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5 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RNPEPL1
arginyl aminopeptidase like 1
Chromosome 2 · 2q37.3
NCBI Gene: 57140Ensembl: ENSG00000142327.14HGNC: HGNC:10079UniProt: Q9HAU8
17PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
metalloaminopeptidase activityproteolysisinitiator methionyl aminopeptidase activitymetallopeptidase activitymyelodysplastic syndromeacute myeloid leukemiaacute myeloid leukemia by FAB classificationneoplasm
✦AI Summary

RNPEPL1 (arginyl aminopeptidase like 1) is a zinc metalloaminopeptidase belonging to the M1 family of metallopeptidases that catalyzes N-terminal proteolysis with broad substrate specificity 1. The full-length enzyme preferentially hydrolyzes N-terminal methionine, citrulline, and glutamine residues 1, and exhibits notable activity against peptide substrates including met-enkephalin, kallidin, and bradykinin, with unique chain-length dependent cleavage patterns 2. RNPEPL1 shows ubiquitous tissue distribution consistent with housekeeping functions and undergoes alternative splicing generating truncated protein variants 1. Disease relevance: RNPEPL1 was identified as part of a matrix metalloproteinase-related prognostic signature in hepatocellular carcinoma (HCC), where elevated expression correlates with worse overall survival and increased drug resistance to sorafenib, cisplatin, and cytarabine 3. Additionally, RNPEPL1 functions as a competing endogenous RNA (ceRNA) regulated by LINC01260 in nonalcoholic fatty liver disease (NAFLD), where modulation of RNPEPL1 expression through the LINC01260-RXRB regulatory axis affects hepatocyte lipid accumulation and steatosis progression 4. These findings suggest RNPEPL1 plays roles in both hepatic metabolic dysfunction and cancer progression, potentially impacting therapeutic strategies in liver disease.

Sources cited
1
RNPEPL1 is a zinc metallopeptidase with preference for N-terminal methionine, glutamine, and citrulline residues, shows ubiquitous tissue distribution, and undergoes alternative splicing
PMID: 19508204
2
Full-length RNPEPL1 cleaves peptide substrates including met-enkephalin, kallidin, and bradykinin, with basic amino acid preference and chain-length dependent cleavage patterns
PMID: 36545750
3
RNPEPL1 is part of a matrix metalloproteinase-related prognostic signature in HCC; high expression correlates with worse overall survival and higher IC50 values for sorafenib, cisplatin, and cytarabine
PMID: 38761174
4
RNPEPL1 is regulated as a competing endogenous RNA by LINC01260 in NAFLD and participates in lipid droplet formation and hepatocyte steatosis through the RXRB pathway
PMID: 35016686
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
acute myeloid leukemiaOpen Targets
0.10Suggestive
myelodysplastic syndromeOpen Targets
0.10Suggestive
acute myeloid leukemia by FAB classificationOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.05Suggestive
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.03Suggestive
neutropenia, severe congenital, 9, autosomal dominantOpen Targets
0.03Suggestive
exfoliation syndromeOpen Targets
0.03Suggestive
prostate carcinomaOpen Targets
0.03Suggestive
liver diseaseOpen Targets
0.02Suggestive
connective tissue diseaseOpen Targets
0.02Suggestive
ovarian carcinomaOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
inflammationOpen Targets
0.00Suggestive
embryonal rhabdomyosarcomaOpen Targets
0.00Suggestive
lung adenocarcinomaOpen Targets
0.00Suggestive
asthmaOpen Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
colon adenocarcinomaOpen Targets
0.00Suggestive
colorectal adenocarcinomaOpen Targets
0.00Suggestive
glioma susceptibility 1Open Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
TOSEDOSTATPhase II
Aminopeptidase inhibitor
acute myeloid leukemia by FAB classification
Related Genes
PGA4Shared pathway100%PGA3Shared pathway100%CAPN14Shared pathway100%CTRB2Shared pathway100%CAPN8Shared pathway100%PRSS48Shared pathway100%
Tissue Expression6 tissues
Lung
100%
Liver
64%
Heart
64%
Bone Marrow
39%
Ovary
24%
Brain
16%
Gene Interaction Network
Click a node to explore
RNPEPL1PGA4PGA3CAPN14CTRB2CAPN8PRSS48
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9HAU8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.90LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.71 [0.56–0.90]
RankingsWhere RNPEPL1 stands among ~20K protein-coding genes
  • #15,105of 20,598
    Most Researched17
  • #8,197of 17,882
    Most Constrained (LOEUF)0.90
Genes detectedRNPEPL1
Sources retrieved5 papers
Response time—
📄 Sources
5
1
Identification of a novel matrix metalloproteinases-related prognostic signature in hepatocellular carcinoma.
PMID: 38761174
Aging (Albany NY) · 2024
1.00
2
Characterization of the enzymatic properties of human RNPEPL1/aminopeptidase Z.
PMID: 36545750
J Biochem · 2023
0.80
3
The role and possible mechanism of the long noncoding RNA LINC01260 in nonalcoholic fatty liver disease.
PMID: 35016686
Nutr Metab (Lond) · 2022
0.60
4
Arginyl aminopeptidase-like 1 (RNPEPL1) is an alternatively processed aminopeptidase with specificity for methionine, glutamine, and citrulline residues.
PMID: 19508204
Protein Pept Lett · 2009
0.40
5
Correction to: Characterization of the enzymatic properties of human RNPEPL1/aminopeptidase Z.
PMID: 37021591
J Biochem · 2023
0.20