Alt. symbols: FACA | FANCH | FAA | FA-H | FAH

Approved name: FA complementation group A
Alt. names: Fanconi anemia complementation group A

Location: 16q24.3: 89726683 - 89816977 (-)
Gene type: protein_coding, 45 transcripts.

Scores: LoFtool: 0.082100 | pLI: 0.00000000 | LOEUF: 1.366

HGNC: 3582

NCBI: 2175, RefSeq: NG_011706.1

Ensembl: ENSG00000187741.16

LRG_495 | Status: public

OMIM: 607139

Expression | ProteinAtlas

FANCA is involved in the cellular process known as the Fanconi anemia (FA) pathway. The FA pathway is activated whenever the DNA replication is blocked due to DNA damage. The FA pathway is particularly responsive to a certain type of DNA damage known as inter-strand cross-links (ICLs). ICLs occur when two DNA nucleotides on opposite strands are abnormally linked together. ICLs can be caused by a buildup of toxic substances produced in the body or by treatment with certain cancer therapy drugs. The FANCA protein is one of the 8 proteins that form the FA core complex. The FA core complex, together with two additional proteins called Fanconi anemia-associated proteins (FAAPs), activates two proteins, called FANCD2 and FANCI, by a monoubiquitination process. The activation of FANCD2 and FANCI, which 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.

Biallelic mutations in FANCA cause Fanconi anemia, complementation group A [MIM:227650]. This is a disorder characterized by a decrease in bone marrow function, an increased risk of cancer, and physical abnormalities. Mutations in the FANCA gene are responsible for 60 to 70 percent of all cases of Fanconi anemia. More than 450 pathogenic mutations in FANCA have been described. These mutations include single-nucleotide variations (SNV) and small insertions or deletions (indels). Some mutations al low production of a FANCA protein that has some residual function; while others prevent the production of any protein. Mutations that prevent all protein production usually lead to a shortage of blood cells at an earlier age and increase the risk of developing leukemia, as compared to mutations that allow for some FANCA protein production. Mutations in the FANCA gene lead to a non-functional FA core complex, which disrupts the entire FA pathway. As a result, 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. [Load More]