SULT2A1
sulfotransferase family 2A member 1
Theoretical — per Powers
Gene summary
A protein-coding gene on chromosome 19 (steroid conjugation and clearance). Encodes a member of the sulfotransferase family. Sulfotransferases aid in the metabolism of drugs and endogenous compounds by converting these substances into more hydrophilic water-soluble sulfate conjugates that can be easily excreted.
Source: NCBI Gene, accessed 2026-10-07.
Protein reference (UniProt)
- Protein
Sulfotransferase 2A1
- Function
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands. Mediates the sulfation of a wide range of steroids and sterols, including pregnenolone, androsterone, DHEA, bile acids, cholesterol and as well many xenobiotics that contain alcohol and phenol functional groups. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Plays an important role in maintening steroid and lipid homeostasis. Plays a key role in bile acid metabolism, mediating formation of 3-sulfated bile acids. In addition, catalyzes the metabolic activation of potent carcinogenic polycyclic arylmethanols (By similarity).
- Subcellular location
Cytoplasm.
- Tissue specificity
Liver, adrenal and at lower level in the kidney. Is present in human fetus in higher level in the adrenal than the liver and the kidney.
Source: UniProtKB/Swiss-Prot Q06520, release 2026_03, licensed CC BY 4.0. This is the protein’s normal biology, not evidence about post-drug syndromes; associated conditions are inherited disorders of the gene, not PFS, PSSD or PRSD.
Why its pathway is in the library
Steroid clearance is the exit route for androgens and their metabolites — the pathway at the center of Powers' PFS model (defective glucuronidation/sulfation trapping androgens intracellularly). Gut bacterial enzymes can undo this clearance, linking it to the microbiome thread.
Written for the whole conjugation & clearance family, not for SULT2A1 specifically.
Powers’ note (his unpublished theorizing)
Named by Powers (DWP-003, unpublished): weakening mutations impair the sulfation exit route for testosterone, amplifying the glucuronidation defect.
Narrative library record
Function
Cytosolic sulfotransferase expressed in liver and adrenal glands that catalyzes the sulfation of steroids and bile acids, converting them into water-soluble sulfate conjugates for excretion; variants are studied for effects on circulating DHEA-sulfate levels.
Corpus relevance
Powers named SULT2A1 in his DWP-003 post (circa May 2026, direct retrieval): weakening mutations impair the sulfation exit route for testosterone, amplifying the core UGT2B17 glucuronidation defect. In his multi-exit model, testosterone must leave the cell via glucuronidation (UGT2B15/2B17), sulfation (SULT2A1), or metabolic conversion - losing both primary exits deepens intracellular androgen trapping, which he proposes leads to receptor downregulation and eventual epigenetic silencing of androgen signaling. SULT2A1 therefore sits in the same defective-exit-routes phenotype as the UGT cluster. Attribution: theoretical-per-Powers (unpublished Reddit theorizing); no PFS patient variant data in corpus.
Powers’ claims naming SULT2A1
- Powers gene claim
SULT2A1 — weakening mutations
Confidence: direct
Weakening mutations in SULT2A1 impair the sulfation exit route for testosterone, amplifying the glucuronidation defect.
SULT2A1PGL-SULT2A1circa May 2026PFS
Mentioned in 5 corpus records
- Powers · Reddit post
I think I have figured out at least one specific phenotype of PFS, and it is different from the "allopregnanolone" theory
u/drwillpowers · r/DrWillPowers
Powers' key genetics-first post: he proposed a specific PFS phenotype whose "base, core defect" is defective UGT2B17, disabling testosterone's main glucuronidation exit pathway. Carriers show shockingly low 3α-androstanediol glucuronide and near-zero urinary…
AKR1C1AKR1C2AKR1C3AKR1C4HSD17B2+3DWP-0032026PFSCore corpus - Powers · Reddit postCurated Powers pick
Had another random PSSD/PFS thought about the glucuronidation theory. Do any of you with PFS have elevated sul...
u/drwillpowers · r/DrWillPowers
Post body unavailable. From the title (truncated in the export at "elevated sul…"), Powers shared a new thought extending his glucuronidation theory and asked PFS patients whether they have elevated sulf- markers — in context, most plausibly…
SULT2A1PRH-14052026-03-30T19:44:12ZPFSPSSDPowers Reddit history - Peer-reviewed paper
SULT2A1 Gene Copy Number Variation is Associated with Urinary Excretion Rate of Steroid Sulfates
Jenny Jakobsson Schulze; Maria Johansson; John-Olof Thörngren; Mats Garle; Anders Rane; Lena Ekström · Frontiers in Endocrinology
In healthy volunteers given exogenous testosterone, the authors tested whether copy-number variation in sulfotransferase genes predicted urinary excretion of steroid sulfates. SULT2A1 copy number was significantly associated with excretion rates of sulfate…
SULT2A1MECH-0192013Systems review · Oct 2026 - Peer-reviewed paper
Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms
Guangju Zhai, Alexander Teumer, Lisette Stolk, John R. B. Perry, Liesbeth Vandenput, Andrea D. Coviello, Annemarie Koster, Jordana T. Bell… · PLoS Genetics
DHEA sulfate is the most abundant circulating adrenal steroid and declines markedly with age, prompting speculation that relative deficiency contributes to age-related disease. A meta-analysis of genome-wide association data in 14,846 individuals identified…
SULT2A1MECH-0402011Systems review · Oct 2026 - Peer-reviewed paperMerged into MECH-019SULT2A1MECH-039Systems review · Oct 2026
Also in steroid conjugation and clearance
All 31 genes- UGT2B17Powers
UDP glucuronosyltransferase family 2 member B17
chr 4· Conjugation & clearance· 30 records - UGT2B15Powers
UDP glucuronosyltransferase family 2 member B15
chr 4· Conjugation & clearance· 13 records - AKR1C2Powers
aldo-keto reductase family 1 member C2
chr 10· Steroid synthesis· 12 records - UGT2B7Powers
UDP glucuronosyltransferase family 2 member B7
chr 4· Conjugation & clearance· 11 records - AKR1C3Powers
aldo-keto reductase family 1 member C3
chr 10· Steroid synthesis· 9 records - AKR1C4Powers
aldo-keto reductase family 1 member C4
chr 10· Steroid synthesis· 8 records - AKR1C1Powers
aldo-keto reductase family 1 member C1
chr 10· Steroid synthesis· 7 records - UGT1A1Powers
UDP glucuronosyltransferase family 1 member A1
chr 2· Conjugation & clearance· 7 records
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