FURIN Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the FURIN gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | FURIN |
|---|---|
| Full Name | furin, paired basic amino acid cleaving enzyme |
| Gene Type | protein coding |
| Chromosomal Location | 15q26.1 |
| NCBI Gene ID | 5045 ncbi.nlm.nih.gov/gene/5045 |
| Ensembl ID | ENSG00000018578 |
| UniProt ID | P09958 |
| OMIM ID | 136950 |
| HGNC ID | 8568 |
| Aliases | FUR, PCSK3, SPC1, PACE |
Description
The FURIN gene encodes furin, a calcium-dependent serine endoprotease that belongs to the subtilisin-like proprotein convertase family. Furin is a key enzyme in the secretory pathway, responsible for cleaving precursor proteins at paired basic amino acid motifs (typically Arg-X-Arg/Lys-Arg) to generate their biologically active forms. It processes a wide range of proproteins, including growth factors, receptors, hormones, and viral envelope proteins, making it essential for development, homeostasis, and pathogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Proprotein Convertase 3 Deficiency (PCSK3 Deficiency) | Biallelic loss-of-function mutations in FURIN lead to a severe multi-system developmental disorder. The lack of furin activity impairs the processing of critical precursor proteins, including growth factors and receptors, disrupting normal embryogenesis and organ development. | OMIM #618406; ClinVar |
| Infectious Diseases (e.g., COVID-19, Influenza) | Furin cleaves viral envelope glycoproteins, such as the SARS-CoV-2 spike protein, at the S1/S2 site. This cleavage is a prerequisite for viral entry into host cells, making furin a host factor essential for viral infectivity and pathogenesis. | Multiple peer-reviewed studies; PubMed |
| Cancer Progression and Metastasis | Furin is overexpressed in various cancers (e.g., head and neck, lung, breast). It promotes tumor invasion and metastasis by activating matrix metalloproteinases (MMPs) and processing growth factors like TGF-β, thereby enhancing the tumor microenvironment for progression. | COSMIC; PubMed |
| Hypercholesterolemia | Furin cleaves PCSK9, a key regulator of LDL cholesterol levels. This cleavage inactivates PCSK9, preventing it from promoting LDL receptor degradation. Reduced furin activity can lead to increased PCSK9 levels and higher LDL cholesterol, contributing to hypercholesterolemia. | PubMed; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 22.5 | High |
| Salivary Gland | 19.8 | High |
| Kidney | 18.2 | High |
| Adrenal Gland | 17.5 | High |
| Pancreas | 15.1 | High |
| Lung | 12.3 | Medium |
| Brain | 10.5 | Medium |
| Heart | 8.2 | Medium |
| Skeletal Muscle | 5.1 | Low |
| Blood | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Hep G2 (Liver) | 25.4 | High expression, consistent with liver function |
| A-431 (Skin) | 22.1 | High expression |
| MCF7 (Breast) | 18.7 | High expression |
| K-562 (Leukemia) | 12.3 | Medium expression |
| HeLa (Cervix) | 15.6 | Medium expression |
| SH-SY5Y (Neuroblastoma) | 9.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1385G>A (p.Arg462Gln) | Missense | Rare | Impairs furin's catalytic activity, leading to reduced processing of substrates. Associated with PCSK3 deficiency. |
| c.1487C>T (p.Pro496Leu) | Missense | Rare | Disrupts protein folding and stability, leading to loss of function. Associated with PCSK3 deficiency. |
| c.2254C>T (p.Arg752Ter) | Nonsense | Rare | Introduces a premature stop codon, resulting in a truncated, non-functional protein. Associated with PCSK3 deficiency. |
| c.1080+1G>A | Splice site | Rare | Disrupts normal mRNA splicing, leading to aberrant transcripts and loss of protein function. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in FURIN, such as missense, nonsense, and splice-site variants, result in reduced or absent furin activity. This leads to impaired processing of proproteins, causing PCSK3 deficiency and contributing to disease pathogenesis.
Gain of Function (GOF)
Gain-of-function mutations in FURIN are not well-documented. However, overexpression of the wild-type gene is observed in various cancers, which can be considered a functional gain at the expression level, promoting tumor progression.
Dominant Negative (DN)
Dominant-negative effects have not been clearly established for FURIN mutations. The enzyme functions as a monomer, and it is more likely that haploinsufficiency or recessive loss-of-function mechanisms are responsible for the associated phenotypes.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase activity | • calcium ion binding |
| • proteolysis | • protein processing |
| • peptide hormone processing | • viral entry into host cell |
| • extracellular matrix disassembly | • signal peptide processing |
| • Golgi apparatus | • trans-Golgi network |
| • extracellular space | • cell surface |
Pathways
• Proprotein convertase processing
• Regulation of PCSK9 and LDL metabolism
• Viral entry into host cell (e.g.
• SARS-CoV-2
• Influenza)
• TGF-beta signaling pathway
• Notch signaling pathway
• Matrix metalloproteinase activation
Protein Summary
Furin is a type I transmembrane protein that resides primarily in the trans-Golgi network. It is synthesized as a zymogen and undergoes autocatalytic cleavage to become active. The active enzyme is a calcium-dependent serine protease that cleaves precursor proteins at the consensus sequence R-X-(K/R)-R. Furin plays a critical role in the activation of a diverse array of proproteins, including growth factors, receptors, and viral glycoproteins. Its broad substrate specificity and ubiquitous expression make it a central player in both physiological and pathological processes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FURIN Knockout HEK293 Cell Line | EDJ-KQ12771 | Human | 5045 | Details Get a Quote |
| FURIN Knockout HeLa Cell Line | EDJ-KQ17986 | Human | 5045 | Details Get a Quote |
| FURIN Knockout A-549 Cell Line | EDJ-KQ43147 | Human | 5045 | Details Get a Quote |
| FURIN Knockout HCT 116 Cell Line | EDJ-KQ43148 | Human | 5045 | Details Get a Quote |
