HS3ST6

Chr 16AD

heparan sulfate-glucosamine 3-sulfotransferase 6

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

NCBI Gene: 64711ENSG00000162040UniProt: Q96QI5OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismADLOEUF 0.881 OMIM phenotype
Clinical Summary— HS3ST6
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.18) despite low pLI — interpret in context.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 96 VUS of 140 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE0.18 (0.07–0.88)
0≤0.351.4
Missense OE1.01 (0.89–1.14)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 1 / 5.4Missense obs/exp: 171 / 169.7Syn Z: 0.78
DN
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.

ClinVar Variant Classifications

140 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic1
VUS96
Likely Benign2
40
Pathogenic
1
Likely Pathogenic
96
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
39
0
40
Likely Pathogenic
0
0
1
0
1
VUS
0
79
17
0
96
Likely Benign
0
0
0
2
2
Benign
0
0
0
0
0
Total080572139

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

View in ClinVar →

Protein Context — Lollipop Plot

HS3ST6 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients