LNPEP

Chr 5

leucyl and cystinyl aminopeptidase

Also known as: CAP, IRAP, P-LAP, PLAP

NCBI Gene: 4012ENSG00000113441UniProt: Q9UIQ6

This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

148
ClinVar variants
22
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— LNPEP
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 121 VUS of 148 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.25LOEUF
pLI 1.000
Z-score 5.87
OE 0.13 (0.07–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
1.44Z-score
OE missense 0.82 (0.76–0.89)
432 obs / 525.1 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.0.13 (0.07–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.76–0.89)
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.0.94
0≤1.21.6
LoF obs/exp: 7 / 53.2Missense obs/exp: 432 / 525.1Syn Z: 0.71

ClinVar Variant Classifications

148 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS121
Likely Benign5
20
Pathogenic
2
Likely Pathogenic
121
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
2
0
2
VUS
0
112
9
0
121
Likely Benign
0
3
2
0
5
Benign
0
0
0
0
0
Total0115330148

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

View in ClinVar →

Protein Context — Lollipop Plot

LNPEP · 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
Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.
Marusina AI et al.·J Invest Dermatol
2023
Identification of a missense variant in LNPEP that confers psoriasis risk.
Cheng H et al.·J Invest Dermatol
2014
A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs.
Venema WJ et al.·Cell Genom
2024
Genetic association of ERAP1 and ERAP2 with eclampsia and preeclampsia in northeastern Brazilian women.
Ferreira LC et al.·Sci Rep
2021
Comparative proteome analysis identified CD44 as a possible serum marker for docetaxel resistance in castration-resistant prostate cancer.
Keresztes D et al.·J Cell Mol Med
2022
CircLNPEP promotes the progression of ovarian cancer through regulating miR-876-3p/ WNT5A axis.
Wang W et al.·Cell Cycle
2021
Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity.
Yong HE et al.·Placenta
2014
A systematic strategy for identifying causal single nucleotide polymorphisms and their target genes on Juvenile arthritis risk haplotypes.
Jiang K et al.·BMC Med Genomics
2024
Association of IL23R and ERAP1 genes with ankylosing spondylitis in a Portuguese population.
Pimentel-Santos FM et al.·Clin Exp Rheumatol
2009
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools