SULT1C3

Summary

SULT1C3 (sulfotransferase family 1C member 3, HGNC:33543) is a protein-coding gene on chromosome 2q12.3, encoding Sulfotransferase 1C3 (Q6IMI6). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor.

Enables 3’-phosphoadenosine 5’-phosphosulfate binding activity and sulfotransferase activity. Involved in 3’-phosphoadenosine 5’-phosphosulfate metabolic process; cholesterol metabolic process; and xenobiotic metabolic process. Predicted to be active in cytoplasm.

Source: NCBI Gene 442038 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_001320878

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33543
Approved symbol	SULT1C3
Name	sulfotransferase family 1C member 3
Location	2q12.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196228
Ensembl biotype	protein_coding
OMIM	617151
Entrez	442038

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000329106, ENST00000681802, ENST00000899643, ENST00000899644

RefSeq mRNA: 2 — MANE Select: NM_001320878 NM_001008743, NM_001320878

CCDS: CCDS33267, CCDS92828

Canonical transcript exons

ENST00000681802 — 8 exons

Exon	Start	End
ENSE00001292358	108255572	108255698
ENSE00001302138	108253345	108253442
ENSE00001311706	108258734	108258828
ENSE00001323839	108252365	108252493
ENSE00003911424	108260568	108260886
ENSE00003913907	108247188	108247366
ENSE00003915516	108258966	108259146
ENSE00003922054	108239968	108240083

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 82.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0408 / max 39.0930, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21852	0.0408	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.48	gold quality
duodenum	UBERON:0002114	70.27	gold quality
small intestine Peyer’s patch	UBERON:0003454	63.49	gold quality
small intestine	UBERON:0002108	61.80	gold quality
mucosa of transverse colon	UBERON:0004991	50.00	gold quality
rectum	UBERON:0001052	47.41	gold quality
colonic epithelium	UBERON:0000397	42.19	gold quality
mucosa of stomach	UBERON:0001199	41.45	silver quality
stomach	UBERON:0000945	40.59	gold quality
body of stomach	UBERON:0001161	39.12	gold quality
bone marrow cell	CL:0002092	38.36	gold quality
intestine	UBERON:0000160	38.35	gold quality
esophagus mucosa	UBERON:0002469	37.96	gold quality
corpus callosum	UBERON:0002336	37.68	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
kidney	UBERON:0002113	36.21	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
tonsil	UBERON:0002372	34.86	gold quality
prostate gland	UBERON:0002367	33.90	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
adult mammalian kidney	UBERON:0000082	32.94	gold quality
bone marrow	UBERON:0002371	32.86	gold quality
adrenal tissue	UBERON:0018303	32.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	32.13	gold quality
thoracic mammary gland	UBERON:0005200	31.79	gold quality
right uterine tube	UBERON:0001302	31.31	gold quality
vermiform appendix	UBERON:0001154	30.78	gold quality
vagina	UBERON:0000996	30.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.96

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• These data indicate that SULT1C3 is expressed in human intestine. (PMID:24335392)
• Our findings are the first to characterize the regulation of human SULT1C2 and SULT1C3 expression by several transcription factor activators. (PMID:24335393)
• PPARgamma regulatory network includes SULT1C3 and imply that this enzyme contributes to the control of such PPARgamma-regulated intestinal processes as growth, differentiation, and metabolism. (PMID:27565680)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sult2st3	ENSDARG00000028367
mus_musculus	Sult1c1	ENSMUSG00000023943
rattus_norvegicus	Sult1c3	ENSRNOG00000011269
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), SULT1A1 (ENSG00000196502), SULT1A2 (ENSG00000197165), SULT1C4 (ENSG00000198075), SULT1C2 (ENSG00000198203), SULT1A4 (ENSG00000213648), SULT1A3 (ENSG00000261052)

Protein

Protein identifiers

Sulfotransferase 1C3 — Q6IMI6 (reviewed: Q6IMI6)

All UniProt accessions (1): Q6IMI6

UniProt curated annotations — full annotation on UniProt →

Function. Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor. Has sulfotransferase activity towards various substrates, such as bile acids, thyroid hormones and toward xenobiotic compounds such as chloro phenols and hydroxypyrenes. Lithocholic acid appears to be the best substrate among the endogenous compounds tested and 3,3’,5,5’-tetrachloro-4,4’-biphenyldiol shows the highest specific activity among the xenobiotic compounds. Exhibits weak sulphating activity and only toward chloro phenols (pentachlorophenol and 3,3’,5,5’-tetrachloro-4,4’-biphenyldiol).

Subcellular location. Cytoplasm.

Tissue specificity. Not detectable in any of the tissues tested. Expressed in the small intestine.

Miscellaneous. SULT1C3 gene appears to be present only in humans and other primates.

Similarity. Belongs to the sulfotransferase 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6IMI6-1	1, D, SULT1C3d	yes
Q6IMI6-2	2, A, SULT1C3a

RefSeq proteins (2): NP_001008743, NP_001307807* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000863	Sulfotransferase_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00685

Catalyzed reactions (Rhea), 3 shown:

• a phenol + 3’-phosphoadenylyl sulfate = an aryl sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:12164)
• 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)

UniProt features (38 total): helix 13, binding site 7, strand 6, turn 5, sequence variant 4, chain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2REO	X-RAY DIFFRACTION	2.65
2H8K	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IMI6-F1	92.36	0.84

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): 117 (proton acceptor)

Ligand- & substrate-binding residues (7): 56–61; 115–117; 139; 147; 202; 236–241; 264–268

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 36 (showing top): chr2q12, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_SULFATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_STEROID_METABOLIC_PROCESS, GOBP_ALCOHOL_METABOLIC_PROCESS, GOMF_SULFUR_COMPOUND_BINDING, GOMF_ARYL_SULFOTRANSFERASE_ACTIVITY, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_SULPHUR_CONTAINING_GROUPS

GO Biological Process (6): lipid metabolic process (GO:0006629), sulfur compound metabolic process (GO:0006790), xenobiotic metabolic process (GO:0006805), cholesterol metabolic process (GO:0008203), 3’-phosphoadenosine 5’-phosphosulfate metabolic process (GO:0050427), sulfation (GO:0051923)

GO Molecular Function (7): alcohol sulfotransferase activity (GO:0004027), aryl sulfotransferase activity (GO:0004062), bile-salt sulfotransferase activity (GO:0047704), 3’-phosphoadenosine 5’-phosphosulfate binding (GO:0050656), protein binding (GO:0005515), sulfotransferase activity (GO:0008146), transferase activity (GO:0016740)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sulfotransferase activity	3
metabolic process	2
sulfur compound metabolic process	2
primary metabolic process	1
cellular response to xenobiotic stimulus	1
sterol metabolic process	1
secondary alcohol metabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside bisphosphate metabolic process	1
oxoacid metabolic process	1
adenyl ribonucleotide binding	1
anion binding	1
sulfur compound binding	1
binding	1
transferase activity, transferring sulphur-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

710 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SULT1C3	CHST6	Q9GZX3	902
SULT1C3	NDST1	P52848	896
SULT1C3	HS3ST1	O14792	848
SULT1C3	PAPSS2	O95340	848
SULT1C3	HS3ST3A1	Q9Y663	833
SULT1C3	HS3ST3B1	Q9Y662	830
SULT1C3	NDST2	P52849	821
SULT1C3	PAPSS1	O43252	818
SULT1C3	HS3ST2	Q9Y278	763
SULT1C3	NDST3	O95803	759
SULT1C3	CHST1	O43916	756
SULT1C3	CHST3	Q7LGC8	750
SULT1C3	CHST5	Q9GZS9	740
SULT1C3	LUM	P51884	729
SULT1C3	HS3ST4	Q9Y661	725

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SULT2B1	SULT1C3	psi-mi:“MI:0915”(physical association)	0.560
SULT1C3	SULT1A3	psi-mi:“MI:0914”(association)	0.350
SULT2B1	SULT1C3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): ATP6V1A (Co-fractionation), SULT1C3 (Co-fractionation), SULT1C3 (Co-fractionation), SULT1C3 (Co-fractionation), SULT1C3 (Co-fractionation), SULT1C3 (Synthetic Lethality), SULT1C3 (Two-hybrid), SULT1A3 (Affinity Capture-MS), SULT1A1 (Affinity Capture-MS), SULT1C3 (Negative Genetic), SULT1C3 (Cross-Linking-MS (XL-MS))

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, G3V9R3, O00338, O35400, O43704, O46503, O46640, O75897, P0DMM9, P0DMN0, P19217, P49887, P49888, P49891, P50236, P50237, P52839, P52840, P52842, P52844, P52847, P63046, P63047, Q29476, Q3T0Y3, Q3UZZ6, Q6IMI6, Q80VR3, Q8BGL3, Q8JG30, Q95JD5, Q9BR01, Q9C9D0, Q9D939, Q9FZ80, Q9QWG7, Q9WUW8, Q9WUW9, B2RVI8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1211 predictions. Top by Δscore:

Variant	Effect	Δscore
2:108255563:T:TA	acceptor_gain	1.0000
2:108255571:GATT:G	acceptor_gain	1.0000
2:108255696:AAGG:A	donor_loss	1.0000
2:108255697:AGG:A	donor_loss	1.0000
2:108255699:GTGA:G	donor_loss	1.0000
2:108255700:T:G	donor_loss	1.0000
2:108258730:CCAGT:C	acceptor_loss	1.0000
2:108258732:A:AG	acceptor_gain	1.0000
2:108258732:AGT:A	acceptor_loss	1.0000
2:108258732:AGTT:A	acceptor_gain	1.0000
2:108258733:G:GT	acceptor_gain	1.0000
2:108258733:GT:G	acceptor_gain	1.0000
2:108258733:GTT:G	acceptor_gain	1.0000
2:108258733:GTTG:G	acceptor_gain	1.0000
2:108258733:GTTGT:G	acceptor_gain	1.0000
2:108258825:AAAA:A	donor_gain	1.0000
2:108258826:AAA:A	donor_gain	1.0000
2:108258827:AA:A	donor_gain	1.0000
2:108258829:G:GG	donor_gain	1.0000
2:108247258:G:GT	donor_gain	0.9900
2:108255568:TCAG:T	acceptor_loss	0.9900
2:108255569:CAGAT:C	acceptor_loss	0.9900
2:108255570:A:AG	acceptor_gain	0.9900
2:108255571:G:GG	acceptor_gain	0.9900
2:108255571:GA:G	acceptor_gain	0.9900
2:108255571:GAT:G	acceptor_gain	0.9900
2:108255699:G:GG	donor_gain	0.9900
2:108258824:AAAAA:A	donor_gain	0.9900
2:108258831:AAGTG:A	donor_loss	0.9900
2:108265237:AGG:A	acceptor_gain	0.9900

AlphaMissense

2063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:108255683:T:C	F171L	0.955
2:108255685:C:A	F171L	0.955
2:108255685:C:G	F171L	0.955
2:108255623:T:C	F151L	0.952
2:108255625:T:A	F151L	0.952
2:108255625:T:G	F151L	0.952
2:108258748:T:A	W181R	0.950
2:108258748:T:C	W181R	0.950
2:108255671:T:C	F167L	0.946
2:108255673:T:A	F167L	0.946
2:108255673:T:G	F167L	0.946
2:108252457:T:C	F89L	0.942
2:108252459:C:A	F89L	0.942
2:108252459:C:G	F89L	0.942
2:108255598:G:C	K142N	0.939
2:108255598:G:T	K142N	0.939
2:108255576:T:A	V135D	0.930
2:108258769:T:A	W188R	0.924
2:108258769:T:C	W188R	0.924
2:108247362:G:C	K56N	0.922
2:108247362:G:T	K56N	0.922
2:108258808:T:C	F201L	0.914
2:108258810:C:A	F201L	0.914
2:108258810:C:G	F201L	0.914
2:108258751:T:C	F182L	0.906
2:108258753:T:A	F182L	0.906
2:108258753:T:G	F182L	0.906
2:108252365:G:T	G58V	0.890
2:108255599:G:C	D143H	0.887
2:108258815:A:T	E203V	0.886

dbSNP variants (sampled 300 via entrez): RS1000012149 (2:108261664 A>G), RS1000197468 (2:108244832 C>A), RS1000227502 (2:108252177 A>AGATG), RS1000254799 (2:108255326 C>T), RS1000595673 (2:108243404 G>C), RS1000749475 (2:108249853 T>C,G), RS1000801659 (2:108249504 A>T), RS1000860368 (2:108257267 T>C), RS1000887649 (2:108263676 A>C), RS1000965897 (2:108263155 G>A), RS1000966758 (2:108256506 G>T), RS1001079117 (2:108257520 T>C), RS1001092408 (2:108250430 G>A,C), RS1001114776 (2:108259152 T>C), RS1001251892 (2:108259478 C>A)

Disease associations

OMIM: gene MIM:617151 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002497_27	Blood pressure	6.000000e-07
GCST002931_10	Aluminium levels	5.000000e-07
GCST003476_3	Eyebrow thickness	1.000000e-07
GCST006227_17	Diastolic blood pressure	2.000000e-07
GCST006228_3	Systolic blood pressure	1.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6722745	Efficacy	3	candesartan	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6722745	SULT1C3	3	3.00	1	candesartan

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
arsenite	decreases expression, increases abundance	1
sodium arsenite	increases abundance, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
antimonite	decreases expression, increases abundance	1
Tolvaptan	increases activity, increases reaction, increases response to substance, increases sulfation	1
Antimony Potassium Tartrate	decreases expression, increases abundance	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Cyclosporine	increases activity, increases reaction, increases response to substance, increases sulfation	1

Clinical trials (associated diseases)

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