DJS is caused by changes (mutations) in the ABCC2 gene. This gene codes for a protein called multidrug resistance protein 2 (MRP2). This protein moves substances out of the cell and is found mainly in the liver but is also present in the kidneys, the intestine, and the placenta. The normal functioning protein works to secrete bilirubin into the bile, which is then transported to the gallbladder where it is stored. When the gall bladder is contracted during digestion, the bile is secreted into the intestine and then passes into the feces. Several different mutations have been identified that alter the function of the carrier protein. This process requires energy in the form of ATP and a common site of mutation is the part of the carrier that coordinates this aspect of the process.
Pregnancy or use of oral contraceptives may cause the disease to become apparent in women when no symptoms appeared previously.
DJS is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.