RALGPS2 – Type 2 Diabetes Mellitus

Two independent genome‑wide association studies have reported suggestive evidence that single nucleotide polymorphisms (SNPs) near RALGPS2 are associated with type 2 diabetes mellitus (PMID:17846124; PMID:22923468). In the 2007 study of Mexican Americans (n = 281 type 2 diabetes cases PMID:17846124), SNPs such as rs2773080 and rs3922812, located in or near RALGPS2, reached suggestive significance levels. This finding was bolstered by a subsequent study in Mexican Mestizos (n = 1,027 cases PMID:22923468), which included RALGPS2 among 24 susceptibility loci evaluated. However, neither study identified a coding (HGVS‑formatted) variant for RALGPS2, and no family‐based segregation data are available, limiting the overall genetic evidence.

Currently, functional evidence supporting a mechanistic role for RALGPS2 in type 2 diabetes is absent. No cellular assays, animal models, or rescue experiments have been reported that directly link aberrant RALGPS2 function to the disease phenotype. Although the repeated identification of SNPs near this gene in different cohorts adds to the body of genetic evidence, the lack of functional studies and clear segregation data confines the overall gene‑disease association to a limited classification. Additional research, including fine‑mapping, functional characterization and evaluation in diverse populations, will be necessary to provide stronger clinical utility. Key take‑home: RALGPS2 is an emerging candidate gene with limited evidence linking it to type 2 diabetes, warranting further investigation before incorporation into diagnostic panels.

References

• Diabetes • 2007 • Identification of type 2 diabetes genes in Mexican Americans through genome‑wide association studies PMID:17846124
• Diabetes • 2012 • Contribution of common genetic variation to the risk of type 2 diabetes in the Mexican Mestizo population PMID:22923468

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