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QDPR
quinoid dihydropteridine reductase
The QDPR gene provides instructions for making an enzyme called quinoid dihydropteridine reductase, which is essential for recycling tetrahydrobiopterin (BH4), a critical cofactor in various metabolic pathways. The QDPR gene encodes the quinoid dihydropteridine reductase enzyme, vital for the regeneration of tetrahydrobiopterin (BH4).
QDPR is located on the short (p) arm of chromosome 4, at band 4p15.32. Arm ratio per GRCh38 - banding schematic.
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Overview
The QDPR gene, short for quinoid dihydropteridine reductase, is a gene located on chromosome 4 that plays a significant role in human biochemistry. It provides the genetic blueprint for an enzyme known as quinoid dihydropteridine reductase. This enzyme is crucial for maintaining the body's supply of tetrahydrobiopterin (BH4), a molecule fundamental to several metabolic processes.
Dysfunction of the QDPR gene can lead to metabolic disorders, specifically conditions related to tetrahydrobiopterin deficiency. Understanding the QDPR gene and its functions is important for diagnosing and managing such inherited conditions.
What the gene does
The primary function of the QDPR gene is to produce the quinoid dihydropteridine reductase enzyme. This enzyme is integral to the recycling pathway of tetrahydrobiopterin (BH4), which acts as a cofactor. A cofactor is a non-protein chemical compound that is required for an enzyme's activity.
Tetrahydrobiopterin is involved in several critical enzymatic reactions, including the processing of various amino acids, which are the building blocks of proteins. For instance, BH4 works with the enzyme phenylalanine hydroxylase to convert phenylalanine into tyrosine. Beyond amino acid metabolism, BH4 is also involved in the synthesis of neurotransmitters, which are chemical messengers that transmit signals between nerve cells in the brain. Once BH4 has participated in these reactions, it is altered and must be regenerated to its active form, a process in which quinoid dihydropteridine reductase plays a key role.
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Chromosome location
The QDPR gene is situated on chromosome 4 at position 4p15.32. This specific location indicates its address within the human genome. The gene encodes a protein that is 244 amino acids in length.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the QDPR gene can alter the function of the quinoid dihydropteridine reductase enzyme. These genetic changes may range from single nucleotide substitutions to larger deletions or insertions. Such alterations can impair the enzyme's ability to recycle tetrahydrobiopterin effectively.
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.278del | p.Gly93fs | Pathogenic/Likely pathogenic | ★★☆☆ | Dihydropteridine reductase deficiency |
c.344C>T | p.Ser115Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Dihydropteridine reductase deficiency |
c.421del | p.Leu141fs | Pathogenic | ★★☆☆ | Dihydropteridine reductase deficiency |
c.436+2552A>G | - | Pathogenic | ★★☆☆ | Dihydropteridine reductase deficiency |
c.449A>G | p.Tyr150Cys | Pathogenic | ★★☆☆ | QDPR-related disorder |
c.472C>T | p.His158Tyr | Pathogenic/Likely pathogenic | ★★☆☆ | Dihydropteridine reductase deficiency |
c.523del | p.Ala175fs | Pathogenic | ★★☆☆ | Dihydropteridine reductase deficiency |
c.545+1G>A | - | Pathogenic | ★★☆☆ | QDPR-related disorder |
c.609dup | p.Pro204fs | Pathogenic/Likely pathogenic | ★★☆☆ | Dihydropteridine reductase deficiency |
c.661C>T | p.Arg221Ter | Pathogenic | ★★☆☆ | Dihydropteridine reductase deficiency |
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 QDPR gene are associated with an inherited metabolic disorder known as Dihydropteridine reductase deficiency. This condition arises due to the enzyme's reduced activity, leading to a shortage of active tetrahydrobiopterin in the body. Dihydropteridine reductase deficiency accounts for a notable proportion of all cases of tetrahydrobiopterin deficiency.
Inheritance pattern
Conditions caused by pathogenic QDPR 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
The QDPR gene is included in several UK NHS national genomic testing panels, reflecting its clinical significance. It is listed as 'green' in the DDG2P panel, and within panels for Dystonia, chorea or related movement disorder, childhood onset (R57), Intellectual disability, Likely inborn error of metabolism (R98), Neurotransmitter disorders, and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the QDPR gene?
The QDPR gene provides instructions for creating the quinoid dihydropteridine reductase enzyme, which is essential for recycling tetrahydrobiopterin (BH4). BH4 acts as a cofactor in processes like amino acid metabolism and neurotransmitter production.
What condition is associated with variants in the QDPR gene?
Variants in the QDPR gene are associated with Dihydropteridine reductase deficiency. This is a form of tetrahydrobiopterin deficiency, which impairs the body's ability to process amino acids and produce neurotransmitters effectively.
How does QDPR relate to neurotransmitters?
The QDPR gene's enzyme helps recycle tetrahydrobiopterin (BH4), which is a crucial cofactor in the synthesis of neurotransmitters. These chemical messengers are vital for proper communication between nerve cells in the brain.
References
- Longo N. Disorders of biopterin metabolism. Journal of inherited metabolic disease. 2009. PMID: 19234759
- Thöny B, Blau N. Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. Human mutation. 2006. PMID: 16917893
- Ponzone A, Spada M, Ferraris S. Dihydropteridine reductase deficiency in man: from biology to treatment. Medicinal research reviews. 2004. PMID: 14705166
- Shintaku H. Disorders of tetrahydrobiopterin metabolism and their treatment. Current drug metabolism. 2002. PMID: 12003346
- Thöny B, Auerbach G, Blau N. Tetrahydrobiopterin biosynthesis, regeneration and functions. The Biochemical journal. 2000. PMID: 10727395
- Romstad A, Kalkanoğlu HS, Coşkun T. Molecular analysis of 16 Turkish families with DHPR deficiency using denaturing gradient gel electrophoresis (DGGE). Human genetics. 2000. PMID: 11153907
- Dianzani I, de Sanctis L, Smooker PM. Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations. Human mutation. 1998. PMID: 9744478