PNPO

Protein identityUniProt · HPA

UniProt accession

Q9NVS9

Gene

PNPO

Ensembl

ENSG00000108439

Chromosome

17

Canonical length

261 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

Quaternary structure

Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

261 residues, UniProt reviewed canonical sequence.

>Q9NVS9|PNPO
     1  MTCWLRGVTA TFGRPAEWPG YLSHLCGRSA AMDLGPMRKS YRGDREAFEE THLTSLDPVK
    61  QFAAWFEEAV QCPDIGEANA MCLATCTRDG KPSARMLLLK GFGKDGFRFF TNFESRKGKE
   121  LDSNPFASLV FYWEPLNRQV RVEGPVKKLP EEEAECYFHS RPKSSQIGAV VSHQSSVIPD
   181  REYLRKKNEE LEQLYQDQEV PKPKSWGGYV LYPQVMEFWQ GQTNRLHDRI VFRRGLPTGD
   241  SPLGPMTHRG EEDWLYERLA P

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PNPO can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

83 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PNPO.

Disease | AllUniProt

Conditions PNPO is implicated in, by any mechanism.

• Pyridoxine-5'-phosphate oxidase deficiency (PNPOD) MIM:610090

Disease | GeneticClinVar

42 pathogenic / likely-pathogenic of 400 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pyridoxal phosphate-responsive seizures
• Inborn genetic diseases
• PNPO-related disorder
• Seizure
• Fetal growth restriction

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.44

gnomAD pLI

0

gnomAD missense Z

0.78

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• pyridoxamine metabolic process
• pyridoxine biosynthetic process
• pyridoxal phosphate biosynthetic process

Molecular functions

• FMN binding
• protein homodimerization activity
• pyridoxal phosphate binding
• pyridoxamine phosphate oxidase activity

Cellular components

• cytosol
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• FMN-binding split barrel
• Pyridoxamine 5'-phosphate oxidase
• Pyridoxamine 5'-phosphate oxidase, N-terminal
• Pyridoxine 5'-phosphate oxidase, dimerisation, C-terminal
• Pyridoxamine 5'-phosphate oxidase, conserved site
• Pyridoxamine 5'-phosphate oxidase
• Pyridoxine 5'-phosphate oxidase C-terminal dimerisation region

KeywordsUniProt

• Epilepsy
• Flavoprotein
• FMN
• Oxidoreductase
• Phosphoprotein
• Pyridoxal phosphate
• Pyridoxine biosynthesis