NPEPPS

Chr 17

aminopeptidase puromycin sensitive

Also known as: AAP-S, MP100, PSA

NCBI Gene: 9520ENSG00000141279UniProt: P55786

This gene encodes the puromycin-sensitive aminopeptidase, a zinc metallopeptidase which hydrolyzes amino acids from the N-terminus of its substrate. The protein has been localized to both the cytoplasm and to cellular membranes. This enzyme degrades enkaphalins in the brain, and studies in mouse suggest that it is involved in proteolytic events regulating the cell cycle. [provided by RefSeq, Jul 2008]

83
ClinVar variants
8
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NPEPPS
⚡
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
8 Pathogenic / Likely Pathogenic· 63 VUS of 83 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.06LOEUF
pLI 1.000
Z-score 6.42
OE 0.00 (0.00–0.06)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
3.98Z-score
OE missense 0.48 (0.43–0.54)
222 obs / 463.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.00 (0.00–0.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.48 (0.43–0.54)
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.0.91
0≤1.21.6
LoF obs/exp: 0 / 48.0Missense obs/exp: 222 / 463.4Syn Z: 0.89

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS63
Likely Benign7
Benign5
7
Pathogenic
1
Likely Pathogenic
63
VUS
7
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
62
1
0
63
Likely Benign
0
2
3
2
7
Benign
0
0
2
3
5
Total06414583

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

View in ClinVar →

Protein Context — Lollipop Plot

NPEPPS · 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
NPEPPS Is a Druggable Driver of Platinum Resistance.
Jones RT et al.·Cancer Res
2024
Customized Chromosomal Microarrays for Neurodevelopmental Disorders.
Rincic M et al.·Genes (Basel)
2025
Identifying Potential Drug Targets in Coronary Atherosclerosis: Insights from the Druggable Genome and Mendelian Randomization.
Liu R et al.·Cardiovasc Drugs Ther
2026
Primary cutaneous apocrine carcinoma with RARA::NPEPPS fusion.
Lenskaya V et al.·J Cutan Pathol
2024Case report
Whole-exome sequencing study identifies four novel gene loci associated with diabetic kidney disease.
Pan Y et al.·Hum Mol Genet
2023
Novel progressive acrodysostosis-like skeletal dysplasia, cerebellar atrophy, and ichthyosis.
Velasco HM et al.·Am J Med Genet A
2020Case report
High Expression of ACOT2 Predicts Worse Overall Survival and Abnormal Lipid Metabolism: A Potential Target for Acute Myeloid Leukemia.
Yin X et al.·J Healthc Eng
2022
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