Defective SLC9A6 does not exchange Na+ for H+ across the early endosome membrane

Stable Identifier
Reaction [transition]
Homo sapiens
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SLC9A6 encodes the sodium/hydrogen exchanger 6 NHE6, a protein ubiquitously expressed but most abundant in mitochondria-rich tissues such as brain, skeletal muscle and heart. It is located on endosomal membranes and thought to play a housekeeping role in pH homeostasis in early endosomes. It mediates the electroneutral exchange of protons for Na+ and K+ across the early and recycling endosome membranes. Defects in SLC9A6 can cause mental retardation, X-linked, syndromic, Christianson type (MRXSCH; MIM:300243), a syndrome characterised by profound mental retardation, epilepsy, ataxia and microcephaly. Mutations in SLC9A6 causing MRXSCH include 255-256del, R468*, H171fs*60, 338-340del and E547* (Gilfillan et al. 2008, Roxrud et al. 2009, Garbern et al. 2010, Schuurs-Hoeijmakers et al. 2013).
Literature References
PubMed ID Title Journal Year
18342287 SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome

Samuelsson, L, Stratton, MR, Edkins, S, Teague, J, Server, A, Gilfillan, GD, Kroken, M, Egeland, T, Undlien, DE, Gecz, J, Eiklid, K, Mattingsdal, M, Turner, G, Stevenson, RE, Christianson, A, Futreal, PA, Tarpey, P, Smith, R, Whibley, A, Strømme, P, Schwartz, C, Raymond, FL, Sjøholm, H, Selmer, KK, Roxrud, I, Stenmark, H, Kyllerman, M

Am. J. Hum. Genet. 2008
20395263 A mutation affecting the sodium/proton exchanger, SLC9A6, causes mental retardation with tau deposition

Friez, MJ, Feldman, G, Lee, VM, Sima, AA, Trojanowski, JQ, Neumann, M, Stevenson, R, Schwartz, CE, Norris, JW, Garbern, JY

Brain 2010
24123876 Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing

Brunner, HG, Greco, D, Janssen, IM, Pfundt, R, Galesi, O, de Vries, BB, van de Vondervoort, II, Hehir-Kwa, JY, del Rosario, M, Schuurs-Hoeijmakers, JH, Veltman, JA, Reitano, S, Vissers, LE, van Bon, BW, van Bokhoven, H, Ockeloen, CW, Neveling, K, Vulto-van Silfhout, AT, Kleefstra, T, de Brouwer, AP, Bongers, EM, Romano, C, de Ligt, J, Fichera, M, Willemsen, MA, Willemsen, MH, Hira, G, Greally, MT, Vitello, A, Gilissen, C, Failla, P

J. Med. Genet. 2013
19619532 Dual degradation mechanisms ensure disposal of NHE6 mutant protein associated with neurological disease

Gilfillan, GD, Strømme, P, Raiborg, C, Roxrud, I, Stenmark, H

Exp. Cell Res. 2009
Catalyst Activity

sodium:proton antiporter activity of SLC9A6 mutants [early endosome membrane]

Normal reaction
Functional status

Loss of function of SLC9A6 mutants [early endosome membrane]

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