Cntn6, an immunoglobulin domain-containing cell adhesion molecule, belongs to the contactin gene superfamily. It is involved in the development of the nervous system, and studies have suggested its possible association with neurodevelopmental and autism spectrum disorders. Also, it may play a role in thyroid hormone biosynthesis through the Notch signaling pathway [4].

In mice, Cntn6 deficiency affects spatial learning and memory, as Cntn6 -/- male mice showed abnormal escape time during the acquisition period of the Morris water maze task, while female mutant mice had mildly affected spatial memory in the probe trial test. This indicates that Cntn6 plays a role in the development of the hippocampus and affects allocentric navigation [2]. Regarding humans, although CNVs of CNTN6 have been associated with neurodevelopmental disorders, their clinical significance remains uncertain. Some studies found no difference in the frequency of rare coding variants between ASD patients and controls, suggesting CNTN6 CNVs may be neutral or modifier variants rather than disease-causing. However, other research showed that CNTN6 deletions and private coding sequence variants were enriched in ASD individuals, and patients with CNTN6 variants had hypersensitive to sounds [1,3].

In conclusion, Cntn6 is crucial for the development of the nervous system, especially for hippocampal-related spatial learning and memory in mice. In humans, its role in neurodevelopmental and autism spectrum disorders is still under exploration. The inconsistent findings from different studies highlight the complexity of understanding Cntn6's function in relation to these diseases [1,2,3].

References:

1. Repnikova, Elena A, Lyalin, Dmitry A, McDonald, Kimberly, Pyatt, Robert E, Hickey, Scott E. 2019. CNTN6 copy number variations: Uncertain clinical significance in individuals with neurodevelopmental disorders. In European journal of medical genetics, 63, 103636. doi:10.1016/j.ejmg.2019.02.008. https://pubmed.ncbi.nlm.nih.gov/30836150/

2. Mu, Di, Xu, Yiliang, Zhao, Tian, Xiao, Zhi-Cheng, Ye, Haihong. 2018. Cntn6 deficiency impairs allocentric navigation in mice. In Brain and behavior, 8, e00969. doi:10.1002/brb3.969. https://pubmed.ncbi.nlm.nih.gov/30106251/

3. Mercati, O, Huguet, G, Danckaert, A, Cloëz-Tayarani, I, Bourgeron, T. 2016. CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders. In Molecular psychiatry, 22, 625-633. doi:10.1038/mp.2016.61. https://pubmed.ncbi.nlm.nih.gov/27166760/

4. Zhang, Hai-Yang, Wu, Feng-Yao, Zhang, Cao-Xu, Song, Huai-Dong, Zhao, Shuang-Xia. 2024. Contactin 6, A Novel Causative Gene for Congenital Hypothyroidism, Mediates Thyroid Hormone Biosynthesis Through Notch Signaling. In Thyroid : official journal of the American Thyroid Association, 34, 324-335. doi:10.1089/thy.2023.0594. https://pubmed.ncbi.nlm.nih.gov/38183624/