SULT2B1

Summary

SULT2B1 (sulfotransferase family 2B member 1, HGNC:11459) is a protein-coding gene on chromosome 19q13.33, encoding Sulfotransferase 2B1 (O00204). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation.

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 sulfates dehydroepiandrosterone but not 4-nitrophenol, a typical substrate for the phenol and estrogen sulfotransferase subfamilies. Two alternatively spliced variants that encode different isoforms have been described.

Source: NCBI Gene 6820 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ichthyosis, congenital, autosomal recessive 14 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 108 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes
• MANE Select transcript: NM_177973

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11459
Approved symbol	SULT2B1
Name	sulfotransferase family 2B member 1
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	HSST2
Ensembl gene	ENSG00000088002
Ensembl biotype	protein_coding
OMIM	604125
Entrez	6820

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000201586, ENST00000323090, ENST00000594274, ENST00000597923

RefSeq mRNA: 2 — MANE Select: NM_177973 NM_004605, NM_177973

CCDS: CCDS12723, CCDS12724

Canonical transcript exons

ENST00000201586 — 7 exons

Exon	Start	End
ENSE00000000125	48599135	48599423
ENSE00000717419	48587229	48587437
ENSE00001244643	48575941	48576083
ENSE00001244662	48552172	48552323
ENSE00003477811	48592722	48592816
ENSE00003634271	48596739	48596919
ENSE00003649054	48591609	48591735

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 99.52.

FANTOM5 (CAGE): breadth broad, TPM avg 13.3250 / max 401.5729, expressed in 256 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176802	11.3945	244
176801	1.9305	209

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.52	gold quality
esophagus mucosa	UBERON:0002469	97.53	gold quality
skin of abdomen	UBERON:0001416	97.37	gold quality
skin of leg	UBERON:0001511	96.72	gold quality
gingival epithelium	UBERON:0001949	96.15	gold quality
gingiva	UBERON:0001828	96.08	gold quality
zone of skin	UBERON:0000014	95.43	gold quality
upper arm skin	UBERON:0004263	94.91	gold quality
pharyngeal mucosa	UBERON:0000355	94.73	gold quality
oral cavity	UBERON:0000167	94.40	gold quality
tongue squamous epithelium	UBERON:0006919	93.10	gold quality
mammalian vulva	UBERON:0000997	92.78	gold quality
upper leg skin	UBERON:0004262	90.27	gold quality
epithelium of esophagus	UBERON:0001976	90.01	gold quality
squamous epithelium	UBERON:0006914	89.94	gold quality
esophagus squamous epithelium	UBERON:0006920	89.26	gold quality
cervix epithelium	UBERON:0004801	88.49	gold quality
penis	UBERON:0000989	88.26	gold quality
endometrium epithelium	UBERON:0004811	87.51	gold quality
type B pancreatic cell	CL:0000169	86.53	gold quality
olfactory bulb	UBERON:0002264	86.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.64	gold quality
vagina	UBERON:0000996	84.20	gold quality
body of tongue	UBERON:0011876	83.75	gold quality
triceps brachii	UBERON:0001509	83.68	gold quality
gluteal muscle	UBERON:0002000	83.35	gold quality
nipple	UBERON:0002030	82.95	gold quality
buccal mucosa cell	CL:0002336	82.02	gold quality
prostate gland	UBERON:0002367	81.27	gold quality
nasal cavity epithelium	UBERON:0005384	80.71	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	3052.34
E-CURD-114	yes	62.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): VDR

Literature-anchored findings (GeneRIF, showing 39)

• alternative splicing of SULT2B1 results in cholesterol sulfotransferase or pregnenolone sulfotransferase (PMID:12145317)
• crystal structure of hydroxysteroid sulfotransferases SULT2B1a and SULT2B1b bound to the substrate donor product 3’-phosphoadenosine 5’-phosphate and acceptor substrate pregnenolone revealed a different catalytic binding orientation (PMID:12923182)
• We have documented the presence of the enzyme (SULT2B1b) that sulfonates cholesterol in human platelets and examined the influence of plasma lipoproteins on the expression and activity of this enzyme (PMID:14676143)
• Differential subcellular localization of SULT2B1b in prostate and placenta suggests that SULT2B1b may be differentially regulated and have different physiological functions in these two hormonally responsive human tissues (PMID:14741047)
• confinement of SULT2B1b to the granular layer coincides with this being the area with the highest cholesterol sulfate content suggesting that the physiologic action of cholesterol sulfate is likely carried out in this region of the living epidermis (PMID:15140224)
• Immunohistochemical localization of SULT2B1b in human tissues showed expression in the cytoplasm of ciliated columnar or cuboidal epithelial cells in terminal bronchia. (PMID:15878639)
• Of five Sp1 elements identified in SULT2B1, two had regulatory activity utilizing immortalized human keratinocytes. (PMID:15953604)
• SULT2B1b, by acting on a variety of oxysterols, offers a potential pathway for modulating in vivo the injurious effects of these compounds. (PMID:17347498)
• Results show SULT2B1 polymorpohisms affect enzyme functions. (PMID:17496163)
• SULT2B1 is involved in reulating prostate cell responsiveness to dehydroepiandrosterone and delta5-androstenediol. (PMID:17626250)
• Data show that SULT2B1b is localized in cytosol and nuclei of cancerous and normal breast tissue, and that African Americans had significantly more SULT2B1b in nuclei of epithelial cells of normal breast tissue compared to Caucasians. (PMID:18586095)
• The expression of SULT2B1b mRNA in endometrial stromal cells is induced by progesterone and that in endometrial epithelial cells is induced by relaxin via the cAMP pathway. (PMID:19243756)
• The Ca(2+)-bound form may be physiologically relevant for stressed cells with an elevated free calcium level. (PMID:20329768)
• Sulfation of 25-hydroxycholesterol by SULT2B1b plays an important role in the maintenance of intracellular lipid homeostasis via the LXR/SREBP-1c signaling pathway in endothelial cells. (PMID:21146170)
• In HT29 cells expression of SULT2B1 was enhanced by probiotic fermentation supernatants without aleurone. (PMID:21840698)
• SULT2B1 is induced by calcitriol activated vitamin D receptor in human prostate cancer cells. (PMID:23579488)
• SULT2B1b expression promotes proliferation of hepatocellular carcinoma cells in vitro and in vivo, which may contribute to the progression of HCC. (PMID:23593328)
• The SULT2B1 isoforms have a unique 50 amino acid carboxy-terminal sequence that is not present in the other human SULT isoforms (review). (PMID:24020383)
• Data indicate that cholesterol sulfate (CS) and SULT2B1b inhibited gluconeogenesis by targeting the gluconeogenic factor hepatocyte nuclear factor 4alpha (HNF4alpha) in both cell cultures and human SULT2B1b transgenic mice. (PMID:24277929)
• This study identified specific germline variations in estradiol metabolism-related pathways, namely CYP1B1, SULT2B1, and HSD17B2, as novel prognostic markers that are cumulatively associated with increased risk of prostate cancer progression (PMID:24682418)
• Overexpression of SULT2B1b is an independent prognostic indicator and promotes cell growth and invasion in colorectal carcinoma. (PMID:26121319)
• It metabolizes breast cancer drugs like afimoxifene and endoxifen by sulfation. (PMID:26169578)
• Since 1’-hydroxyestragole exposure readily produced DNA injury in B-13/H cells, these data suggest that cholangiocarcinomas generated in rats fed estragole may be dependent, in part, on SULT2B1 activation of the 1’-hydroxyestragole metabolite. (PMID:26739637)
• Mutation in SULT2B1 leads to an autosomal-recessive congenital ichthyosis phenotype via increased proliferation of human keratinocytes, thickening of epithelial layers, and altered epidermal cholesterol metabolism. (PMID:28575648)
• Authors conclude that the HNF4alpha-SULT2B1b-CS axis represents a key endogenous mechanism to prevent uncontrolled gluconeogenesis. (PMID:29378829)
• Galeterone and abiraterone are novel inhibitors of DHEA sulfonation, as determined in enzymatic incubations containing human tissue cytosol (liver or intestinal) or human recombinant SULT enzyme (SULT2A1, SULT2B1b, or SULT1E1). (PMID:29436390)
• findings showed clearly the impact of genetic polymorphisms on the cholesterol-sulphating activity of SULT2B1b allozymes, which may underscore the differential metabolism of cholesterol in individuals with different SULT2B1b genotypes (PMID:29701841)
• SULT2B1 expression was significantly higher in colorectal tumor tissues than in normal tissues. (PMID:29766219)
• Sulfotransferase 2B1b (SULT2B1b) interference attenuated the invasion abilities of human hepatocarcinoma BEL-7402cells. SULT2B1b interference inhibited the activation of the beta-catenin/MMP-7 pathway. (PMID:30658852)
• SULT2B1b expression enhances resistance to TNF and may promote prostate cancer. (PMID:30824526)
• SULT2B1b inversely correlates with prostate cancer status, with the highest level in the normal epithelium and lowest in the advanced metastatic prostate cancer. Furthermore, SULT2B1b is mostly located within the luminal layer of the prostate epithelium, suggesting that it may be implicated in luminal differentiation. (PMID:31212370)
• The abundant SULT2B1 expression in normal gastric epithelium might maintain epithelial function via the PI3K/AKT signaling pathway. (PMID:31757214)
• undetectable in nearly all castration-resistant prostate cancer metastases (73 visceral, 82 bone) from 50 autopsy cases (PMID:31894239)
• Data suggest therapeutic approaches to decrease sulphotransferase 2B1b (SULT2B1b) expression might be potentially beneficial for coronary artery disease (CAD) prevention by decreasing intracellular cholesterol. (PMID:31957803)
• The promoter hypermethylation of SULT2B1 accelerates esophagus tumorigenesis via downregulated PER1. (PMID:34730281)
• Macrophage Sult2b1 promotes pathological neovascularization in age-related macular degeneration. (PMID:37550000)
• Reducing SULT2B1 promotes the interaction of LncRNAgga3-204 with SMAD4 to inhibit the macrophage inflammatory response and delay atherosclerosis progression. (PMID:38286358)
• Sulfotransferase SULT2B1 facilitates colon cancer metastasis by promoting SCD1-mediated lipid metabolism. (PMID:38372484)
• Knockdown of sulfotransferase 2B1 suppresses cell migration, invasion and promotes apoptosis in ovarian carcinoma cells via targeting annexin A9. (PMID:38777329)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sult2b1	ENSMUSG00000003271
rattus_norvegicus	Sult2b1	ENSRNOG00000021046
drosophila_melanogaster	St4	FBGN0033887
drosophila_melanogaster	St1	FBGN0034887
drosophila_melanogaster	St3	FBGN0265052

Paralogs (12): SULT2A1 (ENSG00000105398), 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 2B1 — O00204 (reviewed: O00204)

Alternative names: Alcohol sulfotransferase, Hydroxysteroid sulfotransferase 2, Sulfotransferase family 2B member 1, Sulfotransferase family cytosolic 2B member 1

All UniProt accessions (1): O00204

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. Responsible for the sulfation of cholesterol. Catalyzes sulfation of the 3beta-hydroxyl groups of steroids, such as, pregnenolone and dehydroepiandrosterone (DHEA). Preferentially sulfonates cholesterol, while it also has significant activity with pregnenolone and DHEA. Plays a role in epidermal cholesterol metabolism and in the regulation of epidermal proliferation and differentiation. Sulfonates pregnenolone but not cholesterol.

Subcellular location. Cytoplasm. Cytosol. Microsome. Nucleus.

Tissue specificity. Expressed in the stratum granulosum-stratum corneum junction in the skin (at protein level). Expressed highly in placenta, prostate and trachea and lower expression in the small intestine and lung.

Post-translational modifications. Phosphorylated.

Disease relevance. Ichthyosis, congenital, autosomal recessive 14 (ARCI14) [MIM:617571] A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminus, which contains a proline/serine-rich region is involved in nuclear translocation and enzymatic thermostability.

Similarity. Belongs to the sulfotransferase 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00204-1	1, SULT2B1b, B	yes
O00204-2	2, SULT2B1a, A

RefSeq proteins (2): NP_004596, NP_814444* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000863	Sulfotransferase_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00685

Catalyzed reactions (Rhea), 5 shown:

• an alcohol + 3’-phosphoadenylyl sulfate = an alkyl sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:22552)
• 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 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52348)
• pregnenolone + 3’-phosphoadenylyl sulfate = pregnenolone sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52356)
• cholesterol + 3’-phosphoadenylyl sulfate = cholesterol sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52368)

UniProt features (65 total): helix 17, mutagenesis site 12, binding site 9, strand 8, turn 7, sequence variant 5, chain 1, region of interest 1, modified residue 1, splice variant 1, compositionally biased region 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1Q20	X-RAY DIFFRACTION	2.3
1Q1Z	X-RAY DIFFRACTION	2.4
1Q22	X-RAY DIFFRACTION	2.5
1Q1Q	X-RAY DIFFRACTION	2.91

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00204-F1	87.24	0.76

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): 125 (proton acceptor)

Ligand- & substrate-binding residues (9): 210; 244–249; 274–276; 70–75; 98; 103; 125; 147; 155

Post-translational modifications (1): 348

Mutagenesis-validated functional residues (12):

Position	Phenotype
1–23	loss of the cholesterol sulfotransferase activity.
1–18	increases the cholesterol sulfotransferase activity.
19	increases the cholesterol sulfotransferase activity.
20	loss of the cholesterol sulfotransferase activity.
21	increases the cholesterol sulfotransferase activity.
22	increases the cholesterol sulfotransferase activity.
23	loss of the cholesterol sulfotransferase activity.
347	no change in subcellular localization.
348	10-fold increase in specific activity for dhea sulfation. 10-fold increase in substrate affinity for dhea and pregnenolo
348	abolishes nuclear localization.
352	no change in subcellular localization.
357	no change in subcellular localization.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-156584	Cytosolic sulfonation of small molecules

MSigDB gene sets: 256 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_BIOLOGICAL_OXIDATIONS, MORF_MSH3, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, DAZARD_UV_RESPONSE_CLUSTER_G4, MORF_BRCA1, MORF_ATRX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_ESR1, GOBP_SULFATION, CAGCTG_AP4_Q5

GO Biological Process (7): steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), negative regulation of cell population proliferation (GO:0008285), positive regulation of epidermal cell differentiation (GO:0045606), 3’-phosphoadenosine 5’-phosphosulfate metabolic process (GO:0050427), sulfation (GO:0051923), lipid metabolic process (GO:0006629)

GO Molecular Function (10): nucleic acid binding (GO:0003676), sulfotransferase activity (GO:0008146), cholesterol binding (GO:0015485), small molecule binding (GO:0036094), steroid sulfotransferase activity (GO:0050294), cholesterol sulfotransferase activity (GO:0051922), steroid hormone binding (GO:1990239), alcohol sulfotransferase activity (GO:0004027), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
sulfur compound metabolic process	2
sulfotransferase activity	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
lipid metabolic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
epidermal cell differentiation	1
positive regulation of epithelial cell differentiation	1
regulation of epidermal cell differentiation	1
positive regulation of epidermis development	1
purine ribonucleotide metabolic process	1
purine ribonucleoside bisphosphate metabolic process	1
oxoacid metabolic process	1
primary metabolic process	1
transferase activity, transferring sulphur-containing groups	1
sterol binding	1
alcohol binding	1
alcohol sulfotransferase activity	1
steroid binding	1
hormone binding	1
catalytic activity	1
intracellular anatomical structure	1
extracellular vesicle	1
endomembrane system	1

Protein interactions and networks

STRING

772 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SULT2B1	ABCG1	P45844	716
SULT2B1	NR1H2	P55055	678
SULT2B1	SREBF2	Q12772	673
SULT2B1	ABCG5	Q9H222	670
SULT2B1	ABCG8	Q9H221	651
SULT2B1	ABCA1	O95477	643
SULT2B1	XPR1	Q9UBH6	643
SULT2B1	PNPLA1	Q8N8W4	625
SULT2B1	NIPAL4	Q0D2K0	616
SULT2B1	CYP4F22	Q6NT55	611
SULT2B1	SDR9C7	Q8NEX9	595
SULT2B1	CERS3	Q8IU89	588
SULT2B1	ALOX12B	O75342	578
SULT2B1	ALOXE3	Q9BYJ1	571
SULT2B1	SREBF1	P36956	568

IntAct

104 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
SULT2B1	SULT1B1	psi-mi:“MI:0915”(physical association)	0.810
SULT1B1	SULT2B1	psi-mi:“MI:0915”(physical association)	0.810
SULT2B1	FLACC1	psi-mi:“MI:0915”(physical association)	0.760
FLACC1	SULT2B1	psi-mi:“MI:0915”(physical association)	0.760
SULT2B1	FLACC1	psi-mi:“MI:0915”(physical association)	0.720
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
SULT2B1	PRICKLE3	psi-mi:“MI:0915”(physical association)	0.560
ACYP2	SULT2B1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (77): SULT2B1 (Two-hybrid), SULT2B1 (Two-hybrid), SULT2B1 (Two-hybrid), SULT2B1 (Two-hybrid), SULT1B1 (Two-hybrid), ALS2CR12 (Two-hybrid), SULT2B1 (Affinity Capture-MS), SULT2B1 (Affinity Capture-MS), SULT2B1 (Two-hybrid), ALS2CR12 (Two-hybrid), SULT2B1 (Two-hybrid), ALS2CR12 (Two-hybrid), SULT1A1 (Two-hybrid), SULT1B1 (Two-hybrid), SULT2B1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2K5X3B6, B2RVI8, F1QYJ6, O00204, O00338, O35400, O46503, P0CC03, P0DMM9, P0DMN0, P15709, P17988, P22789, P48760, P49887, P49888, P50225, P50226, P50227, P50234, P50235, P50236, P50237, P52840, P52841, P52842, P52843, P52844, P52846, P52847, Q06520, Q16WU7, Q29476, Q29YR5, Q6IMI4, Q6IMI6, Q6PH37, Q6WG17, Q6WG18, Q7Q297

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 62 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cytosolic sulfonation of small molecules	7	98.2×	5e-11
Phase II - Conjugation of compounds	7	52.7×	3e-09
Biological oxidations	8	28.1×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
sulfation	8	156.0×	4e-14
3’-phosphoadenosine 5’-phosphosulfate metabolic process	7	145.6×	3e-12
xenobiotic metabolic process	7	19.3×	6e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	60
Likely benign	21
Benign	14

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
4076976	NM_177973.2(SULT2B1):c.102C>G (p.Tyr34Ter)	Pathogenic
426107	NM_177973.2(SULT2B1):c.446C>T (p.Pro149Leu)	Pathogenic
426108	NM_177973.2(SULT2B1):c.821G>A (p.Arg274Gln)	Pathogenic
426109	NM_177973.2(SULT2B1):c.364dup (p.Met122fs)	Pathogenic
426110	NM_177973.2(SULT2B1):c.71+2T>A	Pathogenic
633833	NM_177973.2(SULT2B1):c.232G>A (p.Glu78Lys)	Likely pathogenic
633834	NM_177973.2(SULT2B1):c.298C>T (p.Arg100Trp)	Likely pathogenic

SpliceAI

891 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48575939:A:AG	acceptor_gain	1.0000
19:48575940:G:GG	acceptor_gain	1.0000
19:48575940:GCC:G	acceptor_gain	1.0000
19:48575940:GCCA:G	acceptor_gain	1.0000
19:48576079:GTCAG:G	donor_gain	1.0000
19:48576083:GG:G	donor_loss	1.0000
19:48576084:GT:G	donor_loss	1.0000
19:48587227:A:AG	acceptor_gain	1.0000
19:48587227:AG:A	acceptor_gain	1.0000
19:48587228:G:GT	acceptor_gain	1.0000
19:48587228:GG:G	acceptor_gain	1.0000
19:48587228:GGC:G	acceptor_gain	1.0000
19:48587228:GGCA:G	acceptor_gain	1.0000
19:48587228:GGCAC:G	acceptor_gain	1.0000
19:48591597:ATCC:A	acceptor_gain	1.0000
19:48591598:T:G	acceptor_gain	1.0000
19:48591604:C:G	acceptor_gain	1.0000
19:48591605:ACAG:A	acceptor_gain	1.0000
19:48591606:CAGGT:C	acceptor_loss	1.0000
19:48591607:AG:A	acceptor_gain	1.0000
19:48591608:G:GC	acceptor_gain	1.0000
19:48591608:G:GG	acceptor_loss	1.0000
19:48591608:GG:G	acceptor_gain	1.0000
19:48591608:GGT:G	acceptor_gain	1.0000
19:48591608:GGTGA:G	acceptor_gain	1.0000
19:48591734:AG:A	donor_loss	1.0000
19:48591735:GG:G	donor_loss	1.0000
19:48591736:G:GA	donor_loss	1.0000
19:48591737:T:G	donor_loss	1.0000
19:48592713:T:A	acceptor_gain	1.0000

AlphaMissense

2419 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48592736:T:A	W189R	0.991
19:48592736:T:C	W189R	0.991
19:48587313:G:C	R100P	0.990
19:48596812:T:A	V240D	0.989
19:48592757:T:A	W196R	0.988
19:48592757:T:C	W196R	0.988
19:48587321:T:A	W103R	0.987
19:48587321:T:C	W103R	0.987
19:48587229:G:T	G72V	0.986
19:48576079:G:C	K70N	0.985
19:48576079:G:T	K70N	0.985
19:48587387:C:G	H125D	0.985
19:48591624:C:A	R147S	0.983
19:48587384:T:C	S124P	0.982
19:48596772:T:C	F227L	0.982
19:48596774:C:A	F227L	0.982
19:48596774:C:G	F227L	0.982
19:48587237:T:A	W75R	0.981
19:48587237:T:C	W75R	0.981
19:48587306:T:A	W98R	0.981
19:48587306:T:C	W98R	0.981
19:48592727:T:C	F186L	0.981
19:48592729:T:A	F186L	0.981
19:48592729:T:G	F186L	0.981
19:48596907:T:C	F272L	0.981
19:48596909:C:A	F272L	0.981
19:48596909:C:G	F272L	0.981
19:48587229:G:A	G72D	0.980
19:48599149:T:A	W281R	0.980
19:48599149:T:C	W281R	0.980

dbSNP variants (sampled 300 via entrez): RS1000126707 (19:48581736 C>A,G,T), RS1000126789 (19:48555564 C>G,T), RS1000149087 (19:48597226 C>T), RS1000210246 (19:48560775 A>G,T), RS1000214252 (19:48570551 C>G,T), RS1000226917 (19:48597934 A>G), RS1000301701 (19:48555393 A>G), RS1000436072 (19:48565998 C>T), RS1000496781 (19:48596088 C>A,G,T), RS1000518364 (19:48555846 T>C), RS1000533982 (19:48559653 G>C), RS1000552027 (19:48569215 G>A), RS1000604850 (19:48560586 A>G), RS1000675925 (19:48565064 C>T), RS1000694553 (19:48591077 C>T)

Disease associations

OMIM: gene MIM:604125 | disease phenotypes: MIM:617571, MIM:242300, MIM:242100

GenCC curated gene-disease

Disease	Classification	Inheritance
ichthyosis, congenital, autosomal recessive 14	Strong	Autosomal recessive
lamellar ichthyosis	Supportive	Autosomal recessive

Mondo (4): ichthyosis, congenital, autosomal recessive 14 (MONDO:0033091), autosomal recessive congenital ichthyosis 1 (MONDO:0009441), autosomal recessive congenital ichthyosis 2 (MONDO:0009439), lamellar ichthyosis (MONDO:0017778)

Orphanet (2): Self-improving collodion baby (Orphanet:281122), Congenital ichthyosiform erythroderma (Orphanet:79394)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000164	Abnormality of the dentition
HP:0000232	Everted lower lip vermilion
HP:0000365	Hearing impairment
HP:0000389	Chronic otitis media
HP:0000491	Keratitis
HP:0000656	Ectropion
HP:0000958	Dry skin
HP:0000962	Hyperkeratosis
HP:0000966	Hypohidrosis
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001597	Abnormal nail morphology
HP:0001944	Dehydration
HP:0002205	Recurrent respiratory infections
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0007479	Congenital nonbullous ichthyosiform erythroderma
HP:0008064	Ichthyosis
HP:0008070	Sparse hair
HP:0010783	Erythema
HP:0011039	Abnormal helix morphology
HP:0025080	Orthokeratotic hyperkeratosis
HP:0040189	Scaling skin
HP:0100543	Cognitive impairment
HP:0100679	Lack of skin elasticity

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002485_9	Elevated serum carcinoembryonic antigen levels	1.000000e-10
GCST004523_1	Resting metabolic rate	5.000000e-07
GCST010134_4	Non-oily fish consumption	3.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005760	serum carcinoembryonic antigen measurement
EFO:0008004	resting metabolic rate measurement
EFO:0008111	diet measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017490	Ichthyosis, Lamellar	C16.131.831.512.400.410; C16.320.850.400.410; C16.614.492.400.410; C17.800.428.333.250.410; C17.800.804.512.400.410; C17.800.827.400.410

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1743297 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10426377	Toxicity	4	anthracyclines and related substances	Neoplasms
rs2302948	Toxicity	3	cytarabine;fludarabine;gemtuzumab ozogamicin;idarubicin	Leukemia;Myeloid;Acute

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2302948	SULT2B1	3	2.75	1	cytarabine;fludarabine;gemtuzumab ozogamicin;idarubicin
rs10426377	SULT2B1	4	-1.50	1	anthracyclines and related substances
rs10426628	SULT2B1		0.00	0
rs777924668	SULT2B1		0.00	0
rs527454384	SULT2B1		0.00	0
rs777140014	SULT2B1		0.00	0
rs746398875	SULT2B1		0.00	0
rs762765702	SULT2B1		0.00	0
rs774212320	SULT2B1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Cadmium	decreases expression, increases response to substance, increases expression	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Valproic Acid	increases methylation, affects expression	2
Cadmium Chloride	decreases expression, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	decreases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	decreases methylation	1
25-hydroxycholesterol	decreases reaction, increases activity	1
sodium arsenate	decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	decreases expression	1
mancozeb	decreases expression	1
arsenite	decreases expression, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
tetrabromobisphenol A	decreases expression	1
benazol P	affects expression	1
antimonite	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
epoxiconazole	decreases expression	1
entinostat	increases expression	1
bisphenol B	decreases expression	1
ormosil	affects binding, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743311	ADMET	Major substrate of human cytosolic sulfotransferase SULT2B1_v1	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01222000	PHASE3	UNKNOWN	Treatment of the Recessive Nonbullous Congenital Ichthyosis by the Epigallocatechine Cutaneous
NCT03041038	PHASE2	COMPLETED	The Efficacy and Safety of Secukinumab in Patients With Ichthyoses
NCT03738800	PHASE2	TERMINATED	A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis
NCT00001292	Not specified	COMPLETED	Study of Scaling Disorders and Other Inherited Skin Diseases