SULT6B1

Summary

SULT6B1 (sulfotransferase family 6B member 1, HGNC:33433) is a protein-coding gene on chromosome 2p22.2, encoding Sulfotransferase 6B1 (Q6IMI4). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of thyroxine.

Predicted to enable sulfotransferase activity. Predicted to be involved in sulfation. Predicted to be located in cytosol. Predicted to be active in cytoplasm.

Source: NCBI Gene 391365 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_001367551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33433
Approved symbol	SULT6B1
Name	sulfotransferase family 6B member 1
Location	2p22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138068
Ensembl biotype	protein_coding
OMIM	617152
Entrez	391365

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 nonsense_mediated_decay

ENST00000407963, ENST00000416345, ENST00000420611, ENST00000433192, ENST00000535679, ENST00000686860, ENST00000688628, ENST00000689208, ENST00000692190

RefSeq mRNA: 2 — MANE Select: NM_001367551 NM_001032377, NM_001367551

CCDS: CCDS33182, CCDS92738

Canonical transcript exons

ENST00000535679 — 7 exons

Exon	Start	End
ENSE00000932512	37179458	37179584
ENSE00000932513	37183425	37183514
ENSE00001212470	37187355	37187467
ENSE00001290321	37167820	37168065
ENSE00001291597	37175132	37175226
ENSE00001309529	37171434	37171590
ENSE00002203591	37188442	37188670

Expression profiles

Bgee: expression breadth broad, 80 present calls, max score 59.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0032 / max 2.2903, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27767	0.0032	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	59.67	gold quality
left testis	UBERON:0004533	58.69	gold quality
right testis	UBERON:0004534	58.16	gold quality
testis	UBERON:0000473	58.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.56	gold quality
granulocyte	CL:0000094	38.28	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
fallopian tube	UBERON:0003889	36.07	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
right uterine tube	UBERON:0001302	34.21	gold quality
duodenum	UBERON:0002114	33.58	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
urinary bladder	UBERON:0001255	33.16	gold quality
muscle tissue	UBERON:0002385	32.40	gold quality
left adrenal gland cortex	UBERON:0035825	32.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
gall bladder	UBERON:0002110	32.02	gold quality
leukocyte	CL:0000738	31.76	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
monocyte	CL:0000576	31.50	gold quality
liver	UBERON:0002107	31.21	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
adult mammalian kidney	UBERON:0000082	30.59	gold quality
left adrenal gland	UBERON:0001234	29.95	gold quality
islet of Langerhans	UBERON:0000006	29.88	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
placenta	UBERON:0001987	29.84	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting SULT6B1, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-93-3P	98.15	66.65	1309

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sult6b1	ENSDARG00000086826
mus_musculus	Sult6b1	ENSMUSG00000038045
rattus_norvegicus	Sult6b1	ENSRNOG00000049335
drosophila_melanogaster	St4	FBGN0033887
drosophila_melanogaster	St1	FBGN0034887
drosophila_melanogaster	St3	FBGN0265052

Paralogs (12): SULT2B1 (ENSG00000088002), SULT2A1 (ENSG00000105398), SULT1E1 (ENSG00000109193), SULT4A1 (ENSG00000130540), SULT1B1 (ENSG00000173597), SULT1C3 (ENSG00000196228), SULT1A1 (ENSG00000196502), SULT1A2 (ENSG00000197165), SULT1C4 (ENSG00000198075), SULT1C2 (ENSG00000198203), SULT1A4 (ENSG00000213648), SULT1A3 (ENSG00000261052)

Protein

Protein identifiers

Sulfotransferase 6B1 — Q6IMI4 (reviewed: Q6IMI4)

Alternative names: Thyroxine sulfotransferase

All UniProt accessions (5): Q6IMI4, A0A0C4DG03, A0A8I5KWB2, A0A8I5KXR4, C9JFH2

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 thyroxine. Involved in the metabolism of thyroxine.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Specifically expressed in kidney and testis.

Similarity. Belongs to the sulfotransferase 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6IMI4-1	1	yes
Q6IMI4-2	2

RefSeq proteins (2): NP_001027549, NP_001354480* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000863	Sulfotransferase_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00685

Enzyme classification (BRENDA):

• EC 2.8.2.2 — alcohol sulfotransferase (BRENDA: 13 organisms, 295 substrates, 100 inhibitors, 159 Km, 25 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
DEHYDROEPIANDROSTERONE	0.0006–0.0179	23
ANDROSTERONE	0.0002–0.0096	11
3’-PHOSPHOADENYLYLSULFATE	0.0001–0.1	6
TRIIODOTHYRONINE	0.0046–0.0143	4
1-BUTANOL	3–106	3
BETA-ESTRADIOL	0.035–0.29	3
ETHANOL	42–47	3
PREGNENOLONE	0.0003–0.0089	3
1-PENTANOL	1.7–19.2	2
1-PROPANOL	24–610	2
3,3’-DIIODOTHYRONINE	0.0029–0.0097	2
4-BUTYLBENZYL ALCOHOL	0.07–0.16	2
4-METHYLBENZYL ALCOHOL	0.07–2.19	2
BENZYL ALCOHOL	0.0685–25.8	2
CHOLESTEROL	0.0017–0.0025	2

Catalyzed reactions (Rhea), 1 shown:

• thyroxine + 3’-phosphoadenylyl sulfate = thyroxine sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:26422)

UniProt features (16 total): sequence variant 7, binding site 6, chain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IMI4-F1	93.44	0.83

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): 118 (proton acceptor)

Ligand- & substrate-binding residues (6): 65–70; 140; 148; 203; 237–242; 259–261

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

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

MSigDB gene sets: 35 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_SULFATION, REACTOME_CYTOSOLIC_SULFONATION_OF_SMALL_MOLECULES, REACTOME_PHASE_II_CONJUGATION_OF_COMPOUNDS, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_SULPHUR_CONTAINING_GROUPS, chr2p22, GSE5503_PLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_UP, LHX9_TARGET_GENES, NKX2_2_TARGET_GENES, ZNF331_TARGET_GENES, ZNF711_TARGET_GENES, ZSCAN2_TARGET_GENES, MIR651_3P, MIR4795_3P, MIR5696

GO Biological Process (1): sulfation (GO:0051923)

GO Molecular Function (2): sulfotransferase activity (GO:0008146), transferase activity (GO:0016740)

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

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
sulfur compound metabolic process	1
transferase activity, transferring sulphur-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SULT6B1	TMEM238	C9JI98	570
SULT6B1	WFIKKN1	Q96NZ8	509
SULT6B1	YJU2	Q9BW85	494
SULT6B1	ZDHHC23	Q8IYP9	487
SULT6B1	CMKLR2	P46091	473
SULT6B1	FRMD1	Q8N878	429
SULT6B1	CDCP2	Q5VXM1	420
SULT6B1	MEOX1	P50221	393
SULT6B1	CFAP91	Q7Z4T9	383
SULT6B1	PAPSS1	O43252	381
SULT6B1	B3GALT4	O96024	338
SULT6B1	PRDM5	Q9NQX1	321
SULT6B1	CD63	P08962	309
SULT6B1	KIF25	Q9UIL4	305
SULT6B1	RSPH9	Q9H1X1	303

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SULT6B1	EMB	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): EMB (Affinity Capture-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, 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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

962 predictions. Top by Δscore:

Variant	Effect	Δscore
2:37175125:ATCT:A	donor_loss	1.0000
2:37175126:TCTCA:T	donor_loss	1.0000
2:37175127:CTCA:C	donor_loss	1.0000
2:37175128:TCAC:T	donor_loss	1.0000
2:37175129:CA:C	donor_loss	1.0000
2:37175130:ACCTC:A	donor_loss	1.0000
2:37175223:GAAA:G	acceptor_gain	1.0000
2:37175225:AA:A	acceptor_gain	1.0000
2:37175227:C:CC	acceptor_gain	1.0000
2:37188441:CCGCA:C	donor_gain	1.0000
2:37171589:TT:T	acceptor_gain	0.9900
2:37171591:C:CC	acceptor_gain	0.9900
2:37175124:AATCT:A	donor_loss	0.9900
2:37175131:CCT:C	donor_gain	0.9900
2:37175224:AAACT:A	acceptor_gain	0.9900
2:37175225:AACTA:A	acceptor_gain	0.9900
2:37175226:ACTA:A	acceptor_gain	0.9900
2:37175227:C:T	acceptor_loss	0.9900
2:37175227:CT:C	acceptor_gain	0.9900
2:37175228:T:A	acceptor_gain	0.9900
2:37187347:GTACT:G	donor_loss	0.9900
2:37187348:TACT:T	donor_loss	0.9900
2:37187349:ACTA:A	donor_loss	0.9900
2:37187350:CTAA:C	donor_loss	0.9900
2:37187351:TAA:T	donor_loss	0.9900
2:37187352:AAC:A	donor_loss	0.9900
2:37187353:A:C	donor_loss	0.9900
2:37187466:ACC:A	acceptor_loss	0.9900
2:37187469:T:G	acceptor_loss	0.9900
2:37188401:A:AC	donor_gain	0.9900

AlphaMissense

2022 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:37171555:G:C	F220L	0.965
2:37171555:G:T	F220L	0.965
2:37171557:A:G	F220L	0.965
2:37179558:T:A	K143N	0.962
2:37179558:T:G	K143N	0.962
2:37179531:G:C	F152L	0.959
2:37179531:G:T	F152L	0.959
2:37179533:A:G	F152L	0.959
2:37188446:C:A	K65N	0.957
2:37188446:C:G	K65N	0.957
2:37179483:G:C	F168L	0.949
2:37179483:G:T	F168L	0.949
2:37179485:A:G	F168L	0.949
2:37179471:G:C	F172L	0.948
2:37179471:G:T	F172L	0.948
2:37179473:A:G	F172L	0.948
2:37175201:A:C	F185L	0.947
2:37175201:A:T	F185L	0.947
2:37175203:A:G	F185L	0.947
2:37175191:A:G	W189R	0.944
2:37175191:A:T	W189R	0.944
2:37188471:T:G	D57A	0.944
2:37188472:C:G	D57H	0.941
2:37179559:T:A	K143I	0.939
2:37188470:G:C	D57E	0.935
2:37188470:G:T	D57E	0.935
2:37179568:C:G	R140P	0.934
2:37171441:G:C	F258L	0.933
2:37171441:G:T	F258L	0.933
2:37171443:A:G	F258L	0.933

dbSNP variants (sampled 300 via entrez): RS1000110601 (2:37167997 C>G), RS1000140487 (2:37197054 C>A), RS1000285569 (2:37192199 A>C,G), RS1000300464 (2:37194574 C>G), RS1000342592 (2:37186942 C>T), RS1000427069 (2:37190151 C>A), RS1000437178 (2:37187151 T>C), RS1000565817 (2:37168228 T>A), RS1000634502 (2:37185710 T>A,C), RS1000643235 (2:37190599 G>A), RS1000717544 (2:37191900 G>T), RS1000730132 (2:37190983 G>A,T), RS1000730535 (2:37194781 G>A), RS1000760215 (2:37191208 G>A,C,T), RS1000773780 (2:37186032 C>T)

Disease associations

OMIM: gene MIM:617152 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002149_12	Schizophrenia	7.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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