SULT1A4

Chr 16

sulfotransferase family 1A member 4

Also known as: HAST3, M-PST, ST1A3, ST1A3/ST1A4, ST1A4, STM, TL-PST

NCBI Gene: 445329 ENSG00000213648 UniProt: P0DMN0 OMIM: 615819

The protein is a phenol sulfotransferase that catalyzes sulfate conjugation of neurotransmitters (dopamine, epinephrine, norepinephrine, serotonin) and thyroid hormones using PAPS as a sulfate donor. SULT1A4 mutations have not been definitively associated with human disease to date. The gene shows low constraint to loss-of-function variation (pLI 0.38, LOEUF 1.74), suggesting haploinsufficiency is likely tolerated.

OMIM 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 phenol sulfotransferase with thermolabile enzyme activity. Four sulfotransferase genes are located on the p arm of chromosome 16, this gene and SULT1A3 arose from a segmental duplication. Read-through transcription exists between this gene and the upstream SLX1B (SLX1 structure-specific endonuclease subunit homolog B) gene that encodes a protein containing GIY-YIG domains. [provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.74

Clinical Summary— SULT1A4

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.74LOEUF

pLI 0.385

Z-score 0.89

OE 0.00 (0.00–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.98Z-score

OE missense 0.23 (0.10–0.60)

3 obs / 12.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.74)

0≤0.351.4

Missense OE?0.23 (0.10–0.60)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

LoF obs/exp: 0 / 0.9Missense obs/exp: 3 / 12.9Syn Z: 0.48

This gene — mechanism propensity

0.6743th %ile

GOF

0.7127th %ile

LOF

0.2289th %ile

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

GOFprediction above median

DNprediction 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.