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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LRRC4C
leucine rich repeat containing 4C
Chromosome 11 · 11p12
NCBI Gene: 57689Ensembl: ENSG00000148948.9HGNC: HGNC:29317UniProt: Q4JIV9
25PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GO:0005615cell adhesion molecule bindingcell-cell adhesion mediator activityregulation of axonogenesissmoking initiationmyopiaplacenta praeviamathematical ability
✦AI Summary

LRRC4C is a leucine-rich repeat protein functioning as an axon guidance molecule with roles in neuronal development and synaptic transmission. As a member of the netrin G family, it mediates cell-cell adhesion and promotes neurite outgrowth in developing thalamic neurons, operating at glutamatergic synapses and the postsynaptic density membrane 1. Diseases associated with LRRC4C dysfunction span multiple systems. In neurodevelopmental disorders, LRRC4C disruptions correlate with autism and sensory processing disorders, with deletions potentially modifying disease severity when inherited alongside other variants 1. GWAS studies identify LRRC4C as a novel susceptibility locus for late-onset Alzheimer's disease (11p12 locus) 2 and pediatric central nervous system tumors, where its axon guidance function during CNS development may influence tumorigenesis 3. In ophthalmology, LRRC4C knockouts show increased axial length and myopic shifts in zebrafish, indicating involvement in refractive error development 4. Educational interactions with LRRC4C variants enhance myopia susceptibility, suggesting gene-environment interactions in neuronal development 5. Clinically, LRRC4C variants influence chr11 migraine treatment response to anti-CGRP monoclonal antibodies, with rs116870564 showing the strongest association 6. Expression levels correlate with poor prognosis in colon and gastric cancers, linked to immune microenvironment alterations 7. Additionally, LRRC4C copy number variations associate with male infertility and meiotic arrest 8.

Sources cited
1
LRRC4C identified as novel cross-population LOAD susceptibility locus at 11p12 with roles in neuronal development
PMID: 40676597
2
LRRC4C knockout zebrafish show increased axial length and myopic shift; gene expressed in retina with functional role in myopia development
PMID: 36737489
3
High LRRC4C expression correlates with poor prognosis in colon and gastric cancers; associated with immune cell infiltration patterns
PMID: 33867855
4
LRRC4C is a netrin G family axon guidance molecule; disruptions cause neurodevelopmental disorders including autism; exonic deletions modify disorder severity
PMID: 27759917
5
LRRC4C variants interact with education level to increase myopia susceptibility; roles in axon guidance and synaptic development
PMID: 36395078
6
LRRC4C copy number variations associated with meiotic arrest and male infertility; localizes to meiotic cells
PMID: 25439847
7
LRRC4C at 11p12 identified as novel candidate susceptibility locus for pediatric CNS tumors; functions as axon guidance molecule in CNS development
PMID: 33226468
8
LRRC4C variant rs116870564 most strongly associated with anti-CGRP monoclonal antibody treatment response in chronic migraine
PMID: 39266962
Disease Associationsⓘ20
smoking initiationOpen Targets
0.45Moderate
myopiaOpen Targets
0.41Moderate
placenta praeviaOpen Targets
0.39Weak
mathematical abilityOpen Targets
0.38Weak
refractive errorOpen Targets
0.36Weak
HypermetropiaOpen Targets
0.35Weak
cervical carcinomaOpen Targets
0.35Weak
liver diseaseOpen Targets
0.34Weak
Parkinson diseaseOpen Targets
0.33Weak
gastroduodenitisOpen Targets
0.32Weak
smoking behaviorOpen Targets
0.32Weak
alcohol drinkingOpen Targets
0.31Weak
smoking cessationOpen Targets
0.30Weak
autoimmune disorder of musculoskeletal systemOpen Targets
0.28Weak
systemic lupus erythematosusOpen Targets
0.28Weak
attention deficit hyperactivity disorderOpen Targets
0.28Weak
substance abuseOpen Targets
0.28Weak
aortic diseaseOpen Targets
0.28Weak
musculoskeletal system diseaseOpen Targets
0.28Weak
obesityOpen Targets
0.28Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DLG4Protein interaction91%WHRNProtein interaction90%NTNG1Protein interaction73%MYO15AProtein interaction72%NTNG2Protein interaction72%LRRC4Shared pathway40%
Tissue Expression6 tissues
Brain
100%
Heart
34%
Liver
9%
Ovary
5%
Lung
4%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
LRRC4CDLG4WHRNNTNG1MYO15ANTNG2LRRC4
PROTEIN STRUCTURE
Preparing viewer…
PDB3ZYJ · 3.25 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.14 [0.07–0.30]
RankingsWhere LRRC4C stands among ~20K protein-coding genes
  • #13,011of 20,598
    Most Researched25
  • #1,119of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedLRRC4C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.
PMID: 40676597
Genome Biol · 2025
1.00
2
Post-GWAS screening of candidate genes for refractive error in mutant zebrafish models.
PMID: 36737489
Sci Rep · 2023
0.90
3
Prognostic value of LRRC4C in Colon and Gastric Cancers correlates with Tumour Microenvironment Immunity.
PMID: 33867855
Int J Biol Sci · 2021
0.80
4
Implication of LRRC4C and DPP6 in neurodevelopmental disorders.
PMID: 27759917
Am J Med Genet A · 2017
0.70
5
Education interacts with genetic variants near GJD2, RBFOX1, LAMA2, KCNQ5 and LRRC4C to confer susceptibility to myopia.
PMID: 36395078
PLoS Genet · 2022
0.60