SFMBT1 – Type 2 Diabetes Mellitus

The association between SFMBT1 and type 2 diabetes mellitus is supported by preliminary genetic evidence. Two independent multi‐patient studies have linked common regulatory variation and copy number deletions in SFMBT1 to glycemic traits. In one study, an eQTL analysis of colon tissue from 40 individuals demonstrated significant enrichment for GWAS signals, including those associated with type 2 diabetes (PMID:25766683). In a separate study, a genome‑wide copy number variation analysis in a Han Chinese cohort identified common deletions in SFMBT1 in 20 individuals, which were associated with fasting plasma glucose levels, a key endophenotype for type 2 diabetes (PMID:28789618).

Although these genetic findings provide an initial link between SFMBT1 and type 2 diabetes, segregation analyses are limited and no extended familial studies have been reported. The CNV study did not document additional affected relatives carrying the deletion, and the replication analysis offered only marginal significance (p ≈ 0.065) in a large population sample. Thus, the overall gene‑disease association remains in the limited range according to current ClinGen criteria.

From a genetic standpoint, the evidence is primarily derived from population‐based case series. The reported CNV, represented here by the example variant c.772_790del (p.Ser258TrpfsTer39), illustrates the type of disruptive alteration identified in SFMBT1. The absence of multiple unrelated probands with a diverse spectrum of pathogenic variants and the lack of robust segregation data contribute to a lower genetic evidence score.

Functional data directly linking SFMBT1 to molecular mechanisms underlying type 2 diabetes are sparse. While SFMBT1 is expressed in metabolic tissues and may play a role in transcriptional regulation during development, experiments specifically addressing its impact on beta‑cell function or glucose homeostasis have not yet been performed. This lack of disease‐focused functional assays translates into a limited functional evidence score.

In summary, although there is converging evidence from eQTL mapping and CNV analysis that implicates SFMBT1 in the modulation of glycemic traits, the overall evidence for a role in type 2 diabetes mellitus is limited. Further investigations, including robust family‐based segregation studies and functional assays relevant to glucose metabolism, are warranted.

Key Take‑home: While SFMBT1 shows promise as a genetic contributor to type 2 diabetes mellitus, its clinical utility remains preliminary pending further corroborative research.

References

• BMC Genomics • 2017 • Genome‑wide copy number variation analysis identified deletions in SFMBT1 associated with fasting plasma glucose in a Han Chinese population PMID:28789618
• BMC Genomics • 2015 • Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci PMID:25766683

Evidence Based Scoring (AI generated)