SULT1A2

Chr 16

sulfotransferase family 1A member 2

Also known as: HAST4, P-PST, P-PST 2, ST1A2, STP2, TSPST2

NCBI Gene: 6799 ENSG00000197165 UniProt: P50226 OMIM: 601292

SULT1A2 encodes a cytosolic sulfotransferase enzyme that catalyzes sulfate conjugation of catecholamines, phenolic drugs, and neurotransmitters using PAPS as a sulfonate donor. The gene is not highly constrained against loss-of-function variants (pLI near 0, LOEUF 1.585), and no clear Mendelian disease associations have been established in the current genetic literature. Clinical significance may relate to individual variation in drug metabolism rather than monogenic neurological disorders.

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 one of two phenol sulfotransferases with thermostable enzyme activity. Two alternatively spliced variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.58

Clinical Summary— SULT1A2

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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

60 VUS of 75 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?

1.58LOEUF

pLI 0.000

Z-score -0.23

OE 1.06 (0.73–1.58)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.85Z-score

OE missense 1.18 (1.05–1.32)

211 obs / 179.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.06 (0.73–1.58)

0≤0.351.4

Missense OE?1.18 (1.05–1.32)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 17 / 16.0Missense obs/exp: 211 / 179.2Syn Z: -0.39

This gene — mechanism propensity

0.6938th %ile

GOF

0.6637th %ile

LOF

0.2484th %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

75 submitted variants in ClinVar

ClinVar

Classification Summary

VUS60

Likely Benign5

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	60	60
Likely Benign	0	5	5
Benign	1	0	1
Total	1	65	66

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

View in ClinVar →

71 pathogenic / likely-pathogenic (of 95) ClinVar copy-number / structural variants overlap SULT1A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →