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PNP
purine nucleoside phosphorylase
The PNP gene encodes the purine nucleoside phosphorylase enzyme, which plays a vital role in immune system function and the breakdown of certain cellular waste products. The PNP gene is responsible for producing an enzyme called purine nucleoside phosphorylase, essential for maintaining a healthy immune system.
PNP is located on the long (q) arm of chromosome 14, at band 14q11.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The PNP gene provides instructions for creating purine nucleoside phosphorylase, an enzyme critical for various bodily processes, particularly within the immune system. This enzyme is widely distributed throughout the body but shows heightened activity in lymphocytes, a type of white blood cell integral to the body's defence against pathogens.
Purine nucleoside phosphorylase is considered a 'housekeeping' enzyme due to its role in clearing specific waste molecules. Alterations in the PNP gene can affect the enzyme's function, potentially leading to compromised immune responses.
What the gene does
The purine nucleoside phosphorylase enzyme, encoded by the PNP gene, performs a crucial function in purine metabolism. Its primary role involves the breakdown of specific waste products, deoxyinosine and deoxyguanosine, which are generated during the normal degradation of DNA. The enzyme facilitates the conversion of deoxyinosine into hypoxanthine and deoxyguanosine into guanine. This process is particularly important in lymphocytes, immune cells that originate in lymphoid tissues like the thymus and lymph nodes before circulating in the blood.
By efficiently processing these waste molecules, the PNP enzyme helps maintain cellular balance and supports the proper functioning of the immune system. When the enzyme is deficient or non-functional, these waste molecules can accumulate, which can be detrimental to lymphocyte development and survival, thereby impairing immune capabilities.
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Chromosome location
The PNP gene is located on chromosome 14, specifically at position 14q11.2. This indicates its position on the long arm (q) of chromosome 14, within region 11, band 2. The gene directs the synthesis of a protein consisting of 289 amino acids.
Protein structure
The purine nucleoside phosphorylase protein is composed of 289 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variations within the PNP gene can impact the function of the purine nucleoside phosphorylase enzyme. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions, potentially altering the protein's structure or reducing its production. Over 35 different mutations in the PNP gene have been identified in individuals with related conditions.
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.12-1G>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | Purine-nucleoside phosphorylase deficiency |
c.171_172delinsTT | p.Arg58Ter | Pathogenic | ★★☆☆ | Purine-nucleoside phosphorylase deficiency |
c.172C>T | p.Arg58Ter | Pathogenic | ★★☆☆ | Purine-nucleoside phosphorylase deficiency |
c.199C>T | p.Arg67Ter | Pathogenic | ★★☆☆ | Purine-nucleoside phosphorylase deficiency |
c.244C>T | p.Gln82Ter | Pathogenic | ★★☆☆ | Purine-nucleoside phosphorylase deficiency |
c.286-18G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Severe combined immunodeficiency disease |
c.437C>T | p.Pro146Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Purine-nucleoside phosphorylase deficiency |
c.601G>T | p.Glu201Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Severe combined immunodeficiency disease |
c.700C>T | p.Arg234Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Purine-nucleoside phosphorylase deficiency |
c.70C>T | p.Arg24Ter | Pathogenic | ★★☆☆ | PNP-related disorder |
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 PNP gene are associated with purine nucleoside phosphorylase deficiency. This condition is an immune system disorder where the body's ability to combat foreign invaders, such as bacteria and viruses, is significantly impaired. Individuals affected by purine nucleoside phosphorylase deficiency typically experience recurrent and potentially life-threatening infections. Some individuals may also present with neurological issues.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic PNP 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 PNP gene is recognised within several NHS Genomic Medicine Service national test panels in the UK. It is included in panels related to COVID-19 research, likely inborn errors of metabolism (R98), primary immunodeficiency or monogenic inflammatory bowel disease (R15), severe combined immunodeficiency with PNP deficiency (R234), and undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main role of the PNP gene?
The PNP gene provides instructions for making an enzyme called purine nucleoside phosphorylase. This enzyme is crucial for the immune system, particularly in lymphocytes, and helps clear waste molecules produced during DNA breakdown.
What happens if the PNP gene doesn't work correctly?
If the PNP gene has pathogenic variants, the purine nucleoside phosphorylase enzyme may not function correctly. This can lead to purine nucleoside phosphorylase deficiency, an immune disorder characterised by recurrent, severe infections and sometimes neurological problems.
Is PNP deficiency inherited?
Yes, purine nucleoside phosphorylase deficiency is typically inherited in an autosomal recessive pattern. This means an individual must inherit two copies of a pathogenic variant in the PNP gene (one from each parent) to develop the condition.
References
- Fekrvand S, Yazdani R, Abolhassani H. The First Purine Nucleoside Phosphorylase Deficiency Patient Resembling IgA Deficiency and a Review of the Literature. Immunological investigations. 2019. PMID: 30885031
- Somech R, Lev A, Grisaru-Soen G. Purine nucleoside phosphorylase deficiency presenting as severe combined immune deficiency. Immunologic research. 2013. PMID: 23371835
- Walker PL, Corrigan A, Arenas M. Purine nucleoside phosphorylase deficiency: a mutation update. Nucleosides, nucleotides & nucleic acids. 2011. PMID: 22132981
- Aytekin C, Dogu F, Tanir G. Purine nucleoside phosphorylase deficiency with fatal course in two sisters. European journal of pediatrics. 2010. PMID: 19657670
- Al-Saud B, Alsmadi O, Al-Muhsen S. A novel mutation in purine nucleoside phosphorylase in a child with normal uric acid levels. Clinical biochemistry. 2009. PMID: 19733163
- Ozkinay F, Pehlivan S, Onay H. Purine nucleoside phosphorylase deficiency in a patient with spastic paraplegia and recurrent infections. Journal of child neurology. 2007. PMID: 17641261
- Nyhan WL. Disorders of purine and pyrimidine metabolism. Molecular genetics and metabolism. 2005. PMID: 16176880
- Grunebaum E, Zhang J, Roifman CM. Novel mutations and hot-spots in patients with purine nucleoside phosphorylase deficiency. Nucleosides, nucleotides & nucleic acids. 2004. PMID: 15571269