PLPBP

Chr 8AR

pyridoxal phosphate binding protein

Also known as: EPEO1, EPVB6D, PROSC

NCBI Gene: 11212 ENSG00000147471 UniProt: O94903 OMIM: 604436

The protein binds pyridoxal 5'-phosphate and regulates intracellular homeostasis of this active form of vitamin B6. Mutations cause early-onset, vitamin B6-dependent epilepsy that follows autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (low pLI score), which is consistent with the recessive inheritance pattern observed clinically.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epilepsy, early-onset, 1, vitamin B6-dependentMIM #617290

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · pyridoxine-dependent epilepsy · AR · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.70

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — PLPBP

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.040

Z-score 2.41

OE 0.33 (0.17–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.98Z-score

OE missense 0.78 (0.68–0.91)

125 obs / 159.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.17–0.70)

0≤0.351.4

Missense OE?0.78 (0.68–0.91)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 5 / 15.1Missense obs/exp: 125 / 159.9Syn Z: -0.38

Background carrier burden — how many people carry a rare variant somewhere in PLPBP?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

337 rare PASS variants

Rare truncating (LoF)

1 in 2,100

64 rare PASS variants

Rare synonymous (reference)

1 in 260

128 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLPBP. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 2,400
South Asian	~43k	1 in 320	1 in 3,100
Remaining (unassigned)	~30k	1 in 130	1 in 820
European (Finnish)	~27k	1 in 650	1 in 3,000
Admixed American	~22k	1 in 330	1 in 820
African / African American	~21k	1 in 310	1 in 710
East Asian	~20k	1 in 180	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 400	none seen
Middle Eastern	~2,884	1 in 290	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓