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 f... See more...

Aliases for PNPO Gene

Aliases for PNPO Gene

  • Pyridoxamine 5'-Phosphate Oxidase 2 3 5
  • Pyridoxal 5'-Phosphate Synthase 2 3
  • Pyridoxine 5'-Phosphate Oxidase 2 3
  • Pyridoxine-5'-Phosphate Oxidase 3 4
  • Pyridoxamine-Phosphate Oxidase 3 4
  • EC 1.4.3.5 4 51
  • PDXPO 2 3
  • Epididymis Secretory Sperm Binding Protein 3
  • Epididymis Secretory Protein Li 302 3
  • HEL-S-302 3
  • PNPO 5

External Ids for PNPO Gene

Previous GeneCards Identifiers for PNPO Gene

  • GC17U990158
  • GC17P046361
  • GC17P046493
  • GC17P043373
  • GC17P046018
  • GC17P041387

Summaries for PNPO Gene

Entrez Gene Summary for PNPO Gene

  • 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]

GeneCards Summary for PNPO Gene

PNPO (Pyridoxamine 5'-Phosphate Oxidase) is a Protein Coding gene. Diseases associated with PNPO include Pyridoxamine 5-Prime-Phosphate Oxidase Deficiency and Neuronopathy, Distal Hereditary Motor, Type Va. Among its related pathways are Folate Metabolism and Metabolism of water-soluble vitamins and cofactors. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and oxidoreductase activity, acting on the CH-NH2 group of donors.

UniProtKB/Swiss-Prot Summary for PNPO Gene

  • Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP).

Gene Wiki entry for PNPO Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PNPO Gene

Genomics for PNPO Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PNPO Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PNPO on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PNPO

Top Transcription factor binding sites by QIAGEN in the PNPO gene promoter:
  • CREB
  • deltaCREB
  • E47
  • IRF-2
  • Max1
  • NF-1
  • NF-1/L
  • Spz1
  • ZIC2

Genomic Locations for PNPO Gene

Genomic Locations for PNPO Gene
chr17:47,941,506-47,949,308
(GRCh38/hg38)
Size:
7,803 bases
Orientation:
Plus strand
chr17:46,018,872-46,026,674
(GRCh37/hg19)
Size:
7,803 bases
Orientation:
Plus strand

Genomic View for PNPO Gene

Genes around PNPO on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PNPO Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PNPO Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PNPO Gene

Proteins for PNPO Gene

  • Protein details for PNPO Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NVS9-PNPO_HUMAN
    Recommended name:
    Pyridoxine-5'-phosphate oxidase
    Protein Accession:
    Q9NVS9
    Secondary Accessions:
    • B4E0V0
    • B4E152
    • B4E1D7
    • D3DTT9

    Protein attributes for PNPO Gene

    Size:
    261 amino acids
    Molecular mass:
    29988 Da
    Cofactor:
    Name=FMN; Xref=ChEBI:CHEBI:58210;
    Quaternary structure:
    • Homodimer.
    SequenceCaution:
    • Sequence=BAG64562.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 2]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Three dimensional structures from OCA and Proteopedia for PNPO Gene

    Alternative splice isoforms for PNPO Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PNPO Gene

Selected DME Specific Peptides for PNPO Gene

Q9NVS9:
  • LYPQVMEFWQGQTNRLHDRIVFRRGL
  • RQVRVEG

Post-translational modifications for PNPO Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for PNPO Gene

Gene Families for PNPO Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for PNPO Gene

InterPro:
Blocks:
  • Pyridoxamine 5'-phosphate oxidase
  • Pyridoxamine 5'-phosphate oxidase-related, FMN-binding core
ProtoNet:

Suggested Antigen Peptide Sequences for PNPO Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ59109, highly similar to Pyridoxine-5'-phosphate oxidase (EC 1.4.3.5) (B4E0V0_HUMAN)
  • cDNA FLJ59599, highly similar to Pyridoxine-5'-phosphate oxidase (EC 1.4.3.5) (B4E152_HUMAN)
  • cDNA FLJ59601, highly similar to Pyridoxine-5'-phosphate oxidase (EC 1.4.3.5) (B4E1D7_HUMAN)
  • Pyridoxamine-phosphate oxidase (PNPO_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NVS9

UniProtKB/Swiss-Prot:

PNPO_HUMAN :
  • Belongs to the pyridoxamine 5'-phosphate oxidase family.
Family:
  • Belongs to the pyridoxamine 5'-phosphate oxidase family.
genes like me logo Genes that share domains with PNPO: view

Function for PNPO Gene

Molecular function for PNPO Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O2 + pyridoxamine 5'-phosphate = H2O2 + NH4(+) + pyridoxal 5'-phosphate; Xref=Rhea:RHEA:15817, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:58451, ChEBI:CHEBI:597326; EC=1.4.3.5;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=O2 + pyridoxine 5'-phosphate = H2O2 + pyridoxal 5'-phosphate; Xref=Rhea:RHEA:15149, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:58589, ChEBI:CHEBI:597326; EC=1.4.3.5;.

Enzyme Numbers (IUBMB) for PNPO Gene

Phenotypes From GWAS Catalog for PNPO Gene

Gene Ontology (GO) - Molecular Function for PNPO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004733 pyridoxamine-phosphate oxidase activity IEA,IDA 12824491
GO:0005515 protein binding IPI 25910212
GO:0010181 FMN binding IEA,IDA 12824491
GO:0016491 oxidoreductase activity IEA --
GO:0016638 oxidoreductase activity, acting on the CH-NH2 group of donors IEA --
genes like me logo Genes that share ontologies with PNPO: view
genes like me logo Genes that share phenotypes with PNPO: view

Human Phenotype Ontology for PNPO Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PNPO

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for PNPO Gene

Localization for PNPO Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PNPO gene
Compartment Confidence
nucleus 5
cytosol 5
mitochondrion 3
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (4)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PNPO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005829 cytosol IDA,TAS --
genes like me logo Genes that share ontologies with PNPO: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for PNPO Gene

Pathways & Interactions for PNPO Gene

genes like me logo Genes that share pathways with PNPO: view

UniProtKB/Swiss-Prot Q9NVS9-PNPO_HUMAN

  • Pathway: Cofactor metabolism; pyridoxal 5'-phosphate salvage; pyridoxal 5'-phosphate from pyridoxamine 5'-phosphate: step 1/1.
  • Pathway: Cofactor metabolism; pyridoxal 5'-phosphate salvage; pyridoxal 5'-phosphate from pyridoxine 5'-phosphate: step 1/1.

Gene Ontology (GO) - Biological Process for PNPO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008615 pyridoxine biosynthetic process IEA --
GO:0042816 vitamin B6 metabolic process TAS --
GO:0042823 pyridoxal phosphate biosynthetic process IEA,IDA 12824491
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with PNPO: view

No data available for SIGNOR curated interactions for PNPO Gene

Drugs & Compounds for PNPO Gene

(12) Drugs for PNPO Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Flavin Mononucleotide Approved, Investigational Pharma Target 12
Pyridoxal Phosphate Approved, Investigational Nutra Target, cofactor 16
Pyridoxine Approved, Investigational, Vet_approved Nutra 229,229
Ammonia Approved Pharma 0
Hydrogen peroxide Approved, Vet_approved Pharma 115

(4) Additional Compounds for PNPO Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PNPO: view

Transcripts for PNPO Gene

mRNA/cDNA for PNPO Gene

1 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
17 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PNPO

Alternative Splicing Database (ASD) splice patterns (SP) for PNPO Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6 ^ 7a · 7b · 7c
SP1: - -
SP2: - - - -
SP3: - - - - -
SP4: - - -
SP5: - - -
SP6: - - - - - - - -
SP7:
SP8: - - -

Relevant External Links for PNPO Gene

GeneLoc Exon Structure for
PNPO

Expression for PNPO Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PNPO Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PNPO Gene

This gene is overexpressed in Liver (x5.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PNPO Gene



Protein tissue co-expression partners for PNPO Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PNPO

SOURCE GeneReport for Unigene cluster for PNPO Gene:

Hs.631742

Evidence on tissue expression from TISSUES for PNPO Gene

  • Nervous system(4.8)
  • Liver(4.7)
  • Thyroid gland(4.2)
  • Kidney(3)
  • Muscle(2.8)
  • Blood(2.2)
  • Intestine(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PNPO Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cerebrospinal fluid
  • ear
  • head
  • meninges
  • neck
Thorax:
  • chest wall
  • heart
Abdomen:
  • abdominal wall
  • adrenal gland
General:
  • blood
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • sweat gland
genes like me logo Genes that share expression patterns with PNPO: view

No data available for Protein differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for PNPO Gene

Orthologs for PNPO Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PNPO Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PNPO 30 31
  • 99.87 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PNPO 30 31
  • 90.42 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PNPO 30 31
  • 90.04 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Pnpo 30 17 31
  • 89.02 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Pnpo 30
  • 88.76 (n)
Oppossum
(Monodelphis domestica)
Mammalia PNPO 31
  • 80 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia PNPO 31
  • 80 (a)
OneToOne
Chicken
(Gallus gallus)
Aves PNPO 30 31
  • 74.79 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PNPO 31
  • 69 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia pnpo 30
  • 67.11 (n)
Str.20417 30
Zebrafish
(Danio rerio)
Actinopterygii pnpo 30 31
  • 64.65 (n)
OneToOne
Dr.14932 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002227 30
  • 54.38 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG31472 30 31
  • 51.72 (n)
OneToMany
CG31473 31
  • 26 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea F57B9.1 30 31
  • 52.62 (n)
OneToOne
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AAR186W 30
  • 50.79 (n)
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0B07062g 30
  • 47.35 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PDX3 30 31 33
  • 46.89 (n)
OneToOne
Bread mold
(Neurospora crassa)
Ascomycetes NCU08269 30
  • 50.81 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPAC1093.02 30
  • 47.78 (n)
Species where no ortholog for PNPO was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for PNPO Gene

ENSEMBL:
Gene Tree for PNPO (if available)
TreeFam:
Gene Tree for PNPO (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PNPO: view image

Paralogs for PNPO Gene

No data available for Paralogs for PNPO Gene

Variants for PNPO Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PNPO Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
642446 Uncertain Significance: Pyridoxal phosphate-responsive seizures 47,941,686(+) G/C MISSENSE_VARIANT
652581 Uncertain Significance: Pyridoxal phosphate-responsive seizures 47,945,984(+) C/T MISSENSE_VARIANT
658245 Likely Pathogenic: Pyridoxal phosphate-responsive seizures 47,946,653(+) G/A NONSENSE
667950 Benign: not provided 47,944,964(+) G/A INTRON_VARIANT
667952 Likely Benign: not provided 47,941,956(+) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for PNPO Gene

Structural Variations from Database of Genomic Variants (DGV) for PNPO Gene

Variant ID Type Subtype PubMed ID
esv1000014 CNV deletion 20482838
nsv2072 CNV deletion 18451855
nsv518892 CNV loss 19592680

Variation tolerance for PNPO Gene

Residual Variation Intolerance Score: 65.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.43; 54.66% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PNPO Gene

Human Gene Mutation Database (HGMD)
PNPO
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PNPO

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PNPO Gene

Disorders for PNPO Gene

MalaCards: The human disease database

(29) MalaCards diseases for PNPO Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search PNPO in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PNPO_HUMAN
  • Pyridoxine-5'-phosphate oxidase deficiency (PNPOD) [MIM:610090]: The main feature of neonatal epileptic encephalopathy is the onset within hours of birth of a severe seizure disorder that does not respond to anticonvulsant drugs and can be fatal. Seizures can cease with the administration of PLP, being resistant to treatment with pyridoxine,. {ECO:0000269 PubMed:15772097, ECO:0000269 PubMed:23708187, ECO:0000269 PubMed:27864847}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for PNPO

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PNPO: view

No data available for Genatlas for PNPO Gene

Publications for PNPO Gene

  1. Association between PNPO and schizophrenia in the Japanese population. (PMID: 17851041) Song H … Ohmori T (Schizophrenia research 2007) 3 23 41
  2. Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. (PMID: 15772097) Mills PB … Clayton PT (Human molecular genetics 2005) 3 4 23
  3. Genomic organization, tissue distribution and deletion mutation of human pyridoxine 5'-phosphate oxidase. (PMID: 15182361) Kang JH … Kwon OS (European journal of biochemistry 2004) 2 3 23
  4. Absence of pyridoxine-5'-phosphate oxidase (PNPO) activity in neoplastic cells: isolation, characterization, and expression of PNPO cDNA. (PMID: 9601034) Ngo EO … Nutter LM (Biochemistry 1998) 2 3 23
  5. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism. (PMID: 18485777) Khayat M … Falik-Zaccai TC (Molecular genetics and metabolism 2008) 3 23

Products for PNPO Gene

Sources for PNPO Gene