HS3ST4 (Heparan Sulfate-Glucosamine 3-Sulfotransferase 4)

A key enzyme in heparan sulfate biosynthesis with implications in cancer and developmental biology

Gene Information Card

Symbol HS3ST4
Full Name Heparan sulfate-glucosamine 3-sulfotransferase 4
Gene Type protein-coding
Chromosomal Location 16p11.2
NCBI Gene ID 9951 ncbi.nlm.nih.gov/gene/9951
Ensembl ID ENSG00000182601
UniProt ID Q9Y661
OMIM ID 604059
HGNC ID 5198
Aliases 3-OST-4, 3OST4

Description

HS3ST4 encodes a member of the heparan sulfate 3-O-sulfotransferase family. This enzyme catalyzes the transfer of sulfate to the 3-OH position of glucosamine residues in heparan sulfate, generating specific binding sites for proteins such as antithrombin III and herpes simplex virus glycoprotein D. HS3ST4 is involved in the biosynthesis of heparan sulfate, a glycosaminoglycan that plays critical roles in cell signaling, growth factor binding, and cell adhesion. The gene is expressed in various tissues, with notable expression in the brain and placenta. Alterations in HS3ST4 expression have been implicated in several cancers and developmental processes.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Cancer (various types) Altered expression of HS3ST4 affects heparan sulfate modification, influencing tumor growth and metastasis. COSMIC and literature reports indicate differential expression in tumors.
Herpes simplex virus infection HS3ST4 generates 3-O-sulfated heparan sulfate that serves as an entry receptor for HSV-1. Functional studies demonstrate binding to HSV-1 glycoprotein D.
Developmental disorders HS3ST4 is expressed in the brain; dysregulation may affect neurodevelopment. Expression data from GTEx and literature.

Expression Profile

Tissue Expression
Tissue nTPM level
Brain 8.2 Medium
Placenta 5.1 Low
Lung 2.3 Low
Kidney 1.8 Low
Liver 0.5 Not detected
Cell Line Expression
Cell Line nTPM Notes
HEK293 3.4 Low expression
HeLa 2.1 Low expression
A549 1.2 Very low
MCF7 0.8 Not detected
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.100G>A (p.Ala34Thr) Missense 0.01% (gnomAD) Unknown; predicted benign
c.250C>T (p.Arg84Trp) Missense 0.005% Unknown; predicted damaging
c.400del (p.Val134fs) Frameshift Rare Loss of function
Mutation functional classification

Loss of Function (LOF)

Frameshift mutations leading to premature stop codons are likely to result in loss of enzyme activity.

Gain of Function (GOF)

No evidence of gain-of-function mutations reported.

Dominant Negative (DN)

No evidence of dominant-negative effects.

Gene Ontology (GO)

• sulfotransferase activity • heparan sulfate sulfotransferase activity
• 3'-phosphoadenosine 5'-phosphosulfate binding • Golgi membrane
• integral component of membrane • heparan sulfate proteoglycan biosynthetic process
• carbohydrate metabolic process

Pathways

• Heparan sulfate biosynthesis
• Glycosaminoglycan metabolism
• Herpes simplex virus entry

Protein Summary

The HS3ST4 protein is a type II transmembrane enzyme localized to the Golgi apparatus. It consists of a short cytoplasmic tail, a transmembrane domain, and a luminal catalytic domain. The enzyme transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the 3-OH position of glucosamine in heparan sulfate. This modification creates specific binding sites for antithrombin III, contributing to anticoagulant activity, and for viral glycoproteins, facilitating viral entry. The protein is ~40 kDa in size and is expressed in a tissue-specific manner.

Related Products

Product name Cat.No. Species Gene ID
HS3ST4 Knockout HEK293 Cell Line EDJ-KQ6838 Human 9951 Details Get a Quote
HS3ST4 Knockout HeLa Cell Line EDJ-KQ55283 Human 9951 Details Get a Quote
HS3ST4 Knockout A-549 Cell Line EDJ-KQ63765 Human 9951 Details Get a Quote
HS3ST4 Knockout HCT 116 Cell Line EDJ-KQ72225 Human 9951 Details Get a Quote
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