Reactome | CLCN7:OSTM1 exchanges Cl- for H+

CLCN7:OSTM1 exchanges Cl- for H+

Stable Identifier

R-HSA-2730959

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, lysosomal lumen, lysosomal membrane

ReviewStatus

5/5

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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 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
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
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