FNDC5
Fibronectin type III domain-containing protein 5; precursor of irisin
Gene Information Card
| Symbol | FNDC5 |
|---|---|
| Full Name | Fibronectin type III domain-containing protein 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p35.1 |
| NCBI Gene ID | 252995 ncbi.nlm.nih.gov/gene/252995 |
| Ensembl ID | ENSG00000160097 |
| UniProt ID | Q8NAU1 |
| OMIM ID | 611906 |
| HGNC ID | 23315 |
| Aliases | FRCP2, irisin, Irisin |
Description
FNDC5 (fibronectin type III domain-containing protein 5) encodes a transmembrane protein that is proteolytically cleaved to release irisin, a myokine secreted primarily by skeletal muscle in response to exercise. Irisin promotes the browning of white adipose tissue, increases energy expenditure, and improves glucose homeostasis. FNDC5 is also expressed in the brain, where it may support neurogenesis and cognitive function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | Reduced FNDC5/irisin expression impairs browning of white adipose tissue, decreasing energy expenditure and promoting fat accumulation. | Clinical studies show lower circulating irisin levels in obese individuals (PMID: 23798048). |
| Type 2 diabetes | Irisin improves insulin sensitivity and glucose uptake in skeletal muscle and adipose tissue. | Meta-analyses report significantly lower irisin levels in T2D patients (PMID: 26052022). |
| Non-alcoholic fatty liver disease (NAFLD) | Irisin reduces hepatic steatosis and inflammation via AMPK signaling. | Cross-sectional studies associate low irisin with NAFLD severity (PMID: 27634332). |
| Alzheimer's disease | FNDC5/irisin upregulates BDNF and protects against synaptic dysfunction and cognitive decline. | Animal models show FNDC5 overexpression improves memory; human studies link exercise-induced irisin to reduced dementia risk (PMID: 30700925). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | High |
| Heart | 8.3 | Medium |
| Brain (cerebellum) | 6.1 | Medium |
| Adipose tissue | 2.4 | Low |
| Liver | 1.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myotubes | 15.2 | Differentiated primary myotubes |
| SH-SY5Y (neuroblastoma) | 7.8 | Neuronal-like cells |
| HepG2 (hepatocellular carcinoma) | 1.5 | Low expression |
| 3T3-L1 (adipocyte) | 3.0 | Differentiated adipocytes |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3480 (G>A) | SNP (intronic) | 5-10% in European populations | Associated with altered irisin levels and obesity risk (PMID: 25541868) |
| rs726344 (C>T) | SNP (intronic) | 15-20% in East Asians | Linked to type 2 diabetes susceptibility (PMID: 26052022) |
| c.364C>T (p.Arg122*) | Nonsense | Rare | Predicted loss of function; no clinical phenotype reported |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg122*) truncate the protein, preventing irisin secretion and reducing browning capacity.
Gain of Function (GOF)
Not well characterized; no activating mutations reported in human populations.
Dominant Negative (DN)
Not described for FNDC5.
View complete mutation data：
Gene Ontology (GO)
| • cell-cell signaling | • positive regulation of cold-induced thermogenesis |
| • positive regulation of mitochondrial uncoupling | • extracellular region |
| • membrane | • protein homodimerization activity |
Pathways
• AMPK signaling pathway
• PPAR signaling pathway
• Thermogenesis
• Adipocytokine signaling pathway
Protein Summary
FNDC5 is a type I transmembrane protein of 212 amino acids. Its N-terminal fibronectin type III domain is cleaved and secreted as irisin (112 amino acids). Irisin circulates as a glycosylated homodimer and binds to an unknown receptor on adipocytes and myocytes, activating p38 MAPK and ERK signaling to induce UCP1 expression and mitochondrial biogenesis. The protein is highly conserved across mammals.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FNDC5 Knockout HEK293 Cell Line | EDJ-KQ2016 | Human | 252995 | Details Get a Quote |
| FNDC5 Knockout A-549 Cell Line | EDJ-KQ22040 | Human | 252995 | Details Get a Quote |
| FNDC5 Knockout HeLa Cell Line | EDJ-KQ59236 | Human | 252995 | Details Get a Quote |
| FNDC5 Knockout HCT 116 Cell Line | EDJ-KQ76087 | Human | 252995 | Details Get a Quote |
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