2.1 Dubin-Johnson syndrome

More than 40 mutations in the ABCC2 gene have been found to cause Dubin-Johnson syndrome. This condition is characterized by jaundice, which is a yellowing of the skin and whites of the eyes, that typically appears during adolescence or early adulthood. Most of the mutations change single protein building blocks (amino acids) in MRP2. A common mutation in Iranian Jews living in Israel who have Dubin-Johnson syndrome replaces the amino acid isoleucine with the amino acid phenylalanine at position 1173 in MRP2 (written as Ile1173Phe or I1173F). Another mutation that is seen more frequently in those affected in Israel's Moroccan-Jewish population replaces the amino acid arginine with the amino acid histidine at position 1150 in MRP2 (written as Arg1150His or R1150H).

ABCC2 gene mutations that cause Dubin-Johnson syndrome have a variety of effects on the structure and function of MRP2. Mutations may alter how the protein is made, impair transport of the protein to the cell surface, or cause the protein to be broken down too quickly. All of these mutations result in a decrease or absence of MRP2 activity at the cell membrane. As a result, the body's ability to release (excrete) bilirubin is impaired. A buildup of bilirubin causes jaundice in people with Dubin-Johnson syndrome. The accumulation of other substances that usually get transported out of tissues by the MRP2 protein can cause additional signs and symptoms in people with Dubin-Johnson syndrome, but these features usually do not cause health problems.