Deleted in colorectal cancer (DCC) (MIM# 120470) encodes the DCC netrin-1 (NTN1) receptor protein, an evolutionarily conserved, single-pass transmembrane glycoprotein belonging to the immunoglobulin superfamily of cell adhesion molecules. DCC is located at 18q21.2 and spans chr18:52,340,172–53,535,903 (GRCh38/hg38). The canonical DCC transcript consists of 29 exons that encode a 159 kDa (1,447 amino acid) protein.
DCC is expressed by commissural axons and binds NTN1, a secreted protein encoded by the NTN1 gene (MIM# 601614), which functions both locally and diffusely as a bifunctional axon guidance cue. DCC is required for the transduction of NTN1-induced attractive and long-range repulsive signaling in the coordinated outgrowth and guidance of commissural axons that cross the anatomical midline of the body.
Monoallelic or biallelic germline variants in DCC disrupt commissural axon guidance, resulting in impaired development and function of tracts such as corticospinal tracts and the corpus callosum. Monoallelic germline variants in DCC are associated with congenital mirror movements isolated agenesis of corpus callosum or both (MIM# 157600). Biallelic germline variants in the DCC gene are associated with developmental split brain syndrome (MIM# 617542).
DCC-related disorders are rare, with 40 families described across the different clinical phenotypes.
DCC