rs4979462

This is a regulatory region variant variant in the TNFSF15 gene.

▶

GWAS Catalog Trait Associations (3)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

primary biliary cirrhosis

Kawashima M et al. “Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population.” Human Molecular Genetics 26(3):650-659 (2017)

Allele C

OR 1.60

p 8.0e-19

N 2,886

Large GWAS

East Asian

biliary liver cirrhosis

Nakamura M et al. “Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.” American Journal of Human Genetics 91(4):721-8 (2012)

Allele T

OR 1.56

p 3.0e-14

N 963

Small GWAS

East Asian

nephrotic syndrome

Jia X et al. “Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome.” Kidney International 98(5):1308-1322 (2020)

Allele T

OR 1.33

p 5.0e-11

N 4,193

Large GWAS

multi-ancestry

▶

Research that mentions this SNP (1)

▶

Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding NF-1

AssociationN=2,370Yuki Hitomi et al.(2015)· Human Genetics

This study identified rs4979462 in the TNFSF15 locus as the causal variant for primary biliary cirrhosis (PBC) susceptibility in the Japanese population through integrated analysis including case-control association (n=1279 PBC cases, n=1091 controls; P=1.85×10⁻¹⁴, OR=1.57) and in vitro functional studies. The PBC-susceptible allele generates a novel NF-1 transcription factor binding site, enhancing TNFSF15 expression and increasing susceptibility to autoimmune liver disease.

Traits studied:Ankylosing spondylitisCrohn's diseaseLeprosyPrimary biliary cirrhosisUlcerative colitis

PubMed DOI Metascience Observatory

About TNFSF15

The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]