The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway
Open accessAbstract
The ABC1 transporter was identified as the defect in Tangier disease by a combined strategy of gene expression microarray analysis, genetic mapping, and biochemical studies. Patients with Tangier disease have a defect in cellular cholesterol removal, which results in near zero plasma levels of HDL and in massive tissue deposition of cholesteryl esters. Blocking the expression or activity of ABC1 reduces apolipoprotein-mediated lipid efflux from cultured cells, and increasing expression of ABC1 enhances it. ABC1 expression is induced by cholesterol loading and cAMP treatment and is reduced upon subsequent cholesterol removal by apolipoproteins. The protein is incorporated into the plasma membrane in proportion to its level of expression. Different mutations were detected in the ABC1 gene of 3 unrelated patients. Thus, ABC1 has the properties of a key protein in the cellular lipid removal pathway, as emphasized by the consequences of its defect in patients with Tangier disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ABCA1 is a protein involved in cholesterol efflux and translocation from the inner leaflet to the outer leaflet of the plasma membrane.
“we identified ABCA1, a protein involved in cholesterol efflux and translocation from the inner leaflet to the outer leaflet of the plasma membrane (4, 27).”
From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [27]
The Discussion (p. R25) identifies ABC1 as pivotal to apolipoprotein-mediated cholesterol efflux and says its cell-surface expression is consistent with lipid transport across the plasma membrane. It does not specify translocation of cholesterol from the inner to the outer leaflet; that mechanism is not established by the cited passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredABCA1 transports cellular cholesterol and phospholipids from cells to lipid-poor apolipoproteins, including apoE, to form high density lipoproteins (HDL).
“It transports cellular cholesterol and phospholipids from cells to lipid-poor apolipoproteins, including apoE, in order to form high density lipoproteins (HDL) (Figure 2) (Lawn et al., 1999).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Lawn et al., 1999
The Discussion (Volume 104, R25) identifies ABC1 as pivotal to apolipoprotein-mediated lipid removal and says its cell-surface location is consistent with transport of cellular lipids to apolipoproteins. The Introduction links acquisition of cholesterol and phospholipids by nascent apo A-I to maturation into HDL. Our copy does not identify apoE as a recipient, and it presents ABC1’s direct transport role as consistent with the evidence rather than established. (LLM, conf=0.88)
Experimental — accuracy not yet measuredABCA1 is a transmembrane protein that plays an important role in the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins.
“ABCA1 is a transmembrane protein that plays an important role in the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins [39].”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [39]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Assmann, G., von Eckardstein, A., and Brewer, H.B. 1995. Familial HDL deficiency: Tangier disease. In The metabolic basis of inherited disease. C.R. Scriver, A.L. Beaudet, W.S. Sly, and D. Valle, editors. McGraw- Hill. New York, NY. 2053-2072.
- Rogler, G., Trümbach, B., Klima, B., Lackner, K.J., and Schmitz, G. 1995. HDL-mediated efflux of The Journal of Clinical Investigation | Volume 104 R31 intracellular cholesterol is impaired in fibroblasts from Tangier disease patients. Arterioscler. Thromb. Vasc. Biol. 15:683-690.
- Oram, J.F., Mendez, A.J., Lymp, J., Kavanagh, T.J., and Halbert, C.L. 1999. Reduction in apolipopro- tein-mediated removal of cellular lipids by immor- talization of human fibroblasts and its reversion by cAMP: lack of effect with Tangier disease cells. J. Lipid Res. In press.
Cited by
Sorted by citations
The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
Chinetti, G., Lestavel, S., Bocher, V., Remaley, A. T., Neve, B., Torra, I. P., Teissier, E., Minnich, A., Jaye, M., Duverger, N., et al. (2001) · Nature Medicine · doi:10.1038/83348 · Cited by 1,170 · see citing works
Bergt, C., Pennathur, S., Fu, X., Byun, J., O'Brien, K., McDonald, T. O., Singh, P., Anantharamaiah, G. M., Chait, A., Brunzell, J., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405292101 · Cited by 454 · see citing works
Self-citationATP-Binding Cassette Cholesterol Transporters and Cardiovascular Disease
Oram, J. F., & Vaughan, A. M. (2006) · Circulation Research · doi:10.1161/01.res.0000250171.54048.5c · Cited by 411 · see citing works
Self-citationOverexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C. L., Bales, K. R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33622 · Cited by 370 · see citing works
Sources of eicosanoid precursor fatty acid pools in tissues
Zhou, L., & Nilsson, Å. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32206-9 · Cited by 184 · see citing works
Molecular Genetics of Late‐Onset Alzheimer's Disease
Kamboh, M. I. (2004) · Annals of Human Genetics · doi:10.1046/j.1529-8817.2004.00110.x · Cited by 170 · see citing works
Microdomains, Inflammation, and Atherosclerosis
Sorci-Thomas, M. G., & Thomas, M. J. (2016) · Circulation Research · doi:10.1161/circresaha.115.306246 · Cited by 165 · see citing works
More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration
Lane-Donovan, C., Philips, G. T., & Herz, J. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.005 · Cited by 158 · see citing works
Minagawa, H., Gong, J., Jung, C., Watanabe, A., Lund‐Katz, S., Phillips, M. C., Saito, H., & Michikawa, M. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22073 · Cited by 90 · see citing works
Basak, J. M., Kim, J., Pyatkivskyy, Y., Wildsmith, K. R., Jiang, H., Parsadanian, M., Patterson, B. W., Bateman, R. J., & Holtzman, D. M. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-14 · Cited by 27 · see citing works
High-density lipoprotein-related cholesterol metabolism in Alzheimer's disease
Pedrini, S., Chatterjee, P., Hone, E., & Martins, R. N. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15170 · Cited by 22 · see citing works
Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells
Bendre, S. V., Wang, Y., Hajyousif, B., K C, R., Bhogale, S. G., Pradeep, D., Krawczynska, N., Schane, C. P., Weisser, E., Singh, A., et al. (2026) · Science Advances · doi:10.1126/sciadv.adx5490 · Cited by 8 · see citing works
“In doing so, we identified ABCA1, a protein involved in cholesterol efflux and translocation from the inner leaflet to the outer leaflet of the plasma membrane ( 6 , 29 ).”
- Authors
- Lawn, R. M., Wade, D. P., Garvin, M. R., Wang, X., Schwartz, K., Porter, J. G., Seilhamer, J. J., Vaughan, A. M., & Oram, J. F.
- Affiliations
- University of Washington (US)
- Corresponding author
- Lawn, Richard M.
- Venue
- Journal of Clinical Investigation
- Published
- 1999-10-15
- Volume
- 104
- Issue
- 8
- Pages
- R25-R31
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC481052
- OpenAlex
- W2032513433
- Cited by
- 724
- References
- 1
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 1 · 2023: 7 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 12 · 2017: 13 · 2016: 18 · 2015: 13 · 2014: 17 · 2013: 8 · 2012: 19
- FWCI
- 84.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Incyte
- National Institutes of Health (5r29hl053451-05)
- National Heart, Lung, and Blood Institute (HL-55362, HL-53451, R01HL055362)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 02456, P01DK002456)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- Tangier disease, cholesterol efflux, HDL cholesterol, plasma membrane proteins, cholesterol loading, cyclic AMP
- MeSH terms
- Adolescent, Animals, Apolipoproteins, Cells, Cultured, Gene Expression Regulation, Glycoproteins, Humans, Male, Mutation, Tangier Disease, ATP-Binding Cassette Transporters, Lipid Metabolism, Mice, ATP Binding Cassette Transporter 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
