PNPO

Chr 17AR

pyridoxamine 5'-phosphate oxidase

Also known as: HEL-S-302, PDXPO

NCBI Gene: 55163 ENSG00000108439 UniProt: Q9NVS9 OMIM: 603287

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.441 OMIM phenotype

Clinical Summary— PNPO

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Gene-Disease Validity (ClinGen)

pyridoxal phosphate-responsive seizures · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

43 unique Pathogenic / Likely Pathogenic· 158 VUS of 402 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PNPO

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.44LOEUF

pLI 0.000

Z-score 0.33

OE 0.90 (0.59–1.44)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.78Z-score

OE missense 0.82 (0.70–0.95)

120 obs / 146.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.90 (0.59–1.44)

0≤0.351.4

Missense OE?0.82 (0.70–0.95)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 13 / 14.4Missense obs/exp: 120 / 146.6Syn Z: 0.37

ClinVar Variant Classifications

402 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic22

VUS158

Likely Benign158

Benign24

Conflicting13

Pathogenic

Likely Pathogenic

158

VUS

158

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	5	2	0	21
Likely Pathogenic	11	10	1	0	22
VUS	1	122	33	2	158
Likely Benign	1	1	71	85	158
Benign	0	0	21	3	24
Conflicting	—				13
Total	27	138	128	90	396

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap PNPO — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →