PNP purine nucleoside phosphorylase [Homo sapiens (human)] - Gene

Summary

Official Symbol: PNPprovided by HGNC
Official Full Name: purine nucleoside phosphorylaseprovided by HGNC
Primary source: HGNC:HGNC:7892
See related: Ensembl:ENSG00000198805 MIM:164050; AllianceGenome:HGNC:7892
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NP; PUNP; PRO1837
Summary: This gene encodes an enzyme which reversibly catalyzes the phosphorolysis of purine nucleosides. The enzyme is trimeric, containing three identical subunits. Mutations which result in nucleoside phosphorylase deficiency result in defective T-cell (cell-mediated) immunity but can also affect B-cell immunity and antibody responses. Neurologic disorders may also be apparent in patients with immune defects. A known polymorphism at aa position 51 that does not affect enzyme activity has been described. A pseudogene has been identified on chromosome 2. [provided by RefSeq, Jul 2008]
Expression: Broad expression in bone marrow (RPKM 94.2), kidney (RPKM 44.4) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q11.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (20469406..20477089)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (14666309..14673992)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (20937565..20945248)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Purine Nucleoside Phosphorylase Deficiency in Two Unrelated Patients with Autoimmune Hemolytic Anemia and Eosinophilia: Two Novel Mutations.
Title: Purine Nucleoside Phosphorylase Deficiency in Two Unrelated Patients with Autoimmune Hemolytic Anemia and Eosinophilia: Two Novel Mutations.
Connecting Conformational Motions to Rapid Dynamics in Human Purine Nucleoside Phosphorylase.
Title: Connecting Conformational Motions to Rapid Dynamics in Human Purine Nucleoside Phosphorylase.
A Case with Purine Nucleoside Phosphorylase Deficiency Suffering from Late-Onset Systemic Lupus Erythematosus and Lymphoma.
Title: A Case with Purine Nucleoside Phosphorylase Deficiency Suffering from Late-Onset Systemic Lupus Erythematosus and Lymphoma.
The study suggests that mass-constrained femtosecond motions at the catalytic site of PNP can improve transition state barrier crossing by more frequent sampling of essential catalytic site contacts.
Title: Inverse enzyme isotope effects in human purine nucleoside phosphorylase with heavy asparagine labels.
The PNP rs1049564 T allele is a loss-of-function variant that induces S-phase block and IFN pathway activation in lymphocytes. The S-phase block could be rescued in our in vitro experiments, suggesting the potential for personalized treatment.
Title: Lupus-Associated Functional Polymorphism in PNP Causes Cell Cycle Abnormalities and Interferon Pathway Activation in Human Immune Cells.
Data show that the mutations in purine nucleoside phosphorylase (PNP) alters the enthalpy-entropy balance with little effect on the catalytic rates.
Title: Thermodynamics of the Purine Nucleoside Phosphorylase Reaction Revealed by Computer Simulations.
Data (including data from empirical valence bond/molecular dynamic simulations) suggest that PNP substrate specificity for inosine and guanosine is a direct result of electrostatic preorganization energy along the reaction coordinate.
Title: Computer Simulations Reveal Substrate Specificity of Glycosidic Bond Cleavage in Native and Mutant Human Purine Nucleoside Phosphorylase.
the binding mechanism of a transition state analogue (DADMe-immucillin-H) to the purine nucleoside phosphorylase (PNP) enzyme, is reported.
Title: The ligand binding mechanism to purine nucleoside phosphorylase elucidated via molecular dynamics and machine learning.
Data show that [15N, 2H]His8-purine nucleoside phosphorylase (PNP) had reduced catalytic site chemistry larger than proportional to the enzymatic mass difference.
Title: Isotope-specific and amino acid-specific heavy atom substitutions alter barrier crossing in human purine nucleoside phosphorylase.
Study of genetic heterogeneity in systemic lupus erythematosus, the top associations in European ancestry were protein kinase, cyclic GMP-dependent, type I (PRKG1) rs7897633 (P(Meta) = 2.75 x 10(-8)) and purine nucleoside phosphorylase (PNP) rs1049564 (P(Meta) = 1.24 x 10(-7)).
Title: Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Purine-nucleoside phosphorylase deficiency MedGen: C0268125 OMIM: 613179 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

humpnu2 (e-PCR)
- UniSTS:75043

NP (e-PCR), detects polymorphism
- UniSTS:503175

SHGC-31518 (e-PCR)
- UniSTS:37005

GDB:181553 (e-PCR)
- UniSTS:155279

RH18070 (e-PCR)
- UniSTS:53149

SHGC-78026 (e-PCR)
- UniSTS:101559

NoName (e-PCR)
- UniSTS:489656

RH78901 (e-PCR)
- UniSTS:9186

Clone Names

FLJ94043, FLJ97288, FLJ97312, MGC117396, MGC125915, MGC125916

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables guanosine phosphorylase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables nucleoside binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphate ion binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables purine nucleobase binding	IDA Inferred from Direct Assay more info	PubMed
enables purine-nucleoside phosphorylase activity	IBA Inferred from Biological aspect of Ancestor more info
enables purine-nucleoside phosphorylase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in IMP catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in allantoin metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in dAMP catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in deoxyadenosine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in deoxyinosine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in immune response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within inosine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in inosine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nicotinamide riboside catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nucleobase-containing compound metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nucleotide biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of alpha-beta T cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-2 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in purine ribonucleoside salvage	IEA Inferred from Electronic Annotation more info
involved_in purine-containing compound salvage	IDA Inferred from Direct Assay more info	PubMed
involved_in response to xenobiotic stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within urate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in secretory granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: purine nucleoside phosphorylase

Names: HEL-S-156an; epididymis secretory sperm binding protein Li 156an; inosine phosphorylase; inosine-guanosine phosphorylase; purine-nucleoside:orthophosphate ribosyltransferase

NP_000261.2

EC 2.4.2.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.