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8 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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LRRC46
leucine rich repeat containing 46
Chromosome 17 · 17q21.32
NCBI Gene: 90506Ensembl: ENSG00000141294.11HGNC: HGNC:25047UniProt: Q96FV0
13PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
spermatogenesissperm flagellum assemblysperm flagellumsperm midpieceasthmaazoospermiaatrial fibrillationChronic Obstructive Asthma
✦AI Summary

LRRC46 (leucine-rich repeat containing 46) is a structural protein with dual roles in reproductive and ocular development. Primarily, LRRC46 is essential for spermatogenesis and male fertility, localizing to the sperm flagellar midpiece and playing a critical role in sperm flagellum biogenesis 1. Loss of LRRC46 function in mice produces multiple morphological abnormalities of sperm flagella (MMAF), resulting in short, coiled, and irregular flagella alongside reduced sperm motility and complete male infertility 1. At the cellular level, LRRC46 is required for proper axonemal and mitochondrial sheath formation within flagella 1. Beyond reproduction, LRRC46 functions in ocular tissue maintenance. The protein is expressed in corneal and scleral tissues, where it regulates collagen synthesis, particularly collagen VIII (Col8a1) 2. LRRC46 deficiency in mice causes corneal and scleral thinning, reduced limbal stem cell activity, and decreased extracellular matrix gene expression, leading to classical myopia phenotypes 2. Clinically, LRRC46 mutations associate with male infertility via MMAF pathogenesis 1. Additionally, LRRC46 has been identified as a candidate gene in cancer contexts, showing altered expression in nasopharyngeal carcinoma and hepatocellular carcinoma, and associated with high-grade serous ovarian cancer susceptibility 3, 4, 5. Its role in cilia-associated gene networks also links LRRC46 to reproductive tract physiology relevant to ectopic pregnancy detection 6.

Sources cited
1
LRRC46 is essential for sperm flagellum biogenesis; its knockout causes MMAF phenotypes with short/coiled flagella and complete male infertility
PMID: 35955660
2
LRRC46 is expressed in cornea and sclera; regulates collagen synthesis and ECM pathways; LRRC46 deficiency causes myopia through corneal/scleral thinning
PMID: 38874710
3
LRRC46 is poorly expressed in nasopharyngeal carcinoma and may serve as a diagnostic marker
PMID: 31863646
4
LRRC46-derived peptide KMFHTLDEL elicits strong immunogenic CD8+ T-cell responses in hepatocellular carcinoma
PMID: 40008881
5
LRRC46 identified as transcriptome-wide association study significant susceptibility gene for high-grade serous ovarian cancer
PMID: 31043753
6
LRRC46 is cilia-associated and shows increased expression in ectopic pregnancy samples; part of 5-gene classifier for pregnancy location determination
PMID: 33771330
7
LRRC46 on chromosome 17 associated with glioblastoma radiographic tumor features
PMID: 31482151
Disease Associationsⓘ20
asthmaOpen Targets
0.19Weak
azoospermiaOpen Targets
0.10Weak
atrial fibrillationOpen Targets
0.10Suggestive
Chronic Obstructive AsthmaOpen Targets
0.10Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
spermatogenic failure 78Open Targets
0.07Suggestive
spermatogenic failure 65Open Targets
0.07Suggestive
spermatogenic failure 10Open Targets
0.07Suggestive
spermatogenic failure 11Open Targets
0.07Suggestive
spermatogenic failure 84Open Targets
0.07Suggestive
spermatogenic failure 93Open Targets
0.07Suggestive
spermatogenic failure 56Open Targets
0.07Suggestive
spermatogenic failure 92Open Targets
0.07Suggestive
spermatogenic failure 94Open Targets
0.07Suggestive
spermatogenic failure, X-linked, 3Open Targets
0.07Suggestive
spermatogenic failure 40Open Targets
0.07Suggestive
spermatogenic failure 54Open Targets
0.07Suggestive
spermatogenic failure 72Open Targets
0.07Suggestive
spermatogenic failure 76Open Targets
0.07Suggestive
spermatogenic failure 80Open Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PACS2Protein interaction74%CFAP54Shared pathway50%SPMIP7Shared pathway50%CBY3Shared pathway50%ARRDC5Shared pathway50%C3orf62Shared pathway50%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
86%
Liver
61%
Brain
50%
Ovary
35%
Heart
23%
Gene Interaction Network
Click a node to explore
LRRC46PACS2CFAP54SPMIP7CBY3ARRDC5C3orf62
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96FV0
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.94LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.62 [0.42–0.94]
RankingsWhere LRRC46 stands among ~20K protein-coding genes
  • #16,212of 20,598
    Most Researched13
  • #8,749of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedLRRC46
Sources retrieved8 papers
Response time—
📄 Sources
8▼
1
Identification of LRRC46 as a novel candidate gene for high myopia.
PMID: 38874710
Sci China Life Sci · 2024
1.00
2
LRRC46 Accumulates at the Midpiece of Sperm Flagella and Is Essential for Spermiogenesis and Male Fertility in Mouse.
PMID: 35955660
Int J Mol Sci · 2022
0.88
3
Identification of Potential Therapeutic Gene Markers in Nasopharyngeal Carcinoma Based on Bioinformatics Analysis.
PMID: 31863646
Clin Transl Sci · 2020
0.75
4
Identification of immunogenic HLA-A*02:01 epitopes associated with HCC for immunotherapy development.
PMID: 40008881
Hepatol Commun · 2025
0.63
5
An intrauterine genomic classifier reliably delineates the location of nonviable pregnancies.
PMID: 33771330
Fertil Steril · 2021
0.50