rs12252
badMag 5.5This is a splice region variant variant in the IFITM3 gene.
Key Literature Trait Associations
Severe Influenza Risk
IFITM3 is a frontline innate immune protein that blocks influenza virus from escaping endosomes during cellular entry. The G allele disrupts a splice donor site, producing a truncated, less effective IFITM3 protein. Carriers are significantly more likely to be hospitalized with severe influenza (~2-2.4x higher odds). Most pronounced in East Asian populations where the G allele is more common (~25-44% vs ~3-5% in Europeans).
COVID-19 severity
The IFITM3 rs12252-C allele has been associated with severe COVID-19 and mortality in several studies, though evidence is mixed. A 2023 meta-analysis of 5 studies (Yu et al.) found CC genotype associated with increased severe COVID-19 risk (OR=1.97, 95% CI 1.06–3.69) and mortality (OR=4.61, 95% CI 1.44–14.75), with stronger effects in Chinese populations. However, a 2024 Brazilian meta-analysis found no significant association in allelic or recessive models, highlighting population heterogeneity. A Saudi cohort study found the G allele (opposite strand notation) associated with mortality (OR=2.2) and hospital admission. Overall, findings suggest a plausible but inconsistent role across ancestries.
▶ClinVar annotation
▶Research that mentions this SNP (3)
▶Ethnic variation in risk genotypes based on single nucleotide polymorphisms (SNPs) of the interferon-inducible transmembrane 3 (IFITM3) gene, a susceptibility factor for pandemic 2009 H1N1 influenza A virusAssociationN=5,900Yong-Chan Kim et al.(2020)· Immunogenetics
This paper compared ethnic variation in IFITM3 gene polymorphisms (rs12252, rs34481144, rs6598045) associated with pandemic H1N1 influenza susceptibility across multiple populations. The authors found significant differences in risk genotype frequencies among ethnic groups: the rs12252 CC genotype was most prevalent in East Asian populations (30%) but absent in Europeans, while rs34481144 AA was highest in Europeans (22%) but absent in East Asian/Korean populations, and rs6598045 showed variation with highest frequencies in Europeans (79%).
▶Pilot screening study of targeted genetic polymorphisms for association with seasonal influenza hospital admissionAssociationN=14,471Tonia C. Carter et al.(2018)· Journal of Medical Virology
This pilot screening study evaluated 32 SNPs in viral immune response genes for association with hospitalized seasonal influenza in adults of European ancestry using a discovery group (26 cases, 993 controls) and two validation groups (84 cases, 4,076 controls; 128 cases, 9,187 controls). The study failed to replicate the previously reported association between IFITM3 rs12252 and hospitalized influenza (P > 0.05), and a preliminary finding of association with SLFN13 rs8072510 (P = 0.0099 in discovery group) was not confirmed in validation groups.
▶Population genetics of IFITM3 in Portugal and Central Africa reveals a potential modifier of influenza severityAssociationN=389Susana David et al.(2018)· Immunogenetics
Population genetics study of IFITM3 variants in Portuguese and Central African populations, analyzing 41 Portuguese influenza A(H1N1)pdm09 patients. The rs34481144-A allele showed a protective effect against severe influenza (OR=0.26, 95% CI 0.07-0.97), while haplotype Hap4 containing this allele was significantly associated with mild disease (OR=0.29, 95% CI 0.10-0.82). The study identified 7 SNPs within the IFITM3 region and estimated the population attributable risk for rs34481144 as 55.91-64.44%.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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