HS3ST6

Chr 16AD

heparan sulfate-glucosamine 3-sulfotransferase 6

Also known as: 3-OST-6, 3OST6, HAE8, HS3ST5

NCBI Gene: 64711 ENSG00000162040 UniProt: Q96QI5 OMIM: 619210

HS3ST6 encodes a heparan sulfate 3-O-sulfotransferase that catalyzes the transfer of sulfate groups to heparan sulfate proteoglycans, modifying their structure and binding properties. Mutations cause hereditary angioedema with autosomal dominant inheritance. The gene shows moderate constraint against loss-of-function variants, suggesting some tolerance to reduced function.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable [heparan sulfate]-glucosamine 3-sulfotransferase activity. Predicted to be involved in heparan sulfate proteoglycan biosynthetic process. Predicted to act upstream of or within blastocyst hatching. Predicted to be located in Golgi membrane. Implicated in hereditary angioedema. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismADLOEUF 0.881 OMIM phenotype

Clinical Summary— HS3ST6

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.18) 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?

0.88LOEUF

pLI 0.436

Z-score 1.76

OE 0.18 (0.07–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.04Z-score

OE missense 1.01 (0.89–1.14)

171 obs / 169.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.18 (0.07–0.88)

0≤0.351.4

Missense OE?1.01 (0.89–1.14)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 1 / 5.4Missense obs/exp: 171 / 169.7Syn Z: 0.78

This gene — mechanism propensity

0.5869th %ile

GOF

0.6443th %ile

LOF

0.4233th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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.