CD101 – Type 1 Diabetes Mellitus

Recent studies have identified rare nucleotide substitutions in CD101 in patients with type 1 diabetes mellitus. In a Japanese family with two affected individuals (PMID:27888582), whole‑exome sequencing and copy‑number analysis revealed co‑segregation of CD101 variants with the disease. In addition, subsequent mutation screening in 127 sporadic type 1 diabetes cases detected two further rare substitutions. In particular, the variant c.2587G>T (p.Val863Leu) was identified and, along with other substitutions, was predicted by in silico analyses to be probably damaging (PMID:27888582).

Given the limited number of affected probands—derived from one familial study and sporadic screening—and the absence of functional studies directly validating a pathogenic mechanism in type 1 diabetes, the overall gene–disease association is classified as Limited. Although functional assessment studies have demonstrated that CD101 variants can alter immune regulation by modifying inflammatory cell phenotypes (PMID:34195685), these experiments were conducted in the context of HIV risk and do not directly support a mechanistic role in type 1 diabetes. Key take‑home: CD101 variants may contribute to type 1 diabetes susceptibility, but further investigation is essential to firmly establish their clinical utility for diagnostic decision‑making and eventual therapeutic targeting.

References

• Journal of diabetes investigation • 2017 • Nucleotide substitutions in CD101, the human homolog of a diabetes susceptibility gene in non‑obese diabetic mouse, in patients with type 1 diabetes PMID:27888582
• Cell reports. Medicine • 2021 • CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions PMID:34195685

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