LDLRAP1 gene

low density lipoprotein receptor adaptor protein 1

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 attaches (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 LDLs circulating in the bloodstream. The LDLRAP1 protein appears to play a critical role in moving these receptors, together with their attached LDLs, from the cell surface to the interior of the cell. Once inside the cell, LDLs are broken down to release cholesterol. The cholesterol is then used by the cell, stored, or removed from the body.

More than 20 mutations in the LDLRAP1 gene have been shown to cause a form of familial hypercholesterolemia 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 LDLs from the bloodstream effectively. Although the receptors can still bind normally to LDLs, these molecules are not properly transported into cells (particularly liver cells). As a result, many extra LDLs remain in the blood.

Because LDLs 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.

Cytogenetic Location: 1p36.11, which is the short (p) arm of chromosome 1 at position 36.11

Molecular Location: base pairs 25,543,588 to 25,590,400 on chromosome 1 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 1p36.11, which is the short (p) arm of chromosome 1 at position 36.11
  • ARH
  • autosomal recessive hypercholesterolemia protein
  • FHCB1
  • FHCB2
  • LDL receptor adaptor protein
  • MGC34705