rs1026364

This is a 3 prime utr variant variant in the USF3 gene.

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GWAS Catalog Trait Associations (1)

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

femoral neck bone mineral density

Estrada K et al. “Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.” Nature Genetics 44(5):491-501 (2012)

Allele T

OR —

β 0.030

p 4.0e-10

N 32,961

Meta-analysisLarge GWAS

multi-ancestry

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ClinVar annotation

Benign★★★☆

2 submitters1 publication

View on ClinVar →

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Research that mentions this SNP (2)

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USF3modulates osteoporosis risk by targetingWNT16,RANKL,RUNX2, and two GWAS lead SNPs rs2908007 and rs4531631

FunctionalWeiyuan 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.

Traits studied:Bone mineral densityOsteoporosis

PubMed DOI Metascience Observatory

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Osteoporosis genome‐wide association study variant c.3781 C>A is regulated by a novel anti‐osteogenic factor miR‐345‐5p

FunctionalYa Wang et al.(2020)· Human Mutation

This functional study investigated the molecular mechanism of the osteoporosis GWAS variant USF3 c.3781C>A (rs1026364), which is associated with femoral neck BMD (P=4.1×10⁻¹⁰). The authors demonstrated that the c.3781A allele creates a functional binding site for hsa-miR-345-5p, which downregulates USF3 expression and inhibits osteogenic differentiation through both USF3-dependent and independent pathways, including direct targeting of RUNX3 and SMAD1.

Traits studied:Bone mineral densityFemoral neck BMDOsteoporosis

PubMed DOI Metascience Observatory

About USF3

This gene encodes a large protein that contains a helix-loop-helix domain and a polyglutamine region. A deletion in the polyglutamine region was associated with risk for thyroid carcinoma. [provided by RefSeq, May 2017]