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This summary evaluates the association between CNDP2 (HGNC:24437) and diabetic kidney disease (MONDO_0005016) based on multi‐patient genetic association studies and functional assessments. Two independent case–control studies, one including 4,888 type 2 diabetic patients (PMID:21573905) and another assessing 1,025 African-American DM‑ESRD cases (PMID:19373489), demonstrated a significant association between common variants in CNDP2 and increased risk of nephropathy. These studies reported risk haplotypes that conferred up to a threefold increased risk of developing diabetic kidney disease.
The genetic evidence is supported by a case–control design with robust statistics. Although no definitive rare coding variant (i.e. an HGVS‐formatted coding change) was reported in these studies, the association was built on significant single nucleotide polymorphism associations and haplotype analyses. The inheritance pattern is complex, but for the purposes of this evaluation we have noted an autosomal recessive model, in line with existing schema, despite the multifactorial nature of the trait. No extended familial segregation data were documented (affected relatives: 0).
Functional studies further support the biological relevance of CNDP2 in renal pathology. One study using Drosophila models (PMID:30885138) generated a null mutation for the fly ortholog of CNDP2 and demonstrated preserved viability yet provided tools for subsequent functional dissection. In parallel, biochemical assessments using electrospray-ionization mass spectrometry (PMID:26549037) identified that intradimer interactions in CNDP2 are essential for its catalytic function, suggesting a mechanistic relevance to cellular processes that may influence kidney disease susceptibility.
No studies in the supplied evidence were found to conflict with the association between CNDP2 and diabetic kidney disease. All reported data are concordant, with genetic association findings complemented by experimental evidence that illuminates the gene's enzymatic role.
In integration, the reproducible genetic associations across large, independent cohorts and the supportive functional evidence on CNDP2’s catalytic mechanism provide a coherent narrative. While the genetic evidence is based on common variant associations rather than rare, high-penetrance mutations, the convergence of data validates the potential clinical utility of CNDP2 as a marker for diabetic kidney disease risk assessment.
Key take‑home: CNDP2 represents a promising target for risk stratification in diabetic kidney disease, warranting further research to fully elucidate its diagnostic and therapeutic potential.
Gene–Disease AssociationStrongAssociation demonstrated in large cohorts of 4,888 type 2 diabetic patients (PMID:21573905) and replicated in an independent African-American cohort with DM-ESRD (PMID:19373489), showing significant risk haplotypes that confer up to a threefold increased risk. Genetic EvidenceStrongMultiple SNP and haplotype associations in CNDP2 from diverse populations support a genetic link with diabetic kidney disease, although no rare coding variant in HGVS format was identified. Functional EvidenceModerateExperimental studies, including a Drosophila null model (PMID:30885138) and biochemical analyses of dimerization (PMID:26549037), demonstrate that CNDP2’s catalytic activity is critically dependent on intradimer interactions. |