor progression. (PMID:24726914)
• pectin induced the expression of HSulf-2 through the interaction with fibronectin, alpha5beta1 integrin, and ERK1/2 (PMID:25036960)
• Substrate specificity of human SULF2. (PMID:25127119)
• Our findings define Sulf-2 as a novel positive regulator of neuroblastoma pathogenicity that contributes to MYCN oncogenicity. (PMID:25164011)
• SULF2 expression in human tumor tissue and cell lines, was assessed. (PMID:25325976)
• SULF2 blood levels increased with age in both healthy and cirrhosis patients.SULF2 blood level was higher in cirrhosis patients than healthy individuals. (PMID:25444749)
• Results show that SULF1 or SULF2 overexpression contributes to colorectal cancer cell proliferation, migration, and invasion. (PMID:25477293)
• SULF2 have a pro-tumorigenic effect in DU-145 and PC3 cancer cells, suggesting an important role of this enzyme in prostatic cancer metastasis. (PMID:25887999)
• Our data confirmed that Sulf2 promoted breast cancer progression and regulated the expression of tumor-related genes in breast cancer. (PMID:26708018)
• Tumor expression of SULF2 may affect prognosis in NSCLC, while blood SULF2 levels may have a significant role in the diagnosis of this fatal disease. (PMID:26882224)
• results demonstrated that SULF2 can mediate the detrimental effects of ionizing radiation in vivo (PMID:26895473)
• SULF2 is a multifaceted protein involved in triglyceride-rich lipoprotein homeostasis and angiogenesis. [review] (PMID:26959705)
• The SULF1/SULF2 activation thus does not only promote regulated foetal growth and injury-induced liver regeneration but also dysregulated tumour growth. (PMID:27013228)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	sulf2b	ENSDARG00000013838
mus_musculus	Sulf2	ENSMUSG00000006800
rattus_norvegicus	Sulf2	ENSRNOG00000006052
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), ARSJ (ENSG00000180801), SGSH (ENSG00000181523), ARSI (ENSG00000183876), ARSH (ENSG00000205667)

Protein

Protein identifiers

Extracellular sulfatase Sulf-2 — Q8IWU5 (reviewed: Q8IWU5)

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

All UniProt accessions (4): Q8IWU5, A0A8V8TMY2, B1AMP9, H0Y872

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.

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

Tissue specificity. Expressed at highest levels in the ovary, skeletal muscle, stomach, brain, uterus, heart, kidney and placenta.

Post-translational modifications. Processing by furin produces a secreted form. Glycosylation at Ser-583 negatively regulates its N-acetylglucosamine-6-sulfatase and arylsulfatase activities. 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.

Miscellaneous. May be due to a competing acceptor splice site.

Similarity. Belongs to the sulfatase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IWU5-1	1	yes
Q8IWU5-2	2

RefSeq proteins (11): NP_001155313, NP_001373977, NP_001373978, NP_001373979, NP_001373980, NP_001373981, NP_001373982, NP_001373983, NP_001373984, NP_061325, NP_940998 (=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 (35 total): glycosylation site 13, binding site 5, sequence variant 4, region of interest 3, mutagenesis site 3, chain 2, signal peptide 1, site 1, modified residue 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWU5-F1	74.16	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): 538–539 (cleavage; by furin); 88 (nucleophile)

Ligand- & substrate-binding residues (5): 317; 318; 52; 53; 88 (via 3-oxoalanine)

Post-translational modifications (1): 88

Glycosylation sites (13): 65, 112, 132, 149, 171, 198, 241, 561, 583, 608, 717, 754, 764

Mutagenesis-validated functional residues (3):

Position	Phenotype
88–89	loss of arylsulfatase activity.
180–182	no effect on n-acetylglucosamine-6-sulfatase activity. significant loss of n-acetylglucosamine-6-sulfatase activity; whe
402–404	no effect on n-acetylglucosamine-6-sulfatase activity. significant loss of n-acetylglucosamine-6-sulfatase activity; whe

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (19): kidney development (GO:0001822), chondrocyte development (GO:0002063), glomerular filtration (GO:0003094), response to wounding (GO:0009611), positive regulation of vascular endothelial growth factor production (GO:0010575), esophagus smooth muscle contraction (GO:0014846), positive regulation of Wnt signaling pathway (GO:0030177), heparan sulfate proteoglycan metabolic process (GO:0030201), glomerular basement membrane development (GO:0032836), glial cell-derived neurotrophic factor receptor signaling pathway (GO:0035860), negative regulation of fibroblast growth factor receptor signaling pathway (GO:0040037), embryonic skeletal system development (GO:0048706), cartilage development (GO:0051216), bone development (GO:0060348), innervation (GO:0060384), positive regulation of canonical Wnt signaling pathway (GO:0090263), liver regeneration (GO:0097421), positive regulation of endothelin production (GO:1904472), regulation of hepatocyte proliferation (GO:2000345)

GO Molecular Function (8): arylsulfatase activity (GO:0004065), calcium ion binding (GO:0005509), glycosaminoglycan binding (GO:0005539), N-acetylglucosamine-6-sulfatase activity (GO:0008449), protein binding (GO:0005515), sulfuric ester hydrolase activity (GO:0008484), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), Golgi stack (GO:0005795), plasma membrane (GO:0005886), cell surface (GO:0009986), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
skeletal system development	3
positive regulation of cytokine production	2
sulfuric ester hydrolase activity	2
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
renal system development	1
chondrocyte differentiation	1
cell development	1
renal filtration	1
response to stress	1
vascular endothelial growth factor production	1
regulation of vascular endothelial growth factor production	1
gastro-intestinal system smooth muscle contraction	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
proteoglycan metabolic process	1
extracellular matrix organization	1
glomerulus development	1
anatomical structure development	1
cell surface receptor protein tyrosine kinase signaling pathway	1
fibroblast growth factor receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of fibroblast growth factor receptor signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
chordate embryonic development	1
connective tissue development	1
nerve development	1
multicellular organismal process	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
liver development	1
animal organ regeneration	1
regulation of endothelin production	1
endothelin production	1
regulation of epithelial cell proliferation	1

Protein interactions and networks

STRING

1298 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SULF2	GPC3	P51654	738
SULF2	FGF13	Q92913	695
SULF2	FGF2	P09038	685
SULF2	HS2ST1	Q7LGA3	665
SULF2	SDC3	O75056	644
SULF2	HS6ST1	O60243	642
SULF2	FURIN	P09958	628
SULF2	NDST1	P52848	605
SULF2	HBEGF	Q99075	595
SULF2	GLCE	O94923	593
SULF2	JAZF1	Q86VZ6	592
SULF2	HS3ST1	O14792	585
SULF2	HS6ST2	Q96MM7	579
SULF2	EXT2	Q93063	576
SULF2	EXT1	Q16394	562

IntAct

66 interactions, top by confidence:

A	B	Type	Score
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
TRPC4AP	SMCHD1	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
CASQ2	PES1	psi-mi:“MI:0914”(association)	0.530
LRRC4C	DVL2	psi-mi:“MI:0914”(association)	0.530
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
SULF2	UBTF	psi-mi:“MI:0914”(association)	0.530
LGALS3BP	SULF2	psi-mi:“MI:0915”(physical association)	0.500
	SULF2	psi-mi:“MI:0210”(hydroxylation reaction)	0.440
	LGALS3BP	psi-mi:“MI:0210”(hydroxylation reaction)	0.440
SULF2		psi-mi:“MI:0915”(physical association)	0.400
SULF2	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF1A	SULF2	psi-mi:“MI:0915”(physical association)	0.400
TNIP1	COCH	psi-mi:“MI:0914”(association)	0.350
	CCN1	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
SPANXN2	ZNF320	psi-mi:“MI:0914”(association)	0.350
PNMA2	TARS3	psi-mi:“MI:0914”(association)	0.350
CDH23	GTPBP10	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
SULF2	CCDC85C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS), SULF2 (Affinity Capture-MS)

ESM2 similar proteins: A2VDP5, O70572, P06802, P08236, P08842, P14000, P15289, P15396, P15589, P15848, P22304, P33727, P50428, P50429, P50430, P51689, P51690, P54793, P80108, P97675, Q08DD1, Q16549, Q32KH8, Q32KH9, Q32KJ9, Q3TYD4, Q4FAT7, Q4R7M2, Q502B3, Q5FYA8, Q5R5M5, Q5R5N6, Q5RB45, Q5U2X4, Q5ZK90, Q60HH5, Q61139, Q62849, Q6DYE8, Q6UWR7

Diamond homologs: A0A455ZJM4, O69787, P08842, P14217, P50426, Q0IHJ2, Q10723, Q148F3, Q1LZH9, Q21376, Q32KH0, Q32KJ2, Q6UWY0, Q8BFR4, Q8CFG0, Q8IWU5, Q8K007, Q8VI60, Q90XB6, Q9D2L1, Q9VEX0, Q797B3, Q8A2F6, Q8IWU6, P15586, P15589, P50427, D4GU60, P54793, Q71WX0, Q8Y4I4, Q928I2, P14000, P15289, P34059, P50428, P50429, P50430, P50473, P51688

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	126
Likely benign	13
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3836 predictions. Top by Δscore:

Variant	Effect	Δscore
20:47659746:A:AC	acceptor_gain	1.0000
20:47659746:A:C	acceptor_gain	1.0000
20:47661894:CAG:C	acceptor_gain	1.0000
20:47661897:C:CC	acceptor_gain	1.0000
20:47661901:T:C	acceptor_gain	1.0000
20:47661901:T:TC	acceptor_gain	1.0000
20:47663064:CTGTA:C	donor_loss	1.0000
20:47663066:GTACC:G	donor_loss	1.0000
20:47663067:TAC:T	donor_loss	1.0000
20:47663068:ACCTG:A	donor_loss	1.0000
20:47663069:C:CA	donor_loss	1.0000
20:47663208:CCCCA:C	acceptor_gain	1.0000
20:47663209:CCCA:C	acceptor_gain	1.0000
20:47663209:CCCAC:C	acceptor_gain	1.0000
20:47663210:CCA:C	acceptor_gain	1.0000
20:47663210:CCAC:C	acceptor_gain	1.0000
20:47663211:CA:C	acceptor_gain	1.0000
20:47663211:CAC:C	acceptor_gain	1.0000
20:47663213:C:CC	acceptor_gain	1.0000
20:47663217:C:CT	acceptor_gain	1.0000
20:47663218:A:T	acceptor_gain	1.0000
20:47663447:GCTC:G	donor_loss	1.0000
20:47663449:TCA:T	donor_loss	1.0000
20:47663450:CA:C	donor_loss	1.0000
20:47663451:A:AC	donor_gain	1.0000
20:47663451:ACGT:A	donor_loss	1.0000
20:47663452:C:CA	donor_gain	1.0000
20:47663452:CG:C	donor_gain	1.0000
20:47663452:CGTGT:C	donor_gain	1.0000
20:47665290:CAAT:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000016076 (20:47732749 A>C,G), RS1000020643 (20:47710840 C>T), RS1000031965 (20:47710573 A>C,G), RS1000070935 (20:47714135 G>A), RS1000088868 (20:47668196 T>C), RS1000131077 (20:47741155 G>A), RS1000141557 (20:47704524 C>T), RS1000148358 (20:47678014 C>A,G,T), RS1000162236 (20:47740925 G>A,C), RS1000185287 (20:47735233 G>A), RS1000199413 (20:47690888 T>A,C), RS1000208591 (20:47698717 G>A), RS1000218270 (20:47699476 A>C), RS1000221430 (20:47693219 C>G), RS1000222687 (20:47662631 G>A)

Disease associations

OMIM: gene MIM:610013 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000280_5	Attention deficit hyperactivity disorder (time to onset)	7.000000e-06
GCST001018_2	Nephrotic syndrome (acquired)	3.000000e-06
GCST003265_446	Post bronchodilator FEV1/FVC ratio in COPD	4.000000e-06
GCST004069_7	Cerebrospinal fluid AB1-42 levels	2.000000e-06
GCST006611_157	HDL cholesterol	1.000000e-12
GCST006631_28	Nicotine dependence and major depression (severity of comorbidity)	8.000000e-06
GCST010107_23	L-selectin levels	8.000000e-06
GCST010241_189	Apolipoprotein A1 levels	2.000000e-27
GCST010241_203	Apolipoprotein A1 levels	1.000000e-09
GCST010242_231	HDL cholesterol levels	1.000000e-08
GCST010242_285	HDL cholesterol levels	4.000000e-28
GCST010562_1	Depressive symptoms x herpes simplex 1 infection interaction	9.000000e-09
GCST010562_8	Depressive symptoms x herpes simplex 1 infection interaction	4.000000e-07
GCST011358_12	Academic attainment (English)	2.000000e-06
GCST012319_17	LDL levels x SSRI levels (escitalopram or citalopram) interaction in schizophrenia or bipolar disorder	9.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007006	depressive symptom measurement
EFO:0009262	nicotine dependence symptom count
EFO:0008202	L-Selectin measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0007036	herpes virus seropositivity
EFO:0011015	educational attainment
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2076549	SULF2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases expression, increases methylation	5
Benzo(a)pyrene	increases expression, increases methylation	4
Cisplatin	affects expression, affects cotreatment, increases expression, decreases expression	4
Valproic Acid	affects expression, increases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
(+)-JQ1 compound	decreases expression	3
Estradiol	affects cotreatment, increases expression	3
Tretinoin	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
bisphenol A	affects cotreatment, increases expression, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Arsenic	increases abundance, affects cotreatment, decreases expression	2
Doxorubicin	increases expression	2
Formaldehyde	decreases expression, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
sotorasib	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
chloroacetaldehyde	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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