CLCN7:OSTM1 exchanges Cl- for H+

Stable Identifier
Reaction [transition]
Homo sapiens
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Chloride channel 7 comprises H+/Cl- exchange transporter 7 (CLCN7) and osteopetrosis-associated transmembrane protein 1 (OSTM1) (Leisle et al. 2011). This complex localises to the lysosomal membrane where it mediates the exchange of Cl- and H+ ions, perhaps playing a role in the acidification of the lysosome (Graves et al. 2008).

Defects in CLCN7 cause osteopetrosis autosomal recessive types 2 and 4 (OPTB2, MIM:166600 and OPTB4, MIM:611490) (Frattini et al. 2003, Pangrazio et al. 2010). Defects in OSTM1 cause osteopetrosis autosomal recessive type 5 (OPTB5, MIM:259720) (Pangrazio et al. 2006).
Literature References
PubMed ID Title Journal Year
14584882 Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis

Albertini, A, Flanagan, A, Orchard, PJ, Van Hove, J, Sobacchi, C, Horwitz, EM, Pangrazio, A, Young, T, Mirolo, M, Ramenghi, U, Abinun, M, Vujic, D, Teti, A, Mihci, E, Frattini, A, Notarangelo, LD, Susani, L, Andolina, M, Villa, A, Vezzoni, P

J. Bone Miner. Res. 2003
16813530 Mutations in OSTM1 (grey lethal) define a particularly severe form of autosomal recessive osteopetrosis with neural involvement

Di Rocco, M, Facchetti, F, Poliani, PL, Pangrazio, A, Megarbane, A, Lucchini, F, Abinun, M, Frattini, A, Rucci, F, Villa, A, Vezzoni, P, Lanino, E, Ravanini, M, Lefranc, G

J. Bone Miner. Res. 2006
18449189 The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes

Curran, PK, Smith, CL, Graves, AR, Mindell, JA

Nature 2008
21527911 ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity

Ludwig, CF, Wagner, FA, Stauber, T, Leisle, L, Jentsch, TJ

EMBO J. 2011
19953639 Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations

Zecca, M, Melis, D, Wright, M, Tamhankar, PM, Abinun, M, Pusch, M, Horwitz, E, Lopez, AG, Villa, A, Lanino, E, Tezcan, I, Van Roij, M, Sobacchi, C, Pangrazio, A, Baumann, C, Phadke, S, Mansour, LS, Vettenranta, K, Caldana, E, Mihci, E, Frattini, A, Bariae, I, Locatelli, F, Orchard, P, Vezzoni, P

Hum. Mutat. 2010
Catalyst Activity

antiporter activity of CLCN7:OSTM1 [lysosomal membrane]

Orthologous Events
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