SULT1A4

Chr 16

sulfotransferase family 1A member 4

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

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.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.74
Clinical SummarySULT1A4
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
78 unique Pathogenic / Likely Pathogenic· 11 VUS of 92 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.74LOEUF
pLI 0.385
Z-score 0.89
OE 0.00 (0.001.74)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.98Z-score
OE missense 0.23 (0.100.60)
3 obs / 12.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.001.74)
00.351.4
Missense OE0.23 (0.100.60)
00.61.4
Synonymous OE0.76
01.21.6
LoF obs/exp: 0 / 0.9Missense obs/exp: 3 / 12.9Syn Z: 0.48
DN
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.

ClinVar Variant Classifications

92 submitted variants in ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic7
VUS11
Likely Benign1
Benign1
71
Pathogenic
7
Likely Pathogenic
11
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
71
Likely Pathogenic
7
VUS
11
Likely Benign
1
Benign
1
Total91

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SULT1A4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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