HGNC Approved Gene Symbol: FANCE
Cytogenetic location: 6p21.31 Genomic coordinates (GRCh38) : 6:35,452,338-35,467,102 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6p21.31 | Fanconi anemia, complementation group E | 600901 | Autosomal recessive | 3 |
By complementation cloning, de Winter et al. (2000) identified the FANCE gene. The deduced 536-amino acid protein contains 2 potential nuclear localization signals.
The FANCE gene contains 10 exons (de Winter et al., 2000).
The FANCE gene maps to chromosome 6p22-p21 (Waisfisz et al., 1999; de Winter et al., 2000).
The Fanconi anemia (FA) nuclear complex (composed of the FA proteins A, C, G and F) is essential for protection against chromosome breakage. It activates the downstream protein FANCD2 (see 227646) by monoubiquitylation; this then forges an association with the BRCA1 (113705) protein at sites of DNA damage. Pace et al. (2002) showed that the FANCE protein is part of this nuclear complex, binding both FANCC (613899) and FANCD2. Indeed, FANCE is required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2. Disease-associated FANCC mutants do not bind to FANCE, cannot accumulate in the nucleus, and are unable to prevent chromosome breakage.
By coimmunoprecipitation of HeLa cell nuclear extracts, Meetei et al. (2003) identified 3 distinct multiprotein complexes associated with BLM (RECQL3; 604610). One of the complexes, designated BRAFT, contained the Fanconi anemia core complementation group proteins FANCA (607139), FANCG (602956), FANCC, FANCE, and FANCF (603467), as well as topoisomerase III-alpha (TOP3A; 601243) and replication protein A (RPA; see 179835). BLM complexes isolated from an FA cell line had a lower molecular mass, likely due to loss of FANCA and other FA components. BLM- and FANCA-associated complexes had DNA unwinding activity, and BLM was required for this activity.
In 3 patients with Fanconi anemia, 2 from Turkey and 1 from Bangladesh, de Winter et al. (2000) identified homozygous mutations in the FANCE gene (613976.0001-613976.0003).
In a Turkish patient with group E Fanconi anemia (FANCE; 600901) reported by Joenje et al. (1997), de Winter et al. (2000) identified homozygosity for a 355C-T transition in the FANCE gene, leading to a gln119-to-ter (Q119X) nonsense change in the protein. The parents and an unaffected brother were heterozygous for the mutation.
In a patient in Bangladesh with group E Fanconi anemia (FANCE; 600901), de Winter et al. (2000) identified homozygosity for a 421C-T transition in exon 2 of the FANCE gene, resulting in an arg141-to-ter (R141X) nonsense change in the protein. The parents were heterozygous for the mutation.
In a Turkish patient (EUFA130) with group E Fanconi anemia (FANCE; 600901) reported by Waisfisz et al. (1999), the first FANCE patient identified by Joenje et al. (1995), de Winter et al. (2000) identified homozygosity for a G-to-A change at position -8 in intron 5 of the FANCE gene, an alternative splice acceptor site. Sequence analysis indicated that this mutation results in false splicing and incorporation of 6 nucleotides from intron 5, including an in-frame stop codon.
de Winter, J. P., Leveille, F., van Berkel, C. G. M., Rooimans, M. A., van der Weel, L., Steltenpool, J., Demuth, I., Morgan, N. V., Alon, N., Bosnoyan-Collins, L., Lightfoot, J., Leegwater, P. A., Waisfisz, Q., Komatsu, K., Arwert, F., Pronk, J. C., Mathew, C. G., Digweed, M., Buchwald, M., Joenje, H. Isolation of a cDNA representing the Fanconi anemia complementation group E gene. Am. J. Hum. Genet. 67: 1306-1308, 2000. Note: Erratum: Am. J. Hum. Genet. 67: 1365 only, 2000. [PubMed: 11001585] [Full Text: https://doi.org/10.1016/S0002-9297(07)62959-0]
Joenje, H., Lo Ten Foe, J. R., Oostra, A. B., van Berkel, C. G. M., Rooimans, M. A., Schroeder-Kurth, T., Wegner, R.-D., Gille, J. J. P., Buchwald, M., Arwert, F. Classification of Fanconi anemia patients by complementation analysis: evidence for a fifth genetic subtype. Blood 86: 2156-2160, 1995. [PubMed: 7662964]
Joenje, H., Oostra, A. B., Wijker, M., di Summa, F. M., van Berkel, C. G. M., Rooimans, M. A., Ebell, W., van Weel, M., Pronk, J. C., Buchwald, M., Arwert, F. Evidence for at least eight Fanconi anemia genes. Am. J. Hum. Genet. 61: 940-944, 1997. [PubMed: 9382107] [Full Text: https://doi.org/10.1086/514881]
Meetei, A. R., Sechi, S., Wallisch, M., Yang, D., Young, M. K., Joenje, H., Hoatlin, M. E., Wang, W. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome. Molec. Cell. Biol. 23: 3417-3426, 2003. [PubMed: 12724401] [Full Text: https://doi.org/10.1128/MCB.23.10.3417-3426.2003]
Pace, P., Johnson, M., Tan, W. M., Mosedale, G., Sng, C., Hoatlin, M., de Winter, J., Joenje, H., Gergely, F., Patel, K. J. FANCE: the link between Fanconi anaemia complex assembly and activity. EMBO J. 21: 3414-3423, 2002. [PubMed: 12093742] [Full Text: https://doi.org/10.1093/emboj/cdf355]
Waisfisz, Q., Saar, K., Morgan, N. V., Altay, C., Leegwater, P. A., de Winter, J. P., Komatsu, K., Evans, G. R., Wegner, R.-D., Reis, A., Joenje, H., Arwert, F., Mathew, C. G., Pronk, J. C., Digweed, M. The Fanconi anemia group E gene, FANCE, maps to chromosome 6p. Am. J. Hum. Genet. 64: 1400-1405, 1999. [PubMed: 10205272] [Full Text: https://doi.org/10.1086/302385]