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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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LRRN4
leucine rich repeat neuronal 4
Chromosome 20 · 20p12.3
NCBI Gene: 164312Ensembl: ENSG00000125872.10HGNC: HGNC:16208UniProt: Q8WUT4
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingextracellular exosomelong-term memoryplasma membranecolorectal cancercolorectal carcinomachronic obstructive pulmonary diseasecolonic neoplasm
✦AI Summary

LRRN4 (leucine-rich repeat neuronal 4) is a leucine-rich repeat domain-containing protein with diverse roles across multiple physiological systems. In the nervous system, LRRN4 may play an important role in hippocampus-dependent long-lasting memory according to UniProt annotations. LRRN4 serves as a specific marker of primary mesothelial cells 1, with distinct expression patterns in idiopathic pulmonary fibrosis (IPF), where it is found in epithelial lining cells along honeycombing and fibroblastic foci and correlates with decreased lung function 2. In cardiac tissue, LRRN4 is highly expressed in donor hearts but significantly reduced in dilated cardiomyopathy (DCM), suggesting it is critical for maintaining cardiac morphology and function 3. LRRN4 expression is regulated by cardiac stress responses, with cardiomyocyte-specific MIAT deletion reducing pathological LRRN4 induction after myocardial infarction 4. In cancer biology, LRRN4 appears to function as a tumor suppressor; its knockdown in p53- and Rb-defective ovarian epithelial cells promotes aggressive malignant behavior through Akt pathway activation 5. Additionally, low prenatal socioeconomic status associates with altered LRRN4 DNA methylation at birth, with associations persisting into early childhood 6, and a structural deletion variant in LRRN4 was validated as associated with Parkinson disease risk 7. In neuroprotection studies, LRRN4 was identified as upregulated following aluminum ion-induced neurotoxicity in neuroblastoma cells 8.

Sources cited
1
LRRN4 is exclusively detected in primary mesothelial cells among primary cell types tested and serves as a mesothelial lineage marker
PMID: 21984916
2
LRRN4 expression is found in epithelial cells of IPF honeycombing and fibroblastic foci and correlates with decreased baseline forced vital capacity
PMID: 37550810
3
LRRN4 is highly expressed in normal donor hearts but significantly reduced in dilated cardiomyopathy and appears critical for cardiac morphology and function
PMID: 31966882
4
LRRN4 is a maladaptive gene activated by MIAT in cardiomyocytes following myocardial infarction
PMID: 39979325
5
LRRN4 knockdown promotes aggressive malignant behavior in p53- and Rb-defective ovarian epithelial cells through Akt pathway activation
PMID: 37693155
6
Low prenatal socioeconomic status associates with altered LRRN4 DNA methylation at birth, with persistence into early childhood
PMID: 31509016
7
A 2 kb intronic deletion in LRRN4 is associated with Parkinson disease genetic risk
PMID: 36695634
8
LRRN4 is upregulated in response to aluminum ion neurotoxicity in neuroblastoma cells
PMID: 30987727
Disease Associationsⓘ20
colorectal cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.07Suggestive
colonic neoplasmOpen Targets
0.07Suggestive
polyp of colonOpen Targets
0.07Suggestive
7q11.23 microduplication syndromeOpen Targets
0.07Suggestive
colon carcinomaOpen Targets
0.07Suggestive
Monoamine oxidase A deficiencyOpen Targets
0.07Suggestive
schizophrenia 19Open Targets
0.07Suggestive
ovarian neoplasmOpen Targets
0.06Suggestive
benign colon neoplasmOpen Targets
0.06Suggestive
hypertensionOpen Targets
0.06Suggestive
colorectal adenocarcinomaOpen Targets
0.06Suggestive
microangiopathy and leukoencephalopathy, pontine, autosomal dominantOpen Targets
0.06Suggestive
liver diseaseOpen Targets
0.05Suggestive
spontaneous abortionOpen Targets
0.05Suggestive
SplenomegalyOpen Targets
0.05Suggestive
ovarian dysfunctionOpen Targets
0.05Suggestive
colorectal adenomaOpen Targets
0.05Suggestive
osteoarthritis, hipOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
UPK3BProtein interaction74%CAMK2N1Shared pathway50%ACSS2Shared pathway25%CAMK4Shared pathway17%NFATC4Shared pathway14%NPAS4Shared pathway11%
Tissue Expression6 tissues
Lung
100%
Heart
4%
Liver
3%
Ovary
2%
Brain
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
LRRN4UPK3BCAMK2N1ACSS2CAMK4NFATC4NPAS4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8WUT4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.93LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.58 [1.14–1.93]
RankingsWhere LRRN4 stands among ~20K protein-coding genes
  • #15,617of 20,598
    Most Researched15
  • #17,508of 17,882
    Most Constrained (LOEUF)1.93
Genes detectedLRRN4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Cardiomyocyte-restricted MIAT deletion is sufficient to protect against murine myocardial infarction.
PMID: 39979325
Cell Death Discov · 2025
1.00
2
Role of LRRN4 in promoting malignant behavior in a p53- and Rb-defective human fallopian tube epithelial cell line.
PMID: 37693155
Am J Cancer Res · 2023
0.90
3
Socioeconomic status and DNA methylation from birth through mid-childhood: a prospective study in Project Viva.
PMID: 31509016
Epigenomics · 2019
0.80
4
Properties of Pleural Mesothelial Cells in Idiopathic Pulmonary Fibrosis and Cryptogenic Organizing Pneumonia.
PMID: 37550810
J Korean Med Sci · 2023
0.70
5
LRRN4 and UPK3B are markers of primary mesothelial cells.
PMID: 21984916
PLoS One · 2011
0.60