Cntn6, a member of the contactin gene superfamily, is an immunoglobulin domain-containing cell adhesion molecule involved in the development of the nervous system [2]. It may also be associated with the Notch signaling pathway in mediating thyroid hormone biosynthesis, as it was recently identified as a novel causative gene for congenital hypothyroidism [5].

In mice, Cntn6 deficiency affects spatial learning and memory, as Cntn6 -/- male mice showed impaired shortening of escape time in the Morris water maze task during the acquisition period, and 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 its association with human diseases, while copy number variations (CNVs) of CNTN6 have been proposed to be associated with neurodevelopmental and autism spectrum disorders, their clinical significance remains uncertain. Some studies found that CNVs involving CNTN6 alone seem to be neutral or possible modifiers rather than disease-causing variants [1]. However, other research showed that CNTN6 deletions and private coding sequence variants were enriched in individuals with autism spectrum disorders (ASDs), and patients carrying CNTN6 variants had hypersensitivity to sounds and changes in wave latency within the auditory pathway [3]. Also, a high proportion of patients with 3p26.3 copy number variations involving the CNTN6 gene presented with various neurodevelopmental disorders [4].

In conclusion, Cntn6 is crucial for the development of the nervous system and may play a role in thyroid hormone biosynthesis. Mouse models have revealed its importance in spatial learning and memory. In humans, although the role of CNTN6 in neurodevelopmental and autism-related disorders is still being clarified, existing research suggests it could be a candidate gene for these conditions, highlighting the value of further functional studies.