Cntn3, a member of the contactin family, is primarily expressed in the nervous system. It plays roles in neural development, likely through its interactions with other proteins. For example, it binds to the Amyloid Precursor Protein (APP), with the second Fibronectin domain (Fn(2)) in Cntn3 and the copper binding domain (CuBD) in APP mediating this interaction [1]. It may also be involved in the receptor tyrosine-protein kinase (ErbB) signalling pathway [2].

In a study on glioblastoma multiforme (GBM), Cntn3 was significantly downregulated, and patients with lower Cntn3 expression had a shorter overall survival time, indicating it could be an independent prognostic indicator for GBM [2]. In tuberous sclerosis complex, Cntn3 expression was lower in cortical tubers during the early postnatal period compared to controls, which may contribute to neuropsychiatric co-morbidities [4]. Also, in a proteomics Mendelian randomization study, the CNTN3/NCSS1 protein level ratio was associated with type 2 diabetes [3].

In conclusion, Cntn3 is important in neural development and its dysregulation is associated with diseases like GBM, tuberous sclerosis complex-related neuropsychiatric co-morbidities, and potentially type 2 diabetes. Understanding Cntn3's function in these contexts may provide insights into disease mechanisms and potential therapeutic targets.

References:

1. Peng, Xi, Williams, John, Smallwood, Philip M, Nathans, Jeremy. 2019. Defining the binding interface of Amyloid Precursor Protein (APP) and Contactin3 (CNTN3) by site-directed mutagenesis. In PloS one, 14, e0219384. doi:10.1371/journal.pone.0219384. https://pubmed.ncbi.nlm.nih.gov/31318883/

2. Zhu, Yi-Fang, Guo, Yuan-Biao, Zhang, Han-Yu, Pan, Bi-Ran, Liu, Lei. 2019. Prognostic significance of contactin 3 expression and associated genes in glioblastoma multiforme. In Oncology letters, 18, 1863-1871. doi:10.3892/ol.2019.10482. https://pubmed.ncbi.nlm.nih.gov/31423255/

3. Zhang, Yue-Yang, Chen, Bing-Xue, Yang, Qin, Wan, Qin. 2024. The causal relationship between plasma protein-to-protein ratios and type 2 diabetes and its complications: Proteomics mendelian randomization study. In Diabetes, obesity & metabolism, 26, 4410-4417. doi:10.1111/dom.15792. https://pubmed.ncbi.nlm.nih.gov/39021342/

4. Korotkov, Anatoly, Luinenburg, Mark J, Romagnolo, Alessia, Mills, James D, Aronica, Eleonora. 2022. Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period. In Journal of neurodevelopmental disorders, 14, 8. doi:10.1186/s11689-022-09416-2. https://pubmed.ncbi.nlm.nih.gov/35030990/