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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SULT1C4
sulfotransferase family 1C member 4
Chromosome 2 · 2q12.3
NCBI Gene: 27233Ensembl: ENSG00000198075.11HGNC: HGNC:11457UniProt: O75897
27PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
aryl sulfotransferase activitysulfotransferase activityethanol catabolic process3'-phosphoadenosine 5'-phosphosulfate metabolic processoropharynx cancerpreeclampsiahypouricemia, renal, 2hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2
✦AI Summary

SULT1C4 encodes a cytosolic sulfotransferase that catalyzes the sulfate conjugation of diverse xenobiotic and endogenous compounds using 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as a sulfonate donor 1. The enzyme demonstrates unique substrate specificity, being the only human SULT capable of sulfating the chemotherapeutic anthracyclines doxorubicin and epirubicin 1. SULT1C4 also metabolizes the tramadol metabolite O-desmethyltramadol with high catalytic efficiency, being 60 times more efficient than SULT1A3 2. The enzyme exhibits regioselective activity, preferentially producing genistein 7-sulfate from the dietary flavonoid genistein 3. SULT1C4 shows distinct developmental expression patterns, with multiple transcript variants expressed at higher levels in prenatal versus postnatal liver, though protein levels remain low due to the predominant transcript variant producing minimal stable protein 4. Genetic polymorphisms in SULT1C4 significantly affect doxorubicin sulfation activity among different allozymes 5 and influence the excretion of phase II flavanone metabolites following citrus consumption 6. In hepatocellular carcinoma, SULT1C4 expression is altered and associated with immune infiltration 7, suggesting potential roles in cancer metabolism and therapeutic response.

Sources cited
1
SULT1C4 is the only human SULT capable of sulfating doxorubicin and epirubicin using PAPS as sulfonate donor
PMID: 26948952
2
SULT1C4 metabolizes O-desmethyltramadol with 60-fold higher catalytic efficiency than SULT1A3
PMID: 28802998
3
SULT1C4 preferentially produces genistein 7-sulfate, demonstrating regioselective activity
PMID: 28286122
4
SULT1C4 has multiple transcript variants with higher prenatal expression, but low protein levels due to predominant variant instability
PMID: 32303576
5
Genetic polymorphisms in SULT1C4 significantly affect doxorubicin sulfation activity among allozymes
PMID: 33950190
6
SULT1C4 SNPs influence excretion of phase II flavanone metabolites after citrus consumption
PMID: 36145145
7
SULT1C4 expression is altered in hepatocellular carcinoma and associated with immune infiltration
PMID: 38411862
Disease Associationsⓘ20
oropharynx cancerOpen Targets
0.13Weak
preeclampsiaOpen Targets
0.06Suggestive
hypouricemia, renal, 2Open Targets
0.03Suggestive
hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2Open Targets
0.03Suggestive
Down syndromeOpen Targets
0.03Suggestive
aortic diseaseOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
ependymomaOpen Targets
0.02Suggestive
intrahepatic cholestasisOpen Targets
0.02Suggestive
lung carcinomaOpen Targets
0.02Suggestive
non-small cell lung carcinomaOpen Targets
0.02Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
colorectal adenocarcinomaOpen Targets
0.01Suggestive
astrocytomaOpen Targets
0.01Suggestive
Autosomal dominant polycystic kidney diseaseOpen Targets
0.01Suggestive
type 2 diabetes mellitusOpen Targets
0.01Suggestive
non-alcoholic steatohepatitisOpen Targets
0.01Suggestive
steatosisOpen Targets
0.00Suggestive
papillary renal cell carcinomaOpen Targets
0.00Suggestive
chronic myelogenous leukemiaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NDST1Protein interaction90%HS3ST1Protein interaction85%HS3ST3A1Protein interaction84%PAPSS2Protein interaction83%PAPSS1Protein interaction83%HS3ST3B1Protein interaction83%
Tissue Expression6 tissues
Ovary
100%
Heart
44%
Brain
34%
Lung
26%
Bone Marrow
16%
Liver
9%
Gene Interaction Network
Click a node to explore
SULT1C4NDST1HS3ST1HS3ST3A1PAPSS2PAPSS1HS3ST3B1
PROTEIN STRUCTURE
Preparing viewer…
PDB2GWH · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.33LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.98 [0.73–1.33]
RankingsWhere SULT1C4 stands among ~20K protein-coding genes
  • #12,689of 20,598
    Most Researched27
  • #13,924of 17,882
    Most Constrained (LOEUF)1.33
Genes detectedSULT1C4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human cytosolic sulfotransferase SULT1C4 mediates the sulfation of doxorubicin and epirubicin.
PMID: 26948952
Drug Metab Pharmacokinet · 2016
1.00
2
Developmental Expression of SULT1C4 Transcript Variants in Human Liver: Implications for Discordance Between SULT1C4 mRNA and Protein Levels.
PMID: 32303576
Drug Metab Dispos · 2020
0.90
3
An integrated investigation of sulfotransferases (SULTs) in hepatocellular carcinoma and identification of the role of SULT2A1 on stemness.
PMID: 38411862
Apoptosis · 2024
0.80
4
On the sulfation of O-desmethyltramadol by human cytosolic sulfotransferases.
PMID: 28802998
Pharmacol Rep · 2017
0.70
5
Molecular and functional characterization of cytosolic sulfotransferases in cynomolgus macaque.
PMID: 31100221
Biochem Pharmacol · 2019
0.60