Mutations associatedwith human diseases in hTRPV4-ARD. (A) Positionsof mutations associated with human inherited diseases that lie withinhTRPV4-ARD. Abbreviations: SEDM, spondyloepiphyseal dysplasia, typeMaroteaux; SMDK, spondylometaphyseal dysplasia, type Kozolowski; MD,metatropic dysplasia; SMA, spinal muscular atrophy; SPMA, scapuloperonealspinal muscular atrophy; CMTC2, Charcot-Marie-Tooth disease type 2C;HMSN2C, hereditary motor and sensory neuropathy 2C. This figure wasinspired by ref (51). (B) Location of the disease-causing mutations within TRPV4-ARD.Shown as spheres are 12 residue positions at which a total of 15 mutationscausing human inherited diseases have been identified. The ATP moleculeis shown as sticks. Skeletal dysplasia and neurophathy mutations aredepicted as green and blue spheres, respectively. (C) Leu199 is locatedat the hydrophobic interface between ANK2 and ANK3. (D) Glu183 andArg232 form a salt bridge on the convex face of TRPV4-ARD. Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel. Inada H, Procko E, Sotomayor M, Gaudet R - Biochemistry (2012). Not Altered. CC.