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AGPS
alkylglycerone phosphate synthase
The AGPS gene provides instructions for alkylglycerone phosphate synthase, an enzyme crucial for synthesising plasmalogens, a type of lipid vital for cell membranes and the nervous system. The AGPS gene encodes the enzyme alkylglycerone phosphate synthase, located within peroxisomes.
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, or alkylglycerone phosphate synthase, is responsible for producing an enzyme of the same name. This enzyme is located in peroxisomes, which are cellular compartments involved in metabolism. Its primary function involves a critical step in the biosynthesis of plasmalogens, a unique class of lipids. These lipids are important components of cell membranes throughout the body and are particularly abundant in the myelin sheath that insulates nerve cells.
What the gene does
The alkylglycerone phosphate synthase enzyme, encoded by the AGPS gene, resides in peroxisomes and is vital for plasmalogen production. Plasmalogens are a type of lipid found in cell membranes across the body and are especially plentiful in myelin, the protective sheath around nerve cells. While their precise roles are still being investigated, researchers suggest plasmalogens may help shield cells from oxidative stress. This occurs when free radicals accumulate to damaging levels. Additionally, these molecules may be important for interactions between lipids and proteins, the transmission of chemical signals within cells, and the process of cell membrane fusion. Impaired function of the AGPS enzyme can lead to a deficiency in plasmalogens, affecting cellular integrity and overall function.
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Chromosome location
The AGPS gene is situated on chromosome 2, specifically at position 2q31.2. This location indicates its position on the long arm of chromosome 2. The gene directs the synthesis of a protein consisting of 658 amino acids.
Protein structure
The AGPS protein is 658 amino acids long. It features several notable regions, including 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. Additionally, two distinct regions, amino acids 615-617 and 654-658, have been identified as important for the enzyme's catalytic activity.
Key variants
Variants within the AGPS gene can lead to changes in the alkylglycerone phosphate synthase enzyme, potentially affecting its structure and function. Such genetic alterations can reduce the enzyme's activity, disrupting the normal production of plasmalogens. The clinical impact of AGPS variants can vary, depending on the specific change and its effect on enzyme efficiency.
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 various conditions, primarily those affecting peroxisomal function and plasmalogen synthesis. The most well-known condition linked to AGPS variants is rhizomelic chondrodysplasia punctata type 3 (RCDP3). At least three mutations in the AGPS gene have been found to cause RCDP3. These genetic changes alter single protein building blocks (amino acids) in alkylglycerone phosphate synthase, which modifies the enzyme's structure and significantly reduces its activity. This reduction in enzyme function impairs peroxisome activity, contributing to the condition.
No disease links recorded for this gene in our reference set.
UK clinical status
The AGPS gene is included in several UK NHS national genomic testing panels, indicating its clinical significance. It is part of panels for conditions such as Bilateral congenital or childhood onset cataracts (R31), Chondrodysplasia punctata, DDG2P, Foetal anomalies (R21), Likely inborn error of metabolism (R98), Peroxisomal disorders, Skeletal dysplasia (R104), and Undiagnosed metabolic disorders. This inclusion reflects its established role in these conditions within the UK healthcare system.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the AGPS gene?
The AGPS gene provides instructions for an enzyme called alkylglycerone phosphate synthase, which is critical for the production of plasmalogens, a type of lipid essential for cell membranes and the nervous system.
What conditions are associated with AGPS gene variants?
Variants in the AGPS gene are primarily associated with rhizomelic chondrodysplasia punctata type 3 (RCDP3), a rare condition affecting skeletal development, vision, and neurological function, due to impaired peroxisomal function and plasmalogen synthesis.
Where is the AGPS gene located?
The AGPS gene is located on chromosome 2, specifically at position 2q31.2. This genomic location is on the long arm of chromosome 2.
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