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This summary describes the association between CLEC5A and Crohn disease. Multiple studies have investigated the role of CLEC5A (HGNC:2054) in the pathogenesis of Crohn disease (MONDO_0005011), primarily through genetic association and gene expression profiling studies. The evidence comes from independent multi‐patient cohorts that analyzed SNP profiles and transcriptional changes in peripheral blood mononuclear cells of affected patients (PMID:29568200) and through genotype‐phenotype correlation studies (PMID:32476786).
The overall clinical validity of the CLEC5A–Crohn disease association is currently classified as Limited. Although there is supportive evidence from a SNP analysis in a cohort of 175 patients and 157 controls (PMID:32476786) and from differential expression profiles in patient PBMCs (PMID:29568200), the statistical significance remains borderline and the number of replication studies is small. In addition, segregation data from affected relatives are not available, which restricts the strength of the genetic evidence.
The genetic evidence supporting this association includes analyses of SNPs within CLEC5A. In one study, the genotype AA of rs1285933 was associated with a higher risk for Crohn disease (recessive model, odds ratio = 1.90) in a sample of 175 cases versus 157 controls (PMID:32476786). Additionally, gene expression profiling revealed significant upregulation of CLEC5A in vitamin D‐treated PBMCs from Crohn disease patients compared to healthy donors (PMID:29568200). Although no specific coding variant in HGVS format was reported, the cumulative data support a putative role for CLEC5A in disease susceptibility.
Functional and experimental evidence for CLEC5A in Crohn disease is limited. Direct functional assays in cellular or animal models specific to Crohn disease are lacking; however, altered CLEC5A expression in patient-derived PBMCs suggests a potential impact on immune regulation in the disease context. The absence of mechanistic studies that directly interrogate the functional consequences of CLEC5A variants in Crohn disease prevents a higher functional evidence tier at present.
Integrating the genetic and experimental findings, the current body of evidence indicates a suggestive but not definitive role for CLEC5A in Crohn disease. The association is based on a combination of borderline SNP association results and gene expression studies, with limited evidence from functional experiments. Additional replication and mechanistic studies are needed to robustly validate the role of CLEC5A in disease pathogenesis.
Key take‑home: Although current data point to a potential involvement of CLEC5A in Crohn disease susceptibility, further comprehensive studies are required to confirm its clinical utility for diagnostic decision‑making and therapeutic targeting.
Gene–Disease AssociationLimitedThe association is supported by a SNP analysis in 175 patients versus 157 controls (PMID:32476786) and by differential expression studies in patient PBMCs (PMID:29568200), but borderline significance and lack of segregation data limit the strength of the evidence. Genetic EvidenceLimitedGenetic analyses, including the potential association of SNP rs1285933 in CLEC5A with Crohn disease in a defined cohort and supportive gene expression data, provide modest evidence for involvement in disease susceptibility. Functional EvidenceLimitedDirect functional assays for CLEC5A in Crohn disease are lacking; however, observed changes in gene expression in patient-derived cells indicate a potential modulatory role. |