ABCG5 gene

The ABCG5 gene (ABCG5 stands for ATP Binding Cassette Subfamily G Member 5) is a protein-coding gene located on chromosome 2p21. The ABCG5 protein encoded by this gene belongs to the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extracellular and intracellular membranes. ABC genes are divided into seven different subfamilies:

• ABC1
• MDR/TAP
• MRP
• ALD
• OABP
• GCN20
• White subfamily

The protein encoded by this gene is a member of the White subfamily. It functions as a semitransporter that limits intestinal absorption and promotes biliary excretion of sterols. The protein is expressed in a tissue-specific manner in the liver, colon, and intestine.

This gene is located in tandem on chromosome 2, head to head with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atherosclerosis and have been observed in patients with sitosterolemia.

ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane. They play an essential role in the selective transport of plant dietary sterols and cholesterol into and out of enterocytes, as well as in selective sterol excretion through the liver into the bile. Required for normal sterol homeostasis. The heterodimer with ABCG8 has ATPase activity.

Sitosterolemia (phytosterolemia, see also phytosterols) is a very rare, autosomal recessive inherited sterol storage disorder characterized by markedly elevated plasma levels of plant sterols. The clinical features of sitosterolemia are xanthomas, premature atherosclerosis, arthritis, and occasionally liver dysfunction and hematologic abnormalities.

1. Bain BJ et al (2016) Phytosterolemia. Am J Hematol 91:643.
2. Wang Z et al (2014) Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia. Am J Hematol 89:320-324.