King’s College: C2CD3 Gene Links to Dental Abnormalities

 King’s College London researchers have identified rare variants in the C2CD3 gene as a cause of dental abnormalities including missing teeth, unusual tooth shapes and natal teeth. Published in PNAS and reported on 26 October 2026, the international study also offers evolutionary insight into how birds lost teeth over 100 million years ago, opening new research territory across the growing dental genetics and developmental biology category.

The team analysed 24 patients with tooth differences, studied C2CD3 disruption in mice, and examined the talpid2 chicken mutant, which carries a C2CD3 variant and develops tooth-like structures in embryos. C2CD3 helps build primary cilia, and disrupting it altered Sonic hedgehog (SHH) signalling pathway activity differently across the upper and lower jaw. In mice, SHH activity increased in the upper jaw and decreased in the lower jaw, producing both extra and missing teeth in different parts of the jaw. Chick embryos showed increased SHH activity in both jaws, suggesting birds may have lost teeth through developmental suppression rather than loss of the underlying machinery.

Professor Abigail Tucker, Professor of Development and Evolution at King’s College London, positioned the work as helping explain why tooth defects occur and refine treatments for patients with complex dental problems. The findings sharpen research positioning across the growing dental genetics category, where emerging approaches include regenerative dentistry and gene-based therapies challenging conventional restorative, orthodontic and implant workflows. Commercial signal extends into the global dental implants and restorative dentistry market dominated by Straumann Group, Nobel Biocare (Envista), Dentsply Sirona, Zimmer Biomet, Henry Schein (BioHorizons) and MegaGen Implants. Adjacent SHH pathway therapeutic development spans Sun Pharma (Odomzo, sonidegib) and Pfizer (Daurismo, glasdegib) in oncology, with potential developmental biology applications.

The commercial signal is a maturing dental genetics research category where C2CD3 and SHH pathway identification opens new diagnostic and potentially regenerative therapeutic territory alongside conventional restorative dentistry workflows. Clinical translation remains early-stage. Expect Straumann Group, Nobel Biocare, Dentsply Sirona, Zimmer Biomet, Henry Schein (BioHorizons), MegaGen Implants and regenerative dentistry specialists to monitor dental genetics research through 2027 and 2028.

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