SULT1B1

Chr 4

sulfotransferase family 1B member 1

ENSG00000173597 UniProt: O43704 OMIM: 608436

SULT1B1 encodes a sulfotransferase enzyme that catalyzes sulfate conjugation of dopamine, thyroid hormones (T3 and reverse T3), and gut bacteria-derived metabolites that can affect brain myelination. The gene is not highly constrained against loss-of-function variants. Pathogenic variants in SULT1B1 have not been established as a cause of Mendelian disease.

OMIM ResearchSummary from RefSeq, UniProt

Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of dopamine, small phenols such as 1-naphthol and p-nitrophenol and thyroid hormones, including 3,3'-diiodothyronine, triidothyronine (T3) and reverse triiodothyronine (rT3) (PubMed:28084139, PubMed:9443824, PubMed:9463486). May play a role in gut microbiota-host metabolic interaction. O-sulfonates 4-ethylphenol (4-EP), a dietary tyrosine-derived metabolite produced by gut bacteria. The product 4-EPS crosses the blood-brain barrier and may negatively regulate oligodendrocyte maturation and myelination, affecting the functional connectivity of different brain regions associated with the limbic system (PubMed:35165440)

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.31

Clinical Summary— SULT1B1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.000

Z-score 0.65

OE 0.82 (0.54–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.45Z-score

OE missense 1.10 (0.97–1.25)

172 obs / 156.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.82 (0.54–1.31)

0≤0.351.4

Missense OE?1.10 (0.97–1.25)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 13 / 15.8Missense obs/exp: 172 / 156.3Syn Z: -1.36

This gene — mechanism propensity

0.7132th %ile

GOF

0.6542th %ile

LOF

0.2288th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.