rs4531631
This is a upstream gene variant variant in the TNFSF11 gene.
▶Research that mentions this SNP (2)
▶USF3modulates osteoporosis risk by targetingWNT16,RANKL,RUNX2, and two GWAS lead SNPs rs2908007 and rs4531631FunctionalWeiyuan Ye et al.(2021)· Human Mutation
This study demonstrates that the transcription factor USF3 modulates osteoporosis risk by antagonistically regulating bone formation and resorption through multiple target genes. USF3 enhances osteoblast differentiation by promoting WNT16 and RUNX2 expression while suppressing osteoclastogenesis by inhibiting RANKL. The GWAS lead variants rs2908007 (WNT16 promoter) and rs4531631 (RANKL promoter) confer allele-specific binding and transactivation by USF3 and associated transcription factors, mechanistically linking genetic variation to osteoporosis susceptibility.
▶Association Between Single Nucleotide Polymorphisms in NFATC1 Signaling Pathway Genes and Susceptibility to Congenital Heart Disease in the Chinese PopulationAssociationN=570Fengyu Wang et al.(2016)· Pediatric Cardiology
Case-control study of 277 Chinese CHD patients and 293 controls examining 29 SNPs in NFATC1 signaling pathway genes (NFATC1, VEGFR, VEGF, RANKL, FGFR1, BCL-6, ZNRD1). After Bonferroni correction, rs4531631 (RANKL) showed significant association with increased CHD risk (homozygous AA vs. GG: OR 2.38, p=0.001; recessive: OR 2.54, p=0.0003), as did rs13317 (FGFR1) (recessive CC vs. CT/TT: OR 2.06, p=0.00196). Authors suggest these variants may be potential biomarkers for genetic diagnosis and treatment of CHD.
About TNFSF11
This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found. [provided by RefSeq, Jul 2008]
View all TNFSF11 variants →Gene information from NCBI Gene. Variant classifications from ClinVar.
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