SULT2A1

Summary

SULT2A1 (sulfotransferase family 2A member 1, HGNC:11458) is a protein-coding gene on chromosome 19q13.33, encoding Sulfotransferase 2A1 (Q06520). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands.

This gene encodes a member of the sulfotransferase family. Sulfotransferases aid in the metabolism of drugs and endogenous compounds by converting these substances into more hydrophilic water-soluble sulfate conjugates that can be easily excreted. This protein catalyzes the sulfation of steroids and bile acids in the liver and adrenal glands, and may have a role in the inherited adrenal androgen excess in women with polycystic ovary syndrome.

Source: NCBI Gene 6822 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 37 total
• Druggable target: yes
• MANE Select transcript: NM_003167

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11458
Approved symbol	SULT2A1
Name	sulfotransferase family 2A member 1
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	DHEA-ST
Ensembl gene	ENSG00000105398
Ensembl biotype	protein_coding
OMIM	125263
Entrez	6822

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000222002, ENST00000903235, ENST00000903236, ENST00000903237, ENST00000903238, ENST00000903239

RefSeq mRNA: 1 — MANE Select: NM_003167 NM_003167

CCDS: CCDS12707

Canonical transcript exons

ENST00000222002 — 6 exons

Exon	Start	End
ENSE00000715952	47874657	47874834
ENSE00000715962	47879036	47879130
ENSE00000715969	47882084	47882210
ENSE00000715991	47883577	47883785
ENSE00001310164	47870467	47871567
ENSE00001321232	47886122	47886315

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 99.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.9604 / max 1020.9269, expressed in 70 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181800	2.4904	64
181799	0.3478	22
181798	0.0687	17
181801	0.0273	7
181797	0.0261	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.83	gold quality
right adrenal gland cortex	UBERON:0035827	99.24	gold quality
jejunal mucosa	UBERON:0000399	98.89	gold quality
right adrenal gland	UBERON:0001233	98.86	gold quality
right lobe of liver	UBERON:0001114	98.83	gold quality
adrenal cortex	UBERON:0001235	98.36	gold quality
liver	UBERON:0002107	98.26	gold quality
left adrenal gland cortex	UBERON:0035825	98.12	gold quality
left adrenal gland	UBERON:0001234	97.75	gold quality
adrenal gland	UBERON:0002369	96.06	gold quality
duodenum	UBERON:0002114	91.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.91	gold quality
buccal mucosa cell	CL:0002336	81.16	silver quality
seminal vesicle	UBERON:0000998	79.19	silver quality
small intestine	UBERON:0002108	73.31	gold quality
jejunum	UBERON:0002115	72.80	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.45	gold quality
cardia of stomach	UBERON:0001162	69.25	silver quality
ileal mucosa	UBERON:0000331	69.08	gold quality
body of stomach	UBERON:0001161	67.42	gold quality
stomach	UBERON:0000945	66.77	gold quality
fundus of stomach	UBERON:0001160	65.12	gold quality
amniotic fluid	UBERON:0000173	64.36	silver quality
lower lobe of lung	UBERON:0008949	59.32	silver quality
endometrium epithelium	UBERON:0004811	56.81	gold quality
cauda epididymis	UBERON:0004360	53.97	silver quality
urinary bladder	UBERON:0001255	53.69	gold quality
pancreatic ductal cell	CL:0002079	52.66	silver quality
cerebellar vermis	UBERON:0004720	51.73	gold quality
Brodmann (1909) area 10	UBERON:0013541	51.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-27	no	4.08
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CEBPA, CEBPG, ESR1, ESRRA, FOXC1, GATA1, GATA2, GATA6, HNF4A, MED1, NR1H4, NR1I2, NR1I3, NR5A1, PPARA, RORA, SF1, TBPL1, TCF3, VDR

miRNA regulators (miRDB)

34 targeting SULT2A1, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-6509-5P	97.39	68.27	969

Literature-anchored findings (GeneRIF, showing 40)

• Crystal structure of human dehydroepiandrosterone sulphotransferase in complex with substrate (PMID:11988089)
• Both steroidogenic factor 1 and GATA-6 were positive regulators of SULT2A1 promoter constructs (PMID:15388788)
• lowered expression in hepatocellular carcinoma tissues involved in metabolism and/or inactivation of sex steroids is consistent with a regulatory role SULT2A1 in the development and/or tumor cell differentiation and progression of human HCC (PMID:15713538)
• Estrogen receptor alphaeffects on SULT2A1 were greater than the stimulation seen in response to steroidogenic factor 1 (SF1). (PMID:15878968)
• The SULT2A1 is the major endogenous enzyme responsible for sulfation of the tibolone metabolites in human postmenopausal tissues. (PMID:16360722)
• the SULT2A1 gene is mediated by SF1 and indirectly regulated by T(3) (PMID:16469813)
• No significant association of the presence of the different SULT2A1 alleles with the occurrence of prostate cancer in black men was detected. (PMID:16617014)
• Methotrexate induction of hSULT2A1 is mediated through hCAR. (PMID:17276571)
• genetic evidence suggesting a potential role of SULT2A1, but not STS, in the inherited adrenal androgen excess of polycystic ovary syndrome (PMID:17426092)
• Two amino acids are identified and characterized for the substrate inhibition of SULT2A1. (PMID:18042734)
• In cortices attached to adrenocortical adenomas, SULT2A1 mRNA expression was present mainly in zona reticularis and extended to zona fasciculata. (PMID:18505908)
• Sulfation of polychlorinated phenols catalyzed by hSULT2A1 may be a significant component of their metabolism in humans. (PMID:18656962)
• Testosterone and insulin appear to be modulators of adrenal androgen production in this human adrenocortical cell model. (PMID:18684447)
• Demonstrate that hSULT2A1 is responsible for the N-sulfation of quinolones and possibly other therapeutic drugs in humans. (PMID:19420132)
• The sulfation kinetics of dehydroepiandrosterone and 15 human bile acids by SULT2A1, was characterized. (PMID:20102295)
• Hydroxysteroid sulfotransferase SULT2A1 is suppressed by the estrogen related receptor alpha (PMID:21513704)
• Serum DHEAS levels are increased in patients with non-alcoholic fatty liver disease with elevated alanine aminotransferase levels. (PMID:21841322)
• Common polymorphisms at POR, SULT2A1 or HSD11B1 were not associated with PA in a Finnish Caucasian population. (PMID:22445027)
• Genetic variants of SULT2A1 do not appear to have an effect on individual DHEA and DHEAS concentrations or the DHEA/DHEAS ratio as a marker of DHEA sulfonation capacity (PMID:23132913)
• SULT2A1 as a novel ROR-alpha and ROR-gamma target gene. (PMID:23211525)
• The simulations predict that the active-site “cap,” which covers both the nucleotide and acceptor binding sites, opens and closes in response to nucleotide. (PMID:23256751)
• A crystallographic and biochemical description of the molecular linkages that couple nucleotide binding and SULT2A1 isomerization. (PMID:23362278)
• These data show an age-related association of polymorphisms in the SULT2A1 gene with lower dehydroepiandrosterone sulfate, suggesting that these polymorphisms may affect dehydroepiandrosterone sulfate concentration in adults. (PMID:23436881)
• formation of disulfide bonds in hSULT2A1 is a potentially important reversible mechanism for alterations in the rates of sulfation of both endogenous and xenobiotic substrates (PMID:23444386)
• Fetal inflammatory response syndrome and funisitis are associated with an elevation of umbilical cord plasma concentrations of soluble sulfotransferase (ST)2. (PMID:23488731)
• Depression following hip fracture with poor long term recovery is associated with a higher serum cortisol:DHEAS ratio. (PMID:23773910)
• Genetic variants in SULT2A1 do not predispose to polycystic ovary syndrome. Although a variant in SULT2A1 decreased the DHEAS to DHEA ratio, no changes in other androgenic hormone levels were observed. (PMID:23861462)
• results established human SULT2A1 as a novel LXRalpha target gene; the expression of LXRalpha is a potential predictor for the expression of SULT2A1 in human liver (PMID:25028566)
• The complete kinetic mechanism of human SULT2A1. (PMID:25056952)
• It turns out the protective effect of DHEA was significantly decreased when Wnt/beta-catenin signaling was activated, while inactivating Wnt/beta-catenin signaling enhanced the effects of DHEA (PMID:25065588)
• molecular dynamic simulations were used to investigate the effect of ligands (cofactor and substrate) on the thermo-denaturation process of hSULT2A1 (PMID:25750022)
• Our results show that SULT2A1 is important in the first trimester; particularly in the adrenals (PMID:25802089)
• The substrate, such as lithocholic acid (LCA), participated in regulating the structure and flexibility of sulfotransferase actively rather than merely being selected passively. (PMID:26149755)
• It metabolizes breast cancer drugs like afinoxifene and endoxifen by sulfation. (PMID:26169578)
• PSC is characterized by disease-specific impairment of SULT2A1 expression following PXR activation, a phenomenon which is not noted in PBC, and may account for the impaired hepatoprotection in PSC. (PMID:26504856)
• Decreased SULT2A1 activity was found in the adrenal zona reticularis in Alzheimer’s disease patients. (PMID:26680489)
• A theoretical study at the level of density functional theory (DFT) was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond interactions, in the active site of enzyme human androsterone sulphotransferase. (PMID:27337388)
• Polymorphisms of SULT2A1 gene is not associated with attention-deficit/hyperactivity disorder. (PMID:28367959)
• Mass spectrometry analysis and structural modeling supported a reaction mechanism which involves the isomerization of Delta(4)-3-ketosteroids from the keto form to an enol form, prior to being subjected to sulfation. Results derived from this study suggested a potential role of SULT2A1 as a Delta(4)-3-ketosteroid sulfotransferase in steroid metabolism (PMID:28782626)
• nine human SULT2A1 allozymes plus the wild-type SULT2A1 were found to display differential sulfating activity toward DHEA and tibolone. Kinetic analysis revealed that different SULT2A1 allozymes exhibited differential substrate affinity and catalytic efficiency toward the two substrates tested. (PMID:29392568)

Cross-species orthologs

25 orthologs

Organism	Symbol	Gene ID
danio_rerio	sult1st4	ENSDARG00000003181
danio_rerio	sult1st3	ENSDARG00000018361
danio_rerio	sult1st1	ENSDARG00000028275
danio_rerio	sult2st3	ENSDARG00000028367
danio_rerio	sult2st1	ENSDARG00000033170
danio_rerio	sult1st2	ENSDARG00000041540
danio_rerio	sult1st7	ENSDARG00000079079
danio_rerio	sult1st9	ENSDARG00000094996
danio_rerio	sult2st2	ENSDARG00000103785
mus_musculus	Sult2a8	ENSMUSG00000030378
mus_musculus	Sult2a6	ENSMUSG00000070810
mus_musculus	Sult2a2	ENSMUSG00000070811
mus_musculus	Sult2a3	ENSMUSG00000074375
mus_musculus	Sult2a4	ENSMUSG00000074377
mus_musculus	Sult2a1	ENSMUSG00000078798
mus_musculus	Sult2a5	ENSMUSG00000078799
mus_musculus	Sult2a7	ENSMUSG00000094156
rattus_norvegicus	Sult2a2	ENSRNOG00000047986
rattus_norvegicus	Sult2a2	ENSRNOG00000062869
rattus_norvegicus	LOC134485278	ENSRNOG00000063815
rattus_norvegicus		ENSRNOG00000078002
rattus_norvegicus		ENSRNOG00000082374
drosophila_melanogaster	St4	FBGN0033887
drosophila_melanogaster	St1	FBGN0034887
drosophila_melanogaster	St3	FBGN0265052

Paralogs (12): SULT2B1 (ENSG00000088002), SULT1E1 (ENSG00000109193), SULT4A1 (ENSG00000130540), SULT6B1 (ENSG00000138068), SULT1B1 (ENSG00000173597), SULT1C3 (ENSG00000196228), SULT1A1 (ENSG00000196502), SULT1A2 (ENSG00000197165), SULT1C4 (ENSG00000198075), SULT1C2 (ENSG00000198203), SULT1A4 (ENSG00000213648), SULT1A3 (ENSG00000261052)

Protein

Protein identifiers

Sulfotransferase 2A1 — Q06520 (reviewed: Q06520)

Alternative names: Bile salt sulfotransferase, Dehydroepiandrosterone sulfotransferase, Hydroxysteroid Sulfotransferase, ST2, SULT2A3

All UniProt accessions (2): Q06520, A8K015

UniProt curated annotations — full annotation on UniProt →

Function. Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands. Mediates the sulfation of a wide range of steroids and sterols, including pregnenolone, androsterone, DHEA, bile acids, cholesterol and as well many xenobiotics that contain alcohol and phenol functional groups. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Plays an important role in maintening steroid and lipid homeostasis. Plays a key role in bile acid metabolism, mediating formation of 3-sulfated bile acids. In addition, catalyzes the metabolic activation of potent carcinogenic polycyclic arylmethanols.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Liver, adrenal and at lower level in the kidney. Is present in human fetus in higher level in the adrenal than the liver and the kidney.

Post-translational modifications. The N-terminus is blocked.

Activity regulation. Subject to substrate inhibition. Alternate orientations for binding of steroid substrates to SULT2A1 may play a role in substrate inhibition.

Similarity. Belongs to the sulfotransferase 1 family.

RefSeq proteins (1): NP_003158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000863	Sulfotransferase_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00685

Catalyzed reactions (Rhea), 12 shown:

• glycolithocholate + 3’-phosphoadenylyl sulfate = glycolithocholate 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:10908)
• taurolithocholate + 3’-phosphoadenylyl sulfate = taurolithocholate 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:14013)
• an alcohol + 3’-phosphoadenylyl sulfate = an alkyl sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:22552)
• lithocholate + 3’-phosphoadenylyl sulfate = lithocholate 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:51064)
• 3beta-hydroxyandrost-5-en-17-one + 3’-phosphoadenylyl sulfate = dehydroepiandrosterone 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:51216)
• (24S)-hydroxycholesterol + 3’-phosphoadenylyl sulfate = (24S)-hydroxycholesterol 24-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52344)
• (24S)-hydroxycholesterol + 3’-phosphoadenylyl sulfate = (24S)-hydroxycholesterol 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52348)
• (24S)-hydroxycholesterol 24-sulfate + 3’-phosphoadenylyl sulfate = (24S)-hydroxycholesterol 3,24-disulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52352)
• pregnenolone + 3’-phosphoadenylyl sulfate = pregnenolone sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52356)
• androsterone + 3’-phosphoadenylyl sulfate = androsterone 3alpha-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:60644)
• deoxycholate + 3’-phosphoadenylyl sulfate = deoxycholate 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:77203)
• glycodeoxycholate + 3’-phosphoadenylyl sulfate = glycodeoxycholate 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:77207)

UniProt features (66 total): helix 19, binding site 14, strand 10, sequence variant 9, mutagenesis site 5, sequence conflict 3, turn 3, chain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
1J99	X-RAY DIFFRACTION	1.99
3F3Y	X-RAY DIFFRACTION	2.2
4IFB	X-RAY DIFFRACTION	2.3
1EFH	X-RAY DIFFRACTION	2.4
2QP3	X-RAY DIFFRACTION	2.6
1OV4	X-RAY DIFFRACTION	2.7
2QP4	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06520-F1	95.50	0.89

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 (1): 99 (proton acceptor)

Ligand- & substrate-binding residues (14): 184; 218; 223; 247; 248; 249; 44; 45; 46; 47; 48; 49 …

Post-translational modifications (1): 251

Mutagenesis-validated functional residues (5):

Position	Phenotype
137	strongly reduces substrate inhibition when adt or dhea are used as substrates.
137	substrate inhibition is completely eliminated for dhea; when associated with a-238.
238	completely eliminates the substrate inhibition when adt is used as substrate. partially eliminates substrate inhibition
238	strongly reduces substrate inhibition when adt or dhea are used as substrates.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-156584	Cytosolic sulfonation of small molecules
R-HSA-1989781	PPARA activates gene expression
R-HSA-9753281	Paracetamol ADME
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-9748784	Drug ADME

MSigDB gene sets: 126 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CERVERA_SDHB_TARGETS_1_DN, TAL1ALPHAE47_01, GOBP_SULFATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, TCF4_Q5, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, NF1_Q6_01

GO Biological Process (12): ethanol catabolic process (GO:0006068), xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), bile acid metabolic process (GO:0008206), lipid catabolic process (GO:0016042), bile acid catabolic process (GO:0030573), thyroid hormone metabolic process (GO:0042403), 3’-phosphoadenosine 5’-phosphosulfate metabolic process (GO:0050427), sulfation (GO:0051923), sensory perception of itch (GO:0160025), lipid metabolic process (GO:0006629)

GO Molecular Function (7): alcohol sulfotransferase activity (GO:0004027), sulfotransferase activity (GO:0008146), bile-salt sulfotransferase activity (GO:0047704), steroid sulfotransferase activity (GO:0050294), 3’-phosphoadenosine 5’-phosphosulfate binding (GO:0050656), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Metabolism	2
Phase II - Conjugation of compounds	1
Regulation of lipid metabolism by PPARalpha	1
Drug ADME	1
Biological oxidations	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sulfotransferase activity	3
lipid metabolic process	2
sulfur compound metabolic process	2
cellular anatomical structure	2
ethanol metabolic process	1
primary alcohol catabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
sterol metabolic process	1
secondary alcohol metabolic process	1
steroid metabolic process	1
monocarboxylic acid metabolic process	1
catabolic process	1
bile acid metabolic process	1
monocarboxylic acid catabolic process	1
modified amino acid metabolic process	1
phenol-containing compound metabolic process	1
hormone metabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside bisphosphate metabolic process	1
oxoacid metabolic process	1
sensory perception	1
primary metabolic process	1
transferase activity, transferring sulphur-containing groups	1
adenyl ribonucleotide binding	1
anion binding	1
sulfur compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SULT2A1	HRC	P23327	817
SULT2A1	CYP11A1	P05108	809
SULT2A1	UGT1A8	Q9HAW9	776
SULT2A1	CYP17A1	P05093	770
SULT2A1	PAPSS2	O95340	765
SULT2A1	SRD5A1	P18405	749
SULT2A1	HSD3B2	P26439	736
SULT2A1	UGT2B4	P06133	734
SULT2A1	HSD3B1	P14060	717
SULT2A1	SRD5A2	P31213	703
SULT2A1	UGT1A1	P22309	673
SULT2A1	UGT1A4	P22310	673
SULT2A1	NR1I2	O75469	672
SULT2A1	UGT1A6	P19224	666
SULT2A1	UGT1A10	Q9HAW8	656

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SULT1B1	SULT2A1	psi-mi:“MI:0915”(physical association)	0.720
SULT2A1	NIF3L1	psi-mi:“MI:0915”(physical association)	0.560
SULT2A1	STAT3	psi-mi:“MI:0915”(physical association)	0.510
STAT3	SULT2A1	psi-mi:“MI:0915”(physical association)	0.510
TMX1	SULT2A1	psi-mi:“MI:0915”(physical association)	0.370
STK3	SULT2A1	psi-mi:“MI:0915”(physical association)	0.370
SULT2A1	PRDX4	psi-mi:“MI:0915”(physical association)	0.370
SULT2A1	SULT1B1	psi-mi:“MI:0915”(physical association)	0.000
SULT2A1	NIF3L1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): SULT1B1 (Two-hybrid), SULT1B1 (Two-hybrid), NIF3L1 (Two-hybrid), SULT2A1 (Affinity Capture-MS), SULT2A1 (Affinity Capture-MS), SULT2A1 (Negative Genetic), SULT2A1 (Negative Genetic), SULT2A1 (Cross-Linking-MS (XL-MS)), SULT2A1 (Affinity Capture-MS), SULT2A1 (Affinity Capture-Western), TMX1 (Two-hybrid), SULT2A1 (Two-hybrid), SULT2A1 (Two-hybrid), SULT2A1 (Two-hybrid)

ESM2 similar proteins: A0A173GP47, A0A1L8HV70, A0A2K5X3B6, B2RVI8, F1QYJ6, G3V9R3, O00338, O43704, O46503, O75897, P0CC03, P15709, P17988, P19217, P22789, P27707, P46560, P48769, P49887, P49888, P49891, P50234, P50235, P50236, P50237, P52840, P52841, P52843, P52844, P52847, Q06520, Q3T0Y3, Q3UZZ6, Q5ZJM7, Q6IMI4, Q6IMI6, Q6PH37, Q6WG17, Q6WG18, Q7T2V2

Diamond homologs: A0A173GP47, A0A2K5X3B6, B2RVI8, F1QYJ6, G3V9R3, O00204, O00338, O35400, O35403, O43704, O46503, O46640, O75897, P0CC03, P0DMM9, P0DMN0, P15709, P17988, P19217, P22789, P49887, P49888, P49891, P50225, P50226, P50227, P50234, P50235, P50236, P50237, P52835, P52836, P52837, P52838, P52840, P52841, P52842, P52843, P52844, P52846

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

726 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47871563:TACAC:T	acceptor_gain	1.0000
19:47871564:ACAC:A	acceptor_gain	1.0000
19:47871565:CAC:C	acceptor_gain	1.0000
19:47871565:CACC:C	acceptor_gain	1.0000
19:47871567:CCTGG:C	acceptor_loss	1.0000
19:47871568:C:CC	acceptor_gain	1.0000
19:47871568:CTGG:C	acceptor_loss	1.0000
19:47871569:T:C	acceptor_loss	1.0000
19:47871575:C:CT	acceptor_gain	1.0000
19:47871576:A:T	acceptor_gain	1.0000
19:47874651:TTTTA:T	donor_loss	1.0000
19:47874652:TTTAC:T	donor_loss	1.0000
19:47874653:TTACC:T	donor_loss	1.0000
19:47874654:TA:T	donor_loss	1.0000
19:47874655:A:T	donor_loss	1.0000
19:47874833:TC:T	acceptor_gain	1.0000
19:47874834:CC:C	acceptor_gain	1.0000
19:47874835:C:CA	acceptor_loss	1.0000
19:47874835:C:CC	acceptor_gain	1.0000
19:47879131:C:CC	acceptor_gain	1.0000
19:47883650:T:A	donor_gain	1.0000
19:47886271:T:TA	donor_gain	1.0000
19:47871566:AC:A	acceptor_gain	0.9900
19:47871567:CC:C	acceptor_gain	0.9900
19:47874830:GTGTC:G	acceptor_gain	0.9900
19:47874831:TGTC:T	acceptor_gain	0.9900
19:47874835:C:T	acceptor_gain	0.9900
19:47879126:TAGCA:T	acceptor_gain	0.9900
19:47879129:CA:C	acceptor_gain	0.9900
19:47882208:CACCT:C	acceptor_gain	0.9900

AlphaMissense

1905 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47886127:T:A	K44I	0.990
19:47886126:T:A	K44N	0.985
19:47886126:T:G	K44N	0.985
19:47874799:G:C	F201L	0.979
19:47874799:G:T	F201L	0.979
19:47874801:A:G	F201L	0.979
19:47879116:A:G	W163R	0.979
19:47879116:A:T	W163R	0.979
19:47879095:A:G	W170R	0.978
19:47879095:A:T	W170R	0.978
19:47883785:C:A	G46V	0.978
19:47882193:T:A	R121S	0.975
19:47882193:T:G	R121S	0.975
19:47883785:C:T	G46E	0.972
19:47882194:C:G	R121T	0.970
19:47886152:C:G	D36H	0.970
19:47874661:T:A	R247S	0.969
19:47874661:T:G	R247S	0.969
19:47883627:G:C	H99D	0.968
19:47883701:C:G	R74P	0.968
19:47874748:G:C	S218R	0.967
19:47874748:G:T	S218R	0.967
19:47874750:T:G	S218R	0.967
19:47871553:A:G	W254R	0.966
19:47871553:A:T	W254R	0.966
19:47886136:G:A	T41I	0.966
19:47886125:A:G	S45P	0.963
19:47882097:A:C	F153L	0.961
19:47882097:A:T	F153L	0.961
19:47882099:A:G	F153L	0.961

dbSNP variants (sampled 300 via entrez): RS1000045453 (19:47883203 G>A,C), RS1000404199 (19:47878037 C>T), RS1000780722 (19:47872657 AAC>A), RS1000823724 (19:47876546 G>C,T), RS1001131665 (19:47887902 T>C), RS1001178769 (19:47881363 G>A), RS1001240271 (19:47882787 C>G,T), RS1001463914 (19:47886782 T>C), RS1001671424 (19:47871445 G>A,C), RS1001711913 (19:47881092 G>A), RS1002008202 (19:47870112 G>C,T), RS1002221302 (19:47874900 G>A), RS1002395070 (19:47881701 A>G), RS1002444296 (19:47875507 G>A), RS1002505929 (19:47874074 A>G)

Disease associations

OMIM: gene MIM:125263 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001038_5	Dehydroepiandrosterone sulphate levels	3.000000e-19
GCST002925_13	Sex hormone levels	2.000000e-06
GCST003725_6	Gallstone disease	1.000000e-07
GCST006249_69	Serum metabolite levels	2.000000e-26
GCST006249_73	Serum metabolite levels	2.000000e-43
GCST006585_963	Blood protein levels	2.000000e-27
GCST007209_23	Gallstone disease	2.000000e-31
GCST007509_3	Cleft palate	8.000000e-08
GCST009364_29	Triglyceride levels x long total sleep time interaction (2df test)	3.000000e-10
GCST009733_238	Urinary metabolite levels in chronic kidney disease	2.000000e-11
GCST009733_98	Urinary metabolite levels in chronic kidney disease	5.000000e-26
GCST010241_313	Apolipoprotein A1 levels	2.000000e-08
GCST010244_369	Triglyceride levels	5.000000e-11
GCST012020_539	Serum metabolite levels	4.000000e-11
GCST012020_540	Serum metabolite levels	6.000000e-20
GCST012020_541	Serum metabolite levels	3.000000e-25
GCST012020_542	Serum metabolite levels	2.000000e-34
GCST012020_543	Serum metabolite levels	6.000000e-35
GCST90013406_144	Liver enzyme levels (alkaline phosphatase)	3.000000e-20
GCST90020091_12	Estradiol levels	2.000000e-10
GCST90093092_6	DHEAS levels	6.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0007001	dehydroepiandrosterone sulphate measurement
EFO:0004530	triglyceride measurement
EFO:0005116	urinary metabolite measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004697	estradiol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2077 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	IC50	50	nM	CHEMBL1552719
6.00	IC50	1010	nM	CHEMBL2325503

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 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
5-[[4-(4-methoxyphenyl)-5-pyridin-4-yl-1,2,4-triazol-3-yl]sulfanylmethyl]-3-(4-methylphenyl)-1,2,4-oxadiazole	1924281: Inhibition of ST (unknown origin)	ic50	0.0500	uM
4-[5-[(E)-2-[4-(2-chlorophenyl)-5-(5-methylsulfonyl-2-pyridinyl)-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl]benzonitrile	1924281: Inhibition of ST (unknown origin)	ic50	1.0100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Dehydroepiandrosterone	increases sulfation, affects metabolic processing, affects reaction, affects binding, increases metabolic processing (+2 more)	10
Cyclosporine	increases abundance, affects cotreatment, decreases expression, decreases activity	7
Chenodeoxycholic Acid	affects cotreatment, decreases expression, increases sulfation	5
bisphenol A	increases response to substance, affects expression, decreases expression, increases methylation, increases metabolic processing	4
Acetaminophen	affects cotreatment, decreases expression, increases expression, decreases reaction	4
Lithocholic Acid	decreases activity, increases abundance, increases sulfation	4
Tetrachlorodibenzodioxin	increases reaction, affects expression, affects cotreatment, decreases expression, increases expression	4
Aflatoxin B1	affects expression, affects cotreatment, increases expression, decreases expression	4
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
Deoxycholic Acid	affects cotreatment, decreases expression	3
Glycochenodeoxycholic Acid	decreases expression, affects cotreatment	3
Glycocholic Acid	affects cotreatment, decreases expression	3
Glycodeoxycholic Acid	affects cotreatment, decreases expression	3
Methotrexate	decreases expression, decreases reaction, increases activity, increases expression	3
Triclosan	affects cotreatment, decreases expression	3
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
2,5-dichlorobiphenyl	affects metabolic processing, decreases reaction, increases sulfation	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
perfluoro-n-nonanoic acid	decreases expression, increases expression	2
Celecoxib	affects reaction, affects sulfation, affects activity, affects cotreatment	2
Bile Acids and Salts	increases sulfation	2
Ethinyl Estradiol	affects cotreatment, affects reaction, affects sulfation, affects metabolic processing, increases metabolic processing	2
Colforsin	decreases expression, increases reaction	2
Hydrogen Peroxide	increases expression, affects expression	2
Oxygen	affects expression, decreases reaction, increases expression, increases reaction, affects cotreatment (+1 more)	2
Polychlorinated Biphenyls	increases sulfation, affects metabolic processing, decreases reaction	2
Quercetin	affects cotreatment, decreases expression	2
Tartrazine	affects cotreatment, decreases expression	2
fluorotelomer sulfonic acids	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 5 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743310	ADMET	Major substrate of human cytosolic sulfotransferase SULT2A1	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition
CHEMBL4482701	Binding	Substrate activity at SULT2A1 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as substrate Km incubated for 15 mins using [35S-]PAPS as sulfate donor by TLC analysis	In vivo imaging of sulfotransferases

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2GV	V79-hSULT2A1	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

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