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Genetics Home Reference: your guide to understanding genetic conditions
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APOB

Reviewed August 2012

What is the official name of the APOB gene?

The official name of this gene is “apolipoprotein B.”

APOB is the gene's official symbol. The APOB gene is also known by other names, listed below.

What is the normal function of the APOB gene?

The APOB gene provides instructions for making two versions of the apolipoprotein B protein, a short version called apolipoprotein B-48 and a longer version known as apolipoprotein B-100. Both of these proteins are components of lipoproteins, which are particles that carry fats and fat-like substances (such as cholesterol) in the blood.

Apolipoprotein B-48 is produced in the intestine, where it is a building block of a type of lipoprotein called a chylomicron. As food is digested after a meal, chylomicrons are formed to carry fat and cholesterol from the intestine into the bloodstream. Chylomicrons are also necessary for the absorption of certain fat-soluble vitamins such as vitamin E and vitamin A.

Apolipoprotein B-100, which is produced in the liver, is a component of several other types of lipoproteins. Specifically, this protein is a building block of very low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs). These related molecules all transport fats and cholesterol in the bloodstream.

Low-density lipoproteins are the primary carriers of cholesterol in the blood. Apolipoprotein B-100 allows these particles to attach to specific receptors on the surface of cells, particularly in the liver. The receptors transport low-density lipoproteins into the cell, where they are broken down to release cholesterol. The cholesterol is then used by the cell, stored, or removed from the body.

How are changes in the APOB gene related to health conditions?

familial hypobetalipoproteinemia - caused by mutations in the APOB gene

More than 90 mutations in the APOB gene have been found to cause familial hypobetalipoproteinemia (FHBL), a disorder that impairs the body's ability to absorb and transport fat. Most APOB gene mutations that cause FHBL lead to the production of apolipoprotein B that is abnormally short.

The severity of the condition largely depends on the length of the abnormal apolipoprotein B. Some mutations in the APOB gene lead to the production of a protein that is shorter than apolipoprotein B-100, but longer than apolipoprotein B-48. In these cases, normal apolipoprotein B-48 is still made in the intestine. The normal-length apolipoprotein B-48 can form chylomicrons normally, but the abnormally short apolipoprotein B-100 produced in the liver is less able to produce lipoproteins. Other mutations result in a protein that is shorter than both apolipoprotein B-48 and apolipoprotein B-100. In these cases, no normal-length apolipoprotein B protein is produced. The severely shortened protein is not able to form lipoproteins in the liver or the intestine. Generally, if both versions of the protein are shorter than apolipoprotein B-48, the signs and symptoms are more severe than if some normal length apolipoprotein B-48 is produced. All of these protein changes lead to a reduction of functional apolipoprotein B. As a result, the transportation of dietary fats and cholesterol is decreased or absent. A decrease in fat transport reduces the body's ability to absorb fats and fat-soluble vitamins from the diet, leading to the signs and symptoms of FHBL.

hypercholesterolemia - caused by mutations in the APOB gene

At least five mutations in the APOB gene are known to cause a form of inherited hypercholesterolemia called familial defective apolipoprotein B-100 (FDB). This condition is characterized by very high levels of cholesterol in the blood and an increased risk of developing heart disease. Each mutation that causes this condition changes a single protein building block (amino acid) in a critical region of apolipoprotein B-100. The altered protein prevents low-density lipoproteins from effectively binding to their receptors on the surface of cells. As a result, fewer low-density lipoproteins are removed from the blood, and cholesterol levels are much higher than normal. As the excess cholesterol circulates through the bloodstream, it is deposited abnormally in tissues such as the skin, tendons, and arteries that supply blood to the heart (coronary arteries). A buildup of cholesterol in the walls of coronary arteries greatly increases a person's risk of having a heart attack.

other disorders - associated with the APOB gene

Researchers are studying other variations (polymorphisms) in the APOB gene that may influence heart disease risk in people without inherited cholesterol disorders. Some studies have found that certain polymorphisms are associated with higher levels of low-density lipoproteins in the blood and an increased chance of developing or dying of heart disease. Other studies, however, have not shown such an association. It is clear that a large number of genetic and lifestyle factors, many of which remain unknown, determine the risk of developing this complex condition.

Where is the APOB gene located?

Cytogenetic Location: 2p24-p23

Molecular Location on chromosome 2: base pairs 21,001,428 to 21,044,072

The APOB gene is located on the short (p) arm of chromosome 2 between positions 24 and 23.

The APOB gene is located on the short (p) arm of chromosome 2 between positions 24 and 23.

More precisely, the APOB gene is located from base pair 21,001,428 to base pair 21,044,072 on chromosome 2.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about APOB?

You and your healthcare professional may find the following resources about APOB helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the APOB gene or gene products?

  • apoB-48
  • apoB-100
  • APOB_HUMAN
  • apolipoprotein B (including Ag(x) antigen)

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding APOB?

amino acid ; apolipoprotein ; arteries ; cell ; cholesterol ; chylomicrons ; coronary ; critical region ; familial ; gene ; heart attack ; inherited ; intestine ; lipoprotein ; low-density lipoproteins ; mutation ; protein ; soluble ; vitamins

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Benn M, Nordestgaard BG, Jensen JS, Grande P, Sillesen H, Tybjaerg-Hansen A. Polymorphism in APOB associated with increased low-density lipoprotein levels in both genders in the general population. J Clin Endocrinol Metab. 2005 Oct;90(10):5797-803. Epub 2005 Jul 19. (http://www.ncbi.nlm.nih.gov/pubmed/16030169?dopt=Abstract)
  • Fouchier SW, Sankatsing RR, Peter J, Castillo S, Pocovi M, Alonso R, Kastelein JJ, Defesche JC. High frequency of APOB gene mutations causing familial hypobetalipoproteinaemia in patients of Dutch and Spanish descent. J Med Genet. 2005 Apr;42(4):e23. (http://www.ncbi.nlm.nih.gov/pubmed/15805152?dopt=Abstract)
  • Hooper AJ, van Bockxmeer FM, Burnett JR. Monogenic hypocholesterolaemic lipid disorders and apolipoprotein B metabolism. Crit Rev Clin Lab Sci. 2005;42(5-6):515-45. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16390683?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/338)
  • Olofsson SO, Borèn J. Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis. J Intern Med. 2005 Nov;258(5):395-410. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16238675?dopt=Abstract)
  • Schonfeld G, Lin X, Yue P. Familial hypobetalipoproteinemia: genetics and metabolism. Cell Mol Life Sci. 2005 Jun;62(12):1372-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15818469?dopt=Abstract)
  • Soufi M, Sattler AM, Maerz W, Starke A, Herzum M, Maisch B, Schaefer JR. A new but frequent mutation of apoB-100-apoB His3543Tyr. Atherosclerosis. 2004 May;174(1):11-6. (http://www.ncbi.nlm.nih.gov/pubmed/15135245?dopt=Abstract)
  • Tarugi P, Averna M, Di Leo E, Cefalù AB, Noto D, Magnolo L, Cattin L, Bertolini S, Calandra S. Molecular diagnosis of hypobetalipoproteinemia: an ENID review. Atherosclerosis. 2007 Dec;195(2):e19-27. Epub 2007 Jun 14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17570373?dopt=Abstract)
  • Tarugi P, Averna M. Hypobetalipoproteinemia: genetics, biochemistry, and clinical spectrum. Adv Clin Chem. 2011;54:81-107. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21874758?dopt=Abstract)
  • van Aalst-Cohen ES, Jansen AC, de Jongh S, de Sauvage Nolting PR, Kastelein JJ. Clinical, diagnostic, and therapeutic aspects of familial hypercholesterolemia. Semin Vasc Med. 2004 Feb;4(1):31-41. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15199431?dopt=Abstract)
  • Vrablík M, Ceska R, Horínek A. Major apolipoprotein B-100 mutations in lipoprotein metabolism and atherosclerosis. Physiol Res. 2001;50(4):337-43. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11551138?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2012
Published: December 22, 2014