CLCN7

Summary

Gene Symbol: CLCN7
Description: chloride voltage-gated channel 7
Alias: CLC-7, CLC7, OPTA2, OPTB4, PPP1R63, H(+)/Cl(-) exchange transporter 7, chloride channel 7 alpha subunit, chloride channel protein 7, chloride channel, voltage-sensitive 7, protein phosphatase 1, regulatory subunit 63
Species: human
Products:     CLCN7

Top Publications

  1. Brandt S, Jentsch T. ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family. FEBS Lett. 1995;377:15-20 pubmed
    ..Hydropathy analysis indicates that domain D4 cannot serve as a transmembrane domain. Both ClC-6 and ClC-7 cannot be expressed as chloride channels in Xenopus oocytes, either singly or in combination. ..
  2. Whyte M, Kempa L, McAlister W, Zhang F, Mumm S, Wenkert D. Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Schönberg disease (Chloride Channel 7 Deficiency Osteopetrosis) among the sclerosing bone disorders. J Bone Miner Res. 2010;25:2515-26 pubmed publisher
    ..Most cases are explained by loss-of-function mutation within the genes that encode either chloride channel 7 (CLCN7) or a vacuolar proton pump subunit (TCIRG1), each compromising acid secretion by osteoclasts...
  3. Schulz P, Werner J, Stauber T, Henriksen K, Fendler K. The G215R mutation in the Cl-/H+-antiporter ClC-7 found in ADO II osteopetrosis does not abolish function but causes a severe trafficking defect. PLoS ONE. 2010;5:e12585 pubmed publisher
    ..Furthermore, the robust solid-supported membrane-based electrophysiological assay is proposed for rapid screening for potential ClC-7 inhibitors which are discussed for treatment of osteoporosis. ..
  4. Cleiren E, Benichou O, Van Hul E, Gram J, Bollerslev J, Singer F, et al. Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Hum Mol Genet. 2001;10:2861-7 pubmed
    ..3, we now report seven different mutations in the gene encoding the ClCN7 chloride channel in all 12 ADO II families analysed...
  5. Campos Xavier A, Saraiva J, Ribeiro L, Munnich A, Cormier Daire V. Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive osteopetrosis. Hum Genet. 2003;112:186-9 pubmed
    ..of autosomal recessive malignant osteopetrosis have been ascribed to mutations in the chloride channel 7 gene (CLCN7), which accounts for all autosomal dominant type II cases reported to date...
  6. Kajiya H, Okamoto F, Ohgi K, Nakao A, Fukushima H, Okabe K. Characteristics of ClC7 Cl- channels and their inhibition in mutant (G215R) associated with autosomal dominant osteopetrosis type II in native osteoclasts and hClcn7 gene-expressing cells. Pflugers Arch. 2009;458:1049-59 pubmed publisher
    ClC7 Cl(-) channels (Clcn7) are crucial for osteoclastic bone resorption and have heterozygous mutation in autosomal osteopetrosis type II (ADO II) patients...
  7. Lange P, Wartosch L, Jentsch T, Fuhrmann J. ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function. Nature. 2006;440:220-3 pubmed
    ..3). The finding that grey-lethal mice, just like ClC-7-deficient mice, show lysosomal storage and neurodegeneration in addition to osteopetrosis implies a more general importance for ClC-7-Ostm1 complexes. ..
  8. Frattini A, Pangrazio A, Susani L, Sobacchi C, Mirolo M, Abinun M, et al. Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. J Bone Miner Res. 2003;18:1740-7 pubmed
    ..patients presenting with a severe clinical picture and diagnosed early in life, 12 bore mutations in the ClCN7 gene, but only 7 of them had the expected two recessive mutations...
  9. Waguespack S, Koller D, White K, Fishburn T, Carn G, Buckwalter K, et al. Chloride channel 7 (ClCN7) gene mutations and autosomal dominant osteopetrosis, type II. J Bone Miner Res. 2003;18:1513-8 pubmed
    ..In 11 of 12 kindreds, five different missense mutations were identified in the ClCN7 gene, indicating the genetic basis and possible dominant negative mechanism for ADO2...

More Information

Publications75

  1. Kornak U, Kasper D, Bösl M, Kaiser E, Schweizer M, Schulz A, et al. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell. 2001;104:205-15 pubmed
    ..We also identified CLCN7 mutations in a patient with human infantile malignant osteopetrosis...
  2. Waguespack S, Hui S, DiMeglio L, Econs M. Autosomal dominant osteopetrosis: clinical severity and natural history of 94 subjects with a chloride channel 7 gene mutation. J Clin Endocrinol Metab. 2007;92:771-8 pubmed
    ..osteopetrosis (ADO) is a sclerosing bone disorder caused by heterozygous mutations in the chloride channel 7 (ClCN7) gene...
  3. Graves A, Curran P, Smith C, Mindell J. The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes. Nature. 2008;453:788-92 pubmed publisher
  4. Henriksen K, Gram J, Neutzsky Wulff A, Jensen V, Dziegiel M, Bollerslev J, et al. Characterization of acid flux in osteoclasts from patients harboring a G215R mutation in ClC-7. Biochem Biophys Res Commun. 2009;378:804-9 pubmed publisher
    ..These data demonstrate that ClC-7 is essential for bone resorption, via its role in acidification of the lysosomes and resorption lacunae in osteoclasts. ..
  5. Henriksen K, Gram J, Schaller S, Dahl B, Dziegiel M, Bollerslev J, et al. Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II. Am J Pathol. 2004;164:1537-45 pubmed
    Autosomal dominant osteopetrosis II (ADOII) is a relatively benign disorder caused by a missense mutation in the ClCN7 gene...
  6. Kohan R, Cismondi I, Oller Ramirez A, Guelbert N, Anzolini T, Alonso G, et al. Therapeutic approaches to the challenge of neuronal ceroid lipofuscinoses. Curr Pharm Biotechnol. 2011;12:867-83 pubmed
    ..ucl.ac.uk/ncl) have been described. Other NCL genes are hypothesized, including CLN4 and CLN9; CLCN6, CLCN7 and possibly SGSH are under study...
  7. Liu M, Zhou Y, Rosen B, van Tassell C, Stella A, Tosser Klopp G, et al. Diversity of copy number variation in the worldwide goat population. Heredity (Edinb). 2019;122:636-646 pubmed publisher
    ..g. EDNRA, ADAMTS20, ASIP, KDM5B, ADAM8, DGAT1, CHRNB1, CLCN7, and EXOSC4), which are involved in local adaptations such as coat color, muscle development, metabolic processes, ..
  8. Howaldt A, Nampoothiri S, Quell L, Ozden A, Fischer Zirnsak B, Collet C, et al. Sclerosing bone dysplasias with hallmarks of dysosteosclerosis in four patients carrying mutations in SLC29A3 and TCIRG1. Bone. 2019;120:495-503 pubmed publisher
    ..After exclusion of mutations in CLCN7 we performed gene panel and exome sequencing. Two novel mutations in SLC29A3 were found in the first two patients...
  9. Suh K, Chon S, Jung W, Choi E. Effects of methylglyoxal on RANKL-induced osteoclast differentiation in RAW264.7 cells. Chem Biol Interact. 2018;296:18-25 pubmed publisher
    ..transcriptase-polymerase chain reaction revealed increased expression of the TRAF6, GAB2, ERK1, c-Fos, NFATc1, CLCN7, and OSTM1 genes, decreased expression of TCIRG and carbonic anhydrase II, and unchanged expression of cathepsin K ..
  10. Witwicka H, Jia H, Kutikov A, Reyes Gutiérrez P, Li X, Odgren P. TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and Resorption. PLoS ONE. 2015;10:e0127537 pubmed publisher
    ..despite the presence of osteoclast acidification factors including carbonic anhydrase II, a3-V-ATPase, and the ClC7 chloride channel. Secretion of TRAP and cathepsin K were also markedly inhibited in knockdown cells...
  11. Khan M, Ullah A, Naeem M. Whole exome sequencing identified two novel homozygous missense variants in the same codon of CLCN7 underlying autosomal recessive infantile malignant osteopetrosis in a Pakistani family. Mol Biol Rep. 2018;45:565-570 pubmed publisher
    ..Two novel homozygous missense variants were found in the same codon 204 of CLCN7 NM_001287.5:c.[610A>T;612C>G] predicting p.(Ser204Trp) variant in the protein...
  12. Alam I, Gray A, Acton D, Gerard O Riley R, Reilly A, Econs M. Interferon Gamma, but not Calcitriol Improves the Osteopetrotic Phenotypes in ADO2 Mice. J Bone Miner Res. 2015;30:2005-13 pubmed publisher
    ..that usually results from heterozygous missense dominant negative mutations in the chloride channel 7 gene (CLCN7)...
  13. Wen X, Lacruz R, Paine M. Dental and Cranial Pathologies in Mice Lacking the Cl(-) /H(+) -Exchanger ClC-7. Anat Rec (Hoboken). 2015;298:1502-8 pubmed publisher
    ..These data demonstrate that ClC-7 deficiency impacts the development of the dentition and calvaria, but does not significantly disrupt amelogenesis. ..
  14. Henriksen K, Thudium C, Christiansen C, Karsdal M. Novel targets for the prevention of osteoporosis - lessons learned from studies of metabolic bone disorders. Expert Opin Ther Targets. 2015;19:1575-84 pubmed publisher
  15. Duncan E, Danoy P, Kemp J, Leo P, McCloskey E, Nicholson G, et al. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk. PLoS Genet. 2011;7:e1001372 pubmed publisher
    ..Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets...
  16. Li X, Su N, Li C, Yang J, Du X, Chen L. [Genetic analysis of a novel mutation resulting in autosomal dominant osteopetrosis II]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2014;31:612-4 pubmed publisher
    To analyze potential mutation of chloride channel 7(CLCN7) gene in a patient with autosomal dominant osteopetrosis II (ADO II). Genomic DNA was extracted from peripheral blood samples from the patient and 100 healthy subjects...
  17. Saito A, Nagaishi K, Iba K, Mizue Y, Chikenji T, Otani M, et al. Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived mesenchymal stem cells and promote their therapeutic effects on ovariectomised rats. Sci Rep. 2018;8:1161 pubmed publisher
    ..primary mouse bone marrow cell-induced osteoclasts via suppression of osteoclast-specific genes, such as Nfatc1, Clcn7, Atp6i and Dc-stamp, by co-culture with OVX-MSCs-WJ in vitro...
  18. Turner A, Sasse J, Varadi A. Development and validation of a high throughput, closed tube method for the determination of haemoglobin alpha gene (HBA1 and HBA2) numbers by gene ratio assay copy enumeration-PCR (GRACE-PCR). BMC Med Genet. 2015;16:115 pubmed publisher
    ..amplification of targets in the α-globin genes (HBA1 and HBA2) and the chloride channel voltage sensitive 7 (CLCN7) reference gene...
  19. Festa M, Lagostena L, Carpaneto A. Using the plant vacuole as a biological system to investigate the functional properties of exogenous channels and transporters. Biochim Biophys Acta. 2016;1858:607-12 pubmed publisher
    ..This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale. ..
  20. Guo J, Bervoets T, Henriksen K, Everts V, Bronckers A. Null mutation of chloride channel 7 (Clcn7) impairs dental root formation but does not affect enamel mineralization. Cell Tissue Res. 2016;363:361-70 pubmed publisher
    ..Craniofacial bones and developing teeth in Clcn7(-/-) mice were examined by micro-CT, immunohistochemistry, quantified histomorphometry and electron microscopy...
  21. Palagano E, Susani L, Menale C, Ramenghi U, Berger M, Uva P, et al. Synonymous Mutations Add a Layer of Complexity in the Diagnosis of Human Osteopetrosis. J Bone Miner Res. 2017;32:99-105 pubmed publisher
    ..the presence of a synonymous variant in known ARO genes, namely in the TCIRG1 gene in one patient and in the CLCN7 in the other patient, predicted to impact on the splicing process...
  22. Wang H, Pan M, Ni J, Zhang Y, Zhang Y, Gao S, et al. ClC-7 Deficiency Impairs Tooth Development and Eruption. Sci Rep. 2016;6:19971 pubmed publisher
    b>CLCN7 gene encodes the voltage gated chloride channel 7 (ClC-7) in humans. The mutations in CLCN7 have been associated with osteopetrosis in connection to the abnormal osteoclasts functions...
  23. Wong C, Gregory S, Hu H, Chao Y, Sepulveda V, He Y, et al. Lysosomal Degradation Is Required for Sustained Phagocytosis of Bacteria by Macrophages. Cell Host Microbe. 2017;21:719-730.e6 pubmed publisher
    ..and mammalian macrophages, lysosomal dysfunction due to loss of the endolysosomal Cl- transporter ClC-b/CLCN7 delayed degradation of internalized bacteria...
  24. Maurizi A, Capulli M, Patel R, Curle A, Rucci N, Teti A. RNA interference therapy for autosomal dominant osteopetrosis type 2. Towards the preclinical development. Bone. 2018;110:343-354 pubmed publisher
    ..Dominant negative mutations of the CLCN7 gene affect about 70% of ADO2 patients...
  25. Teti A, Econs M. Osteopetroses, emphasizing potential approaches to treatment. Bone. 2017;102:50-59 pubmed publisher
    ..Dominant osteopetrosis is so far associated only with mutations in the CLCN7 gene and, although described as a benign form, it can be severely debilitating, although not at the same level as ..
  26. Ledemazel J, Plantaz D, Pagnier A, Girard P, Lasfargue M, Hullo E, et al. [Malignant infantile osteopetrosis: Case report of a 5-month-old boy]. Arch Pediatr. 2016;23:389-93 pubmed publisher
    ..The genetic investigation confirmed the diagnosis. Compound heterozygous mutations in the CLCN7 gene were identified, including an as yet undescribed mutation...
  27. Simanovsky N, Rozovsky K, Hiller N, Weintraub M, Stepensky P. Extending the Spectrum of Radiological Findings in Patients With Severe Osteopetrosis and Different Genetic Backgrounds. Pediatr Blood Cancer. 2016;63:1222-6 pubmed publisher
    ..TCIRG1 gene, five with mutations in the SNX10 gene, four children harbored RANK mutations, and one patient had a CLCN7 mutation...
  28. Marcoline F, Ishida Y, Mindell J, Nayak S, Grabe M. A mathematical model of osteoclast acidification during bone resorption. Bone. 2016;93:167-180 pubmed publisher
  29. Kurita T, Yamamura H, Suzuki Y, Giles W, Imaizumi Y. The ClC-7 Chloride Channel Is Downregulated by Hypoosmotic Stress in Human Chondrocytes. Mol Pharmacol. 2015;88:113-20 pubmed publisher
    ..These findings suggest novel targets for therapeutic intervention(s) and drug development for OA. ..
  30. Heon E, Piguet B, Munier F, Sneed S, Morgan C, Forni S, et al. Linkage of autosomal dominant radial drusen (malattia leventinese) to chromosome 2p16-21. Arch Ophthalmol. 1996;114:193-8 pubmed
    ..This is an important step toward actually isolating the disease-causing gene. In addition, this information can be used to evaluate other familial drusen phenotypes such as Doyne's macular dystrophy for a possible allelic relationship. ..
  31. Bonapace G, Moricca M, Talarico V, Graziano F, Pensabene L, Miniero R. Identification of two novel mutations on CLCN7 gene in a patient with malignant ostopetrosis. Ital J Pediatr. 2014;40:90 pubmed publisher
    ..Many experimental evidences point out on a specific role for CLCN7, the gene encoding the chloride channel protein subunit alfa and for TCIRG1, the gene encoding an osteoclast ..
  32. Zhang Z, He J, Zhang H, Hu W, Fu W, Gu J, et al. Identification of the CLCN7 gene mutations in two Chinese families with autosomal dominant osteopetrosis (type II). J Bone Miner Metab. 2009;27:444-51 pubmed publisher
    ..Recent studies have reported loss-of-function mutations in the chloride channel 7 (CLCN7) gene as a cause of autosomal dominant osteopetrosis type II (ADO-II)...
  33. Barvencik F, Kurth I, Koehne T, Stauber T, Zustin J, Tsiakas K, et al. CLCN7 and TCIRG1 mutations differentially affect bone matrix mineralization in osteopetrotic individuals. J Bone Miner Res. 2014;29:982-91 pubmed publisher
    Osteopetrosis is an inherited disorder of impaired bone resorption, with the most commonly affected genes being CLCN7 and TCIRG1, encoding the Cl(-) /H(+) exchanger CLC-7 and the a3 subunit of the vacuolar H(+) -ATPase, respectively...
  34. Harada K, Toyooka S, Maitra A, Maruyama R, Toyooka K, Timmons C, et al. Aberrant promoter methylation and silencing of the RASSF1A gene in pediatric tumors and cell lines. Oncogene. 2002;21:4345-9 pubmed
    ..In five of six cell lines, restoration of RASSF1A mRNA was confirmed by RT-PCR. Our findings indicate that aberrant promoter methylation of RASSF1A may contribute to the pathogenesis of many different forms of pediatric tumors. ..
  35. Pang Q, Chi Y, Zhao Z, Xing X, Li M, Wang O, et al. Novel mutations of CLCN7 cause autosomal dominant osteopetrosis type II (ADO-II) and intermediate autosomal recessive osteopetrosis (IARO) in Chinese patients. Osteoporos Int. 2016;27:1047-1055 pubmed publisher
    Osteopetrosis is a group of genetic bone disorders. Mutations in the chloride channel 7 gene (CLCN7) lead to chloride channel defect, which results in autosomal dominant osteopetrosis type II (ADO-II), autosomal recessive osteopetrosis (..
  36. Eggermont J. The exon-intron architecture of human chloride channel genes is not conserved. Biochim Biophys Acta. 1998;1397:156-60 pubmed
    ..The corresponding region (3.4 kbp) of the human CLCN7 gene has now been cloned and sequenced...
  37. Butscheidt S, Rolvien T, Kornak U, Schmidt F, Schinke T, Amling M, et al. Clinical Significance of DXA and HR-pQCT in Autosomal Dominant Osteopetrosis (ADO II). Calcif Tissue Int. 2018;102:41-52 pubmed publisher
    ..While one of the most common forms of HBM is CLCN7-related autosomal dominant osteopetrosis type II (ADO II), there is no consensus on diagnostic thresholds...
  38. Zhang X, Wei Z, He J, Wang C, Zhang Z. Novel mutations of CLCN7 cause autosomal dominant osteopetrosis type II (ADOII) and intermediate autosomal recessive osteopetrosis (ARO) in seven Chinese families. Postgrad Med. 2017;129:934-942 pubmed publisher
    ..osteopetrosis type II (ADOII, OPTA2 MIM 166600) and autosomal recessive osteopetrosis, autosomal recessive 4 (ARO, OPTB4 MIM 611490)...
  39. Lennon G, Auffray C, Polymeropoulos M, Soares M. The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression. Genomics. 1996;33:151-2 pubmed
  40. White K, Koller D, Takacs I, Buckwalter K, Foroud T, Econs M. Locus heterogeneity of autosomal dominant osteopetrosis (ADO). J Clin Endocrinol Metab. 1999;84:1047-51 pubmed
    ..Our results demonstrate that there is locus heterogeneity of this disorder; therefore, mutations in at least two different genes can give rise to the ADO phenotype. ..
  41. Zhang X, He J, Fu W, Wang C, Zhang Z. Novel mutations of TCIRG1 cause a malignant and mild phenotype of autosomal recessive osteopetrosis (ARO) in four Chinese families. Acta Pharmacol Sin. 2017;38:1456-1465 pubmed publisher
    ..Six additional genes (TNFSF11, TNFRSF11A, CLCN7, OSTM1, SNX10, PLEKHM1) were also found to be associated with human ARO...
  42. Chu K, Koller D, Ichikawa S, Snyder R, Curry L, Lai D, et al. CLCN7 polymorphisms and bone mineral density in healthy premenopausal white women and in white men. Bone. 2008;43:995-8 pubmed publisher
    Mutations in the chloride channel 7 gene (CLCN7) cause osteopetrosis, and polymorphisms of CLCN7 in the non-disease allele are associated with penetrance of the autosomal dominant osteopetrosis (ADO) phenotype...
  43. Piret S, Gorvin C, Trinh A, Taylor J, Lise S, Taylor J, et al. Autosomal dominant osteopetrosis associated with renal tubular acidosis is due to a CLCN7 mutation. Am J Med Genet A. 2016;170:2988-2992 pubmed publisher
    ..643G>A; p.Gly215Arg) in the gene encoding the chloride/proton antiporter 7 (gene CLCN7, protein CLC-7), which was confirmed by amplification refractory mutation system (ARMS)-PCR, and to be present in ..
  44. Huang Q, Li G, Kung A. The -9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPalpha and FOXA1 binding is associated with osteoporosis. Bone. 2009;45:289-94 pubmed publisher
    ..We sought to determine whether the allelic variation in seven monogenic bone disease genes (CLCN7, TCIRGI, SOST, CA2, CSTK, TGFB1 and SLC26A2) contributes to osteoporosis/bone mineral density (BMD) variation in ..
  45. Zheng H, Zhang Z, He J, Fu W, Wang C, Zhang Z. Identification of two novel CLCN7 gene mutations in three Chinese families with autosomal dominant osteopetrosis type II. Joint Bone Spine. 2014;81:188-9 pubmed publisher
  46. Supanchart C, Wartosch L, Schlack C, Kühnisch J, Felsenberg D, Fuhrmann J, et al. ClC-7 expression levels critically regulate bone turnover, but not gastric acid secretion. Bone. 2014;58:92-102 pubmed publisher
    ..Crossing of these mice with Clcn7(-/-) mutants rescued the osteopetrotic phenotype to variable degrees...
  47. Furthner D, Biebl A, Weinzettel R, Schmitt K, Lahr G, Ebetsberger G, et al. Osteopetrosis due to homozygous chloride channel ClCN7 mutation mimicking metabolic disease with haematological and neurological impairment. Klin Padiatr. 2010;222:180-3 pubmed publisher
    ..old male Turkish patient suffering from osteopetrosis caused by a homozygous mutation in the chloride channel gene ClCN7 with developing pancytopenia and severe neurological impairment...
  48. Alam I, McQueen A, Acton D, Reilly A, Gerard O Riley R, Oakes D, et al. Phenotypic severity of autosomal dominant osteopetrosis type II (ADO2) mice on different genetic backgrounds recapitulates the features of human disease. Bone. 2017;94:34-41 pubmed publisher
    ..ADO2 is caused by missense mutations in the chloride channel 7 (CLCN7) gene characterized by osteosclerosis with multiple fractures...
  49. Pettersson U, Albagha O, Mirolo M, Taranta A, Frattini A, McGuigan F, et al. Polymorphisms of the CLCN7 gene are associated with BMD in women. J Bone Miner Res. 2005;20:1960-7 pubmed
    ..show that a common polymorphism causing a valine to methionine amino acid substitution at codon 418 (V418M) in the CLCN7 gene is associated with femoral neck BMD in women...
  50. Mazzolari E, Forino C, Razza A, Porta F, Villa A, Notarangelo L. A single-center experience in 20 patients with infantile malignant osteopetrosis. Am J Hematol. 2009;84:473-9 pubmed publisher
    ..Mean age at diagnosis was 3.9 months, and mean follow-up was 66.75 months. Mutations in TCIRG1, OSTM1, ClCN7, and TNFRSF11A genes were detected in nine, three, one, and one patients, respectively...
  51. Steinmann M, Schmidt R, Macedo J, Kunz Renggli C, Bütikofer P, Rentsch D, et al. Identification and characterization of the three members of the CLC family of anion transport proteins in Trypanosoma brucei. PLoS ONE. 2017;12:e0188219 pubmed publisher
    ..Currents are sensitive to low concentrations of DIDS, insensitive to the pH in the range 5.4 to 8.4 and larger in nitrate than in chloride medium...
  52. Deng H, He D, Rong P, Xu H, Yuan L, Li L, et al. Novel CLCN7 mutation identified in a Han Chinese family with autosomal dominant osteopetrosis-2. Mol Pain. 2016;12: pubmed publisher
    ..2350A>T (p.R784W) in the chloride channel 7 gene (CLCN7) was identified. This variant cosegregated with the disorder in the family but was not observed in 800 controls...
  53. Wang C, Zhang H, He J, Gu J, Hu W, Hu Y, et al. The virulence gene and clinical phenotypes of osteopetrosis in the Chinese population: six novel mutations of the CLCN7 gene in twelve osteopetrosis families. J Bone Miner Metab. 2012;30:338-48 pubmed publisher
    ..The entire coding region and adjacent splice sites of the CLCN7, TCIRG1, LRP5 and SOST genes were amplified and directly sequenced...
  54. Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017;129:1768-1778 pubmed publisher
    ..screen, TFEB (master transcriptional regulator of lysosomal biogenesis) and endosomal/lysosomal genes CLCN7, OSTM1, and SNX10 were identified as important determinants of apilimod sensitivity...
  55. Kornak U, Ostertag A, Branger S, Benichou O, De Vernejoul M. Polymorphisms in the CLCN7 gene modulate bone density in postmenopausal women and in patients with autosomal dominant osteopetrosis type II. J Clin Endocrinol Metab. 2006;91:995-1000 pubmed
    ..The fact that mutations in the ClC-7 chloride channel cause autosomal dominant osteopetrosis (ADOII) make the CLCN7 gene an attractive candidate for the regulation of bone density...
  56. Phadke S, Fischer B, Gupta N, Ranganath P, Kabra M, Kornak U. Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosis. Indian J Med Res. 2010;131:508-14 pubmed
    ..We investigated the main genetic causes of ARO in eight Indian patients with early postnatal onset and the typical severe clinical course including visual impairment and anaemia...
  57. Zheng H, Shao C, Zheng Y, He J, Fu W, Wang C, et al. Two novel mutations of CLCN7 gene in Chinese families with autosomal dominant osteopetrosis (type II). J Bone Miner Metab. 2016;34:440-6 pubmed publisher
    ..Chloride channel 7 (CLCN7) has been reported to be the causative gene...
  58. Letizia C, Taranta A, Migliaccio S, Caliumi C, Diacinti D, Delfini E, et al. Type II benign osteopetrosis (Albers-Schönberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations. Calcif Tissue Int. 2004;74:42-6 pubmed
    ..and found to harbor a novel mutation in exon 25 of the gene encoding for the osteoclast-specific chloride channel, CLCN7, inherited from the father, who was asymptomatic...
  59. Caetano Lopes J, Lessard S, Hann S, Espinoza K, Kang K, Lim K, et al. Clcn7F318L/+ as a new mouse model of Albers-Schönberg disease. Bone. 2017;105:253-261 pubmed publisher
    Dominant negative mutations in CLCN7, which encodes a homodimeric chloride channel needed for matrix acidification by osteoclasts, cause Albers-Schönberg disease (also known as autosomal dominant osteopetrosis type 2)...
  60. Zeng B, Li R, Hu Y, Hu B, Zhao Q, Liu H, et al. A novel mutation and a known mutation in the CLCN7 gene associated with relatively stable infantile malignant osteopetrosis in a Chinese patient. Gene. 2016;576:176-81 pubmed publisher
    Osteopetrosis is a group of heterogeneous disorders caused by the dysfunction of osteoclasts. The CLCN7 and TCIRG1 genes are the major obligate genes responsible for infantile malignant osteopetrosis (IMO)...
  61. Köttgen M, Benzing T, Simmen T, Tauber R, Buchholz B, Feliciangeli S, et al. Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation. EMBO J. 2005;24:705-16 pubmed
    ..Furthermore, PACS proteins may represent a novel molecular mechanism for ion channel trafficking, directing acidic cluster-containing ion channels to distinct subcellular compartments. ..
  62. Leisle L, Ludwig C, Wagner F, Jentsch T, Stauber T. ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity. EMBO J. 2011;30:2140-52 pubmed publisher
    ..Reversal potentials of tail currents revealed a 2Cl(-)/1H(+)-exchange stoichiometry. Several disease-causing CLCN7 mutations accelerated gating...
  63. Pangrazio A, Pusch M, Caldana E, Frattini A, Lanino E, Tamhankar P, et al. Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations. Hum Mutat. 2010;31:E1071-80 pubmed publisher
    ..While several genes have been involved in the pathogenesis of the different types of osteopetroses, the CLCN7 gene has drawn the attention of many researchers, as mutations within this gene are associated with very different ..
  64. Shamriz O, Shaag A, Yaacov B, Nasereddin A, Weintraub M, Elpeleg O, et al. The use of whole exome sequencing for the diagnosis of autosomal recessive malignant infantile osteopetrosis. Clin Genet. 2017;92:80-85 pubmed publisher
    ..patients with malignant infantile osteopetrosis (MIOP) and identified mutations in four MIOP-related genes (CLCN7, TCIRG1, SNX10, and TNFRSF11A). We report these patients, describe the mutations and review the current literature. ..
  65. Foote J, Behe P, Frampton M, Levine A, Segal A. An Exploration of Charge Compensating Ion Channels across the Phagocytic Vacuole of Neutrophils. Front Pharmacol. 2017;8:94 pubmed publisher
    ..to identify specific channels, we tested neutrophils from knock-out mouse models including CLIC1, ClC3, ClC4, ClC7, KCC3, KCNQ1, KCNE3, KCNJ15, TRPC1/3/5/6, TRPA1/TRPV1, TRPM2, and TRPV2, and double knockouts of CLIC1, ClC3, KCC3, ..