SULT1A1

Summary

SULT1A1 (sulfotransferase family 1A member 1, HGNC:11453) is a protein-coding gene on chromosome 16p11.2, encoding Sulfotransferase 1A1 (P50225). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a wide variety of acceptor molecules bearing a hydroxyl or an amine group.

Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene encodes one of two phenol sulfotransferases with thermostable enzyme activity. Multiple alternatively spliced variants that encode two isoforms have been identified for this gene.

Source: NCBI Gene 6817 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 81 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11453
Approved symbol	SULT1A1
Name	sulfotransferase family 1A member 1
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	P-PST
Ensembl gene	ENSG00000196502
Ensembl biotype	protein_coding
OMIM	171150
Entrez	6817

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 28 protein_coding

ENST00000314752, ENST00000566189, ENST00000567512, ENST00000569554, ENST00000898553, ENST00000898554, ENST00000898555, ENST00000898556, ENST00000898557, ENST00000898558, ENST00000898559, ENST00000898560, ENST00000898561, ENST00000898562, ENST00000898563, ENST00000898564, ENST00000898565, ENST00000898566, ENST00000898567, ENST00000898568, ENST00000898569, ENST00000898570, ENST00000898571, ENST00000898572, ENST00000915946, ENST00000957339, ENST00000957340, ENST00000957341

RefSeq mRNA: 9 — MANE Select: NM_001055 NM_001055, NM_001394421, NM_001394422, NM_001394423, NM_001394424, NM_001394425, NM_177529, NM_177530, NM_177534

CCDS: CCDS32420

Canonical transcript exons

ENST00000314752 — 8 exons

Exon	Start	End
ENSE00002614752	28609931	28610044
ENSE00003513609	28608478	28608603
ENSE00003520723	28606951	28607077
ENSE00003559732	28608708	28608859
ENSE00003602768	28606056	28606236
ENSE00003605182	28606761	28606855
ENSE00003660816	28605258	28605933
ENSE00003661443	28608291	28608388

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1417 / max 164.5924, expressed in 1342 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156902	4.9710	914
156903	4.2080	1025
156908	0.5045	228
156910	0.4753	239
156905	0.3479	182
156904	0.2731	144
156909	0.2008	109
156901	0.1610	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.65	gold quality
right lobe of liver	UBERON:0001114	97.80	gold quality
right adrenal gland cortex	UBERON:0035827	97.80	gold quality
right adrenal gland	UBERON:0001233	97.06	gold quality
left adrenal gland	UBERON:0001234	96.20	gold quality
monocyte	CL:0000576	95.92	gold quality
leukocyte	CL:0000738	95.92	gold quality
left adrenal gland cortex	UBERON:0035825	95.85	gold quality
adrenal cortex	UBERON:0001235	94.52	gold quality
granulocyte	CL:0000094	94.35	gold quality
adrenal gland	UBERON:0002369	93.30	gold quality
rectum	UBERON:0001052	93.04	gold quality
right lobe of thyroid gland	UBERON:0001119	92.61	gold quality
right lung	UBERON:0002167	92.52	gold quality
spleen	UBERON:0002106	92.08	gold quality
left lobe of thyroid gland	UBERON:0001120	91.71	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.50	gold quality
upper lobe of left lung	UBERON:0008952	91.47	gold quality
transverse colon	UBERON:0001157	91.46	gold quality
cerebellar hemisphere	UBERON:0002245	91.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.04	gold quality
cerebellar cortex	UBERON:0002129	91.01	gold quality
thyroid gland	UBERON:0002046	90.58	gold quality
adenohypophysis	UBERON:0002196	90.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.45	gold quality
right frontal lobe	UBERON:0002810	89.92	gold quality
cerebellum	UBERON:0002037	89.75	gold quality
putamen	UBERON:0001874	89.59	gold quality
prefrontal cortex	UBERON:0000451	89.47	gold quality
upper lobe of lung	UBERON:0008948	89.41	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	72.51
E-ANND-3	yes	18.68
E-GEOD-124858	no	18.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, DRD1, ELK3, GABPA, MAPK1, MAPK3, NR3C1, SP1, TCF3, ZNF2

miRNA regulators (miRDB)

4 targeting SULT1A1, 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-4437	99.52	65.29	1266
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-1285-5P	98.01	68.71	779

Literature-anchored findings (GeneRIF, showing 40)

• The high activity SULT1A1*1 allozyme protects against dietary and/or environmental chemicals involved in the pathogenesis of colorectal cancer. (PMID:11692076)
• genetic polymorphism in SULT1A1 gene may be associated with increased lung cancer risk (PMID:11804685)
• 7-OH-flavone sulfotransferase followed Michaelis-Menten kinetics (PMID:12162852)
• The SULT1A1 R213H polymorphism is not linked with colorectal cancer in an elderly Australian population. (PMID:12165038)
• There is an an association between genotype and survival of breast cancer patients receiving tamoxifen therapy (PMID:12419790)
• SULT1A1 his(213) allele is important in the development of esophageal cancer in men. (PMID:12455060)
• the relationship among the polymorphisms of this enzyme and SULT1A2 in different types of cancers in Taiwanese (PMID:12469224)
• the crystal structure of SULT1A1 provides the molecular basis for substrate inhibition and how the enzyme sulfonates a wide variety of lipophilic compounds (PMID:12471039)
• the differential substrate specificity of the two enzymes M-PST and P-PST for the thirteen drug compounds tested (PMID:12761191)
• study of arginine residues in the active site of human phenol sulfotransferase (PMID:12867416)
• P. 1038 “…clearly expressed…SULT1A1…” P. 1040 “…SULT1A1…which belongs to phase II metabolism,…significantly expressed in HepG2.” (PMID:12867492)
• We conclude that smoking increases risk of colorectal adenomas and that SULT1A1 and NAT2 only modestly modify this association. (PMID:14618622)
• Sulfotransferase 1A1 polymorphism is associated with bladder cancer (PMID:14643027)
• SULT1A1 slow acetylator genotype might modulate the effect of carcinogenic arylamines contained in tobacco smoke, and has a tendency to present a higher risk for highly differentiated tumors among heavy-smokers. (PMID:14648207)
• SULT1A1 polymorphism is associated with susceptibility to lung cancer in relation to tobacco smoking (PMID:14688021)
• In SULT1A1, substrate inhibition occurs with pNP as the substrate but not with dopamine; residue Phe-247 of SULT1A1, which interacts with both p-nitrophenol molecules in the active site, is important for substrate inhibition (PMID:14871892)
• SULT1A1 His allele was positively associated with the risk of breast cancer in Chinese women (PMID:15093672)
• SULT1A1 promoter was shown to be dependent on the presence of Sp1 and Ets transcription factor binding sites. (PMID:15383623)
• No significant association found for breast cancer risk. (PMID:15894657)
• SULT1A1*2 and SULT1A2*2 are the major allelic variants in the Korean population. (PMID:16133548)
• Postmenopausal women carrying the variant SULT1A1 His allele may be more susceptible to estrogen-induced carcinogenesis in mammary tissue. (PMID:16175316)
• x-ray crystallographic structure of human SULT1A1 with estradiol (PMID:16221673)
• SULT1A1 genotype did not correlate with any prognostic or predictive markers associated with breast cancer. (PMID:16317586)
• Progressive SULT1A1 methylation within the promoter area of the gene occurs during breast carcinogenesis. (PMID:16328031)
• Sulfation of resveratrol in human liver: evidence of a major role for the sulfotransferases SULT1A1. (PMID:16418064)
• The SULT1A1*2 allele and long-term use of estrogen replacement therapy were associated with statistically significantly higher risk of endometrial cancer (PMID:16985250)
• Results indicate that the SULT1A1 genotype may play an important role in the risk of developing lung cancer, especially in cigarette smokers. (PMID:17074589)
• The presence of SULT1A1 gene deletions and duplications, representing an additional source of variability in the metabolic activity of this enzyme, is demonstrated. (PMID:17189289)
• Apigenin, epicatechin, and resveratrol exhibited SULT1a1 allele-specific variation in sulfation, with SULT1A1*1 and *3 acting as normal-activity allozymes and SULT1A*2 as low-activity allozyme. (PMID:17293380)
• SULT1A1 polymorphism is associated with primary brain tumors (PMID:17605044)
• SULT1A1 polymorphism is associated with urothelial cancer (PMID:17619904)
• Increased generation of urinary 8-hydroxy-2’-deoxyguanosine was found in betel-quid chewers with SULT1A1 and GSTP1 genotypes that affect susceptibility to DNA damage. (PMID:17912498)
• SULT1A1/SULT1A2 gene complex showed suggestive haplotypic association in the family-based cardiovascular disease study, with the greatest increase in risk conferred by the SULT1A2 235T allele (PMID:18259693)
• a decreased single nucleotide polymorphism of CYP1A1 and an increased single nucleotide polymorphism for SULT1A1 and SULT1E1 genes may be risk factors for endometrial cancer in Caucasians. (PMID:18318428)
• The aim of the study was to investigate NAT1, NAT2, GSTM1, GSTT1, GSTP1, SULT1A1, XRCC1, XRCC3 and XPD genetic polymorphisms, coffee consumption and risk of bladder cancer (BC) through a hospital-based case-control study. (PMID:18365755)
• The study showed a null association of SULT1A1 polymorphism with familial prostate cancer risk in the Japanese population. (PMID:18368507)
• SULT1A1 polymorphism is associated with ovarian cancer (PMID:18497059)
• The CYP1A2 and NAT1 but not SULT1A1 and NAT2 genotypes showed significant interactions with heavy smoking in women not men (PMID:18499698)
• SULT1A1 mRNA is expressed in human skin, at similar levels in men and women. SULT1A1 levels are not altered by topical 17-beta-estradiol treatment. (PMID:18794456)
• The SULT1A1*2 revealed contrasting risk association for upper aerodigestive tract cancers and conferred significant increased risk of breast cancer to Asian but not Causcasian women in patients with multiple tobacco-related cancers (PMID:18854828)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	sult1st4	ENSDARG00000003181
danio_rerio	sult5a1	ENSDARG00000007769
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	Sult5a1	ENSMUSG00000000739
rattus_norvegicus	Sult5a1	ENSRNOG00000015695
drosophila_melanogaster	St4	FBGN0033887
drosophila_melanogaster	St1	FBGN0034887
drosophila_melanogaster	St3	FBGN0265052

Paralogs (12): SULT2B1 (ENSG00000088002), SULT2A1 (ENSG00000105398), SULT1E1 (ENSG00000109193), SULT4A1 (ENSG00000130540), SULT6B1 (ENSG00000138068), SULT1B1 (ENSG00000173597), SULT1C3 (ENSG00000196228), SULT1A2 (ENSG00000197165), SULT1C4 (ENSG00000198075), SULT1C2 (ENSG00000198203), SULT1A4 (ENSG00000213648), SULT1A3 (ENSG00000261052)

Protein

Protein identifiers

Sulfotransferase 1A1 — P50225 (reviewed: P50225)

Alternative names: Aryl sulfotransferase 1, HAST1/HAST2, Phenol sulfotransferase 1, Phenol-sulfating phenol sulfotransferase 1, ST1A3, Thermostable phenol sulfotransferase

All UniProt accessions (3): P50225, H3BQX5, H3BRY5

UniProt curated annotations — full annotation on UniProt →

Function. Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a wide variety of acceptor molecules bearing a hydroxyl or an amine group. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Displays broad substrate specificity for small phenolic compounds. Plays an important role in the sulfonation of endogenous molecules such as steroid hormones. Mediates the sulfate conjugation of a variety of xenobiotics, including the drugs acetaminophen and minoxidil. Mediates also the metabolic activation of carcinogenic N-hydroxyarylamines leading to highly reactive intermediates capable of forming DNA adducts, potentially resulting in mutagenesis. May play a role in gut microbiota-host metabolic interaction. O-sulfonates 4-ethylphenol (4-EP), a dietary tyrosine-derived metabolite produced by gut bacteria. The product 4-EPS crosses the blood-brain barrier and may negatively regulate oligodendrocyte maturation and myelination, affecting the functional connectivity of different brain regions associated with the limbic system. Catalyzes the sulfate conjugation of dopamine. Catalyzes the sulfation of T4 (L-thyroxine/3,5,3’,5’-tetraiodothyronine), T3 (3,5,3’-triiodothyronine), rT3 (3,3’,5’-triiodothyronine) and 3,3’-T2 (3,3’-diiodothyronine), with a substrate preference of 3,3’-T2 > rT3 > T3 > T4.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Liver, lung, adrenal, brain, platelets and skin.

Polymorphism. There are several alleles. The sequence shown is that of allele SULT1A1*3.

Similarity. Belongs to the sulfotransferase 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P50225-1	1	yes
P50225-2	2

RefSeq proteins (9): NP_001046, NP_001381350, NP_001381351, NP_001381352, NP_001381353, NP_001381354, NP_803565, NP_803566, NP_803878 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000863	Sulfotransferase_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00685

Enzyme classification (BRENDA):

• EC 2.8.2.1 — aryl sulfotransferase (BRENDA: 19 organisms, 630 substrates, 215 inhibitors, 314 Km, 55 kcat entries)
• EC 2.8.2.2 — alcohol sulfotransferase (BRENDA: 13 organisms, 295 substrates, 100 inhibitors, 159 Km, 25 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
DOPAMINE	0.0006–11.3	39
4-NITROPHENOL	0.0001–30.9	36
DEHYDROEPIANDROSTERONE	0.0006–0.0179	23
3’-PHOSPHOADENYLYLSULFATE	0.0003–0.51	17
ACETAMINOPHEN	0.43–4.5	14
MORPHINE	3.8–10	13
O-DESMETHYL TRAMADOL	0.27–0.8	13
TAPENTADOL	0.09–0.84	13
3’-PHOSPHOADENYLYL SULFATE	0.0008–0.024	12
ANDROSTERONE	0.0002–0.0096	11
DAIDZEIN	0.0005–0.407	8
GENISTEIN	0.0005–0.371	8
6-HYDROXYMELATONIN	0.018–0.065	6
3’-PHOSPHOADENYLYLSULFATE	0.0001–0.1	6
7-HYDROXYCOUMARIN	0.0005–0.003	4

Catalyzed reactions (Rhea), 10 shown:

• a phenol + 3’-phosphoadenylyl sulfate = an aryl sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:12164)
• 17beta-estradiol + 3’-phosphoadenylyl sulfate = 17beta-estradiol 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52372)
• 4-nitrophenol + 3’-phosphoadenylyl sulfate = 4-nitrophenyl sulfate + adenosine 3’,5’-bisphosphate (RHEA:66548)
• 3,3’,5-triiodo-L-thyronine + 3’-phosphoadenylyl sulfate = 3,3’,5-triiodo-L-thyronine sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67876)
• dopamine + 3’-phosphoadenylyl sulfate = dopamine 3-O-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67880)
• dopamine + 3’-phosphoadenylyl sulfate = dopamine 4-O-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67884)
• 3,3’,5’-triiodo-L-thyronine + 3’-phosphoadenylyl sulfate = 3,3’,5’-triiodo-L-thyronine sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67888)
• 3,3’-diiodo-L-thyronine + 3’-phosphoadenylyl sulfate = 3,3’-diiodo-L-thyronine sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:67892)
• 4-ethylphenol + 3’-phosphoadenylyl sulfate = 4-ethylphenyl sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:70607)
• L-thyroxine + 3’-phosphoadenylyl sulfate = L-thyroxine sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:83575)

UniProt features (54 total): helix 15, sequence variant 7, binding site 7, strand 7, turn 7, sequence conflict 5, mutagenesis site 2, chain 1, active site 1, splice variant 1, modified residue 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
1LS6	X-RAY DIFFRACTION	1.9
3U3O	X-RAY DIFFRACTION	2
1Z28	X-RAY DIFFRACTION	2.3
2D06	X-RAY DIFFRACTION	2.3
3U3M	X-RAY DIFFRACTION	2.3
3QVV	X-RAY DIFFRACTION	2.35
3U3K	X-RAY DIFFRACTION	2.36
3U3R	X-RAY DIFFRACTION	2.36
3QVU	X-RAY DIFFRACTION	2.5
4GRA	X-RAY DIFFRACTION	2.56
3U3J	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50225-F1	96.79	0.97

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): 108 (proton acceptor)

Ligand- & substrate-binding residues (7): 48–53; 106–108; 130; 138; 193; 227–232; 255–259

Post-translational modifications (1): 138

Mutagenesis-validated functional residues (2):

Position	Phenotype
70	increased sensitivity of enzyme activity to heat inactivation.
249	increased activity towards p-nitrophenol.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-156584	Cytosolic sulfonation of small molecules
R-HSA-9753281	Paracetamol ADME
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations
R-HSA-9748784	Drug ADME

MSigDB gene sets: 187 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_SULFATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, RODRIGUES_NTN1_TARGETS_DN, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, ONKEN_UVEAL_MELANOMA_UP, GOBP_DOPAMINE_METABOLIC_PROCESS, ENGELMANN_CANCER_PROGENITORS_UP, chr16p11

GO Biological Process (12): ethanol catabolic process (GO:0006068), xenobiotic metabolic process (GO:0006805), estrogen metabolic process (GO:0008210), amine metabolic process (GO:0009308), flavonoid metabolic process (GO:0009812), thyroid hormone metabolic process (GO:0042403), dopamine catabolic process (GO:0042420), 3’-phosphoadenosine 5’-phosphosulfate metabolic process (GO:0050427), sulfation (GO:0051923), catecholamine metabolic process (GO:0006584), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202)

GO Molecular Function (7): aryl sulfotransferase activity (GO:0004062), sulfotransferase activity (GO:0008146), flavonol 3-sulfotransferase activity (GO:0047894), 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-4 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Drug ADME	1
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	3
sulfotransferase activity	3
hormone metabolic process	2
sulfur compound metabolic process	2
cellular anatomical structure	2
ethanol metabolic process	1
primary alcohol catabolic process	1
cellular response to xenobiotic stimulus	1
steroid metabolic process	1
modified amino acid metabolic process	1
phenol-containing compound metabolic process	1
dopamine metabolic process	1
catecholamine catabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside bisphosphate metabolic process	1
oxoacid metabolic process	1
biogenic amine metabolic process	1
catechol-containing compound metabolic process	1
primary metabolic process	1
lipid 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

866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SULT1A1	GOT1	P17174	786
SULT1A1	STS	P08842	747
SULT1A1	CYP1B1	Q16678	747
SULT1A1	SULT1A3	P0DMM9	745
SULT1A1	CYP2C9	P11712	742
SULT1A1	UGT1A6	P19224	739
SULT1A1	UGT1A10	Q9HAW8	735
SULT1A1	UGT1A4	P22310	735
SULT1A1	UGT1A7	Q9HAW7	735
SULT1A1	UGT1A8	Q9HAW9	735
SULT1A1	UGT1A1	P22309	732
SULT1A1	CYP1A2	P05177	694
SULT1A1	CYP1A1	P04798	689
SULT1A1	UGT2B15	P23765	657
SULT1A1	SLC35A2	P78381	641

IntAct

27 interactions, top by confidence:

A	B	Type	Score
SULT1A1	SULT2B1	psi-mi:“MI:0915”(physical association)	0.830
SULT2B1	SULT1A1	psi-mi:“MI:0915”(physical association)	0.830
SULT1A1	SULT2B1	psi-mi:“MI:0914”(association)	0.830
FOXR1	YEATS4	psi-mi:“MI:0914”(association)	0.640
STAP1	SULT1A1	psi-mi:“MI:0914”(association)	0.530
SULT1C2	SULT1C4	psi-mi:“MI:0914”(association)	0.530
STK4	EIF3CL	psi-mi:“MI:0914”(association)	0.350
SULT4A1		psi-mi:“MI:0914”(association)	0.350
SULT1A1		psi-mi:“MI:0914”(association)	0.350
SULT1C2		psi-mi:“MI:0914”(association)	0.350
SULT4A1	SULT1A3	psi-mi:“MI:0914”(association)	0.350
SULT1A1	SULT1A3	psi-mi:“MI:0914”(association)	0.350
SULT1C3	SULT1A3	psi-mi:“MI:0914”(association)	0.350
SULT1A2	SULT2B1	psi-mi:“MI:0914”(association)	0.350
SULT4A1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
sopD2	RPS10-NUDT3	psi-mi:“MI:2364”(proximity)	0.270
SULT1A1		psi-mi:“MI:0915”(physical association)	0.000
dapF	SULT1A1	psi-mi:“MI:0915”(physical association)	0.000
SULT1A1	ppc	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (97): SULT2B1 (Two-hybrid), SULT1A1 (Affinity Capture-MS), SULT1A1 (Affinity Capture-MS), SULT1A1 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS), SULT1A2 (Affinity Capture-MS), SULT1A1 (Affinity Capture-MS), SULT1A1 (Co-fractionation), SULT1A1 (Two-hybrid), SULT1A2 (Affinity Capture-MS), SULT1A3 (Affinity Capture-MS), SULT1A1 (Affinity Capture-MS), SULT1A1 (Affinity Capture-MS), SULT1A1 (Affinity Capture-MS), SULT1A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2K5X3B6, B2RVI8, F1QYJ6, G3V9R3, O00338, O43704, O46503, O75897, P0CC03, P0DMM9, P0DMN0, P15709, P17988, P19217, P22789, P49887, P49888, P49891, P50225, P50226, P50227, P50234, P50235, P50236, P50237, P52840, P52841, P52842, P52843, P52844, P52846, P52847, Q06520, Q29476, Q3T0Y3, Q3UZZ6, Q6IMI4, Q6IMI6, Q6PH37, Q6WG17

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
sulfation	7	614.4×	1e-17
3’-phosphoadenosine 5’-phosphosulfate metabolic process	6	561.7×	6e-15
xenobiotic metabolic process	5	62.1×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

654 predictions. Top by Δscore:

Variant	Effect	Δscore
16:28605929:CATGC:C	acceptor_gain	1.0000
16:28605930:ATGC:A	acceptor_gain	1.0000
16:28605931:TGC:T	acceptor_gain	1.0000
16:28605932:GC:G	acceptor_gain	1.0000
16:28605933:CC:C	acceptor_gain	1.0000
16:28605934:C:CA	acceptor_loss	1.0000
16:28605934:C:CC	acceptor_gain	1.0000
16:28606052:CCAC:C	donor_loss	1.0000
16:28606052:CCACC:C	donor_gain	1.0000
16:28606053:CACC:C	donor_loss	1.0000
16:28606054:A:AC	donor_gain	1.0000
16:28606055:C:CC	donor_gain	1.0000
16:28606055:C:CG	donor_loss	1.0000
16:28606055:CCT:C	donor_gain	1.0000
16:28606055:CCTTT:C	donor_gain	1.0000
16:28606059:T:A	donor_gain	1.0000
16:28606275:C:CC	acceptor_gain	1.0000
16:28606756:CTCA:C	donor_loss	1.0000
16:28606757:TCA:T	donor_loss	1.0000
16:28606758:CA:C	donor_loss	1.0000
16:28606759:ACCT:A	donor_gain	1.0000
16:28606760:CCTC:C	donor_gain	1.0000
16:28606762:T:TA	donor_gain	1.0000
16:28606856:C:CC	acceptor_gain	1.0000
16:28606949:ACCTT:A	donor_loss	1.0000
16:28606950:C:T	donor_loss	1.0000
16:28606969:T:TA	donor_gain	1.0000
16:28607074:CCAC:C	acceptor_gain	1.0000
16:28607075:CAC:C	acceptor_gain	1.0000
16:28607075:CACC:C	acceptor_gain	1.0000

AlphaMissense

1955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:28608712:C:A	K48N	0.996
16:28608712:C:G	K48N	0.996
16:28606066:G:C	F255L	0.992
16:28606066:G:T	F255L	0.992
16:28606068:A:G	F255L	0.992
16:28607024:G:C	F142L	0.992
16:28607024:G:T	F142L	0.992
16:28607026:A:G	F142L	0.992
16:28607051:C:A	K133N	0.991
16:28607051:C:G	K133N	0.991
16:28608603:C:A	G50V	0.991
16:28608587:G:C	S55R	0.988
16:28608587:G:T	S55R	0.988
16:28608589:T:G	S55R	0.988
16:28606060:C:A	R257S	0.986
16:28606060:C:G	R257S	0.986
16:28606976:G:C	F158L	0.986
16:28606976:G:T	F158L	0.986
16:28606978:A:G	F158L	0.986
16:28608603:C:T	G50D	0.986
16:28606841:A:G	W172R	0.985
16:28606841:A:T	W172R	0.985
16:28606964:G:C	F162L	0.985
16:28606964:G:T	F162L	0.985
16:28606966:A:G	F162L	0.985
16:28607050:C:G	D134H	0.985
16:28608341:G:C	H108D	0.985
16:28608509:G:C	F81L	0.985
16:28608509:G:T	F81L	0.985
16:28608511:A:G	F81L	0.985

dbSNP variants (sampled 300 via entrez): RS1000110349 (16:28624920 G>T), RS1000133438 (16:28610571 G>A), RS1000323806 (16:28624627 G>C), RS1000818955 (16:28618052 T>TA), RS1000935596 (16:28623526 A>C,G), RS1001094593 (16:28623362 G>A), RS1001468882 (16:28618748 C>T), RS1001541598 (16:28608107 G>A,T), RS1001637076 (16:28609750 T>C), RS1002283864 (16:28622946 C>A), RS1002643257 (16:28607441 G>A), RS1003049169 (16:28615761 C>T), RS1003251185 (16:28621829 C>T), RS1003470869 (16:28616163 C>A), RS1003650048 (16:28605661 C>T)

Disease associations

OMIM: gene MIM:171150 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000531_2	Inflammatory bowel disease (early onset)	2.000000e-09
GCST001725_52	Inflammatory bowel disease	1.000000e-21
GCST002598_62	Educational attainment	1.000000e-06
GCST004131_83	Inflammatory bowel disease	2.000000e-12
GCST004132_69	Crohn’s disease	3.000000e-10
GCST005316_203	Intelligence (MTAG)	1.000000e-08
GCST005316_469	Intelligence (MTAG)	3.000000e-11
GCST005316_511	Intelligence (MTAG)	1.000000e-10
GCST005529_3	Ankylosing spondylitis	3.000000e-09
GCST005529_60	Ankylosing spondylitis	1.000000e-07
GCST006269_1040	General cognitive ability	2.000000e-08
GCST006269_1094	General cognitive ability	6.000000e-11
GCST006269_600	General cognitive ability	1.000000e-13
GCST006409_24	Allergic rhinitis	5.000000e-10
GCST007044_23	Extremely high intelligence	2.000000e-08
GCST007241_10	Obesity (extreme)	3.000000e-08
GCST007293_116	Body fat distribution (arm fat ratio)	2.000000e-08
GCST007293_16	Body fat distribution (arm fat ratio)	4.000000e-09
GCST007293_43	Body fat distribution (arm fat ratio)	2.000000e-12
GCST007294_71	Body fat distribution (trunk fat ratio)	2.000000e-12
GCST007294_97	Body fat distribution (trunk fat ratio)	1.000000e-11
GCST007295_20	Body fat distribution (leg fat ratio)	3.000000e-06
GCST007295_44	Body fat distribution (leg fat ratio)	1.000000e-21
GCST007295_79	Body fat distribution (leg fat ratio)	2.000000e-24
GCST007323_5	Risk-taking tendency (4-domain principal component model)	4.000000e-09
GCST007732_16	Allergic disease (asthma, hay fever or eczema)	2.000000e-06
GCST007732_5	Allergic disease (asthma, hay fever or eczema)	5.000000e-06
GCST010133_15	Lamb consumption	3.000000e-08
GCST010703_152	Brain morphology (MOSTest)	3.000000e-09
GCST90020028_1492	Hip circumference adjusted for BMI	2.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0004337	intelligence
EFO:0007041	obese body mass index status
EFO:0004341	body fat distribution
EFO:0008579	risk-taking behaviour
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1743291 (SINGLE PROTEIN), CHEMBL3542433 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 163,901 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL135	ESTRADIOL	4	123,080
CHEMBL691	ETHINYL ESTRADIOL	4	40,543
CHEMBL93124	PITTSBURGH COMPOUND B UNLABELLED	2	278

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

PharmGKB clinical annotations

28 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1042008	Metabolism/PK	3	acetaminophen
rs1042008	Metabolism/PK	3	tapentadol
rs1042008	Metabolism/PK	3	desmethylnaproxen
rs1042028	Metabolism/PK	3	tapentadol
rs1042028	Metabolism/PK	3	desmethylnaproxen
rs1042028	Metabolism/PK	3	acetaminophen
rs1042028	Toxicity	3	conjugated estrogens	Endometrial Neoplasms
rs1042028	Efficacy	3	acetaminophen	Pain
rs28374453	Metabolism/PK	3	tapentadol
rs28374453	Metabolism/PK	3	desmethylnaproxen
rs28374453	Metabolism/PK	3	acetaminophen
rs544820732	Metabolism/PK	3	acetaminophen
rs544820732	Metabolism/PK	3	desmethylnaproxen
rs544820732	Metabolism/PK	3	tapentadol
rs552524124	Metabolism/PK	3	tapentadol
rs552524124	Metabolism/PK	3	acetaminophen
rs552524124	Metabolism/PK	3	desmethylnaproxen
rs72547527	Metabolism/PK	3	acetaminophen
rs72547527	Metabolism/PK	3	desmethylnaproxen
rs72547527	Metabolism/PK	3	tapentadol
rs758145522	Metabolism/PK	3	desmethylnaproxen
rs758145522	Metabolism/PK	3	tapentadol
rs758145522	Metabolism/PK	3	acetaminophen
rs765399160	Metabolism/PK	3	desmethylnaproxen
rs765399160	Metabolism/PK	3	acetaminophen
rs767487725	Metabolism/PK	3	acetaminophen
rs767487725	Metabolism/PK	3	tapentadol
rs767487725	Metabolism/PK	3	desmethylnaproxen

PharmGKB variants

12 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs750155	NPIPB8, SULT1A1		0.00	0
rs1801030	NPIPB8, SULT1A1, SULT1A2		0.00	0
rs3760091	NPIPB8, SULT1A1		0.00	0
rs28374453	NPIPB8, SULT1A1	3	0.00	3	tapentadol;acetaminophen;desmethylnaproxen
rs544820732	SULT1A1	3	0.00	3	acetaminophen;desmethylnaproxen;tapentadol
rs765399160	SULT1A1	3	0.00	2	acetaminophen;desmethylnaproxen
rs1042008	SULT1A1	3	0.00	3	acetaminophen;desmethylnaproxen;tapentadol
rs767487725	SULT1A1	3	0.00	3	acetaminophen;desmethylnaproxen;tapentadol
rs552524124	SULT1A1	3	0.00	3	desmethylnaproxen;tapentadol;acetaminophen
rs758145522	SULT1A1	3	0.00	3	tapentadol;acetaminophen;desmethylnaproxen
rs72547527	SULT1A1	3	0.00	3	desmethylnaproxen;tapentadol;acetaminophen
rs1042028	SULT1A1	3	1.75	5	tapentadol;conjugated estrogens;desmethylnaproxen;acetaminophen

ChEMBL bioactivities

12 potent at pChembl≥5 of 12 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.37	Kd	4.3	nM	ETHINYL ESTRADIOL
8.29	Ki	5.1	nM	PITTSBURGH COMPOUND B UNLABELLED
8.05	Ki	8.9	nM	ETHINYL ESTRADIOL
7.83	Ki	14.9	nM	ETHINYL ESTRADIOL
7.72	Ki	19	nM	ETHINYL ESTRADIOL
7.70	IC50	20	nM	ETHINYL ESTRADIOL
7.62	Ki	24	nM	CHEMBL4557856
7.00	Ki	100	nM	CHEMBL4525617
6.85	Ki	140	nM	CHEMBL490084
6.30	Kd	500	nM	ETHINYL ESTRADIOL
5.92	Kd	1200	nM	ESTRADIOL
5.64	Kd	2300	nM	ESTRADIOL

PubChem BioAssay actives

8 with measured affinity, of 20 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
ethinyl estradiol	1222382: Binding affinity to human SULT1A1 expressed in Escherichia coli assessed as change in intrinsic fluorescence in presence of 3’,5’-phosphoadenosine	kd	0.0043	uM
Estradiol	1222382: Binding affinity to human SULT1A1 expressed in Escherichia coli assessed as change in intrinsic fluorescence in presence of 3’,5’-phosphoadenosine	kd	1.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
4-nitrophenol	decreases sulfation, affects binding, affects sulfation, increases metabolic processing, decreases reaction (+1 more)	12
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases activity, decreases response to substance, decreases reaction, increases sulfation, decreases expression (+6 more)	10
bisphenol A	affects expression, decreases expression, increases metabolic processing, increases sulfation, decreases reaction (+1 more)	5
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression, affects cotreatment (+1 more)	5
Estradiol	increases sulfation, decreases expression, affects sulfation, affects cotreatment, decreases reaction (+1 more)	5
Valproic Acid	affects cotreatment, increases expression	5
5-hydroxymethylfurfural	affects activity, affects metabolic processing, affects cotreatment, increases response to substance, increases activity (+1 more)	4
Polychlorinated Biphenyls	affects expression, affects metabolic processing, decreases reaction, increases sulfation	4
Quercetin	affects cotreatment, decreases sulfation, decreases reaction, decreases expression, increases sulfation	4
Aflatoxin B1	affects cotreatment, decreases expression, increases methylation	4
2,6-dichloro-4-nitrophenol	decreases activity, decreases response to substance, decreases reaction, increases sulfation	3
1-methylpyrene	affects cotreatment, decreases reaction, increases mutagenesis, increases response to substance	3
1-hydroxymethylpyrene	affects cotreatment, decreases reaction, increases mutagenesis, increases response to substance, increases activity	3
3-nitrobenzanthrone	affects cotreatment, increases activity, increases reduction, increases mutagenesis, increases response to substance	3
Resveratrol	increases expression, increases sulfation	3
Acetaminophen	affects cotreatment, decreases expression	3
Pentachlorophenol	decreases activity, affects cotreatment, decreases reaction, increases activity, affects binding (+2 more)	3
Phosphoadenosine Phosphosulfate	increases reduction, increases sulfation, affects cotreatment, decreases reaction, increases activity	3
furfuryl alcohol	increases metabolic processing	2
afimoxifene	affects response to substance, increases metabolic processing, increases abundance, increases sulfation, increases response to substance (+3 more)	2
2-amino-3-methyl-9H-pyrido(2,3-b)indole	increases metabolic processing, increases response to substance, increases activity, increases sulfation	2
sodium arsenite	increases expression, increases methylation	2
tetrabromobisphenol A	affects cotreatment, decreases reaction, increases activity, decreases expression	2
1-hydroxypyrene	decreases activity, decreases reaction, increases sulfation, increases reaction, increases metabolic processing	2
mercuric bromide	increases expression, affects cotreatment	2
2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases metabolic processing, increases activity	2
entinostat	affects cotreatment, increases expression	2
2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct	decreases abundance, decreases activity, increases abundance, increases metabolic processing	2
Cisplatin	affects cotreatment, increases expression, affects response to substance	2
Dopamine	increases sulfation, increases metabolic processing, decreases reaction	2

ChEMBL screening assays

19 unique, capped per target: 15 admet, 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743314	ADMET	Major substrate of human cytosolic sulfotransferase SULT1A1	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition
CHEMBL4482682	Binding	Inhibition of SULT1A1 (unknown origin) expressed in baculovirus infected Sf9 cells incubated for 15 mins using para-nitrophenol as substrate by TLC analysis	In vivo imaging of sulfotransferases

Cellosaurus cell lines

4 cell lines: 3 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5A60	V79MZh2E1/hSULT1A1	Spontaneously immortalized cell line	Male
CVCL_A2GW	V79-hSULT1A1	Spontaneously immortalized cell line	Male
CVCL_A2GY	V79MZh1A2/hSULT1A1	Spontaneously immortalized cell line	Male
CVCL_E2L7	HAP1 SULT1A1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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