EXTL2
protein-codingexostosin like glycosyltransferase 2, the group of Exostosin glycosyltransferase family
Gene summary
Enables alpha-1,4-N-acetylgalactosaminyltransferase activity and glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity. Involved in N-acetylglucosamine metabolic process and UDP-N-acetylgalactosamine metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EXTL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001033025.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 30 | 4 | 34 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 31 | 4 | 0 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001028197.1 | 4 | MANE Select | |
| Ensembl | ENSP00000359132.3 | 4 | MANE Select | |
| RefSeq | NP_001248369.1 | 4 | Standard | |
| RefSeq | NP_001248370.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human)
- XBP1(S) activates chaperone genes
- Proteoglycan biosynthesis
- heparan sulfate biosynthesis (late stages)
- heparan sulfate biosynthesis
Biological Process
- N-acetylglucosamine metabolic process
- protein glycosylation
- heparan sulfate proteoglycan biosynthetic process
- UDP-N-acetylgalactosamine metabolic process
- IRE1-mediated unfolded protein response
Molecular Function
- glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity
- glycosaminoglycan binding
- manganese ion binding
- alpha-1,4-N-acetylgalactosaminyltransferase activity
- glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferase activity
Cellular Component
- extracellular region
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370114
- Coding exons
- 4
- Length
- 23612
- Individuals with no LoFs
- 125648
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 36
- Defined
- 125684
- p
- 0.000143
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.831 | 146 | 177 | 0.824 | 0.00000835 | 2188 |
| Missense (PolyPhen) | 51 | 66.509 | 0.76682 | 871 | ||
| Synonymous | 0.315 | 58 | 61.1 | 0.949 | 0.00000289 | 621 |
| Loss of Function | 1.49 | 8 | 14.0 | 0.571 | 8.67e-7 | 159 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000066 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Glycosyltransferase required for the biosynthesis of heparan-sulfate and responsible for the alternating addition of beta-1-4-linked glucuronic acid (GlcA) and alpha-1-4-linked N- acetylglucosamine (GlcNAc) units to nascent heparan sulfate chains. {ECO:0000269|PubMed:10318803}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.387
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.107
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |