Von Willebrand factor A domain-containing protein 8 (VWA8)

Von Willebrand factor A domain-containing protein 8 (VWA8) is a **mitochondrial AAA+ ATPase** with a conserved von Willebrand factor type A domain. It mainly localizes to the **mitochondrial matrix**, especially in highly energetic tissues like liver, kidney, heart, pancreas, and skeletal muscle[1][2][4]. VWA8 exists in both long and short isoforms (VWA8a, VWA8b), both possessing ATPase activity dependent on Walker A and Walker B sequence motifs[4]. Its expression increases under metabolic stress, such as high-fat feeding in mice, implying a role in mitochondrial metabolism and possibly energy homeostasis[2][4].\n\nMutations in VWA8 are linked to rare developmental syndromes (including global developmental delay, microcephaly, scoliosis, and cardiovascular malformations)[1]. Mice and zebrafish knockout models show mitochondrial defects, altered oxidative metabolism, and skeletal anomalies, implicating VWA8 in mitochondrial protein quality control and cellular energy processes[1][2]. Genome-wide association studies suggest possible links with neuropsychiatric disorders and migraines, though these associations are not mechanistically defined[1].\n\nDespite having ATPase activity and homology to motor proteins, the specific physiological function of VWA8 remains largely unknown[4]. As of now, it has **no recognized role as a drug target**, nor are there interacting drugs or clinical biomarkers based on its function or expression.\n\n**In summary, VWA8 is a poorly characterized mitochondrial ATPase with links to rare developmental disease when mutated, but it is not currently a recognized therapeutic target or biomarker.**

Other names

KIAA0564P7BP2PEX7-binding protein 2Pex7p-binding protein 2RP97VWA8von Willebrand factor A domain-containing protein 8