ALG10
protein-codingALG10 alpha-1,2-glucosyltransferase, the group of Alpha-1,2-glucosyltransferases
Gene summary
This gene encodes a membrane-associated protein that adds the third glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. That is, it transfers the terminal glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc2Man9GlcNAc(2)-PP-Dol. The rat protein homolog was shown to specifically modulate the gating function of the rat neuronal ether-a-go-go (EAG) potassium ion channel. [provided by RefSeq, Jan 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0015286
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0015286
Submitter: ClinGen
*ALG10* was first reported in relation to autosomal recessive congenital disorder of glycosylation in 2018 (Courage et al., PMID: 33798445). One unique frameshift variant that has been reported in one proband in one publication is included in this curation. The proband also had a homozygous variant in *ALG10B*, which could not be ruled out as a contributing factor to the proband’s phenotype. This gene-disease relationship is also supported by a yeast model (Burda et al, PMID: 9597543) showing that *ALG10* is required for the terminal glucosylation step of the lipid-linked core oligosaccharide. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date April 3, 2025 (SOP Version 11).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ALG10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032834.4. 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 | 1 | 2 | 2 | 5 | ||
| missense | 1 | 70 | 3 | 2 | 76 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 2 | 71 | 5 | 4 | 82 |
Highest pathogenic variant AF is 6.840853e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_116223.3 | 3 | MANE Select | |
| Ensembl | ENSP00000266483.2 | 3 | MANE Select | |
| Ensembl | ENSP00000444084.1 | 3 | Standard | |
| Ensembl | ENSP00000444084.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- N-Glycan biosynthesis - Homo sapiens (human)
- Post-translational protein modification
- Metabolism of proteins
- Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
- Asparagine N-linked glycosylation
Biological Process
- dolichol-linked oligosaccharide biosynthetic process
Molecular Function
- dolichyl-phosphate-glucose-glycolipid alpha-glucosyltransferase activity
- dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity
Cellular Component
- endoplasmic reticulum membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000266483
- Coding exons
- 3
- Length
- 7414
- Individuals with no LoFs
- 125695
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 53
- Defined
- 125748
- p
- 0.000211
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0283 | 234 | 233 | 1.01 | 0.0000112 | 3103 |
| Missense (PolyPhen) | 69 | 77.977 | 0.88488 | 1040 | ||
| Synonymous | -0.219 | 88 | 85.4 | 1.03 | 0.00000410 | 910 |
| Loss of Function | 0.985 | 11 | 15.1 | 0.727 | 6.48e-7 | 223 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0.0012 | 0.0012 | notable |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00023 | 0.00022 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Adds the third glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc(2)Man(9)GlcNAc(2)-PP-Dol.;
Intolerance Scores
- LoFtool
- 0.652
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 33.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.372
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |