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ALG6
ALG6 alpha-1,3-glucosyltransferase
The ALG6 gene provides instructions for an enzyme crucial in glycosylation, a process that attaches sugar molecules to proteins and fats, essential for their proper function. ALG6 codes for alpha-1,3-glucosyltransferase, an enzyme involved in adding glucose to oligosaccharide chains during glycosylation.
ALG6 is located on the short (p) arm of chromosome 1, at band 1p31.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The ALG6 gene, also known as ALG6 alpha-1,3-glucosyltransferase, plays a significant role in human biology by directing the production of an enzyme involved in glycosylation. Glycosylation is a fundamental cellular process where sugar molecules (oligosaccharides) are attached to proteins and fats, enabling them to perform a wide array of functions within the body. Understanding the ALG6 gene is important for its link to inherited conditions affecting this critical biological pathway.
What the gene does
The ALG6 gene encodes an enzyme called alpha-1,3-glucosyltransferase, which is a key component of the glycosylation pathway. Specifically, this enzyme is responsible for transferring a glucose sugar molecule to a growing oligosaccharide chain. This stepwise assembly of sugar molecules forms complex chains that are subsequently attached to proteins and lipids. These modifications are essential for the correct folding, stability, and function of a diverse range of molecules, impacting cellular communication, immune response, and overall development. Variants in the ALG6 gene can lead to an enzyme with reduced or absent activity, disrupting this vital process.
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Chromosome location
The ALG6 gene is situated on the short arm of chromosome 1, at position 1p31.3. This genomic location helps in identifying and studying the gene's context within the human genome. The precise location facilitates genetic mapping and diagnostic investigations related to conditions associated with ALG6.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the ALG6 gene can alter the function of the alpha-1,3-glucosyltransferase enzyme. These genetic changes may range from single nucleotide substitutions to larger deletions or insertions, potentially leading to a dysfunctional or non-functional protein. The presence of certain pathogenic variants is associated with an increased risk of developing inherited conditions related to impaired glycosylation.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1000delinsGG | p.Leu334fs | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.100_101del | p.Met34fs | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.114T>G | p.Tyr38Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.1246_1250del | p.Leu416fs | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-related disorder |
c.12G>A | p.Trp4Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.1326+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.136G>T | p.Glu46Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.168G>A | p.Trp56Ter | Pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.226dup | p.Thr76fs | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.658A>T | p.Lys220Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the ALG6 gene are primarily associated with ALG6-Congenital Disorder of Glycosylation (also known as congenital disorder of glycosylation type Ic). This inherited condition typically presents with a range of symptoms, including developmental delay, vision problems, and seizures. It is classified as an autosomal recessive condition, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to be affected.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic ALG6 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
In the UK, the ALG6 gene is included on several NHS clinical panels, indicating its recognised clinical significance. It is listed as 'green' on PanelApp for conditions such as Congenital disorders of glycosylation, Early onset or syndromic epilepsy, Foetal anomalies, Intellectual disability, Likely inborn error of metabolism, and Undiagnosed metabolic disorders. This widespread inclusion highlights the importance of ALG6 in diagnosing various complex conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is glycosylation and why is it important?
Glycosylation is a biochemical process where sugar molecules (oligosaccharides) are attached to proteins and lipids. This modification is crucial for the proper folding, stability, and function of these molecules, impacting many essential biological processes like immune response and cell signalling.
What is ALG6-Congenital Disorder of Glycosylation?
ALG6-Congenital Disorder of Glycosylation (ALG6-CDG) is an inherited condition caused by pathogenic variants in the ALG6 gene. It results in a deficiency of the ALG6 enzyme, leading to impaired glycosylation and symptoms such as developmental delay, vision problems, and seizures.
How is ALG6-CDG inherited?
ALG6-CDG is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of a pathogenic variant in the ALG6 gene, one from each parent, to develop the condition. Parents who each carry one copy of the pathogenic variant are typically unaffected themselves but are carriers.
References
- Westphal V, Xiao M, Kwok PY. Identification of a frequent variant in ALG6, the cause of Congenital Disorder of Glycosylation-Ic. Human mutation. 2003. PMID: 14517965
- Grünewald S, Imbach T, Huijben K. Clinical and biochemical characteristics of congenital disorder of glycosylation type Ic, the first recognized endoplasmic reticulum defect in N-glycan synthesis. Annals of neurology. 2000. PMID: 10852543
- Imbach T, Burda P, Kuhnert P. A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic. Proceedings of the National Academy of Sciences of the United States of America. 1999. PMID: 10359825
- Adam MP, Bick S, Mirzaa GM. Congenital Disorders of N-Linked Glycosylation and Multiple Pathway Overview – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1993. PMID: 20301507