EXTL3: Exostosin Like Glycosyltransferase 3
A key enzyme in heparan sulfate biosynthesis, associated with skeletal dysplasia and immune deficiency.
Gene Information Card
| Symbol | EXTL3 |
|---|---|
| Full Name | Exostosin Like Glycosyltransferase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 8p21.1 |
| NCBI Gene ID | 2137 ncbi.nlm.nih.gov/gene/2137 |
| Ensembl ID | ENSG00000104419 |
| UniProt ID | O43909 |
| OMIM ID | 605744 |
| HGNC ID | 3518 |
| Aliases | EXTL1L, EXTL3L, REG, EXTL1-like, EXT-related gene 3 |
Description
EXTL3 encodes a glycosyltransferase involved in the biosynthesis of heparan sulfate, a critical component of the extracellular matrix. The enzyme catalyzes the initiation and elongation of heparan sulfate chains. Mutations in EXTL3 cause autosomal recessive skeletal dysplasia with severe combined immunodeficiency (SCID), highlighting its role in both skeletal development and immune function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Skeletal dysplasia with severe combined immunodeficiency (SCID) | Loss-of-function mutations impair heparan sulfate synthesis, disrupting bone growth and immune cell development. | OMIM #617425; PMID: 28190455 |
| Immunodeficiency 80 with or without congenital cardiomyopathy | Defective EXTL3 leads to impaired lymphocyte development and function. | ClinVar; PMID: 28190455 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.3 | Medium |
| Bone marrow | 9.8 | Medium |
| Small intestine | 8.5 | Medium |
| Liver | 6.2 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 10.5 | Moderate expression |
| K562 | 7.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.958C>T (p.Arg320*) | Nonsense | Rare | Loss of function; truncated protein |
| c.1120G>A (p.Gly374Arg) | Missense | Rare | Impaired enzymatic activity |
| c.1723C>T (p.Arg575Trp) | Missense | Rare | Reduced heparan sulfate synthesis |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish glycosyltransferase activity, leading to heparan sulfate deficiency.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Heparan sulfate biosynthesis (Reactome: R-HSA-2022928)
• Glycosaminoglycan metabolism (KEGG: hsa00532)
Protein Summary
EXTL3 is a 919-amino acid type II transmembrane protein localized to the Golgi apparatus. It functions as a bifunctional glycosyltransferase: it initiates heparan sulfate chain elongation by transferring N-acetylglucosamine to the tetrasaccharide linker, and also elongates the chain. The protein contains a conserved glycosyltransferase domain and is essential for normal skeletal patterning and immune system development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EXTL3 Knockout HEK293 Cell Line | EDJ-KQ1890 | Human | 2137 | Details Get a Quote |
| EXTL3 Knockout A-549 Cell Line | EDJ-KQ21788 | Human | 2137 | Details Get a Quote |
| EXTL3 Knockout HCT 116 Cell Line | EDJ-KQ21789 | Human | 2137 | Details Get a Quote |
| EXTL3 Knockout HeLa Cell Line | EDJ-KQ21790 | Human | 2137 | Details Get a Quote |
