HS6ST3

Chr 13

heparan sulfate 6-O-sulfotransferase 3

Also known as: HS6ST-3

The HS6ST3 protein is a 6-O-sulfation enzyme that catalyzes the transfer of sulfate to heparan sulfate, generating structures required for interactions with various proteins involved in proliferation, differentiation, adhesion, migration, and inflammation. This gene is highly constrained against loss-of-function variants (pLI=0.99, LOEUF=0.22), suggesting that mutations would likely cause severe developmental disorders, though specific disease associations have not yet been established. Any associated conditions would follow an autosomal inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.22
Clinical SummaryHS6ST3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
83 unique Pathogenic / Likely Pathogenic· 92 VUS of 180 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 0.990
Z-score 3.45
OE 0.00 (0.000.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.19Z-score
OE missense 0.79 (0.710.89)
207 obs / 261.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.22)
00.351.4
Missense OE0.79 (0.710.89)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 0 / 13.8Missense obs/exp: 207 / 261.2Syn Z: 1.17

ClinVar Variant Classifications

180 submitted variants in ClinVar

Classification Summary

Pathogenic83
VUS92
Likely Benign2
Benign1
83
Pathogenic
92
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
83
0
83
Likely Pathogenic
0
0
0
0
0
VUS
0
79
13
0
92
Likely Benign
0
1
0
1
2
Benign
0
0
1
0
1
Total080971178

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

View in ClinVar →

Protein Context — Lollipop Plot

HS6ST3 · 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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