CLCN7:OSTM1 exchanges Cl- for H+

Stable Identifier
R-HSA-2730959
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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
16813530 Mutations in OSTM1 (grey lethal) define a particularly severe form of autosomal recessive osteopetrosis with neural involvement

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

J. Bone Miner. Res. 2006
14584882 Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis

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

J. Bone Miner. Res. 2003
18449189 The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes

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

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

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

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

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

Hum. Mutat. 2010
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
antiporter activity of CLCN7:OSTM1 [lysosomal membrane]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created