The FANCC gene provides instructions for making a protein that is involved in a cell process known as the Fanconi anemia (FA) pathway. The FA pathway is turned on (activated) when the process of making new copies of DNA, called DNA replication, is blocked due to DNA damage. The FA pathway is particularly responsive to a certain type of DNA damage known as interstrand cross-links (ICLs). ICLs occur when two DNA building blocks (nucleotides) on opposite strands of DNA are abnormally attached or linked together, which stops the process of DNA replication. ICLs can be caused by a buildup of toxic substances produced in the body or by treatment with certain cancer therapy drugs.
The FANCC protein is one of a group of proteins known as the FA core complex. The FA core complex is composed of eight FA proteins (including FANCC) and two proteins called Fanconi anemia-associated proteins (FAAPs). This complex activates two proteins, called FANCD2 and FANCI, by attaching a single molecule called ubiquitin to each of them (a process called monoubiquitination). The activation of these two proteins, which attach (bind) together to form the ID protein complex, attract DNA repair proteins to the area of DNA damage so the error can be corrected and DNA replication can continue.
Health Conditions Related to Genetic Changes
At least 50 mutations in the FANCC gene have been found to cause Fanconi anemia, a disorder characterized by a decrease in bone marrow function, an increased cancer risk, and physical abnormalities. Mutations in the FANCC gene are responsible for about 15 percent of all cases of Fanconi anemia. A particular mutation in the FANCC gene has been found in people with Central and Eastern European (Ashkenazi) Jewish background. This mutation (written as 456+4A>T) disrupts the way the gene's instructions are used to make the protein. Individuals with this mutation tend to have more severe signs and symptoms than people who have some of the other mutations in the FANCC gene.
Most mutations in the FANCC gene that cause Fanconi anemia lead to absent or reduced protein function. As a result, the FA core complex cannot function and the entire FA pathway is disrupted. Due to the disrupted pathway, DNA damage is not repaired efficiently and ICLs build up over time. The ICLs stall DNA replication, ultimately resulting in either abnormal cell death due to an inability make new DNA molecules or uncontrolled cell growth due to a lack of DNA repair processes. Cells that divide quickly, such as bone marrow cells and cells of the developing fetus, are particularly affected. The death of these cells results in the decrease in blood cells and the physical abnormalities characteristic of Fanconi anemia. When the buildup of errors in DNA leads to uncontrolled cell growth, affected individuals can develop leukemia or other cancers.More About This Health Condition
Other Names for This Gene
- Fanconi anemia complementation group C
- Fanconi anemia, complementation group C
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- de Winter JP, Joenje H. The genetic and molecular basis of Fanconi anemia. Mutat Res. 2009 Jul 31;668(1-2):11-9. doi: 10.1016/j.mrfmmm.2008.11.004. Epub 2008 Nov 14. Review. Citation on PubMed
- Deakyne JS, Mazin AV. Fanconi anemia: at the crossroads of DNA repair. Biochemistry (Mosc). 2011 Jan;76(1):36-48. Review. Citation on PubMed
- Kee Y, D'Andrea AD. Expanded roles of the Fanconi anemia pathway in preserving genomic stability. Genes Dev. 2010 Aug 15;24(16):1680-94. doi: 10.1101/gad.1955310. Review. Citation on PubMed or Free article on PubMed Central
- Kitao H, Takata M. Fanconi anemia: a disorder defective in the DNA damage response. Int J Hematol. 2011 Apr;93(4):417-424. doi: 10.1007/s12185-011-0777-z. Epub 2011 Feb 18. Review. Citation on PubMed
- Mathew CG. Fanconi anaemia genes and susceptibility to cancer. Oncogene. 2006 Sep 25;25(43):5875-84. Review. Citation on PubMed
- Taniguchi T, D'Andrea AD. Molecular pathogenesis of Fanconi anemia: recent progress. Blood. 2006 Jun 1;107(11):4223-33. Epub 2006 Feb 21. Review. Citation on PubMed