Defective ABCA1 does not transport CHOL from transport vesicle membrane to plasma membrane

Stable Identifier
Reaction [transition]
Homo sapiens
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In an ATP-dependent reaction, ATP-binding cassette sub-family A member 1 (ABCA1) mediates the movement of intracellular cholesterol (CHOL) to the extracellular face of the plasma membrane. Cholesterol associated with cytosolic vesicles is a substrate for this reaction. Under physiologocal conditions, the active form of ABCA1 is predominantly a tetramer, which is post-translationally modified (palmitoylated and phosphorylated) and is associated with apolipoprotein A-I (APOA1). Defects in ABCA1 can cause Tangier disease (TGD; MIM:205400 aka high density lipoprotein deficiency type 1), an autosomal recessive disorder characterised by significantly reduced levels of plasma high density lipoproteins (HDL) resulting in tissue accumulation of cholesterol esters. Low HDL levels are among the most common biochemical abnormalities observed in coronary heart disease (CHD) patients. Mutations causing TGD include C1417R, Q537R, S1446L, N935S, W590S and R587W (Brooks-Wilson et al. 1999, Lapicka-Bodzioch et al. 2001, Guo et al. 2002, Tanaka et al. 2003).
Literature References
PubMed ID Title Journal Year
12509412 Effects of mutations of ABCA1 in the first extracellular domain on subcellular trafficking and ATP binding/hydrolysis

Murata, M, Amachi, T, Matsuo, M, Ohnishi, T, Tanaka, AR, Kano, F, Abe-Dohmae, S, Kioka, N, Yokoyama, S, Morinaga, G, Okuhira, K, Aoki, R, Ikeda, Y, Ueda, K

J. Biol. Chem. 2003
10431236 Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency

Mott, S, van Dam, M, Zhang, LH, Martindale, D, Roomp, K, Molhuizen, HO, Ashbourne-Excoffon, KJ, Kastelein, JJ, Clee, SM, Hayden, MR, Sensen, CW, Frohlich, J, Koop, B, Genest, J, Pimstone, S, Brewer, C, Yu, L, Morgan, K, Marcil, M, Collins, JA, Denis, M, Loubser, O, Brooks-Wilson, A, Scherer, S, Ouelette, BF, Fichter, K

Nat. Genet. 1999
11476961 Homogeneous assay based on 52 primer sets to scan for mutations of the ABCA1 gene and its application in genetic analysis of a new patient with familial high-density lipoprotein deficiency syndrome

Bodzioch, M, Krüll, M, Schmitz, G, Kielar, D, Lapicka-Bodzioch, K, Hubacek, J, Böttcher, A, Kiec, B, Probst, M, Suttorp, N, Aslanidis, C, Andrikovics, H

Biochim. Biophys. Acta 2001
12111381 Double deletions and missense mutations in the first nucleotide-binding fold of the ATP-binding cassette transporter A1 ( ABCA1) gene in Japanese patients with Tangier disease

Schmitz, G, Suzumura, T, Yu, W, Hayakawa, T, Sano, R, Higashikata, T, Mabuchi, H, Nohara, A, Wakasugi, K, Inazu, A, Yoshida, K, Okamoto, M, Suehiro, T, Guo, Z

J. Hum. Genet. 2002
Catalyst Activity

cholesterol transfer activity of APOA1(25-266):ABCA1 mutants [plasma membrane]

Normal reaction
Functional status

Loss of function of APOA1(25-266):ABCA1 mutants [plasma membrane]

Name Identifier Synonyms
Tangier disease DOID:1388 familial alpha-lipoprotein deficiency, familial hypoalphalipoproteinemia, familial high density lipoprotein deficiency
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