SULT1E1

Chr 4

sulfotransferase family 1E member 1

Also known as: EST, EST-1, ST1E1, STE

NCBI Gene: 6783 ENSG00000109193 UniProt: P49888

The SULT1E1 protein is a sulfotransferase enzyme that catalyzes sulfate conjugation of estradiol and estrone, serving as a key regulator of estrogen homeostasis by inactivating these hormones through sulfation. The gene is highly constrained against loss-of-function variants, but no Mendelian diseases have been definitively associated with SULT1E1 mutations in current clinical genetics practice. Research suggests potential roles in neurodevelopment through metabolism of gut bacteria-derived compounds that may affect oligodendrocyte maturation and brain connectivity.

ResearchSummary from RefSeq, UniProt

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 encodes a protein that transfers a sulfo moiety to and from estrone, which may control levels of estrogen receptors. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.27

Clinical Summary— SULT1E1

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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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ClinVar Variants

36 VUS of 50 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.000

Z-score 0.78

OE 0.78 (0.50–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.12Z-score

OE missense 0.97 (0.85–1.11)

148 obs / 152.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.50–1.27)

0≤0.351.4

Missense OE?0.97 (0.85–1.11)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 12 / 15.3Missense obs/exp: 148 / 152.2Syn Z: 0.52

This gene — mechanism propensity

0.7229th %ile

GOF

0.6541th %ile

LOF

0.1895th %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.

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

VUS36

Likely Benign4

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	36	0	36
Likely Benign	1	3	4
Benign	0	2	2
Total	37	5	42

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

22 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap SULT1E1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →