HS6ST3

Chr 13

heparan sulfate 6-O-sulfotransferase 3

Also known as: HS6ST-3

NCBI Gene: 266722 ENSG00000185352 UniProt: Q8IZP7

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.

ResearchSummary from RefSeq, UniProt

Heparan sulfate (HS) sulfotransferases, such as HS6ST3, modify HS to generate structures required for interactions between HS and a variety of proteins. These interactions are implicated in proliferation and differentiation, adhesion, migration, inflammation, blood coagulation, and other diverse processes (Habuchi et al., 2000 [PubMed 10644753]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.22

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 0.990

Z-score 3.45

OE 0.00 (0.00–0.22)

Highly constrained

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

Missense Constraint?

1.19Z-score

OE missense 0.79 (0.71–0.89)

207 obs / 261.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.22)

0≤0.351.4

Missense OE?0.79 (0.71–0.89)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 0 / 13.8Missense obs/exp: 207 / 261.2Syn Z: 1.17

Background carrier burden — how many people carry a rare variant somewhere in HS6ST3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 91

629 rare PASS variants

Rare truncating (LoF)

1 in 2,600

46 rare PASS variants

Rare synonymous (reference)

1 in 290

262 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HS6ST3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 4,800
South Asian	~43k	1 in 120	1 in 4,400
Remaining (unassigned)	~30k	1 in 91	1 in 3,100
European (Finnish)	~27k	1 in 320	≈ 1 in 13,000
Admixed American	~22k	1 in 70	1 in 2,400
African / African American	~21k	1 in 110	≈ 1 in 6,400
East Asian	~20k	1 in 100	≈ 1 in 4,100
Ashkenazi Jewish	~13k	1 in 390	1 in 2,000
Middle Eastern	~2,884	1 in 110	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓