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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LRIG3
leucine rich repeats and immunoglobulin like domains 3
Chromosome 12 · 12q14.1
NCBI Gene: 121227Ensembl: ENSG00000139263.12HGNC: HGNC:30991UniProt: C9K080
53PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GO:0005615protein bindingsensory perception of soundplasma membraneosteoarthritis, hipsmoking initiationtotal hip arthroplastynon-small cell lung carcinoma
✦AI Summary

LRIG3 (leucine-rich repeats and immunoglobulin-like domains 3) is a single-pass transmembrane protein with dual roles in development and cancer biology. During embryonic development, LRIG3 may regulate craniofacial and inner ear morphogenesis, potentially controlling lateral semicircular canal formation by restricting NTN1 expression within the otic vesicle epithelium. In cancer pathogenesis, LRIG3 functions as a tumor suppressor gene. Mechanistically, LRIG3 regulates cell proliferation, apoptosis, invasion, and migration through modulation of growth factor signaling pathways, particularly EGFR and MET/PI3K/Akt cascades 1. Decreased LRIG3 expression correlates with increased cancer cell proliferation and invasion across multiple malignancies 2345. A soluble ectodomain form (sLRIG3) also exhibits tumor-suppressive activity 6. Clinically, LRIG3 expression is a significant prognostic indicator: high expression associates with improved overall survival in cervical adenocarcinoma, glioblastoma, and prostate cancer 763. Recently, LRIG3 was identified as a target of let-7b-5p microRNA, with this pathway modulating microglial pyroptosis and promoting motor function recovery in spinal cord injury models 8. These findings establish LRIG3 as clinically relevant for cancer prognosis and potentially therapeutic intervention.

Sources cited
1
LRIG3 is a single-pass transmembrane protein with prognostic value; high LRIG3 expression associated with good survival in multiple cancer types
PMID: 25180912
2
LRIG3 expression decreases during cervical cancer development; reduced LRIG3 increases EGFR expression, cell proliferation, and invasion
PMID: 26390694
3
Overexpressed LRIG3 inhibits prostate cancer cell viability, adhesion, migration, and invasion while promoting apoptosis
PMID: 30412760
4
LRIG3 silencing decreases bladder cancer cell proliferation and promotes apoptosis
PMID: 21505989
5
LRIG3 knockdown increases glioblastoma cell invasion, adhesion, and growth; LRIG3 may regulate EGFR signaling as a tumor suppressor
PMID: 19200647
6
LRIG3 and soluble LRIG3 (sLRIG3) inhibit glioblastoma growth and invasion through MET/PI3K/Akt pathway regulation; sLRIG3 correlates with overall survival
PMID: 31245283
7
High LRIG3 expression correlates with improved survival in cervical adenocarcinoma and positive HPV status
PMID: 23165628
8
LRIG3 is a target of let-7b-5p microRNA; iPSC-NSC-derived exosomal let-7b-5p regulates LRIG3 to modulate microglial pyroptosis and improve motor function after spinal cord injury
PMID: 38982427
Disease Associationsⓘ20
osteoarthritis, hipOpen Targets
0.47Moderate
smoking initiationOpen Targets
0.42Moderate
total hip arthroplastyOpen Targets
0.42Moderate
non-small cell lung carcinomaOpen Targets
0.37Weak
lung adenocarcinomaOpen Targets
0.37Weak
acinar lung adenocarcinomaOpen Targets
0.37Weak
bile duct carcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
lymphoid neoplasmOpen Targets
0.37Weak
esophageal diseaseOpen Targets
0.34Weak
osteoarthritisOpen Targets
0.33Weak
cholesteatoma of middle earOpen Targets
0.32Weak
hepatocellular carcinomaOpen Targets
0.30Weak
urinary bladder carcinomaOpen Targets
0.28Weak
bladder transitional cell carcinomaOpen Targets
0.28Weak
cervical squamous cell carcinomaOpen Targets
0.28Weak
breast carcinomaOpen Targets
0.28Weak
head and neck squamous cell carcinomaOpen Targets
0.28Weak
gastroesophageal junction adenocarcinomaOpen Targets
0.28Weak
squamous cell lung carcinomaOpen Targets
0.28Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ZNF354AShared pathway100%LRIG2Shared pathway100%CLRN3Shared pathway100%GRXCR2Shared pathway100%CEACAM16Shared pathway100%LHFPL3Shared pathway100%
Tissue Expression6 tissues
Ovary
100%
Heart
38%
Lung
37%
Liver
36%
Brain
14%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
LRIG3ZNF354ALRIG2CLRN3GRXCR2CEACAM16LHFPL3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6UXM1
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.66 [0.55–0.81]
RankingsWhere LRIG3 stands among ~20K protein-coding genes
  • #8,452of 20,598
    Most Researched53
  • #6,720of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedLRIG3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
IPSC-NSCs-derived exosomal let-7b-5p improves motor function after spinal cord Injury by modulating microglial/macrophage pyroptosis.
PMID: 38982427
J Nanobiotechnology · 2024
1.00
2
Expression and significance of LRIG3 in human cervical squamous cell carcinoma.
PMID: 26390694
Eur J Gynaecol Oncol · 2015
0.90
3
Overexpressed LRIG3 gene ameliorates prostate cancer through suppression of cell invasion and migration.
PMID: 30412760
Int J Biol Macromol · 2019
0.80
4
Effect of silencing LRIG3 gene on the proliferation and apoptosis of bladder cancer T24 cells.
PMID: 21505989
J Huazhong Univ Sci Technolog Med Sci · 2011
0.70
5
LRIG and cancer prognosis.
PMID: 25180912
Acta Oncol · 2014
0.60