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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PLPBP
pyridoxal phosphate binding protein
Chromosome 8 Β· 8p11.23
NCBI Gene: 11212Ensembl: ENSG00000147471.13HGNC: HGNC:9457UniProt: O94903
47PubMed Papers
21Diseases
0Drugs
23Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrioncytosolpyridoxal phosphate bindingvitamin B6 metabolic processpyridoxine-dependent epilepsygenetic disordermathematical abilityLiver abscess
✦AI Summary

PLPBP (pyridoxal phosphate binding protein) is a conserved intracellular protein that plays a critical role in vitamin B6 homeostasis by regulating pyridoxal 5'-phosphate (PLP), the active form of vitamin B6 1. The protein functions as a PLP-binding protein that maintains proper B6 vitamer pools and prevents the toxic accumulation of pyridoxine 5'-phosphate (PNP) 23. PLPBP localizes to mitochondria and cytosol, where it likely facilitates the efficient turnover of protein-bound B6 vitamers and helps balance different B6 metabolite pools 4. Loss of PLPBP function disrupts vitamin B6 homeostasis and impairs PLP-dependent enzymatic pathways including amino acid metabolism, neurotransmitter synthesis (particularly GABA), and one-carbon metabolism 43. Biallelic mutations in PLPBP cause autosomal-recessive vitamin B6-dependent epilepsy with early neonatal onset 15. Most patients present with seizures within the first 24 hours of life, often accompanied by antenatal anomalies, microcephaly, and white matter abnormalities 5. Disease severity correlates with variant type: missense and compound heterozygous variants produce attenuated phenotypes, while truncating variants cause severe disease with potential early mortality 5. All affected individuals show lifelong responsiveness to high-dose pyridoxine or PLP treatment, enabling seizure control and improved neurodevelopmental outcomes 1. Recent expert consensus endorses PLPBP screening in newborn genetic screening programs due to the treatable nature of this disorder 6.

Sources cited
1
PLPBP is an intracellular PLP-binding protein involved in B6 homeostasis; mutations cause vitamin B6-dependent epilepsy responsive to pyridoxine/PLP therapy
PMID: 30671974
2
PLPBP disruption perturbs pyridoxamine 5'-phosphate (PMP) homeostasis, resulting in pathological accumulation of pyridoxine 5'-phosphate (PNP)
PMID: 34978460
3
YggS/PLPBP is critical for maintaining low PNP levels and balancing B6 vitamers; disruption perturbs amino acid and one-carbon metabolism
PMID: 35803498
4
PLPBP localizes to mitochondria and is essential for B6 homeostasis; variants cause vitamin B6-dependent epilepsy with seizures, disrupted amino acid/neurotransmitter metabolism, and altered B6 vitamer levels
PMID: 30668673
5
PLPBP deficiency causes autosomal-recessive vitamin B6-dependent epilepsy with early neonatal onset, white matter abnormalities, and microcephaly; disease severity correlates with variant type
PMID: 41671913
6
Rare disease experts recommend PLPBP inclusion in newborn genome sequencing (β‰₯85% consensus) due to the treatable nature of associated vitamin B6-dependent epilepsy
PMID: 37155167
Disease Associationsβ“˜21
pyridoxine-dependent epilepsyOpen Targets
0.72Strong
genetic disorderOpen Targets
0.41Moderate
mathematical abilityOpen Targets
0.06Suggestive
Liver abscessOpen Targets
0.04Suggestive
squamous cell carcinomaOpen Targets
0.03Suggestive
ovarian neoplasmOpen Targets
0.03Suggestive
Peptic ulcerOpen Targets
0.03Suggestive
adolescent idiopathic scoliosisOpen Targets
0.02Suggestive
smoking initiationOpen Targets
0.02Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.02Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
Epileptic encephalopathyOpen Targets
0.02Suggestive
EncephalopathyOpen Targets
0.01Suggestive
epilepsyOpen Targets
0.01Suggestive
non-small cell lung carcinomaOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
diabetic nephropathyOpen Targets
0.01Suggestive
HypsarrhythmiaOpen Targets
0.01Suggestive
protein S deficiencyOpen Targets
0.01Suggestive
Epilepsy, early-onset, 1, vitamin B6-dependentUniProt
Pathogenic Variants23
NM_007198.4(PLPBP):c.249_252del (p.Ser84fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 84
NM_007198.4(PLPBP):c.370_373del (p.Asp124fs)Pathogenic
not provided|Epilepsy, early-onset, vitamin B6-dependent
β˜…β˜…β˜†β˜†2025β†’ Residue 124
NM_007198.4(PLPBP):c.207+1G>TPathogenic
Epilepsy, early-onset, vitamin B6-dependent|not provided
β˜…β˜…β˜†β˜†2025
NM_007198.4(PLPBP):c.722G>A (p.Arg241Gln)Pathogenic
Epilepsy, early-onset, vitamin B6-dependent|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 241
NM_007198.4(PLPBP):c.260C>T (p.Pro87Leu)Pathogenic
Epilepsy, early-onset, vitamin B6-dependent|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 87
NM_007198.4(PLPBP):c.320-2A>GPathogenic
Epilepsy, early-onset, vitamin B6-dependent|not provided
β˜…β˜…β˜†β˜†2022
NM_007198.4(PLPBP):c.207+1G>APathogenic
Epilepsy, early-onset, vitamin B6-dependent|not provided
β˜…β˜†β˜†β˜†2025
NM_007198.4(PLPBP):c.122G>A (p.Arg41Gln)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 41
NM_007198.4(PLPBP):c.47_48dup (p.Leu17fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 17
NM_007198.4(PLPBP):c.207+1G>CPathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_007198.4(PLPBP):c.614G>A (p.Arg205Gln)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 205
NM_007198.4(PLPBP):c.316del (p.Met106fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 106
NM_007198.4(PLPBP):c.292C>T (p.Gln98Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 98
NM_007198.4(PLPBP):c.207C>A (p.Tyr69Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 69
NM_007198.4(PLPBP):c.389G>A (p.Trp130Ter)Likely pathogenic
Epilepsy, early-onset, vitamin B6-dependent
β˜…β˜†β˜†β˜†2023β†’ Residue 130
NM_007198.4(PLPBP):c.319+1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_007198.4(PLPBP):c.35dup (p.Val13fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2022β†’ Residue 13
NM_007198.4(PLPBP):c.6G>A (p.Trp2Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 2
NM_007198.4(PLPBP):c.47_53del (p.Ala16fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 16
NM_007198.4(PLPBP):c.387del (p.Trp130fs)Pathogenic
Epilepsy, early-onset, vitamin B6-dependent
β˜…β˜†β˜†β˜†2019β†’ Residue 130
View on ClinVar β†—
Related Genes
PNPOProtein interaction100%PDXKProtein interaction86%LACC1Protein interaction83%ERLIN2Protein interaction77%ALDH7A1Co-mentioned in literature20%
Tissue Expression6 tissues
Heart
100%
Liver
86%
Brain
66%
Lung
50%
Ovary
40%
Bone Marrow
26%
Gene Interaction Network
Click a node to explore
PLPBPPNPOPDXKLACC1ERLIN2ALDH7A1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O94903
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.05LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.73 [0.52–1.05]
RankingsWhere PLPBP stands among ~20K protein-coding genes
  • #9,257of 20,598
    Most Researched47
  • #2,068of 5,498
    Most Pathogenic Variants23
  • #10,488of 17,882
    Most Constrained (LOEUF)1.05
Genes detectedPLPBP
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Disorders affecting vitamin B
PMID: 30671974
J Inherit Metab Dis Β· 2019
1.00
2
PMID: 36795901
0.90
3
Biochemical and Proteomic Studies of Human Pyridoxal 5'-Phosphate-Binding Protein (PLPBP).
PMID: 31825581
ACS Chem Biol Β· 2020
0.80
4
Perspectives of Rare Disease Experts on Newborn Genome Sequencing.
PMID: 37155167
JAMA Netw Open Β· 2023
0.70
5
Mechanism of Pyridoxine 5'-Phosphate Accumulation in Pyridoxal 5'-Phosphate-Binding Protein Deficiency.
PMID: 34978460
J Bacteriol Β· 2022
0.60