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AGPS
alkylglycerone phosphate synthase
The *AGPS* gene provides instructions for producing alkylglycerone phosphate synthase, an enzyme crucial for synthesising plasmalogens, which are important lipids found in cell membranes and myelin. The *AGPS* gene is essential for proper peroxisomal function and lipid metabolism.
AGPS is located on the long (q) arm of chromosome 2, at band 2q31.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The *AGPS* gene encodes the enzyme alkylglycerone phosphate synthase, which plays a pivotal role in the biosynthesis of plasmalogens. These unique phospholipids are abundant in cell membranes throughout the body and are particularly concentrated in myelin, the protective sheath around nerve cells.
Disruptions in *AGPS* gene function can lead to impaired plasmalogen production, affecting cell membrane integrity and neurological development.
What the gene does
The alkylglycerone phosphate synthase enzyme, encoded by the *AGPS* gene, is located within peroxisomes, which are cellular compartments responsible for various metabolic processes. Within these peroxisomes, the enzyme carries out a critical step in the creation of plasmalogens. These lipid molecules are integral components of cell membranes and are particularly rich in the myelin that insulates nerve cells.
While the full range of plasmalogen functions is still being researched, they are thought to protect cells from oxidative stress caused by unstable molecules called free radicals. Plasmalogens may also contribute to interactions between lipids and proteins, facilitate chemical signalling within cells, and play a role in cell membrane fusion.
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Chromosome location
The *AGPS* gene is situated on chromosome 2 at position 2q31.2. This location indicates its specific address within the human genome.
Protein structure
The alkylglycerone phosphate synthase protein consists of 658 amino acids. It features two disordered regions at amino acids 1-41 and 63-86. A significant FAD-binding PCMH-type domain is located between amino acids 202 and 384. Furthermore, specific regions important for enzyme activity have been identified at amino acids 615-617 and 654-658.
Key variants
Variants in the *AGPS* gene can alter the structure and function of the alkylglycerone phosphate synthase enzyme. These genetic changes can affect the enzyme's ability to synthesise plasmalogens, leading to a reduction in their cellular levels and impacting various physiological processes.
Sample of pathogenic variants
9 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.544C>T | p.Arg182Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Rhizomelic chondrodysplasia punctata type 3 |
g.(178362494_178364345)_(178372760_178378546)del | - | Pathogenic | ★☆☆☆ | Rhizomelic chondrodysplasia punctata |
c.1543C>T | p.Arg515Ter | Pathogenic | ★☆☆☆ | not provided |
c.1663_1666dup | p.Gly556fs | Pathogenic | ★☆☆☆ | not provided |
c.1736dup | p.Tyr580fs | Pathogenic | ★☆☆☆ | Rhizomelic chondrodysplasia punctata type 3 |
c.549del | p.Phe184fs | Pathogenic | ★☆☆☆ | not provided |
c.638-1G>A | - | Pathogenic | ★☆☆☆ | Rhizomelic chondrodysplasia punctata type 3 |
c.1406T>C | p.Leu469Pro | Pathogenic | - | Rhizomelic chondrodysplasia punctata type 3 |
c.1703C>T | p.Thr568Met | Pathogenic | - | Rhizomelic chondrodysplasia punctata type 3 |
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
Variants in the *AGPS* gene are associated with inherited conditions such as rhizomelic chondrodysplasia punctata type 3 (RCDP3). This condition is characterised by skeletal abnormalities, cataracts, and severe developmental delays, often resulting from insufficient plasmalogen levels due to impaired enzyme function.
No disease links recorded for this gene in our reference set.
UK clinical status
The *AGPS* gene is included on several NHS Genomic Medicine Service clinical panels, indicating its recognised role in various inherited conditions. These panels include those for Bilateral congenital or childhood onset cataracts, Chondrodysplasia punctata, DDG2P, Foetal anomalies (R21), Likely inborn error of metabolism (R98), Peroxisomal disorders, Skeletal dysplasia (R104), and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What are plasmalogens?
Plasmalogens are a unique type of lipid molecule that are abundant in cell membranes throughout the body, particularly in the myelin sheath that insulates nerve cells. They are thought to play roles in protecting cells from oxidative stress and facilitating cellular communication.
What is rhizomelic chondrodysplasia punctata type 3 (RCDP3)?
RCDP3 is an inherited condition caused by variants in the *AGPS* gene. It is characterised by skeletal abnormalities, cataracts, and significant developmental delays, all linked to a deficiency in plasmalogens.
Where is the AGPS gene located?
The *AGPS* gene is located on chromosome 2 at band 2q31.2. This specific genomic address helps in identifying and studying the gene.
References
- Thai TP, Rodemer C, Jauch A. Impaired membrane traffic in defective ether lipid biosynthesis. Human molecular genetics. 2001. PMID: 11152660
- de Vet EC, Ijlst L, Oostheim W. Alkyl-dihydroxyacetonephosphate synthase. Fate in peroxisome biogenesis disorders and identification of the point mutation underlying a single enzyme deficiency. The Journal of biological chemistry. 1998. PMID: 9553082
- van den Bosch H, de Vet EC. Alkyl-dihydroxyacetonephosphate synthase. Biochimica et biophysica acta. 1997. PMID: 9370314
- Wanders RJ, Dekker C, Hovarth VA. Human alkyldihydroxyacetonephosphate synthase deficiency: a new peroxisomal disorder. Journal of inherited metabolic disease. 1994. PMID: 7807941