Afadin, adherens junction formation factor (AFDN)

Afadin (encoded by the AFDN gene, also known as MLLT4) is a multi-domain adaptor protein critical for the establishment and maintenance of cell–cell contacts, particularly in the assembly and integrity of adherens junctions in epithelial and other tissues[7][5][1][3]. It interacts with nectins and the actin cytoskeleton to mediate cell adhesion, playing a key organizational role in embryonic development, epithelial morphogenesis, and the maintenance of tissue structure[1][7]. Afadin acts as a downstream effector of RAS GTPases (such as HRAS, RAP1A, and RAP2A) and links signaling events to changes in cell polarity and motility, especially in processes driven by growth factors and oncogenic RAS signaling[1]. Afadin forms complex networks at cell junctions by binding to other adhesion and polarity proteins, such as SCRIB, PVRL2/nectin-2, PVRL3/nectin-3, CTNND1/p120-catenin, CTNNA1/α-catenin, JAM-A, ZO-1, and Eph receptors[1][3]. In addition to its structural and signaling functions, AFDN is involved in disease pathogenesis as a fusion partner of the MLL gene (as MLLT4), driving leukemias with t(6;11) chromosomal translocation[5]. Loss or mutation of Afadin is associated with cancer cell invasion, loss of polarity, and metastasis, highlighting its importance in tumor suppression and tissue integrity[1][5][3][7]. Notes: - Afadin is not considered a typical “therapeutic target” (receptor, enzyme, transporter); rather, it is a cytoskeletal/adaptor protein. It is, however, relevant in understanding cancer biology and metastasis. - No approved drugs are known to directly target Afadin, nor is it frequently used as a clinical biomarker or target in drug development as of late 2024. - Major disease roles center on cancer (including leukemia and solid tumors), especially those involving adherens junction disruption and loss of epithelial polarity.

Other names

AF-6AF6MLLT4Protein AF-6ALL1-fused gene from chromosome 6 proteinMLL-AF6l-afadins-afadinI-afadinafadin-65033403D15ENSG00000130396afadin