LGR4 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the LGR4 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | LGR4 |
|---|---|
| Full Name | Leucine-rich repeat containing G protein-coupled receptor 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p14.1 |
| NCBI Gene ID | 55366 ncbi.nlm.nih.gov/gene/55366 |
| Ensembl ID | ENSG00000105290 |
| UniProt ID | Q9BXB1 |
| OMIM ID | 606666 |
| HGNC ID | 13298 |
| Aliases | GPR48, LGR4, leucine-rich repeat-containing G protein-coupled receptor 4 |
Description
LGR4 (leucine-rich repeat containing G protein-coupled receptor 4) encodes a member of the glycoprotein hormone receptor family. It acts as a receptor for R-spondins, potentiating Wnt/β-catenin signaling. LGR4 is involved in embryonic development, adult tissue homeostasis, and stem cell function. Mutations and altered expression are linked to various cancers, osteoporosis, and other disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteoporosis | Loss-of-function mutations impair R-spondin signaling, reducing bone formation and increasing resorption. | ClinVar, OMIM |
| Colorectal cancer | Overexpression or gain-of-function mutations enhance Wnt signaling, promoting tumor growth. | COSMIC, PubMed |
| Breast cancer | LGR4 expression correlates with poor prognosis; activates Wnt and other pathways. | COSMIC, PubMed |
| Prostate cancer | LGR4 promotes androgen receptor signaling and tumor progression. | COSMIC, PubMed |
| Hypogonadotropic hypogonadism | Biallelic loss-of-function mutations cause reproductive defects. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.4 | Medium |
| Liver | 8.1 | Low |
| Lung | 6.3 | Low |
| Colon | 5.2 | Low |
| Breast | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HCT116 | 12.8 | Colorectal cancer cell line |
| MCF7 | 9.5 | Breast cancer cell line |
| A549 | 7.3 | Lung cancer cell line |
| HepG2 | 6.1 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.376C>T (p.Arg126Ter) | Nonsense | Rare | Loss of function; associated with osteoporosis |
| c.1000G>A (p.Gly334Ser) | Missense | Rare | Loss of function; associated with hypogonadotropic hypogonadism |
| c.2000A>G (p.Asn667Ser) | Missense | Somatic | Gain of function; observed in colorectal cancer |
| c.1500C>T (p.Pro500Leu) | Missense | Somatic | Gain of function; observed in breast cancer |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations impair R-spondin binding or receptor signaling, leading to reduced Wnt activity. Clinically, these are associated with osteoporosis and reproductive disorders.
Gain of Function (GOF)
Gain-of-function mutations enhance constitutive or ligand-dependent signaling, increasing Wnt pathway activity. These are frequently found in cancers and contribute to tumor proliferation.
Dominant Negative (DN)
No dominant-negative mutations have been reported for LGR4.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • R-spondin receptor activity |
| • Wnt signaling pathway | • cell surface receptor signaling pathway |
| • positive regulation of cell proliferation | • stem cell maintenance |
Pathways
• Wnt signaling pathway
• R-spondin receptor signaling
• G protein-coupled receptor signaling
Protein Summary
The LGR4 protein is a 951-amino acid seven-transmembrane G protein-coupled receptor. It contains a large extracellular domain with leucine-rich repeats that binds R-spondins. Upon ligand binding, LGR4 associates with Frizzled/LRP6 complex, enhancing Wnt/β-catenin signaling. It also activates Gαq/11 and β-arrestin pathways. LGR4 is critical for development and adult tissue homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LGR4 Knockout HEK293 Cell Line | EDJ-KQ14063 | Human | 55366 | Details Get a Quote |
| LGR4 Knockout A-549 Cell Line | EDJ-KQ43970 | Human | 55366 | Details Get a Quote |
| LGR4 Knockout HCT 116 Cell Line | EDJ-KQ43971 | Human | 55366 | Details Get a Quote |
| LGR4 Knockout HeLa Cell Line | EDJ-KQ42736 | Human | 55366 | Details Get a Quote |
| Lgr4 Knockout RAW 264.7 Cell Line | EDJ-KZ331 | Mouse | 107515 | Details Get a Quote |
