DENN domain-containing protein 6A (DENND6A)

DENND6A (DENN domain-containing protein 6A), also known as FAM116A, is a member of the DENN domain protein family, which serve as guanine nucleotide exchange factors (GEFs) for Rab small GTPases[1][2][3]. DENND6A functions primarily in vesicular trafficking and is required for the proper positioning of lysosomes within the cell. It acts as a GEF for Rabs, notably Rab34 and Rab14, and is recruited by the lysosomal GTPase Arl8b to facilitate lysosome retrograde transport by activating Rab34; this enables the recruitment of the RILP/dynein complex, driving lysosomes toward the cell center, a process crucial for steady-state autophagy[1][2][4]. Loss of DENND6A disrupts lysosomal clustering, impairs autophagic flux, and alters cell-cell adhesion through effects on cadherin-mediated processes[1][2][3]. DENND6A is linked to disease pathways, particularly those involving neurodegeneration when lysosome function or positioning is compromised[1][2]. There are no known drugs, biomarkers, or direct therapeutic efforts currently targeting DENND6A.

Other names

FAM116ADENN domain containing 6AFLJ34969AFI1ADENN domain-containing protein 6ADENN/MADD domain containing 6Afamily with sequence similarity 116 member Aprotein FAM116A