PLPBP

Chr 8AR

pyridoxal phosphate binding protein

Also known as: EPEO1, EPVB6D, PROSC

NCBI Gene: 11212ENSG00000147471UniProt: O94903

This gene encodes a pyridoxal 5'-phosphate binding protein involved in the homeostatic regulation of intracellular pyridoxal 5'-phosphate. This gene has a tumor suppressive effect on hepatocellular carcinoma and other solid tumors of epithelial origin. Naturally occurring mutations in this gene are associated with a pyridoxine-dependent epilepsy. [provided by RefSeq, Mar 2017]

Primary Disease Associations & Inheritance

Epilepsy, early-onset, 1, vitamin B6-dependentMIM #617290
AR
350
ClinVar variants
83
Pathogenic / LP
0.04
pLI score
0
Active trials
Clinical Summary— PLPBP
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
83 Pathogenic / Likely Pathogenic· 115 VUS of 350 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.70LOEUF
pLI 0.040
Z-score 2.41
OE 0.33 (0.17–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.98Z-score
OE missense 0.78 (0.68–0.91)
125 obs / 159.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.17–0.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.68–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 5 / 15.1Missense obs/exp: 125 / 159.9Syn Z: -0.38

ClinVar Variant Classifications

350 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic74
Likely Pathogenic9
VUS115
Likely Benign133
Benign11
Conflicting8
74
Pathogenic
9
Likely Pathogenic
115
VUS
133
Likely Benign
11
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
1
63
0
74
Likely Pathogenic
2
4
3
0
9
VUS
3
98
11
3
115
Likely Benign
1
8
60
64
133
Benign
0
2
7
2
11
Conflicting
—8
Total1611314469350

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

View in ClinVar →

Protein Context — Lollipop Plot

PLPBP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PLPBP-related vitamin-B6-dependent epilepsy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Epilepsy, early-onset, 1, vitamin B6-dependent

MIM #617290

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PLPBP
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Disorders affecting vitamin B(6) metabolism.
Wilson MP et al.·J Inherit Metab Dis
2019Review
Exploring the clinical, neuroimaging, and genetic spectrum of PLPBP deficiency: multicenter case series and systematic review.
Alsini H et al.·Mol Genet Metab
2026Review
PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights.
Johnstone DL et al.·Brain
2019
Optimal management after paediatric lumbar puncture: a randomized controlled trial.
Hu B et al.·BMC Neurol
2019
Infantile Spasms without Hypsarrhythmia and Paroxysmal Eye-Head Movements in an Infant with a Pyridoxine-Dependent Epilepsy due to PLPBP/PLPHP Deficiency.
Kalser J et al.·Neuropediatrics
2023
Clinical Profile, Genotypes, and Outcomes in Children with Pyridoxine Dependent Epilepsy (PDE): A Single Center Experience from Southern India.
Gowda VK et al.·Indian Pediatr
2025
Host Plasma Microenvironment in Immunometabolically Impaired HIV Infection Leads to Dysregulated Monocyte Function and Synaptic Transmission Ex Vivo.
Mikaeloff F et al.·Adv Sci (Weinh)
2025
Clinical and genetic features in pyridoxine-dependent epilepsy: a Chinese cohort study.
Jiao X et al.·Dev Med Child Neurol
2020Cohort
Pyridoxine-dependent Epilepsy caused by a Novel homozygous mutation in PLPBP Gene.
İpek R et al.·Metab Brain Dis
2022Case report
Late-onset Vitamin B6-dependent epilepsy caused by compound heterozygous pathogenic PLPBP variants.
Nakamura S et al.·Eur J Med Genet
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PLPBP Deficiency
Al-Shekaili H et al.
1993🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools