FANCE |
- 30
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- FANCE (HGNC:3586) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- FA complementation group E
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- FACE
- Alias symbols
- FAE
- %HI
- 62.05(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 0.89(Read more about gnomAD LOEUF score)
- Cytoband
- 6p21.31
- Genomic Coordinates
-
GRCh37/hg19: chr6:35420115-35434879 NCBI Ensembl UCSC GRCh38/hg38: chr6:35452338-35467102 NCBI Ensembl UCSC - MANE Select Transcript
- NM_021922.3 ENST00000229769.3 (Read more about MANE Select)
- Function
- As part of the Fanconi anemia (FA) complex functions in DNA cross-links repair. Required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2. {ECO:0000269|PubMed:12093742, ECO:0000269|PubMed:17296736}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-12599
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Gene Associated with Autosomal Recessive Phenotype
(30)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
06/12/2020
Haploinsufficiency (HI) Score Details
HI Score:
30
HI Evidence Strength:
Gene Associated with Autosomal Recessive Phenotype
(Disclaimer)
HI Disease:
- Fanconi anemia complementation group E Monarch
HI Evidence Comments:
FANCE is associated with an autosomal recessive Fanconi anemia phenotype and is located on chromosome 16p13.3. Clinical manifestations of Fanconi anemia are diverse and variable. FANCE is a morbid OMIM disease gene. The following captures well established studies describing patients with variants in this gene
1. PMID 11001585: de Winter et al., 2000 (AJHG) performed mutation screening, 3 patients with Fanconi anemia. They were of Turkish and Bangladeshi ethnicity and were identified to harbor separate homozygous mutations in FANCE (Table 1). Two of these mutations were nonsense changes and one was a splice site change creating an inframe stop codon. Parents and unaffected sibling were found to be heterozygous carriers for the nonsense mutations. No overt phenotype was reported in the carriers.
2. PMID 17924555: Ameziane et al, 2008 in Human Mutation performed mutation screening by DHPLC followed by Sanger sequencing. The authors report on two separate homozygous alterations resulting in nonsense variants in FANCE from Fanconi anemia patients. A third alteration was found on one allele and mutation on remaining allele was not detected (Table 1).
3. PMID 31586946: Bogliolo et al., 2020 (Journal of Med Gen) report on one of the largest series of undefined FA patients analyzed by exome sequencing. A novel heterozygous frameshift variant was detected in FANCE (c.929dupC) in one individual. A putative second mutation was not detected in this individual (see Table 1).
Taken together, these studies suggest that there is no increased risk reported to develop cancer or another type of disease among Fanconi anemia heterozygotes or mutation carriers (PMID: 22778927).
Of note, no deletions involving FANCE or focal deletions of this gene longer than 500bp reported in ClinVar. No deletions reported in DECIPHER. One deletion, 78 kb, involving FANCE and 5 adjacent genes reported in DGV (nsv602910; Cooper et al. 2011) among individuals in the healthy population. In gnomAD, the pLI score is reported as 0 (62.04 in DECIPHER) with several loss of function (LoF) variants reported across the gene (no homozygotes reported for LoF); this data does not support a model for haploinsufficiency.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No focal duplications of FANCE reported in ClinVar or DGV (accessed June 2020). In gnomAD structural variants dataset (v2.1, accessed June 2020), partial duplications involving only a portion of FANCE have been recorded in the healthy population.
Genomic View
Select assembly:
(NC_000006.11)
(NC_000006.12)