LGR5 Gene: Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5

A stem cell marker and key player in Wnt signaling, implicated in cancer and tissue regeneration.

Gene Information Card

Symbol LGR5
Full Name Leucine rich repeat containing G protein-coupled receptor 5
Gene Type protein coding
Chromosomal Location 12q21.1
NCBI Gene ID 8549 ncbi.nlm.nih.gov/gene/8549
Ensembl ID ENSG00000139292
UniProt ID O75473
OMIM ID 606667
HGNC ID 4501
Aliases GPR49, GRP49, FEX, HG38

Description

LGR5 (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5) encodes a seven-transmembrane receptor that is a well-established marker of adult stem cells in various tissues, including the intestine, stomach, hair follicles, and liver. It functions as a receptor for R-spondins, which potentiate Wnt signaling, crucial for stem cell maintenance, proliferation, and tissue regeneration. LGR5 is also implicated in cancer, where its overexpression is associated with tumor growth and poor prognosis.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Colorectal cancer LGR5 marks cancer stem cells; overexpression enhances Wnt signaling, promoting tumor initiation and progression. High expression correlates with poor survival (PMID: 25705862).
Hepatocellular carcinoma LGR5+ cells contribute to tumor growth and recurrence; activation of Wnt/β-catenin pathway. Upregulated in HCC tissues (PMID: 26045157).
Gastric cancer LGR5+ cells are associated with cancer stemness and chemoresistance. Expression linked to advanced stage (PMID: 26907580).
Basal cell carcinoma LGR5 marks tumor-propagating cells; aberrant Wnt signaling drives tumorigenesis. LGR5+ cells show high tumorigenic potential (PMID: 22438019).

Expression Profile

Tissue Expression
Tissue nTPM level
Small intestine 12.5 High
Colon 10.2 High
Stomach 8.4 Medium
Liver 3.1 Low
Skin 2.0 Low
Cell Line Expression
Cell Line nTPM Notes
Caco-2 15.3 Colorectal adenocarcinoma cell line; high expression
HCT116 12.8 Colorectal carcinoma; moderate-high
HepG2 4.2 Hepatocellular carcinoma; low
MCF7 1.5 Breast cancer; low
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.557C>T (p.Ser186Phe) Missense 0.01% (COSMIC) Unknown; may affect receptor function
c.1120A>G (p.Ile374Val) Missense 0.005% (COSMIC) Not characterized
c.1654C>T (p.Arg552Trp) Missense 0.002% (COSMIC) Potential impact on signaling
Mutation functional classification

Loss of Function (LOF)

Rare truncating mutations have been reported in some cancers, potentially reducing receptor activity, but functional validation is limited.

Gain of Function (GOF)

Amplification or overexpression of LGR5 is common in cancers, leading to enhanced Wnt signaling and stemness, but specific activating point mutations are not well documented.

Dominant Negative (DN)

No evidence for dominant-negative LGR5 mutations.

Gene Ontology (GO)

• G protein-coupled receptor activity • transmembrane signaling receptor activity
• Wnt signaling pathway • stem cell population maintenance
• positive regulation of cell proliferation • cell surface receptor signaling pathway

Pathways

Wnt signaling pathway
R-spondin receptor pathway
Stem cell regulation

Protein Summary

LGR5 is a 907-amino acid protein with a large extracellular domain containing leucine-rich repeats, a seven-transmembrane domain, and a cytoplasmic tail. It binds R-spondins, which enhance Wnt signaling by stabilizing Frizzled receptors. LGR5 is predominantly expressed on the surface of adult stem cells, where it maintains stemness and promotes tissue homeostasis. In cancer, LGR5 marks cancer stem cells and contributes to tumor heterogeneity and therapy resistance.

Related Products

Product name Cat.No. Species Gene ID
LGR5 Knockout HEK293 Cell Line EDJ-KQ113 Human 8549 Details Get a Quote
LGR5 Knockout HeLa Cell Line EDJ-KQ18448 Human 8549 Details Get a Quote
LGR5 Knockout A-549 Cell Line EDJ-KQ63423 Human 8549 Details Get a Quote
LGR5 Knockout HCT 116 Cell Line EDJ-KQ71889 Human 8549 Details Get a Quote
Displaying Records 1 To 4 Of 4 Records
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