Defective ABCA1 causes Tangier disease

Stable Identifier
R-HSA-5682113
Type
Pathway
Species
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 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 post-translationally modified (palmitoylated and phosphorylated), predominantly a tetramer 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 (Brooks-Wilson et al. 1999). Low HDL levels are among the most common biochemical abnormalities observed in coronary heart disease (CHD) patients (Kolovou et al. 2006, Iatan et al. 2008, Iatan et al. 2012).

Literature References
PubMed ID Title Journal Year
16611066 Tangier disease four decades of research: a reflection of the importance of HDL

Kolovou, GD, Mikhailidis, DP, Anagnostopoulou, KK, Daskalopoulou, SS, Cokkinos, DV

Curr. Med. Chem. 2006
22528521 Genetics of cholesterol efflux

Iatan, I, Palmyre, A, Alrasheed, S, Ruel, I, Genest, J

Curr Atheroscler Rep 2012
10431236 Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency

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

Nat. Genet. 1999
18706283 Effect of ABCA1 mutations on risk for myocardial infarction

Iatan, I, Alrasadi, K, Ruel, I, Alwaili, K, Genest, J

Curr Atheroscler Rep 2008
Participants
Participant Of
Disease
Name Identifier Synonyms
Tangier disease 1388 familial alpha-lipoprotein deficiency, familial hypoalphalipoproteinemia, familial high density lipoprotein deficiency
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