PNPO Gene

Name	pyridoxamine 5'-phosphate oxidase
Description	The enzyme encoded by this gene catalyzes the terminal, rate-limiting step in the synthesis of pyridoxal 5'-phosphate, also known as vitamin B6. Vitamin B6 is a required co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. Mutations in this gene result in pyridoxamine 5'-phosphate oxidase (PNPO) deficiency, a form of neonatal epileptic encephalopathy. [provided by RefSeq, Oct 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPyridox(am)ine 5′‐phosphate oxidase (PNPO) is an essential enzyme in vitamin B6 metabolism that catalyzes the oxidation of pyridoxine 5′‐phosphate and pyridoxamine 5′‐phosphate into pyridoxal 5′‐phosphate (PLP), the active coenzyme required by more than 140 PLP‐dependent enzymes involved in neurotransmitter synthesis and amino acid metabolism. Multiple clinical studies have shown that loss‐of‐function mutations in PNPO underlie neonatal epileptic encephalopathy, a devastating disorder in which seizures are often resistant to conventional anticonvulsants and pyridoxine yet responsive to direct PLP administration. In addition, altered PNPO activity has been linked to a broader spectrum of epilepsies and, by influencing PLP‐dependent metabolic pathways, may even contribute to susceptibility for neuropsychiatric conditions such as schizophrenia. The widespread tissue expression and tight transcriptional regulation of the PNPO gene underscore its critical role in maintaining neurochemical balance and proper enzyme function across diverse tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed molecular and structural studies have elucidated the catalytic mechanism of PNPO and the impact of pathogenic mutations on its function. For instance, variants such as R229W and D33V have been shown to dramatically reduce substrate affinity, significantly impair the binding of the FMN cofactor, and disrupt proper allosteric regulation by PLP; these perturbations together lead to a marked decrease in enzyme efficiency. Complementary gene analyses have revealed that PNPO is encoded by a housekeeping gene characterized by a lack of a classical TATA-box and the presence of CpG islands and Sp1-binding sites, reflecting a tightly controlled, tissue-specific expression that is critical for sustaining vitamin B6 homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its pivotal neurological function, PNPO has emerged as a factor in oncogenesis. In epithelial ovarian cancer and breast invasive ductal carcinoma, PNPO is found to be overexpressed, and its suppression in cellular models leads to reduced cell proliferation, migration, invasion, and tumor growth. These studies also indicate that PNPO expression is modulated by extracellular signals such as transforming growth factor‑β via microRNAs, hinting at a feedback loop whereby increased PLP levels can downregulate PNPO. Such findings not only extend the functional repertoire of PNPO to include roles in tumor progression but also suggest that it may serve as a novel tissue biomarker and therapeutic target in cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Philippa B Mills, Robert A H Surtees, Michael P Champion, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi120"}], "href": "https://doi.org/10.1093/hmg/ddi120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15772097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15772097"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Philippa B Mills, Stephane S M Camuzeaux, Emma J Footitt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awu051"}], "href": "https://doi.org/10.1093/brain/awu051"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24645144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24645144"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Michael Steffens, Costin Leu, Ann-Kathrin Ruppert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds373"}], "href": "https://doi.org/10.1093/hmg/dds373"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22949513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22949513"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Barbara Plecko, Karl Paul, Philippa Mills, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyridoxine responsiveness in novel mutations of the PNPO gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000000344"}], "href": "https://doi.org/10.1212/WNL.0000000000000344"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24658933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24658933"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Morad Khayat, Stanley H Korman, Pnina Frankel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2008.04.008"}], "href": "https://doi.org/10.1016/j.ymgme.2008.04.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18485777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18485777"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Martino L di Salvo, Mario Mastrangelo, Isabel Nogués, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyridoxine-5'-phosphate oxidase (Pnpo) deficiency: Clinical and biochemical alterations associated with the C.347g>A (P.·Arg116gln) mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2017.08.003"}], "href": "https://doi.org/10.1016/j.ymgme.2017.08.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28818555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28818555"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Anna Barile, Isabel Nogués, Martino L di Salvo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular characterization of pyridoxine 5'-phosphate oxidase and its pathogenic forms associated with neonatal epileptic encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-70598-7"}], "href": "https://doi.org/10.1038/s41598-020-70598-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32788630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32788630"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Malak Alghamdi, Fahad A Bashiri, Marwa Abdelhakim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phenotypic and molecular spectrum of pyridoxamine-5'-phosphate oxidase deficiency: A scoping review of 87 cases of pyridoxamine-5'-phosphate oxidase deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13843"}], "href": "https://doi.org/10.1111/cge.13843"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32888189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32888189"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "M Veeravigrom, P Damrongphol, R Ittiwut, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pyridoxal 5ꞌ-phosphate-responsive epilepsy with novel mutations in the PNPO gene: a case report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Mol Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4238/2015.October.29.34"}], "href": "https://doi.org/10.4238/2015.October.29.34"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26535729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26535729"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hongwei Song, Shu-ichi Ueno, Shusuke Numata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between PNPO and schizophrenia in the Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Schizophr Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.schres.2007.08.004"}], "href": "https://doi.org/10.1016/j.schres.2007.08.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17851041"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17851041"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Faik N Musayev, Martino L Di Salvo, Mario A Saavedra, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Pyridoxine 5'-phosphate oxidase is correlated with human breast invasive ductal carcinoma development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.101908"}], "href": "https://doi.org/10.18632/aging.101908"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30982780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30982780"}]}]}]}
Synonyms	PDXPO, HEL-S-302
Proteins	PNPO_HUMAN
NCBI Gene ID	55163
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PNPO has 6,255 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 126 datasets.

Click the + buttons to view associations for PNPO from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PNPO Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PNPO gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PNPO gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PNPO gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PNPO gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PNPO gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PNPO gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PNPO gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PNPO gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PNPO gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PNPO gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PNPO gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PNPO gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PNPO protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PNPO gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PNPO gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PNPO gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PNPO gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with PNPO gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PNPO gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PNPO protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PNPO gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PNPO protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PNPO protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PNPO protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PNPO protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PNPO gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PNPO gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PNPO gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PNPO gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PNPO protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PNPO gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving PNPO gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PNPO gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PNPO gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PNPO gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PNPO gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PNPO gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PNPO gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PNPO protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PNPO gene from the ENCODE Histone Modification Site Profiles dataset.