FGL1 (Fibrinogen Like 1): Structure, Function, and Clinical Relevance
A comprehensive overview of the FGL1 gene, including its genomic context, protein function, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | FGL1 |
|---|---|
| Full Name | Fibrinogen Like 1 |
| Gene Type | protein coding |
| Chromosomal Location | 8p22 |
| NCBI Gene ID | 2267 ncbi.nlm.nih.gov/gene/2267 |
| Ensembl ID | ENSG00000104760 |
| UniProt ID | Q08830 |
| OMIM ID | 605776 |
| HGNC ID | 3652 |
| Aliases | hepassocin, LFIRE-1, HP-041, fibrinogen-like protein 1 |
Description
FGL1 (Fibrinogen Like 1) is a protein-coding gene located on chromosome 8p22. It encodes a fibrinogen-related protein that is primarily secreted by the liver. FGL1 is involved in various biological processes, including hepatocyte proliferation, liver regeneration, and immune regulation. Notably, FGL1 has been identified as a major ligand for the immune checkpoint receptor LAG-3, playing a role in tumor immune evasion. Its expression is often dysregulated in cancers, particularly hepatocellular carcinoma, making it a potential biomarker and therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Overexpression of FGL1 in tumor cells promotes immune evasion by binding to LAG-3 on T cells, inhibiting T cell activation and cytokine production. | Multiple studies (e.g., Wang et al., 2019, Cancer Cell) demonstrate high FGL1 expression in HCC and correlation with poor prognosis. |
| Colorectal cancer | Elevated FGL1 expression is associated with tumor progression and immune suppression, potentially via LAG-3 interaction. | Clinical and experimental evidence from studies such as those in OncoImmunology (2020) and Cancer Immunology Research. |
| Non-small cell lung cancer | FGL1 expression in tumor tissues correlates with reduced T cell infiltration and worse survival, suggesting its role in immune checkpoint regulation. | Studies in Lung Cancer (2021) and Journal of Thoracic Oncology. |
| Liver fibrosis/cirrhosis | FGL1 is involved in liver regeneration and fibrogenesis; altered expression may contribute to chronic liver disease progression. | Experimental models and clinical observations (e.g., Hepatology Research, 2015). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High |
| Kidney | Low | Low |
| Small intestine | Low | Low |
| Lung | Low | Low |
| Spleen | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | High | Hepatocellular carcinoma cell line with high FGL1 expression. |
| Huh7 (liver cancer) | High | Another HCC cell line showing elevated FGL1. |
| A549 (lung cancer) | Low | Lung adenocarcinoma cell line with low FGL1 expression. |
| MCF7 (breast cancer) | Low | Breast cancer cell line with minimal FGL1 expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.104C>T (p.Pro35Leu) | Missense | Rare (MAF <0.01) | Potential impact on protein structure; clinical significance unknown. |
| c.457G>A (p.Val153Ile) | Missense | Rare | May affect ligand binding; not well characterized. |
| c.789delC (p.Pro264fs) | Frameshift | Very rare | Predicted to cause loss of function; observed in cancer samples. |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense mutations that truncate the protein likely lead to loss of function, potentially affecting hepatocyte proliferation and immune regulation.
Gain of Function (GOF)
Missense mutations that enhance FGL1 binding to LAG-3 could lead to increased immune evasion, but such variants are not well documented.
Dominant Negative (DN)
No evidence for dominant-negative effects; FGL1 functions as a secreted protein, and mutations are unlikely to exert dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • hepatocyte growth factor receptor binding | • receptor ligand activity |
| • fibrinogen binding | • extracellular space |
| • extracellular region | • positive regulation of cell population proliferation |
| • negative regulation of T cell activation | • liver regeneration |
| • immune response |
Pathways
• LAG-3 immune checkpoint pathway
• Hepatocyte proliferation and liver regeneration
• Fibrinogen-related signaling
Protein Summary
The FGL1 protein (UniProt Q08830) is a secreted fibrinogen-related protein of approximately 70 kDa. It contains a fibrinogen C-terminal domain and is primarily produced by the liver. FGL1 is involved in liver regeneration and hepatocyte mitogenesis. More recently, it has been identified as a ligand for LAG-3 (CD223), an inhibitory immune checkpoint receptor expressed on T cells. FGL1-LAG-3 interaction suppresses T cell function, contributing to tumor immune evasion. This makes FGL1 a promising target for cancer immunotherapy, with antibodies blocking FGL1-LAG-3 interaction being investigated.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FGL1 Knockout HEK293 Cell Line | EDJ-KQ4592 | Human | 2267 | Details Get a Quote |
| FGL1 Knockout A-549 Cell Line | EDJ-KQ27254 | Human | 2267 | Details Get a Quote |
| FGL1 Knockout HeLa Cell Line | EDJ-KQ53233 | Human | 2267 | Details Get a Quote |
| FGL1 Knockout HCT 116 Cell Line | EDJ-KQ70198 | Human | 2267 | Details Get a Quote |
| FGL1 Knockdown HEK293 Stable Cell Line | EDJ-KD002 | Human | 2267 | Details Get a Quote |
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