TCF7L2
Transcription factor 7-like 2
Gene Number: 6934
Location: 10q25.2–q25.3
Key Functions: Glucose metabolism regulation, insulin secretion control, Wnt/β-catenin signaling modulation, type 2 diabetes susceptibility
TCF7L2 (transcription factor 7-like 2) encodes a transcription factor that plays a central role in the Wnt signaling pathway, a fundamental molecular cascade involved in cell growth, differentiation, and metabolic regulation. Within the context of metabolism, TCF7L2 acts as a key regulator of genes controlling glucose homeostasis, insulin biosynthesis, and secretion in pancreatic β-cells. It also influences hepatic glucose output and the insulin sensitivity of peripheral tissues.
The Wnt/β-catenin–TCF7L2 complex activates or represses the transcription of target genes in response to nutrient and hormonal cues, coordinating the fine balance between insulin production and glucose utilization. TCF7L2 helps maintain β-cell integrity and functional adaptability, especially under metabolic stress conditions.
Genetic variants in TCF7L2—most notably rs7903146 (C>T)—are among the strongest known genetic determinants of type 2 diabetes (T2D). The risk allele is associated with impaired insulin secretion, diminished incretin (GLP-1–mediated) effects, and elevated fasting and postprandial glucose levels. Unlike many other diabetes-related genes, TCF7L2 variants exert their influence primarily through β-cell dysfunction rather than obesity or insulin resistance.
Altered TCF7L2 expression has also been linked to disruptions in hepatic glucose metabolism, lipid regulation, and intestinal hormone signaling. These mechanisms collectively contribute to glucose intolerance and diabetes progression. Beyond its metabolic roles, the Wnt/TCF7L2 axis has broader biological relevance, influencing pathways related to cell proliferation and differentiation—thereby connecting metabolic health to tissue repair and, in some contexts, tumorigenesis.
SNP ID | Your Genotype | Alternative Alleles | Interpretation |
|---|---|---|---|
rs7903146 | No matching variant or no valid DNA data | T | No interpretation available |
rs4506565 | No matching variant or no valid DNA data | T | No interpretation available |
rs12255372 | No matching variant or no valid DNA data | T | No interpretation available |
rs7903146
CC – Typical risk level for type 2 diabetes (R).
CT – Elevated risk of T2D (OR ≈ 1.41) (R).
TT – High risk of T2D (OR ≈ 1.97) (R).
Functional effect: The T allele reduces insulin secretion and impairs incretin (e.g., GLP-1) action by increasing TCF7L2 expression in pancreatic islets—conferring the strongest inherited T2D risk observed genome-wide (R).
rs4506565
AA – Normal; associated with typical T2D risk (R).
AT – Increased T2D risk (OR ≈ 1.4) (R).
TT – Higher T2D risk (OR ≈ 1.9) (R).
Functional effect: The T allele tags the same disease-associated haplotype as rs7903146 and predicts similar risk and pathophysiological features—making it nearly interchangeable for T2D susceptibility assessments (R).
rs12255372
GG – Baseline diabetes risk (R).
GT – Elevated T2D risk (R).
TT – Elevated T2D risk (stronger than GT) (R).
Functional effect: The T allele disrupts TCF7L2 regulation — potentially by altering enhancer activity — and is strongly linked by GWAS to increased risk of T2D across multiple populations (R).
Learn more about what you can do to mitigate risks, and other factors involved by becoming a member of GenesUnveiled today!