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.
View complete mutation data:
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 Services
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 |