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This summary reviews the evidence evaluating the association between the dendritic cell nuclear protein-1 gene (DCANP1, HGNC:24459) and major depressive disorder (MONDO_0002009). Initial candidate gene studies in United Kingdom cohorts suggested a potential link based on modest statistical associations, but these early findings were derived from relatively small sample sizes without extensive segregation data (PMID:20351714). The early evidence did not provide clear variant-level detail for DCANP1, and no robust causative coding changes have been consistently identified.
Subsequent investigations, particularly in the Han Chinese population, systematically evaluated eight single nucleotide polymorphisms across the entire gene, including the variant rs12520799. In this study comprising 574 patients and 642 controls (PMID:23619526), no significant differences were observed after correction for multiple comparisons. Moreover, a meta-analysis incorporating both Chinese and European cohorts reinforced the lack of association between DCANP1 variants and major depressive disorder, thereby challenging the validity of the initial positive association.
Genetic evidence for DCANP1 is limited; no segregation data or family-based evidence supports a Mendelian mode of inheritance for major depressive disorder. Although candidate gene approaches previously implicated DCANP1 in the disorder, the absence of a reproducible variant—such as a clearly defined coding change like c.772_790del (p.Ser258TrpfsTer39) seen in other gene assessments—underscores the limitations of the genetic findings. The evidence does not support the presence of recurrent or founder variants contributing to disease risk.
Functional and experimental studies evaluating DCANP1 have not demonstrated a convincing mechanism of pathogenicity. There are no established functional assays, cellular or animal models, or rescue experiments that confirm a role for DCANP1 in the neurobiology of major depressive disorder. The lack of experimentally validated evidence further diminishes the likelihood that DCANP1 alterations drive disease pathology.
Integrating the genetic and experimental findings, the overall evidence for a DCANP1–major depressive disorder association is highly conflicting. The initial candidate findings have not been replicated in larger, more rigorous analyses, and the functional data remain unconvincing. As such, the clinical utility of DCANP1 for diagnostic decision‑making in major depressive disorder remains unsupported. Additional large-scale studies and more refined functional assays would be required to establish any definitive role for DCANP1.
Key Take‑home Sentence: Currently, the evidence does not support a clinically actionable association between DCANP1 and major depressive disorder, limiting its use in diagnostic and commercial settings.
Gene–Disease AssociationDisputedInitial candidate study findings in a UK population (PMID:20351714) were not replicated in a Han Chinese cohort of 574 cases and 642 controls with meta-analysis further refuting association (PMID:23619526). Genetic EvidenceLimitedNo clear coding variants or segregation data were identified for DCANP1, and the candidate gene association lacked robust replication. Functional EvidenceLimitedThere are no functional assays, cellular/animal models, or rescue experiments that support a pathogenic role of DCANP1 in major depressive disorder. |