PNPO

Chr 17

pyridoxamine 5'-phosphate oxidase

This enzyme catalyzes the oxidation of pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into pyridoxal 5'-phosphate (vitamin B6), which serves as an essential cofactor for neurotransmitter synthesis and homocysteine metabolism. Mutations cause pyridoxamine 5'-phosphate oxidase deficiency, a form of neonatal epileptic encephalopathy with autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants, consistent with the recessive disease pattern.

ResearchSummary from RefSeq, OMIM, UniProt

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

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPyridoxine-5'-phosphate oxidase deficiency

Clinical highlights

Management implications

Responds to pyridoxal-5-phosphate (and some to pyridoxine); untreated it is severe.Treat empirically with PLP in neonatal epileptic encephalopathy — the difference is life-altering.

PNPO: treatable — pyridoxal-5'-phosphate

Gene-disease validity (ClinGen)

pyridoxal phosphate-responsive seizures · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.44

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (2)

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omim: Error: OMIM fetch failed: 429

Treatment implicationsTreatable

PNPO deficiency (pyridoxal-5-phosphate-dependent epilepsy)

Treat empirically with PLP in neonatal epileptic encephalopathy — the difference is life-altering.

Responds to pyridoxal-5-phosphate (and some to pyridoxine); untreated it is severe.

Treatment of choice

pyridoxal-5'-phosphate (PLP)

Mills et al. 2014, Brain. Confirm with a neurologist and current guidelines. Functional class (GOF/LOF) is from published functional/segregation data, never inferred from the variant. As of 2026-07. Curated from the clinical genetics/neurology literature (cited per gene). Decision-support, not prescribing.