The human ATP-binding cassette (ABC) transporter superfamily

Area of Science:

• Genomics
• Molecular Biology
• Human Genetics

Background:

• ATP-binding cassette (ABC) transporters are membrane proteins involved in substrate transport.
• Mutations in ABC genes are associated with 21 Mendelian inherited human disorders, including cystic fibrosis and transport defects.
• Understanding ABC transporter function is vital for studying these diseases.

Purpose of the Study:

• To compile data and create tools for studying human ABC transporter function.
• To analyze ABC gene conservation and mutation phenotypes.
• To investigate the role of ABC genes in human diseases and cancer.

Main Methods:

• Data compilation from genomics databases.
• Analysis of ABC gene conservation across species and populations.
• Surveying phenotypes of ABC gene mutations in mouse models.
• Genome-wide association studies and whole-exome sequencing of tumors.

Main Results:

• Mouse models with ABC gene disruptions often mimic human disease phenotypes.
• Several ABCA family genes, with unknown human function, show cholesterol-related phenotypes in mice.
• ABC gene mutations are not common in most cancers, but specific genes are overexpressed in certain tumor types.
• Many human ABC genes are essential, exhibiting low genetic diversity, while others show higher diversity.

Conclusions:

• Mouse models are valuable tools for studying human ABC transporter function and related diseases.
• Genetic analyses reveal conserved functions and suggest new research avenues for ABC transporters.
• ABC genes play essential roles in human health, with varying levels of genetic diversity and implications for disease and cancer.