SGSM2 – Type 2 Diabetes Mellitus

This summary evaluates the association between SGSM2 (HGNC:29026) and type 2 diabetes mellitus (MONDO_0005148) based on multi‐patient genetic studies. Two large-scale exome and genome-wide association studies have identified low-frequency coding variants in SGSM2 that are significantly associated with insulin processing and secretion dysregulation, a hallmark of type 2 diabetes (PMID:23263489) (PMID:21873549).

The overall genetic evidence is supported by analyses of substantial cohorts; the first study evaluated 8,229 Finnish males and the second a meta-analysis of 10,701 nondiabetic adults followed by larger replication cohorts. In both studies, the presence of SGSM2 variants was robustly linked to perturbations in fasting proinsulin levels which underscores its role in insulin processing pathways (PMID:23263489) (PMID:21873549).

Although the detailed variant spectrum for SGSM2 is not fully enumerated in the reports, the genetic data consistently implicate coding changes that affect protein function. In the absence of a directly reported HGVS string in the source evidence, the variant list remains currently unpopulated pending further reports.

The inheritance pattern in type 2 diabetes mellitus is complex, with multiple susceptibility loci contributing to disease risk. Thus, SGSM2 should be considered as a contributor within a multifactorial genetic architecture rather than following a simple Mendelian mode.

There is limited direct functional experimental evidence provided in these studies. Inferences regarding the mechanism of pathogenicity are primarily drawn from the association with altered insulin processing, suggesting that SGSM2 may influence glucose homeostasis through effects on beta-cell function. However, formal cellular or animal model validation remains to be completed.

Taken together, the integration of genetic association data from two independent large cohorts supports a strong link between SGSM2 and type 2 diabetes mellitus. While additional functional assessments are warranted to fully elucidate the biological mechanism, the current evidence is sufficiently robust to inform diagnostic decision‑making and further clinical investigation.

Key Take‑home: SGSM2 is strongly supported as a genetic contributor to type 2 diabetes mellitus, with compelling genetic association data that can be leveraged for diagnostic and commercial applications.

References

• Nature Genetics • 2013 • Exome array analysis identifies new loci and low‑frequency variants influencing insulin processing and secretion PMID:23263489
• Diabetes • 2011 • Genome‑wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes PMID:21873549

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