LEAP2

Chr 5

liver enriched antimicrobial peptide 2

Also known as: LEAP-2

NCBI Gene: 116842ENSG00000164406UniProt: Q969E1

This gene encodes a cysteine-rich cationic antimicrobial peptide that is expressed predominantly in the liver. The mature peptide has activity against gram-positive bacteria and yeasts. [provided by RefSeq, Sep 2014]

34
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— LEAP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 18 VUS of 34 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

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.
1.87LOEUF
pLI 0.001
Z-score -0.17
OE 1.10 (0.52–1.87)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.01Z-score
OE missense 1.00 (0.78–1.28)
44 obs / 44.2 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.1.10 (0.52–1.87)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.78–1.28)
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.1.17
0≤1.21.6
LoF obs/exp: 4 / 3.6Missense obs/exp: 44 / 44.2Syn Z: -0.54

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS18
Likely Benign1
14
Pathogenic
1
Likely Pathogenic
18
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
1
0
1
VUS
0
15
3
0
18
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total01519034

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

View in ClinVar →

Protein Context — Lollipop Plot

LEAP2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.
Si S et al.·Genome Med
2024
Metabolomic signature and molecular profile of normal and degenerated human intervertebral disc cells.
Francisco V et al.·Spine J
2023
Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males.
Pedersen MGB et al.·Am J Clin Nutr
2023Clinical trial
LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men.
Hagemann CA et al.·Cell Rep Med
2022
Hormonal predictors of the insulin sensitive phenotype in humans.
Ahmed MB et al.·Biomol Biomed
2025
Identification and Metabolic Profiling of a Novel Human Gut-derived LEAP2 Fragment.
Hagemann CA et al.·J Clin Endocrinol Metab
2021
Transcriptomic signatures during normothermic liver machine perfusion correspond with graft quality and predict the early graft function.
Hautz T et al.·EBioMedicine
2024
Plasma LEAP2 concentration is associated with attention and cognitive responses to low-calorie food cues in men depending on body weight status.
Andreoli MF et al.·Physiol Behav
2025Clinical trial
Liver Expressed Antimicrobial Peptide 2 is Associated with Steatosis in Mice and Humans.
Ma X et al.·Exp Clin Endocrinol Diabetes
2021
Peptide with Dual Roles in Immune and Metabolic Regulation: Liver-Expressed Antimicrobial Peptide-2 (LEAP-2).
Li Y et al.·Molecules
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Diabetes Mellitus Type 2Fecal Microbiota Transplantation (FMT)Oral Glucose Tolerance Test

Fecal Microbiota Transplantation Intervention on Microbiota Composition and Insulin Sensitivity in Diabetes

RECRUITING
NCT07375797Phase NACentral Jutland Regional HospitalStarted 2026-02-05
Fecal Microbial TransplantationPlacebo
ObesityObesity, Infant

Maternal Characteristics Associated With Child Growth and Adiposity

RECRUITING
NCT05798676Instituto de Desarrollo e Investigaciones Pediátricas Prof. Dr. Fernando E. ViteriStarted 2019-05-02
overweight/obesity

External Resources

Links to major genomics databases and tools