rs7984870

This is a upstream gene variant variant in the TNFSF11 gene.

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Research that mentions this SNP (1)

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A functional RANKL polymorphism associated with younger age at onset of rheumatoid arthritis
AssociationN=1,589Tan W. et al.(2010)· Arthritis & Rheumatism

This study fine-mapped the RANKL locus and identified rs7984870 (CC genotype) as a functional promoter variant consistently associated with younger age of rheumatoid arthritis (RA) onset in seropositive (RF+ or ACPA+) patients across three independent cohorts (European American and African American). The C allele conferred approximately 2-fold higher plasma RANKL levels and increased promoter activity via binding to transcription factor SOX5, with mean associations of 8.2 years earlier RA onset in WCPR, 4.7 years in BRASS, and 6.7 years in CLEAR cohorts when combined with HLA-DRB1 shared epitope.

Traits studied:ACPA+ RAAge at RA onsetRF+ RARheumatoid arthritisSeropositive RA
PubMedDOIMetascience Observatory

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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