SULT1A3

Chr 16

sulfotransferase family 1A member 3

Also known as: HAST, HAST3, M-PST, ST1A3, ST1A3/ST1A4, ST1A4, ST1A5, STM

NCBI Gene: 6818 ENSG00000261052 UniProt: P0DMM9 OMIM: 600641

SULT1A3 encodes a sulfotransferase enzyme that catalyzes sulfate conjugation of neurotransmitters including dopamine, epinephrine, norepinephrine, and serotonin, as well as thyroid hormones. Currently, no specific disease associations have been established for pathogenic variants in this gene. The gene shows moderate tolerance to loss-of-function variants with a LOEUF score of 1.79.

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 SULT1A4 arose from a segmental duplication. This gene is the most centromeric of the four sulfotransferase genes. Read-through transcription exists between this gene and the upstream SLX1A (SLX1 structure-specific endonuclease subunit homolog A) gene that encodes a protein containing GIY-YIG domains. [provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.79

Clinical Summary— SULT1A3

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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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ClinVar Variants

1 VUS of 1 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.79LOEUF

pLI 0.363

Z-score 0.79

OE 0.00 (0.00–1.79)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.70Z-score

OE missense 0.42 (0.22–0.89)

5 obs / 11.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.79)

0≤0.351.4

Missense OE?0.42 (0.22–0.89)

0≤0.61.4

Synonymous OE?0.21

0≤1.21.6

LoF obs/exp: 0 / 0.7Missense obs/exp: 5 / 11.8Syn Z: 1.36

This gene — mechanism propensity

0.6842th %ile

GOF

0.7028th %ile

LOF

0.2189th %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

1 submitted variants in ClinVar

ClinVar

Classification Summary

VUS1

VUS

Curated Variants Distribution

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

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	—	—	—	—	0
Likely Pathogenic	—	—	—	—	0
VUS	—	—	—	—	1
Likely Benign	—	—	—	—	0
Benign	—	—	—	—	0
Total	—				1

Counts from ClinVar esearch · Updated hourly

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90 pathogenic / likely-pathogenic (of 98) ClinVar copy-number / structural variants overlap SULT1A3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →