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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FURIN
furin, paired basic amino acid cleaving enzyme
Chromosome 15 · 15q26.1
NCBI Gene: 5045Ensembl: ENSG00000140564.14HGNC: HGNC:8568UniProt: P09958
340PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedProtease
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
Golgi membraneGO:0005615cholesterol homeostasisprotein processingcoronary artery diseasehypertensionmyocardial infarctioncardiovascular disease
✦AI Summary

FURIN is a ubiquitously expressed proprotein convertase that cleaves dibasic and polybasic amino acid motifs in precursor proteins to generate mature, active forms 1. Primary functions include processing TGF-β signaling components, with mutations impairing pro-TGF-β maturation and downstream SMAD2 phosphorylation, affecting aortic structural integrity 2. FURIN also processes viral glycoproteins critical for pathogenic infection—notably cleaving SARS-CoV-2 spike protein at the S1/S2 junction to facilitate viral entry 1, and processing mumps and Ebola envelope proteins 3. Clinically, rare FURIN variants predispose to aortic aneurysms, with 3.7% of aneurysm patients carrying heterozygous variants that reduce enzyme activity and impair collagen/fibrillin organization 2. FURIN expression correlates with COVID-19 severity—elevated sputum levels associate with neutrophilic asthma and inflammasome activation, increasing COVID-19 mortality risk 4. FURIN gene polymorphisms (rs6226) independently predict severe COVID-19 outcomes and susceptibility in certain populations 5. Additionally, FURIN-mediated apelin maturation promotes colorectal cancer metastasis, making proapelin cleavage-site inhibition a therapeutic strategy 6. FURIN inhibition represents a promising therapeutic target since somatic cell knockout is viable, while germline loss is embryonic lethal 1.

Sources cited
1
FURIN variants impair pro-TGF-β processing and cause aortic aneurysms through disrupted TGF-β signaling
PMID: 38636100
2
FURIN is a ubiquitously expressed proprotein convertase that cleaves SARS-CoV-2 spike protein; knockout in somatic cells is viable while germline loss is embryonic lethal
PMID: 34340303
3
Elevated sputum FURIN levels associate with neutrophilic severe asthma and inflammasome activation, potentially increasing COVID-19 morbidity/mortality
PMID: 33413387
4
FURIN rs6226 polymorphisms independently predict COVID-19 susceptibility and severity outcomes
PMID: 38703289
5
FURIN processes proapelin to mature apelin, which promotes colorectal cancer metastasis
PMID: 39962271
6
FURIN processes Ebola virus envelope glycoprotein; can be targeted by host MARCH proteins
PMID: 38299743
Disease Associationsⓘ20
coronary artery diseaseOpen Targets
0.58Moderate
hypertensionOpen Targets
0.57Moderate
myocardial infarctionOpen Targets
0.55Moderate
cardiovascular diseaseOpen Targets
0.54Moderate
Myocardial IschemiaOpen Targets
0.53Moderate
angina pectorisOpen Targets
0.53Moderate
COVID-19Open Targets
0.53Moderate
Abnormality of the skeletal systemOpen Targets
0.50Moderate
alcohol drinkingOpen Targets
0.50Moderate
essential hypertensionOpen Targets
0.50Moderate
heart diseaseOpen Targets
0.49Moderate
osteoarthritis, hipOpen Targets
0.48Moderate
anthrax infectionOpen Targets
0.47Moderate
dengue diseaseOpen Targets
0.47Moderate
osteoarthritis, kneeOpen Targets
0.45Moderate
coronary atherosclerosisOpen Targets
0.45Moderate
coffee consumptionOpen Targets
0.44Moderate
occlusion precerebral arteryOpen Targets
0.43Moderate
atrial fibrillationOpen Targets
0.43Moderate
atrial flutterOpen Targets
0.43Moderate
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PDGFAProtein interaction100%ERVW-1Protein interaction100%SMAD3Protein interaction99%TNFProtein interaction97%PACS1Protein interaction96%F2Protein interaction93%
Tissue Expression6 tissues
Liver
100%
Lung
30%
Bone Marrow
25%
Heart
12%
Ovary
8%
Brain
6%
Gene Interaction Network
Click a node to explore
FURINPDGFAERVW-1SMAD3TNFPACS1F2
PROTEIN STRUCTURE
Preparing viewer…
PDB7LCU · 1.24 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.20 [0.14–0.30]
RankingsWhere FURIN stands among ~20K protein-coding genes
  • #945of 20,598
    Most Researched340 · top 5%
  • #1,138of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedFURIN
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-β signalling.
PMID: 38636100
Cardiovasc Res · 2024
1.00
2
Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma.
PMID: 33413387
Respir Res · 2021
0.90
3
Neuropilin-1 is a host factor for SARS-CoV-2 infection.
PMID: 33082294
Science · 2020
0.80
4
Kallikrein-8 mediates furin-independent Activin-A precursor processing to stimulate tumor growth in melanoma.
PMID: 40064965
Nat Commun · 2025
0.72
5
Repression of apelin Furin cleavage sites provides antimetastatic strategy in colorectal cancer.
PMID: 39962271
EMBO Mol Med · 2025
0.70