PEBP4

Chr 8

phosphatidylethanolamine binding protein 4

Also known as: CORK-1, CORK1, GWTM1933, HEL-S-300, PEBP-4, PRO4408, hPEBP4

PEBP4 encodes a phosphatidylethanolamine-binding protein that binds lipids, inhibits serine proteases, and promotes AKT phosphorylation in the PI3K-AKT signaling pathway. The gene is not highly constrained against loss-of-function variants, and no established human diseases have been definitively linked to PEBP4 mutations in the current literature.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
83
P/LP submissions
0%
P/LP missense
1.29
LOEUF
DN
Mechanism· predicted
Clinical SummaryPEBP4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
83 unique Pathogenic / Likely Pathogenic· 60 VUS of 152 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.29LOEUF
pLI 0.000
Z-score 0.89
OE 0.71 (0.421.29)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.67Z-score
OE missense 1.17 (1.021.33)
150 obs / 128.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.71 (0.421.29)
00.351.4
Missense OE1.17 (1.021.33)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 8 / 11.2Missense obs/exp: 150 / 128.7Syn Z: -0.63
DN
0.6259th %ile
GOF
0.5169th %ile
LOF
0.2679th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

152 submitted variants in ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic4
VUS60
Likely Benign5
79
Pathogenic
4
Likely Pathogenic
60
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
4
0
4
VUS
0
52
8
0
60
Likely Benign
0
4
1
0
5
Benign
0
0
0
0
0
Total056920148

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

View in ClinVar →

Protein Context — Lollipop Plot

PEBP4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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