PNPO

pyridoxamine 5'-phosphate oxidase

Basic information

Region (hg38): 17:47941505-47949308

Links

ENSG00000108439 ∙ NCBI:55163 ∙ OMIM:603287 ∙ HGNC:30260 ∙ Uniprot:Q9NVS9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pyridoxal phosphate-responsive seizures (Supportive), mode of inheritance: AR
• pyridoxal phosphate-responsive seizures (Definitive), mode of inheritance: AR
• pyridoxal phosphate-responsive seizures (Strong), mode of inheritance: AR
• pyridoxal phosphate-responsive seizures (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pyridoxamine 5'-phosphate oxidase deficiency	AR	Biochemical; Neurologic	Individuals may manifest with severe seizures starting in the immediate neonatal period (or even before birth), and medical treatment (with pyridoxal phosphate) can be effective as an antiepileptic agent	Biochemical; Neurologic	12200739; 12747882; 15772097; 24266778; 24658933; 28331464

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PNPO gene.

• Pyridoxal phosphate-responsive seizures (278 variants)
• not provided (77 variants)
• Inborn genetic diseases (30 variants)
• not specified (26 variants)
• Fetal growth restriction;Seizure;Growth delay (1 variants)
• Neuronopathy, distal hereditary motor, type 5A (1 variants)
• PNPO-related condition (1 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PNPO gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	54	3	59
missense	5	6	113	1		125
nonsense	2	3				5
start loss		1		1		2
frameshift	3	1	1			5
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	3				5
splice region		1	7	11		19
non coding			29	36	22	87
Total	12	14	148	92	25

Highest pathogenic variant AF is 0.000118

Variants in PNPO

This is a list of pathogenic ClinVar variants found in the PNPO region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-47941561-G-A		Pyridoxal phosphate-responsive seizures	Likely benign (Jan 13, 2018)
17-47941638-G-C		not specified	Likely benign (Apr 12, 2016)
17-47941648-A-G		not specified	Likely benign (Aug 04, 2017)
17-47941652-G-A		not specified	Likely benign (Sep 14, 2017)
17-47941653-G-A		Pyridoxal phosphate-responsive seizures	Uncertain significance (Jan 12, 2018)
17-47941657-A-G		Pyridoxal phosphate-responsive seizures	Uncertain significance (Jan 13, 2018)
17-47941658-C-T		Pyridoxal phosphate-responsive seizures	Uncertain significance (Jan 13, 2018)
17-47941659-G-A		not specified	Likely benign (Jan 31, 2018)
17-47941669-G-GC		not specified	Likely benign (Aug 25, 2017)
17-47941670-C-A		not specified	Likely benign (Jun 08, 2012)
17-47941677-T-C		Pyridoxal phosphate-responsive seizures	Conflicting classifications of pathogenicity (Mar 12, 2022)
17-47941678-G-T			Likely pathogenic (Dec 04, 2018)
17-47941679-A-G		Pyridoxal phosphate-responsive seizures	Uncertain significance (Dec 30, 2019)
17-47941681-G-A		Pyridoxal phosphate-responsive seizures	Likely benign (Oct 19, 2023)
17-47941684-C-T		Pyridoxal phosphate-responsive seizures	Likely benign (Sep 29, 2023)
17-47941686-G-C		Pyridoxal phosphate-responsive seizures	Uncertain significance (Jul 26, 2022)
17-47941687-G-T		Pyridoxal phosphate-responsive seizures	Uncertain significance (Oct 24, 2022)
17-47941691-C-A		Pyridoxal phosphate-responsive seizures • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 07, 2024)
17-47941691-C-T		Pyridoxal phosphate-responsive seizures	Uncertain significance (Jan 11, 2022)
17-47941693-G-A		Pyridoxal phosphate-responsive seizures	Likely benign (Sep 23, 2023)
17-47941695-G-A		Pyridoxal phosphate-responsive seizures	Uncertain significance (Oct 28, 2021)
17-47941697-G-A		Pyridoxal phosphate-responsive seizures	Uncertain significance (Jun 27, 2022)
17-47941702-G-A		Pyridoxal phosphate-responsive seizures	Likely benign (Dec 06, 2022)
17-47941703-G-C		Pyridoxal phosphate-responsive seizures	Uncertain significance (Jul 19, 2022)
17-47941705-G-A		Pyridoxal phosphate-responsive seizures	Likely benign (Oct 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PNPO	protein_coding	protein_coding	ENST00000225573	7	6783

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.10e-8	0.187	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.781	120	147	0.818	0.00000873	1685
Missense in Polyphen		63	59.493	1.0589		654
Synonymous	0.371	48	51.4	0.934	0.00000253	500
Loss of Function	0.334	13	14.4	0.905	6.95e-7	159

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.000272	0.000272
South Asian	0.000163	0.000163
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the oxidation of either pyridoxine 5'- phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP). {ECO:0000269|PubMed:12824491}.
• Disease: DISEASE: 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.
• Pathway: Vitamin B6 metabolism - Homo sapiens (human);Hypophosphatasia;Vitamin B6 Metabolism;Selenium Micronutrient Network;Vitamin B6-dependent and responsive disorders;Metabolism;Vitamins B6 activation to pyridoxal phosphate;Metabolism of water-soluble vitamins and cofactors;pyridoxal 5,-phosphate salvage;Metabolism of vitamins and cofactors;Vitamin B6 metabolism (Consensus)

Recessive Scores

• pRec: 0.236

Intolerance Scores

• loftool: 0.652
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.89

Haploinsufficiency Scores

• pHI: 0.340
• hipred: N
• hipred_score: 0.335
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pnpo

Gene ontology

• Biological process: pyridoxine biosynthetic process;vitamin B6 metabolic process;pyridoxal phosphate biosynthetic process;oxidation-reduction process
• Cellular component: nucleoplasm;cytosol
• Molecular function: pyridoxamine-phosphate oxidase activity;protein binding;FMN binding;pyridoxal phosphate binding;protein homodimerization activity