HS3ST2

Chr 16

heparan sulfate-glucosamine 3-sulfotransferase 2

Also known as: 30ST2, 3OST2

The protein is a heparan sulfate 3-O-sulfotransferase that catalyzes the transfer of sulfate groups to specific glucosamine residues on heparan sulfate chains, which are critical for various cellular signaling processes in the nervous system. Mutations cause autosomal recessive intellectual disability with behavioral abnormalities and seizures, typically manifesting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.686), suggesting some intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.69
Clinical SummaryHS3ST2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.100
Z-score 2.37
OE 0.30 (0.150.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.30Z-score
OE missense 0.56 (0.480.65)
123 obs / 219.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.30 (0.150.69)
00.351.4
Missense OE0.56 (0.480.65)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 4 / 13.3Missense obs/exp: 123 / 219.0Syn Z: -1.47
DN
0.6551th %ile
GOF
0.6442th %ile
LOF
0.3453th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HS3ST2 · 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.

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Clinical Literature
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