CHST3 Gene: Carbohydrate Sulfotransferase 3 – Function, Disease Associations, and Expression
Comprehensive biomedical overview of CHST3, including gene card, expression data, mutations, and clinical significance.
Gene Information Card
| Symbol | CHST3 |
|---|---|
| Full Name | Carbohydrate sulfotransferase 3 |
| Gene Type | protein coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 9469 ncbi.nlm.nih.gov/gene/9469 |
| Ensembl ID | ENSG00000122863 |
| UniProt ID | Q7LGC8 |
| OMIM ID | 603799 |
| HGNC ID | 1971 |
| Aliases | C6ST, C6ST1, chondroitin 6-O-sulfotransferase 1 |
Description
The CHST3 gene encodes carbohydrate sulfotransferase 3, an enzyme that catalyzes the transfer of sulfate to position 6 of the N-acetylgalactosamine residue of chondroitin. This modification is critical for the proper synthesis of chondroitin sulfate proteoglycans, which are essential components of cartilage and other connective tissues. Mutations in CHST3 cause autosomal recessive spondyloepiphyseal dysplasia with congenital joint dislocations (SEDCJD), characterized by severe skeletal abnormalities. The enzyme is localized to the Golgi apparatus and is expressed in various tissues, with highest levels in cartilage and bone.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spondyloepiphyseal dysplasia with congenital joint dislocations (SEDCJD) | Loss-of-function mutations in CHST3 lead to reduced chondroitin 6-O-sulfation, impairing cartilage matrix integrity and skeletal development. | OMIM #603799; ClinVar records pathogenic variants. |
| Multiple epiphyseal dysplasia (MED) (rare) | Some CHST3 mutations may cause a milder phenotype resembling MED, with epiphyseal abnormalities. | Case reports in literature; ClinVar. |
| Osteoarthritis susceptibility (possible) | Altered chondroitin sulfation may contribute to cartilage degeneration, but evidence is limited. | Association studies; not yet confirmed. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cartilage | High | nTPM not available from GTEx; RNA-seq data from Human Protein Atlas shows high expression in cartilage. |
| Bone | Medium | nTPM not available; moderate expression in bone tissue. |
| Liver | Low | nTPM ~5 (GTEx) |
| Kidney | Low | nTPM ~4 (GTEx) |
| Brain | Low | nTPM ~3 (GTEx) |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Chondrocytes | High | Primary chondrocytes show high CHST3 expression. |
| Osteoblasts | Medium | Moderate expression in osteoblast cell lines. |
| HeLa | Low | nTPM ~2 (Human Protein Atlas) |
| HepG2 | Low | nTPM ~1 (Human Protein Atlas) |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.559C>T (p.Arg187*) | Nonsense | Rare | Premature stop codon leading to truncated protein and loss of function. |
| c.680G>A (p.Arg227His) | Missense | Rare | Amino acid substitution affecting catalytic activity. |
| c.1003C>T (p.Arg335Trp) | Missense | Rare | Impairs enzyme function; associated with SEDCJD. |
| c.1150G>A (p.Gly384Ser) | Missense | Rare | Reduced sulfotransferase activity. |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic CHST3 mutations are loss-of-function, leading to reduced or absent chondroitin 6-O-sulfotransferase activity, causing skeletal dysplasia.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CHST3.
Dominant Negative (DN)
No dominant-negative effects documented; CHST3 disorders are autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • sulfotransferase activity | • carbohydrate binding |
| • Golgi apparatus | • chondroitin sulfate biosynthetic process |
| • protein modification process |
Pathways
• Chondroitin sulfate biosynthesis
• Glycosaminoglycan metabolism
• Sulfur metabolism
Protein Summary
The CHST3 protein is a type II transmembrane glycoprotein localized to the Golgi apparatus. It transfers sulfate from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to the C6 hydroxyl group of N-acetylgalactosamine residues in chondroitin. This modification is essential for the formation of chondroitin sulfate chains, which are critical for cartilage extracellular matrix function. The protein consists of a short cytoplasmic tail, a transmembrane domain, and a large luminal catalytic domain. Defects in this enzyme disrupt normal skeletal development, leading to severe growth and joint abnormalities.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHST3 Knockout HEK293 Cell Line | EDJ-KQ6597 | Human | 9469 | Details Get a Quote |
| CHST3 Knockout HeLa Cell Line | EDJ-KQ29477 | Human | 9469 | Details Get a Quote |
| CHST3 Knockout A-549 Cell Line | EDJ-KQ30819 | Human | 9469 | Details Get a Quote |
| CHST3 Knockout HCT 116 Cell Line | EDJ-KQ30820 | Human | 9469 | Details Get a Quote |
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