Defective SLC22A5 does not cotransport CAR, Na+ from extracellular region to cytosol

Stable Identifier
Reaction [transition]
Homo sapiens
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SLC22A5 encodes the organic cation/carnitine transporter 2 (OCTN2). It is a sodium-dependent, high affinity carnitine cotransporter which maintain systemic and tissue concentrations of carnitine. Carnitine is essential for beta-oxidation of long-chain fatty acids to produce ATP. SLC22A5 is strongly expressed in the kidney, skeletal muscle, heart and placenta. Defects in SLC22A5 are the cause of systemic primary carnitine deficiency (CDSP; MIM:212140), an autosomal recessive disorder of fatty-acid oxidation caused by defective carnitine transport resulting in cardiac, skeletal, or metabolic symptoms. If diagnosed early, all clinical symptoms can be completely reversed with a carnitine supplement. However, if left untreated, patients will develop lethal heart failure. Mutations that can cause CDSP include W132*, P478L, R169Q, R169W, R254* and G15W (Nezu et al. 1999, Tang et al. 1999, Burwinkel et al. 1999, Wang et al. 2000, Tang et al. 2002, El-Hattab et al. 2010).
Literature References
PubMed ID Title Journal Year
20027113 Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects

Scaglia, F, Wong, LJ, Li, FY, Adams, DJ, Kobori, JA, Bawle, EV, El-Hattab, AW, Powell, BR, Shen, J, Graham, B, Wahl, E

Genet. Med. 2010
10072434 Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency

Hui, J, Wu, X, Tang, NL, Hjelm, NM, Wanders, RJA, Ganapathy, V, Seth, P, Yuen, PM, Fok, TF

Hum Mol Genet 1999
9916797 Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter

Ohura, T, Kato, H, Yoshino, M, Takada, G, Nikaido, H, Oku, A, Shimane, M, Matsuishi, T, Hayakawa, J, Tsujimoto, G, Nezu, J, Sai, Y, Tsuji, A, Shoji, Y, Ohashi, R, Koizumi, A, Yabuuchi, H, Hashimoto, N, Tamai, I

Nat. Genet. 1999
10425211 Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality

Kreuder, J, Vorgerd, M, Schweitzer, S, Burwinkel, B, Kilimann, MW, Gerbitz, KD, Gempel, K

Biochem. Biophys. Res. Commun. 1999
11058897 Functional analysis of mutations in the OCTN2 transporter causing primary carnitine deficiency: lack of genotype-phenotype correlation

Taroni, F, Longo, N, Garavaglia, B, Wang, Y

Hum. Mutat. 2000
12204000 A founder mutation (R254X) of SLC22A5 (OCTN2) in Chinese primary carnitine deficiency patients

Zhang, WM, Chan, RT, Fung, LM, Tang, NL, Law, LK, Hwu, WL

Hum. Mutat. 2002
Catalyst Activity

carnitine transmembrane transporter activity of SLC22A5 mutants [plasma membrane]

Normal reaction
Functional status

Loss of function of SLC22A5 mutants [plasma membrane]

Name Identifier Synonyms
systemic primary carnitine deficiency disease DOID:14365 carnitine uptake defect, carnitine transporter deficiency, primary carnitine deficiency, deficiency of plasma-membrane carnitine transporter, renal carnitine transport defect (disorder)
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