Alt. symbols: KIAA1794 | FLJ10719

Approved name: FA complementation group I
Alt. names: KIAA1794, Fanconi anemia complementation group I

Location: 15q26.1: 89243945 - 89317261 (+)
Gene type: protein_coding, 27 transcripts.

Scores: LoFtool: 0.265000 | pLI: 0.00000000 | LOEUF: 1.024

HGNC: 25568

NCBI: 55215, RefSeq: NG_011736.1

Ensembl: ENSG00000140525.20

LRG_500 | Status: public

OMIM: 611360

Expression | ProteinAtlas

FANCI plays an essential role in DNA double-strand break (DSB) repair via homologous recombination (HR), as well as in interstrand DNA cross-link (ICL) repair by promoting FANCL-mediated FANCD2 monoubiquitination and recruitment to DNA repair sites. As such, it participates in S phase and G2 phase checkpoint activation upon DNA damage and is required for maintaining genome stability.

Biallelic homozygous or compound heterozygous mutations in FANCI are associated with Fanconi anemia (FA) complementation group I [MIM:609053]. Missense, nonsense, frameshift, and splice site mutations in FANCI have all been described. FA is a multi-system syndrome featuring a broad spectrum of congenital anomalies in addition to bone marrow failure and increased risk for malignancy. Physical abnormalities are present in ~75% and include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, while the incidence of acute myeloid leukemia (AML) is 13% by age 50. Moreover, due to the involvement of FA genes in key DNA repair pathways, these individuals are also at increased risk for solid tumors – particularly of the head and neck, skin, gastrointestinal tract, and genitourinary tract; for some FA genes (i.e. BRCA1, PALB2), this may occur with even 1 heterozygous mutation, but this has not been definitively demonstrated for FANCI carriers. Of note, while digenic causes of FA have been proposed (PMID: 33224012; Murad et al. AJMB 2019), those involving FANCI mutations have thus far not been described. [Load More]