2.A.31.1.5
Boron transporter, NcBC1 or BTR1 or SLC4a11. In the absence of borate, it functions as a Na⁺ and OH^- (H⁺) channel. In the presence of borate, it functions as an electrogenic Na⁺-coupled borate cotransporter (Park et al., 2004).  Three genetic corneal dystrophies (congenital hereditary endothelial dystrophy type 2 (CHED2), Harboyan syndrome and Fuchs endothelial corneal dystrophy (FECD) arise from mutations of the SLC4a11 gene, which cause blindness from fluid accumulation in the corneal stroma.  It can mediate water flux at a rate comparable to aquaporin in a process that is independent of solute transport (Vilas et al. 2013).  The system has been reviewed by Patel and Parker 2015.  A 3-d homology model rationalizes various pathology-causing mutations (Badior et al. 2016). SLC4A11 is also a cell adhesion molecule involving extracellular loop 3, and cell adhesion defects contribute to FECD and CHED pathology (Malhotra et al. 2019). pH-dependence of Slc4a11-mediated H⁺ conductance is influenced by intracellular lysine residues and modified by disease-linked mutations (Quade et al. 2020). Corneal dystrophy mutations R125H and R804H disable SLC4A11 by altering the extracellular pH dependence of the intracellular pK that governs H⁺/OH^- transport  (Quade et al. 2022).  Structural insights into the conformational changes of BTR1/SLC4A11 in complex with PIP(2) have been described (Lu et al. 2023).  Mutations in SLC4A11 can give rise to autosomal recessive congenital hereditary corneal dystrophy (Chibani et al. 2022).