Annotated PGx Gene Information for SULT1A1
Submitted by: Michelle Hildebrandt, Araba Adjei, Richard Weinshilboum, and Julie A. Johnson(PPII)
Reviewed by: Zeruesenay Desta, Anne Nguyen, and David Flockhart (COBRA)
Submitted date: January 19, 2007
| Gene HGNC Name: | SULT1A1 |
|---|---|
| Gene Common Name: | SULT1A1 |
| Introductory Information: |
Sulfotransferase 1A1 (SULT1A1) catalyzes the sulfate conjugation of phenolic compounds including steroid hormones, catecholamines and phenolic drugs and also in the bioactivation of procarcinogens [reviewed in PMID: 9141497]. The gene was cloned in 1996 [PMID: 9014197] and is located on chromosome 16 in close proximity to the three other members of the SULT1A subfamily - SULT1A2, SULT1A3 and SULT1A4 [PMID: 8912648, 15358107]. The gene consists of 7 coding exons and 3 alternatively spliced upstream non-coding exons. The open reading frame is 885 nucleotides long and encodes a 295 amino acid protein which is present in many human tissues, including liver, kidney and platelet. Large individual variations in SULT1A1 enzyme activity have been observed. Platelet enzyme activity varied more than 50-fold and thermal stability varied over 10-fold in 905 subjects [PMID: 9345314]. Three non-synonymous SNPs were identified in SULT1A1 and one allele, SULT1A1*2 (213Arg>His, 638G>A), with an allele frequency of ~30% was shown to be associated with both low activity and thermal stability in the platelet and low thermal stability in the liver [PMID: 9345314, 10413297]. Three additional amino acid sequence variants (Met223Val, Arg37Gln, Phe247Leu) have also been reported with allele frequencies less than 2% in a Caucasian population [PMID: 10413297, 16801938]. Other SNPs within the 5'-flanking region have been reported to influence enzymatic activity, and are in linkage disequilibrium with SULT1A1*2 [PMID: 15970794]. Finally, copy number variants of functional significance have also recently been reported [PMID: 17189289]. Because of the importance of sulfation in the metabolism and biotransformation of estrogen and other steroid hormones, SULT1A1*2 has been extensively studied in relationship to hormone-dependent cancers. To date, the studies have been inconclusive with varying results. This gene has also been implicated in other malignancies including colorectal and esophageal cancer [PMID: 16425401, 16272171]. |
| Key PubMed IDs: | 9345314, 10413297 |
| Drugs/Substrates: | SULT1A1 metabolizes several phenolic substrates including simple phenolic compounds (4-nitrophenol which is used as a probe substrate [PMID: 10441143, 8423770]); drugs (acetaminophen [PMID: 6957279], minoxidil [PMID: 2390100]); estrogens (estrone, B-estradiol [PMID: 9068609], 2-hydroxyestrone, 2-hydroxyestradiol, 4-hydroxyestrone, 4-hydroxyestradiol [PMID: 11906176]) and synthetic estrogenic compounds (trans-4-hydroxytamoxifen [PMID: 12034366], diethylstilbestrol [PMID: 9068609], 2-methoxy estradiol [PMID: 11062153]). 2,6-dichloro-4-nitrophenol inhibits SULT1A1 activity [PMID: 6573904, 6576122, 1687013]. SULT1A1 also bioactivates procarcinogens including N-hydroxy metabolites of 2-amino-3-methylimidazo[4,5-f]guinoline [PMID: 16708048], and other procarcinogens reviewed by Glatt [PMID: 9141497]. |
| Phenotypes/Diseases: | Breast cancer [PMID: 14520706, 16141802, 15377847, 15093672]. Prostate cancer [PMID: 14973106, 10959796]. Colorectal cancer [PMID: 16425401]. Esophageal cancer [PMID: 16272171]. |
| Important Variants: | SULT1A1*2: 638 G>A , SULT1A1*3: 667 A>G , SULT1A1: -624 G>C , SULT1A1: -396 G>A |
| Important Haplotypes: | SULT1A1(638G>A, -624G>C and -396A>G) |