HS3ST4

Chr 16

heparan sulfate-glucosamine 3-sulfotransferase 4

Also known as: 3-OST-4, 30ST4, 3OST4, h3-OST-4

NCBI Gene: 9951 ENSG00000182601 UniProt: Q9Y661 OMIM: 604059

The HS3ST4 protein is a sulfotransferase enzyme that catalyzes the transfer of sulfate groups to specific glucosamine residues in heparan sulfate, modifying this important cell surface glycosaminoglycan. This gene is highly constrained against loss-of-function variants, but disease-causing mutations and associated clinical phenotypes have not yet been established in humans. Inheritance pattern remains to be determined as pathogenic variants have not been reported.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes the enzyme heparan sulfate D-glucosaminyl 3-O-sulfotransferase 4. This enzyme generates 3-O-sulfated glucosaminyl residues in heparan sulfate. Cell surface heparan sulfate is used as a receptor by herpes simplex virus type 1 (HSV-1), and expression of this gene is thought to play a role in HSV-1 pathogenesis. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.49

Clinical Summary— HS3ST4

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

62 VUS of 66 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.796

Z-score 2.57

OE 0.10 (0.04–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.87Z-score

OE missense 0.82 (0.72–0.94)

158 obs / 192.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.49)

0≤0.351.4

Missense OE?0.82 (0.72–0.94)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 1 / 9.6Missense obs/exp: 158 / 192.0Syn Z: -1.43

ClinVar Variant Classifications

66 submitted variants in ClinVar

ClinVar

Classification Summary

VUS62

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	62	0	62
Likely Benign	0	1	1
Benign	0	0	0
Total	62	1	63

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap HS3ST4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →