Ccdc32-flox Mouse

CCDC32, also known as C15orf57, is an endocytic accessory protein with a significant role in clathrin-mediated endocytosis (CME), a process essential for maintaining cellular homeostasis [1]. It is also involved in the assembly of the AP2 adaptor complex, a key player in CME [2].

Loss-of-function mutations in CCDC32 cause a congenital syndrome characterized by craniofacial, cardiac, and neurodevelopmental anomalies. Zebrafish models with ccdc32 depletion recapitulate human phenotypes, and ccdc32 is required for normal cilia formation in zebrafish embryos and mammalian cell culture, suggesting ciliary defects contribute to the disorder's pathomechanism [3]. In patients with cardio-facio-neuro-developmental syndrome (CFNDS), homozygous loss-of-function variants in CCDC32 have been identified, and ccdc32 deletion in zebrafish implies a ciliary contribution to the pathomechanism [4]. A novel homozygous deletion in CCDC32 gene was also reported to cause CFNDS [5]. Additionally, CCDC32 gene fusions, such as CCDC32-CBX3, were found in MYCN non-amplified neuroblastoma and acute myeloid leukemia patients, affecting gene expression and potentially contributing to treatment resistance [6,7]. CCDC32 was also identified as a new gene with potential biological relevance to colorectal cancer through gene-gene interaction studies [8], and it was found to interact with the C-terminal fragment of annexin A2 in yeast two-hybrid screening [9].

In summary, CCDC32 is crucial for clathrin-mediated endocytosis and AP2 adaptor complex assembly. Its loss-of-function mutations lead to severe congenital syndromes involving craniofacial, cardiac, and neurodevelopmental anomalies. The use of zebrafish models has been instrumental in understanding its role in these disease conditions. Studies on gene fusions and interactions of CCDC32 also suggest its potential involvement in various cancers, highlighting its significance in multiple biological processes and disease areas.