- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_03
,
released September 17, 2026
This report describes pyridoxamine 5'-phosphate oxidase deficiency (PNPOD), also known as pyridoxal phosphate-responsive seizures; PNPOD exhibits autosomal recessive inheritance. The human gene implicated in this disease is pyridoxamine 5'-phosphate oxidase (PNPO). There is a high-ranking ortholog of PNPO in Drosophila, sgll, along with two moderately-scoring orthologs, CG31473 and CG15343. Several alleles of sgll have been generated, including a hypomorph, an sgRNA KO construct, and multiple RNAi targeting constructs.
A UAS construct of the wild-type Hsap\PNPO gene been introduced into flies. Functional complementation (heterologous rescue) of the seizure and lethal phenotypes of loss-of-function sgll mutations has been demonstrated. Disease-implicated variants have been assessed, using knock-in constructs of the human gene to replace the fly sgll gene; see the 'Disease-Implicated Variants' table below.
sgll loss-of-function mutants are auxotrophs: they thrive on standard fly food, but die within six days if fed a diet lacking vitamin B6, such as agar with 4% sucrose. Animals carrying loss-of-function sgll mutations exhibit spontaneous seizures before they die. Glucose metabolism phenotypes are also observed: reduced adult body size, hyperglycemia and accumulation of large lipid droplets in the fat body. sgll mutations can be complemented by supplementing the 4% sucrose food with pyridoxine or pyridoxal 5'-phosphate (PLP), both forms of vitamin B6.
[updated Apr. 2022 by FlyBase; FBrf0222196]
[PYRIDOXAMINE 5-PRIME-PHOSPHATE OXIDASE DEFICIENCY; PNPOD](https://omim.org/entry/610090)
[PYRIDOXAMINE 5-PRIME-PHOSPHATE OXIDASE; PNPO](https://omim.org/entry/603287)
Vitamin B6 deficiency is a rare but treatable cause of neonatal and infantile seizures and neurodevelopmental disability. Delayed treatment in children with early onset seizures is associated with increased risk of learning difficulties and cerebral palsy. (Ware et al. 2013, pubmed:24266778)
PNPOD is an autosomal recessive inborn error of metabolism resulting in vitamin B6 deficiency that manifests as neonatal-onset severe seizures and subsequent encephalopathy. [from MIM:610090, 2019.05.16, referencing Plecko et al. 2014, pubmed:24658933]
Pyridoxamine 5-prime-phosphate oxidase deficiency (PNPOD) is caused by homozygous or compound heterozygous mutation in the PNPO gene. Multiple independent mutations have been documented. [from MIM:610090, 2019.05.16]
PNPO is a rate-limiting enzyme that converts dietary vitamin B6 such as pyridoxine to its only active form, pyridoxal 5'-phosphate (PLP). Pyridoxine and pyridoxamine are inactive forms of dietary vitamin B6. (Chi et al. 2014, FBrf0225400; Garrido-Franco 2003, pubmed:12686115)
One human gene to many Drosophila genes.
Best score, high-ranking ortholog.