Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein (apo-) B100 is the exclusive apolipoprotein of low density lipoproteins (LDL0, which transport most of the plasma cholesterol in humans. Mutations in apo-B100 can cause either hypocholesterolemia or hypercholesterolemia. Familial hypobetalipoproteinemia, which leads to hypocholesterolemia, has been shown to be caused by defects in the apo-B gene that terminate translation prematurely and result in the production of truncated proteins. The mutations responsible for the hypocholesterolemia have been either single nucleotide substitutions or deletions. Familial defective apo-B100, which leads to hypercholesterolemia, is caused by a point mutation in the receptor-binding domain of apo-B100. The mutation disrupts the binding of LDL to the LDL receptor, thereby disrupting LDL receptor-mediated catabolism and resulting in hypercholesterolemia. A variant form of apo-B, apo-B48, is also critical for lipoprotein metabolism. Apolipoprotein B48 is obligatory for the secretion of chylomicrons. It is formed from an RNA-edited apo-B mRNA in which codon 2153 has been converted from a CAA (glutamine) codon to a premature UAA (stop) codon. The first cytosine in this codon is deaminated to form uracil. The minimum nucleotide recognition sequence for the editing mechanism has been reported to be between 26 and more than 63 nucleotides surrounding codon 2153. The apo-B mRNA editing mechanism, which appears to be a cytosine deaminase, and its regulation are being actively investigated.
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PMID:Mutations and variants of apolipoprotein B that affect plasma cholesterol levels. 185 54

The gene encoding human apo B has been mapped to the short arm of chromosome 2 in the p23-p24 region. The apo B gene extends over 43 kb and is composed of 29 exons and 28 introns. Both apo B 100 and apo B 48 were encoded by the same gene. All intestinal cDNA clones contained a single C to T base substitution in the codon CAA encoding Gln2153 in apo B 100 cDNA, resulting in a translational stop. In human intestinal cells, apo B mRNA is recognized by a specific enzyme that modifies cytosine 6666 to a uracil, introducing a stop codon. Recently, a human apo B mRNA editing protein was cloned. The cDNA sequence predicts a translation product of 236-aa residues. The human apo B mRNA editing protein is a cytidine deaminase and exists as a homodimer. Familial hypobetalipoproteinemia can be caused by mutations in the apoB gene that interfere with the translation of a full-length apo B molecule. Frequently, a truncated apo B molecule can be detected in the plasma lipoproteins of familial hypobetalipoproteinemia. Abetalipoproteinemia is caused by defect of the gene encoding the large subunit of a microsomal triglyceride transfer protein.
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PMID:[Apolipoprotein B]. 785 98

Familial hypobetalipoproteinemia is caused by mutations in the apolipoprotein (apo) B gene. We identified a 57-year-old woman whose plasma total cholesterol and apoB levels were 2.17 mmol/L and 0.03 g/L, respectively. Separation of plasma lipoproteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the absence of apoB-100 and the presence of a faster-migrating form of apoB with an apparent Mr of 195 kDa. Direct sequencing of a polymerase chain reaction-amplified fragment of the patient's apoB gene DNA revealed a single C-->T transition at nucleotide 5472 that converts glutamine 1755 (CAA) to a stop codon (TAA). We predict this novel nonsense mutation of the apoB gene to produce a truncated protein that contains 1754 amino-terminal amino acid residues of apoB-100. We designated this mutant form of apoB apoB-38.7 by following the centile nomenclature of the apoB species. The same mutation was found in both of her children. The proband revealed clinical findings of retinitis pigmentosa, acanthocytosis, and loss of deep tendon reflexes that are characteristic of severe hypobetalipoproteinemia. In addition, the proband had type II diabetes mellitus with nephropathy, anemia, cholelithiasis, hepatic hemangioma, bronchiectasis, and extensive calcification of major arteries including, the celiac, splenic, and renal. In summary, we have found a novel truncated apoB, apoB-38.7, in a patient with an unusual presentation of hypobetalipoproteinemia that includes diabetes mellitus and extensive arterial calcification.
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PMID:A truncated species of apolipoprotein B (B-38.7) in a patient with homozygous hypobetalipoproteinemia associated with diabetes mellitus. 971 41