FAM83H

FAM83H is a protein-coding gene in humans that encodes the FAM83H protein, a member of the FAM83 family. The protein is conserved across species and contains a shared N-terminal domain (DUF1669) with a more variable C-terminal region. The precise biological function of FAM83H is not fully defined, but it is thought to participate in cellular signaling and cytoskeletal organization, and it has a proposed role in enamel formation during tooth development.

Pathogenic variants in FAM83H are associated with amelogenesis imperfecta, a collection of inherited enamel defects. Most disease-causing mutations are truncating variants that occur in the gene’s last exons, producing shortened proteins. These truncated proteins are believed to disrupt normal enamel formation, leading to generalized enamel hypoplasia with irregular, rough tooth surfaces and increased vulnerability to wear and decay. The condition is typically inherited in an autosomal dominant pattern, with affected individuals exhibiting enamel defects from tooth eruption onward.

Expression data indicate that FAM83H is active in dental tissues during amelogenesis and also in several epithelial tissues beyond the teeth. Ongoing research aims to clarify the protein’s exact molecular role, its interactions with signaling pathways, and how different variants influence the dental phenotype. Understanding FAM83H helps illuminate the molecular basis of enamel formation and the genetic basis of certain forms of amelogenesis imperfecta.