PNP

purine nucleoside phosphorylase

Basic information

Region (hg38): 14:20461991-20477094

Previous symbols: [ "NP" ]

Links

ENSG00000198805 ∙ NCBI:4860 ∙ OMIM:164050 ∙ HGNC:7892 ∙ Uniprot:P00491 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• purine nucleoside phosphorylase deficiency (Supportive), mode of inheritance: AR
• purine nucleoside phosphorylase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Purine nucleoside phosphorylase deficiency	AR	Allergy/Immunology/Infectious ; Oncologic	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Surveillance for malignancy (eg, lymphoma has been described) can be beneficial; BMT/HSCT has been reported	Allergy/Immunology/Infectious; Biochemical; Neurologic; Oncologic	5579411; 825775; 102751; 111549; 6774252; 3029074; 1931007; 1384322; 8774508; 8931706; 9067751; 9737781; 11498751; 11453975; 11902746; 17910661; 18208442; 19584574; 19733163; 19657670; 20544539; 22132981

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PNP gene.

• Purine-nucleoside phosphorylase deficiency (197 variants)
• not provided (22 variants)
• not specified (12 variants)
• Severe combined immunodeficiency disease (3 variants)
• Inborn genetic diseases (2 variants)
• NUCLEOSIDE PHOSPHORYLASE POLYMORPHISM (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PNP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	33	2	36
missense	1	6	81	3	1	92
nonsense	6	2				8
start loss						0
frameshift	3		1			4
inframe indel		1				1
splice donor/acceptor (+/-2bp)		2				2
splice region			7	12	1	20
non coding		1	11	18	13	43
Total	10	12	94	54	16

Highest pathogenic variant AF is 0.0000394

Variants in PNP

This is a list of pathogenic ClinVar variants found in the PNP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-20469375-G-A		Purine-nucleoside phosphorylase deficiency	Uncertain significance (Jan 12, 2018)
14-20469396-C-A		Purine-nucleoside phosphorylase deficiency	Uncertain significance (Jan 13, 2018)
14-20469429-G-A		Purine-nucleoside phosphorylase deficiency	Benign (Jan 12, 2018)
14-20469434-G-T		Purine-nucleoside phosphorylase deficiency	Benign (Jan 12, 2018)
14-20469442-C-G		Purine-nucleoside phosphorylase deficiency	Benign (Jan 12, 2018)
14-20469528-G-C		Purine-nucleoside phosphorylase deficiency	Uncertain significance (Sep 01, 2021)
14-20469534-G-C		Purine-nucleoside phosphorylase deficiency	Uncertain significance (Sep 27, 2023)
14-20469537-T-A		Purine-nucleoside phosphorylase deficiency	Likely pathogenic (May 05, 2023)
14-20469538-G-A		Purine-nucleoside phosphorylase deficiency	Uncertain significance (Jun 27, 2022)
14-20469540-G-T		Purine-nucleoside phosphorylase deficiency	Uncertain significance (Jul 14, 2022)
14-20469546-C-T		Purine-nucleoside phosphorylase deficiency	Likely benign (May 27, 2022)
14-20469548-C-A		Purine-nucleoside phosphorylase deficiency	Likely benign (Feb 10, 2023)
14-20469550-A-G		Purine-nucleoside phosphorylase deficiency	Likely benign (Jun 16, 2023)
14-20469550-AGGCCCGCAG-A		Purine-nucleoside phosphorylase deficiency	Likely benign (Nov 08, 2023)
14-20469553-C-T		Purine-nucleoside phosphorylase deficiency	Likely benign (Oct 25, 2023)
14-20472290-A-T		not specified • Purine-nucleoside phosphorylase deficiency	Benign (Jan 29, 2024)
14-20472292-AT-A		Purine-nucleoside phosphorylase deficiency	Benign (Nov 13, 2021)
14-20472299-C-A			Benign (Nov 02, 2018)
14-20472300-T-A		Purine-nucleoside phosphorylase deficiency	Likely benign (Apr 10, 2022)
14-20472300-TC-T		Purine-nucleoside phosphorylase deficiency	Benign (Jul 17, 2023)
14-20472301-C-A		Purine-nucleoside phosphorylase deficiency	Uncertain significance (Jan 12, 2018)
14-20472302-C-T		Purine-nucleoside phosphorylase deficiency	Likely benign (Aug 23, 2022)
14-20472307-G-C		Purine-nucleoside phosphorylase deficiency • Immunodeficiency due to purine nucleoside phosphorylase deficiency	Pathogenic/Likely pathogenic (Mar 14, 2024)
14-20472309-T-C		Purine-nucleoside phosphorylase deficiency	Uncertain significance (Jul 05, 2022)
14-20472311-C-T		Purine-nucleoside phosphorylase deficiency	Likely benign (Oct 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PNP	protein_coding	protein_coding	ENST00000361505	6	8141

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000700	0.737	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.439	146	162	0.903	0.00000861	1898
Missense in Polyphen		51	60.787	0.83899		763
Synonymous	-0.0240	57	56.8	1.00	0.00000286	571
Loss of Function	1.14	10	14.7	0.679	9.54e-7	135

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000149	0.000149
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta- (deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate. {ECO:0000269|PubMed:2104852}.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Nicotinate and nicotinamide metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Nicotinate and Nicotinamide Metabolism;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in squamous cell - TarBase;Neutrophil degranulation;purine ribonucleosides degradation to ribose-1-phosphate;Nucleobase catabolism;Metabolism of nucleotides;purine deoxyribonucleosides degradation;guanosine nucleotides degradation;urate biosynthesis/inosine 5,-phosphate degradation;adenosine nucleotides degradation;purine nucleotides degradation;Innate Immune System;Immune System;Metabolism;Nicotinate Nicotinamide metabolism;guanine and guanosine salvage;Nucleotide salvage;Purine salvage;arsenate detoxification I (glutaredoxin);Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage;Purine catabolism;adenine and adenosine salvage III (Consensus)

Recessive Scores

• pRec: 0.352

Intolerance Scores

• loftool: 0.289
• rvis_EVS: 0.59
• rvis_percentile_EVS: 82.51

Haploinsufficiency Scores

• pHI: 0.423
• hipred: N
• hipred_score: 0.331
• ghis: 0.398

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pnp2

Gene ontology

• Biological process: nucleobase-containing compound metabolic process;inosine catabolic process;purine nucleotide catabolic process;nicotinamide riboside catabolic process;immune response;NAD biosynthesis via nicotinamide riboside salvage pathway;urate biosynthetic process;positive regulation of T cell proliferation;response to drug;purine-containing compound salvage;neutrophil degranulation;positive regulation of alpha-beta T cell differentiation;interleukin-2 secretion
• Cellular component: extracellular region;nucleus;cytoplasm;cytosol;cytoskeleton;secretory granule lumen;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: nucleoside binding;purine nucleobase binding;purine-nucleoside phosphorylase activity;drug binding;phosphate ion binding