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Genetics Home Reference: your guide to understanding genetic conditions
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LDLRAP1

Reviewed March 2007

What is the official name of the LDLRAP1 gene?

The official name of this gene is “low density lipoprotein receptor adaptor protein 1.”

LDLRAP1 is the gene's official symbol. The LDLRAP1 gene is also known by other names, listed below.

What is the normal function of the LDLRAP1 gene?

The LDLRAP1 gene (also known as ARH) provides instructions for making a protein that helps remove cholesterol from the bloodstream. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals. The function of the LDLRAP1 protein is particularly important in the liver, which is the organ responsible for clearing most excess cholesterol from the body.

The LDLRAP1 protein interacts with a protein called a low-density lipoprotein receptor. This type of receptor binds to particles called low-density lipoproteins (LDLs), which are the primary carriers of cholesterol in the blood. The receptors sit on the outer surface of cells, where they pick up low-density lipoproteins circulating in the bloodstream. The LDLRAP1 protein appears to play a critical role in moving these receptors, together with their attached low-density lipoproteins, from the cell surface to the interior of the cell. Once inside the cell, low-density lipoproteins 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 LDLRAP1 gene related to health conditions?

hypercholesterolemia - caused by mutations in the LDLRAP1 gene

More than 10 mutations in the LDLRAP1 gene have been shown to cause a form of inherited high cholesterol called autosomal recessive hypercholesterolemia. These mutations lead to the production of an abnormally small, nonfunctional version of the LDLRAP1 protein or prevent cells from making any of this protein. Without the LDLRAP1 protein, low-density lipoprotein receptors are unable to remove low-density lipoproteins from the bloodstream effectively. Although the receptors can still bind normally to low-density lipoproteins, these molecules are not properly transported into cells (particularly liver cells). As a result, many extra low-density lipoproteins remain in the blood.

Because low-density lipoproteins are major carriers of cholesterol in the blood, people with mutations in the LDLRAP1 gene have very high blood levels of cholesterol. 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.

Where is the LDLRAP1 gene located?

Cytogenetic Location: 1p36-p35

Molecular Location on chromosome 1: base pairs 25,543,579 to 25,591,210

The LDLRAP1 gene is located on the short (p) arm of chromosome 1 between positions 36 and 35.

The LDLRAP1 gene is located on the short (p) arm of chromosome 1 between positions 36 and 35.

More precisely, the LDLRAP1 gene is located from base pair 25,543,579 to base pair 25,591,210 on chromosome 1.

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 LDLRAP1?

You and your healthcare professional may find the following resources about LDLRAP1 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 LDLRAP1 gene or gene products?

  • ARH
  • ARH_HUMAN
  • autosomal recessive hypercholesterolemia protein
  • FHCB1
  • FHCB2
  • LDL receptor adaptor protein
  • MGC34705

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 LDLRAP1?

arteries ; autosomal ; autosomal recessive ; cell ; cholesterol ; coronary ; endocytosis ; gene ; heart attack ; inherited ; LDL ; lipoprotein ; low-density lipoproteins ; protein ; receptor ; recessive

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

References

  • Garcia CK, Wilund K, Arca M, Zuliani G, Fellin R, Maioli M, Calandra S, Bertolini S, Cossu F, Grishin N, Barnes R, Cohen JC, Hobbs HH. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science. 2001 May 18;292(5520):1394-8. Epub 2001 Apr 26. (http://www.ncbi.nlm.nih.gov/pubmed/11326085?dopt=Abstract)
  • Garuti R, Jones C, Li WP, Michaely P, Herz J, Gerard RD, Cohen JC, Hobbs HH. The modular adaptor protein autosomal recessive hypercholesterolemia (ARH) promotes low density lipoprotein receptor clustering into clathrin-coated pits. J Biol Chem. 2005 Dec 9;280(49):40996-1004. Epub 2005 Sep 22. (http://www.ncbi.nlm.nih.gov/pubmed/16179341?dopt=Abstract)
  • Michaely P, Li WP, Anderson RG, Cohen JC, Hobbs HH. The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits. J Biol Chem. 2004 Aug 6;279(32):34023-31. Epub 2004 May 27. (http://www.ncbi.nlm.nih.gov/pubmed/15166224?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/26119)
  • Sirinian MI, Belleudi F, Campagna F, Ceridono M, Garofalo T, Quagliarini F, Verna R, Calandra S, Bertolini S, Sorice M, Torrisi MR, Arca M. Adaptor protein ARH is recruited to the plasma membrane by low density lipoprotein (LDL) binding and modulates endocytosis of the LDL/LDL receptor complex in hepatocytes. J Biol Chem. 2005 Nov 18;280(46):38416-23. Epub 2005 Aug 29. (http://www.ncbi.nlm.nih.gov/pubmed/16129683?dopt=Abstract)
  • Soutar AK, Naoumova RP, Traub LM. Genetics, clinical phenotype, and molecular cell biology of autosomal recessive hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2003 Nov 1;23(11):1963-70. Epub 2003 Sep 4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12958046?dopt=Abstract)
  • Soutar AK, Naoumova RP. Autosomal recessive hypercholesterolemia. Semin Vasc Med. 2004 Aug;4(3):241-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15630633?dopt=Abstract)
  • Wilund KR, Yi M, Campagna F, Arca M, Zuliani G, Fellin R, Ho YK, Garcia JV, Hobbs HH, Cohen JC. Molecular mechanisms of autosomal recessive hypercholesterolemia. Hum Mol Genet. 2002 Nov 15;11(24):3019-30. (http://www.ncbi.nlm.nih.gov/pubmed/12417523?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: March 2007
Published: December 16, 2014