rs7903146 — TCF7L2 Intron 3 (C>T)
Risk factor · ~30% global (T allele)
rs7903146 is the most significant TCF7L2 variant for type 2 diabetes risk, with consistent replication across >100 GWAS studies. The T allele increases diabetes risk by ~40% per copy and affects beta-cell function through the Wnt/incretin signaling cascade.
Molecular Mechanism
Located in a region of open chromatin in pancreatic islets, rs7903146 T allele increases TCF7L2 expression in islets but alters its downstream transcriptional targets, reducing proinsulin processing and impairing glucose-stimulated insulin secretion.
Peptide Therapeutic Relevance
As with rs12255372, this variant supports the therapeutic rationale for GLP-1 and incretin-targeting peptides. PepFold designs candidates informed by the specific protein regions affected by TCF7L2 dysregulation.
Gene: TCF7L2 (Transcription Factor 7-Like 2)
Key transcription factor in the Wnt signaling pathway. Regulates incretin hormone expression (GLP-1, GIP) and pancreatic beta-cell proliferation and function.
Chromosome 10q25.2
Condition: Type 2 Diabetes
A metabolic disorder characterized by insulin resistance and progressive beta-cell dysfunction. TCF7L2 variants are the strongest common genetic risk factors. GLP-1 receptor agonist peptides have revolutionized treatment.
Prevalence: ~537 million adults worldwide (IDF 2021), ~10.5% of global adult population
Related Variants
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