CHM

The CHM gene provides instructions for producing the Rab escort protein-1 (REP-1), which is active (expressed) throughout the body. As an escort protein, REP-1 attaches (binds) to one of a number of Rab proteins. Following a chemical modification, REP-1 then directs the Rab protein to the membrane of one of the cell's compartments (organelles). While attached to the membrane, the Rab protein plays a role in directing the movement of proteins and organelles within cells (intracellular trafficking). After the Rab protein has reached its destination, it is released by REP-1 which then attaches to another Rab protein to begin the process again.

choroideremia - caused by mutations in the CHM gene

More than a hundred mutations in the CHM gene have been found to cause choroideremia. Nearly all of these mutations lead to the production of an abnormally small, nonfunctional REP-1 protein. A lack of functional REP-1 disrupts the ability of Rab proteins to aid in intracellular trafficking. The immobility of proteins and organelles within the cell cause the cell to die prematurely.

The REP-1 protein is active (expressed) throughout the body, as is a similar protein, REP-2. It is thought that when REP-1 is nonfunctional, REP-2 can perform the protein escort duties of REP-1 in many of the body's tissues. Very little of the REP-2 protein is present in the light sensitive-tissue at the back of the eye (the retina), however, so it cannot compensate for the loss of REP-1 in this tissue. This loss of REP-1 function and subsequent misplacement of Rab proteins within the cells of the retina causes the progressive vision loss characteristic of choroideremia.