{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC4A11 is an integral membrane protein predominantly expressed in corneal endothelial cells—and in certain inner ear cells—whose genetic alterations underlie a spectrum of corneal dystrophies, including congenital hereditary endothelial dystrophy (CHED2), Fuchs endothelial corneal dystrophy (FECD), and Harboyan syndrome. Although initially proposed as a sodium‐borate cotransporter"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", subsequent genetic and biochemical studies established that SLC4A11 is essential for maintaining corneal transparency by regulating ionic homeostasis and fluid transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Mutations in SLC4A11 disrupt these critical functions by impairing plasma membrane trafficking and folding, as evidenced by studies in late‐onset FECD and CHED patients."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed functional analyses have clarified that under physiological conditions SLC4A11 does not operate as a bicarbonate or borate transporter. Instead, it functions as an electrogenic ion transporter that facilitates the movement of H⁺ equivalents—operating in a Na⁺‐coupled hydroxide (or H⁺) transport mode—and can also mediate NH₃/H⁺ co‐transport with a stoichiometry near 1:2. This transport activity drives an osmotically induced water flux, albeit at a rate about half that seen with classical aquaporins, and is finely regulated by pH; both intracellular and extracellular alkalinization enhance its activity. Notably, certain disease‐causing mutations lead to shifts in these pH dependencies, thereby reducing functional localization to the cell surface."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its ion and water transport roles, SLC4A11 contributes to the structural integrity of the corneal endothelium by promoting cell adhesion—its extracellular loop domains (particularly EL3) interact with key components of the extracellular matrix such as COL8A2. This adhesion function, together with its ability to modulate responses to oxidative stress and maintain mitochondrial integrity, underscores its multifaceted role in corneal homeostasis. Defects in these activities, whether by misfolding, aberrant trafficking, or altered pH sensitivity, are central to the pathophysiology of corneal endothelial dystrophies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "45"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eranga N Vithana, Patricio E Morgan, Vedam Ramprasad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLC4A11 mutations in Fuchs endothelial corneal dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddm337"}], "href": "https://doi.org/10.1093/hmg/ddm337"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18024964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18024964"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eranga N Vithana, Patricio Morgan, Periasamy Sundaresan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1824"}], "href": "https://doi.org/10.1038/ng1824"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16767101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16767101"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "S Amer Riazuddin, Eranga N Vithana, Li-Fong Seet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Missense mutations in the sodium borate cotransporter SLC4A11 cause late-onset Fuchs corneal dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21356"}], "href": "https://doi.org/10.1002/humu.21356"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20848555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20848555"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Julie Desir, Graciela Moya, Orit Reish, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Borate transporter SLC4A11 mutations cause both Harboyan syndrome and non-syndromic corneal endothelial dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2006.046904"}], "href": "https://doi.org/10.1136/jmg.2006.046904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17220209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17220209"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiaodong Jiao, Afia Sultana, Prashant Garg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autosomal recessive corneal endothelial dystrophy (CHED2) is associated with mutations in SLC4A11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2006.044644"}], "href": "https://doi.org/10.1136/jmg.2006.044644"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16825429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16825429"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Gonzalo L Vilas, Sampath K Loganathan, Jun Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transmembrane water-flux through SLC4A11: a route defective in genetic corneal diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt307"}], "href": "https://doi.org/10.1093/hmg/ddt307"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23813972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23813972"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Afia Sultana, Prashant Garg, Balasubramanya Ramamurthy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutational spectrum of the SLC4A11 gene in autosomal recessive congenital hereditary endothelial dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17679935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17679935"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Boomiraj Hemadevi, Reiner A Veitia, Muthiah Srinivasan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of mutations in the SLC4A11 gene in patients with recessive congenital hereditary endothelial dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Ophthalmol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archopht.126.5.700"}], "href": "https://doi.org/10.1001/archopht.126.5.700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18474783"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18474783"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Wenlin Zhang, Diego G Ogando, Joseph A Bonanno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human SLC4A11 Is a Novel NH3/H+ Co-transporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.627455"}], "href": "https://doi.org/10.1074/jbc.M114.627455"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26018076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26018076"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Vedam L Ramprasad, Neil D Ebenezer, Tin Aung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel SLC4A11 mutations in patients with recessive congenital hereditary endothelial dystrophy (CHED2). Mutation in brief #958. Online."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.9487"}], "href": "https://doi.org/10.1002/humu.9487"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17397048"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17397048"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Diego G Ogando, Supriya S Jalimarada, Wenlin Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLC4A11 is an EIPA-sensitive Na(+) permeable pHi regulator."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00056.2013"}], "href": "https://doi.org/10.1152/ajpcell.00056.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23864606"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23864606"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Anthony J Aldave, Vivek S Yellore, Nirit Bourla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autosomal recessive CHED associated with novel compound heterozygous mutations in SLC4A11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cornea (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/ICO.0b013e318074bb01"}], "href": "https://doi.org/10.1097/ICO.0b013e318074bb01"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17667634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17667634"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Arun Kumar, Soma Bhattacharjee, Durgappa Ravi Prakash, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic analysis of two Indian families affected with congenital hereditary endothelial dystrophy: two novel mutations in SLC4A11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17262014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17262014"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Gonzalo L Vilas, Sampath K Loganathan, Anita Quon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oligomerization of SLC4A11 protein and the severity of FECD and CHED2 corneal dystrophies caused by SLC4A11 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21655"}], "href": "https://doi.org/10.1002/humu.21655"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22072594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22072594"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Gonzalo L Vilas, Patricio E Morgan, Sampath K Loganathan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A biochemical framework for SLC4A11, the plasma membrane protein defective in corneal dystrophies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi101887z"}], "href": "https://doi.org/10.1021/bi101887z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21288032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21288032"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Sanjukta Guha, Sunita Chaurasia, Charanya Ramachandran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-03654-4"}], "href": "https://doi.org/10.1038/s41598-017-03654-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28642546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28642546"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Liyo Kao, Rustam Azimov, Natalia Abuladze, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human SLC4A11-C functions as a DIDS-stimulatable H⁺(OH⁻) permeation pathway: partial correction of R109H mutant transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00271.2014"}], "href": "https://doi.org/10.1152/ajpcell.00271.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25394471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25394471"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jun Liu, Li-Fong Seet, Li Wei Koh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Depletion of SLC4A11 causes cell death by apoptosis in an immortalized human corneal endothelial cell line."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.11-8724"}], "href": "https://doi.org/10.1167/iovs.11-8724"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22447871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22447871"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Mohammed A Aldahmesh, Arif O Khan, Brian F Meyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutational spectrum of SLC4A11 in autosomal recessive CHED in Saudi Arabia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.08-3006"}], "href": "https://doi.org/10.1167/iovs.08-3006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19369245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19369245"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Evan J Myers, Aniko Marshall, Michael L Jennings, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mouse Slc4a11 expressed in Xenopus oocytes is an ideally selective H+/OH- conductance pathway that is stimulated by rises in intracellular and extracellular pH."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00259.2016"}], "href": "https://doi.org/10.1152/ajpcell.00259.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27681179"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27681179"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Sangita P Patel, Mark D Parker "}, {"type": "b", "children": [{"type": "t", "text": "SLC4A11 and the Pathophysiology of Congenital Hereditary Endothelial Dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2015/475392"}], "href": "https://doi.org/10.1155/2015/475392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26451371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26451371"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Sampath K Loganathan, Hans-Peter Schneider, Patricio E Morgan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00078.2016"}], "href": "https://doi.org/10.1152/ajpcell.00078.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27558157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27558157"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Sayoko E Moroi, Parag A Gokhale, Miriam T Schteingart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinicopathologic correlation and genetic analysis in a case of posterior polymorphous corneal dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Ophthalmol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0002-9394(02)02032-9"}], "href": "https://doi.org/10.1016/s0002-9394(02"}, {"type": "t", "text": "02032-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12654361"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12654361"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Liyo Kao, Rustam Azimov, Xuesi M Shao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multifunctional ion transport properties of human SLC4A11: comparison of the SLC4A11-B and SLC4A11-C variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00233.2016"}], "href": "https://doi.org/10.1152/ajpcell.00233.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27581649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27581649"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Jodhbir Singh Mehta, Boomiraj Hemadevi, Eranga N Vithana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Absence of phenotype-genotype correlation of patients expressing mutations in the SLC4A11 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cornea (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/ICO.0b013e3181ae9038"}], "href": "https://doi.org/10.1097/ICO.0b013e3181ae9038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20118786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20118786"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Jae-hyung Kim, Jung Min Ko, Hungwon Tchah "}, {"type": "b", "children": [{"type": "t", "text": "Fuchs Endothelial Corneal Dystrophy in a Heterozygous Carrier of Congenital Hereditary Endothelial Dystrophy Type 2 with a Novel Mutation in SLC4A11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmic Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/13816810.2014.881510"}], "href": "https://doi.org/10.3109/13816810.2014.881510"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24502824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24502824"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Hamidreza Moazzeni, Mohammad Ali Javadi, Danial Asgari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Observation of nine previously reported and 10 non-reported "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SLC4A11"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutations among 20 Iranian CHED probands and identification of an "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "MPDZ"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutation as possible cause of CHED and FECD in one family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Ophthalmol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/bjophthalmol-2019-314377"}], "href": "https://doi.org/10.1136/bjophthalmol-2019-314377"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31420327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31420327"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Shimin Li, Karmjot Singh Hundal, Xingjuan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "R125H, W240S, C386R, and V507I SLC4A11 mutations associated with corneal endothelial dystrophy affect the transporter function but not trafficking in PS120 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Eye Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.exer.2018.12.003"}], "href": "https://doi.org/10.1016/j.exer.2018.12.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30557570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30557570"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Lianzhi Qin, Ting Li, Yuhua Liu "}, {"type": "b", "children": [{"type": "t", "text": "High SLC4A11 expression is an independent predictor for poor overall survival in grade 3/4 serous ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0187385"}], "href": "https://doi.org/10.1371/journal.pone.0187385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29091960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29091960"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Haiba Kaul, Maryam Suman, Zoya Khan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Missense mutation in SLC4A11 in two Pakistani families affected with congenital hereditary endothelial dystrophy (CHED2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Optom (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cxo.12276"}], "href": "https://doi.org/10.1111/cxo.12276"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26286922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26286922"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "M J Abramowicz, J Albuquerque-Silva, A Zanen "}, {"type": "b", "children": [{"type": "t", "text": "Corneal dystrophy and perceptive deafness (Harboyan syndrome): CDPD1 maps to 20p13."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.39.2.110"}], "href": "https://doi.org/10.1136/jmg.39.2.110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11836359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11836359"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Hui Tang, Wen Zhang, Xin-Min Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset Fuchs corneal dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2016.2570"}], "href": "https://doi.org/10.3892/ijmm.2016.2570"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27121161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27121161"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Stuart J Smith, Norma Towers, Kim Demetriou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective heart chamber growth and myofibrillogenesis after knockout of adprhl1 gene function by targeted disruption of the ancestral catalytic active site."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0235433"}], "href": "https://doi.org/10.1371/journal.pone.0235433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32726316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32726316"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Babu Lal Kumawat, Ranjan Gupta, Arundhati Sharma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Delayed onset of congenital hereditary endothelial dystrophy due to compound heterozygous SLC4A11 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Indian J Ophthalmol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4103/0301-4738.190100"}], "href": "https://doi.org/10.4103/0301-4738.190100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27609159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27609159"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Bianca N Quade, Aniko Marshall, Mark D Parker "}, {"type": "b", "children": [{"type": "t", "text": "pH dependence of the Slc4a11-mediated H"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " conductance is influenced by intracellular lysine residues and modified by disease-linked mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00128.2020"}], "href": "https://doi.org/10.1152/ajpcell.00128.2020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32520610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32520610"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Khrishen Cunnusamy, Charles B Bowman, Walter Beebe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Congenital Corneal Endothelial Dystrophies Resulting From Novel De Novo Mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cornea (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/ICO.0000000000000670"}], "href": "https://doi.org/10.1097/ICO.0000000000000670"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26619383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26619383"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Darpan Malhotra, Sampath K Loganathan, Anthony M Chiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Corneal Expression of SLC4A11, a Gene Mutated in Endothelial Corneal Dystrophies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-46094-y"}], "href": "https://doi.org/10.1038/s41598-019-46094-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31273259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31273259"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Kumari Alka, Joseph R Casey "}, {"type": "b", "children": [{"type": "t", "text": "Molecular phenotype of SLC4A11 missense mutants: Setting the stage for personalized medicine in corneal dystrophies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.23401"}], "href": "https://doi.org/10.1002/humu.23401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29327391"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29327391"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Salina Siddiqui, Juan Carlos Zenteno, Aine Rice, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Congenital hereditary endothelial dystrophy caused by SLC4A11 mutations progresses to Harboyan syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cornea (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/ICO.0000000000000041"}], "href": "https://doi.org/10.1097/ICO.0000000000000041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24351571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24351571"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Srinivas Gopinath Kodaganur, Saketh Kapoor, Avinash M Veerappa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation analysis of the SLC4A11 gene in Indian families with congenital hereditary endothelial dystrophy 2 and a review of the literature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2013)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23922488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23922488"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Nagasamy Soumittra, Sampath K Loganathan, Dharanija Madhavan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biosynthetic and functional defects in newly identified SLC4A11 mutants and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2014.55"}], "href": "https://doi.org/10.1038/jhg.2014.55"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25007886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25007886"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Shaival S Shah, Ali Al-Rajhi, James D Brandt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation in the SLC4A11 gene associated with autosomal recessive congenital hereditary endothelial dystrophy in a large Saudi family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmic Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/13816810701850033"}], "href": "https://doi.org/10.1080/13816810701850033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18363173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18363173"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Dorota M Nowak, Justyna A Karolak, Joanna Kubiak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Substitution at IL1RN and deletion at SLC4A11 segregating with phenotype in familial keratoconus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.13-11592"}], "href": "https://doi.org/10.1167/iovs.13-11592"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23462747"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23462747"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Sanhita Roy, D C Praneetha, Venkata Pulla Rao Vendra "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the Corneal Endothelial Dystrophy-Associated Gene SLC4A11 Render the Cells More Vulnerable to Oxidative Insults."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cornea (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/ICO.0000000000000421"}], "href": "https://doi.org/10.1097/ICO.0000000000000421"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25811729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25811729"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Mollie A Minear, Yi-Ju Li, Jacqueline Rimmler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic screen of African Americans with Fuchs endothelial corneal dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2013)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24348007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24348007"}]}]}]}