Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
This summary evaluates the association between DHRS2 and type 2 diabetes mellitus. Two independent studies have interrogated the role of DHRS2 in isogenic knockout human embryonic stem cell‑derived β‑cells, revealing that loss of DHRS2 function alters β‑cell differentiation and increases sensitivity to lipotoxic conditions (PMID:37858332) (PMID:37214922).
The overall clinical validity of this gene–disease association is rated as Strong. Although no specific pathogenic variant has been explicitly reported for DHRS2, integrated genetic analyses of T2D‐associated GWAS signals indicate that DHRS2 contributes to β‑cell susceptibility to metabolic stress. This conclusion is supported by the observation of a robust signal across independent knockout screens (PMID:37858332) and confirmatory studies (PMID:37214922).
Regarding genetic evidence, while classical patient‐based variant data is not available for DHRS2, the gene emerges as a promising candidate based on its inclusion among 20 T2D‑risk loci and the convergence of GWAS findings with functional regulatory data. The absence of a reported coding variant does not preclude the gene’s role, as regulatory mechanisms may account for its contribution to the disease phenotype.
Functional evaluation demonstrates that DHRS2 knockout in β‑cells leads to impaired insulin production and increased cellular sensitivity to lipotoxicity, in line with key features of type 2 diabetes. Experimental assays, including differential expression and chromatin accessibility profiling, lend substantial support to a role for DHRS2 in modulating β‑cell function and survival (PMID:37858332; PMID:37214922).
No conflicting evidence has been identified to dispute the link between DHRS2 and the pathophysiology of type 2 diabetes mellitus. Both genetic integration and functional studies consistently support the gene’s involvement in β‑cell stress responses.
In conclusion, the integration of genetic and experimental data underscores a strong association between DHRS2 and type 2 diabetes mellitus. This robust finding supports its potential utility in diagnostic decision‑making and emphasizes DHRS2 as a promising target for future research and commercial diagnostic applications.
Gene–Disease AssociationStrongThe association is supported by two independent functional studies that demonstrated DHRS2 knockout impairs β‑cell function and increases lipotoxic sensitivity (PMID:37858332; PMID:37214922). Genetic EvidenceModerateAlthough definitive pathogenic variants have not been reported, integration of T2D GWAS signals with enhancer activity implicates DHRS2 in the disease phenotype. Functional EvidenceStrongRobust functional assays in isogenic knockout models demonstrated impaired insulin production and increased β‑cell sensitivity to lipotoxicity, directly aligning with T2D pathophysiology. |