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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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THOP1
thimet oligopeptidase 1
Chromosome 19 · 19p13.3
NCBI Gene: 7064Ensembl: ENSG00000172009.16HGNC: HGNC:11793UniProt: P52888
73PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcytosolmitochondrial intermembrane spacemetalloendopeptidase activityHypercholesterolemianeurodegenerative diseaseasthmaatrial fibrillation
✦AI Summary

THOP1 is a metalloendopeptidase ubiquitously distributed in mammalian tissues that catalyzes the degradation of neuropeptides under 20 amino acids 1. It functions as a cytoplasmic peptidase involved in processing intracellular peptides and has been implicated in generating amyloidogenic fragments through proteolysis 1. Beyond peptide metabolism, THOP1 regulates metabolic homeostasis; THOP1-null mice show increased susceptibility to obesity, insulin resistance, and non-alcoholic liver steatosis when fed high-fat diets, suggesting roles in lipid metabolism and glucose control 1. Clinically, THOP1 demonstrates significance across multiple pathologies. Low THOP1 expression in non-small cell lung cancer independently predicts decreased disease-free and overall survival, implicating THOP1 as a potential prognostic biomarker 2. Reduced THOP1 expression in background liver tissue associated with hepatocellular carcinoma predicts worse prognosis 3. THOP1 was identified as part of a diagnostic biomarker panel distinguishing dementia with Lewy bodies from Alzheimer's disease in cerebrospinal fluid 4. A genetic pattern including THOP1 on chromosome 19 shows significant association with late-onset Alzheimer's disease risk, particularly in European populations 5. Additionally, circulating THOP1 levels associate with metabolic complications in type 2 diabetes and hepatic steatosis in Prader-Willi syndrome 6, 7.

Sources cited
1
THOP1 is a ubiquitous metallopeptidase involved in neuropeptide degradation and intracellular peptide processing; THOP1-knockout mice show increased obesity, insulin resistance, and liver steatosis on high-fat diet
PMID: 32847123
2
Low THOP1 expression in non-small cell lung cancer independently predicts decreased disease-free survival and overall survival
PMID: 25180910
3
Reduced THOP1 expression in background liver tissue of hepatocellular carcinoma is an independent prognostic factor for poor prognosis
PMID: 24604581
4
THOP1 is part of a 6-protein CSF biomarker panel that discriminates dementia with Lewy bodies from Alzheimer's disease
PMID: 37704597
5
A genetic pattern including THOP1 on chromosome 19 is significantly associated with late-onset Alzheimer's disease risk, particularly in European populations
PMID: 40149871
6
THOP1 expression in plasma associates with progressive chronic kidney disease in severe insulin-resistant diabetes subtype
PMID: 39059739
7
Circulating THOP1 levels associate with hepatic steatosis severity in Prader-Willi syndrome and contribute to metabolic biomarker models
PMID: 38034016
Disease Associationsⓘ20
HypercholesterolemiaOpen Targets
0.39Weak
neurodegenerative diseaseOpen Targets
0.37Weak
asthmaOpen Targets
0.29Weak
atrial fibrillationOpen Targets
0.17Weak
neuroendocrine neoplasmOpen Targets
0.12Weak
Alzheimer diseaseOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
Lewy body dementiaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.04Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.04Suggestive
Cernunnos-XLF deficiencyOpen Targets
0.04Suggestive
autoimmune lymphoproliferative syndrome type 4Open Targets
0.04Suggestive
RAS-associated autoimmune leukoproliferative diseaseOpen Targets
0.04Suggestive
macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing lossOpen Targets
0.03Suggestive
MYH9-related diseaseOpen Targets
0.03Suggestive
autoimmune thrombocytopenic purpuraOpen Targets
0.03Suggestive
X-linked retinoschisisOpen Targets
0.03Suggestive
Bernard-Soulier syndromeOpen Targets
0.03Suggestive
neutropenia, severe congenital, 1, autosomal dominantOpen Targets
0.03Suggestive
retinitis pigmentosa and erythrocytic microcytosisOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TPP2Shared pathway100%KNG1Protein interaction99%PREPProtein interaction82%BLMHShared pathway67%PGA4Shared pathway50%PGA3Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
68%
Ovary
46%
Brain
39%
Lung
27%
Heart
24%
Gene Interaction Network
Click a node to explore
THOP1TPP2KNG1PREPBLMHPGA4PGA3
PROTEIN STRUCTURE
Preparing viewer…
PDB2O36 · 1.95 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.88LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.69 [0.55–0.88]
RankingsWhere THOP1 stands among ~20K protein-coding genes
  • #6,515of 20,598
    Most Researched73
  • #7,760of 17,882
    Most Constrained (LOEUF)0.88
Genes detectedTHOP1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions.
PMID: 32847123
Biomolecules · 2020
1.00
2
CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease.
PMID: 37704597
Nat Commun · 2023
0.90
3
Human endopeptidase 24.15 (THOP1) is localized on chromosome 19p13.3 and is excluded from the linkage region for late-onset Alzheimer disease.
PMID: 9790774
Genomics · 1998
0.80
4
Expression of THOP1 and its relationship to prognosis in non-small cell lung cancer.
PMID: 25180910
PLoS One · 2014
0.70
5
Proteomics profiling and association with cardiorenal complications in type 2 diabetes subtypes in Asian population.
PMID: 39059739
Diabetes Res Clin Pract · 2024
0.60