FANCE
protein-codingFA complementation group E, the group of FA core complex|FA complementation groups
Gene summary
The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group E. [provided by RefSeq, Jul 2008]
- FACE
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0010953
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0010953
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0010953
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0010953
Submitter: Natera
Inheritance Pattern: AR
Disease ID:MONDO:0019391
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0010953
Submitter: ClinGen
FANCE is one of the 23 FA or FA-like genes known to cause autosomal recessive Fanconi anemia (FA) characterized by bone marrow failure, developmental abnormalities, cancer predisposition, and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C. The first patients with FA complementation group E were reported in 1996 (PMID: 9147877, 7662964). Five homozygous variants in the FANCE gene were observed in individuals with FA complementation group E, and three of these variants were reported to segregate with disease in three small families, suggesting homozygous loss of function is the mechanism of tumorigenesis for this disorder (PMID: 11001585, 17924555). This gene-disease relationship is further supported by rescue cell culture model, protein interaction and functional alteration studies. In summary, FANCE is definitively associated with FA complementation group E. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal
Intervention: Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Oncologic
Rationale: Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended; Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FANCE variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021922.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 208 | 212 | |||
| missense | 1 | 322 | 19 | 3 | 345 | |
| nonsense | 8 | 11 | 2 | 21 | ||
| start loss | 2 | 3 | 5 | |||
| frameshift | 15 | 29 | 5 | 49 | ||
| splice donor/acceptor (+/-2bp) | 1 | 16 | 5 | 22 | ||
| Total | 24 | 59 | 341 | 227 | 3 | 654 |
Highest pathogenic variant AF is 0.000107212756
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_068741.1 | 10 | MANE Select | |
| Ensembl | ENSP00000229769.2 | 10 | MANE Select | |
| RefSeq | NP_001397805.1 | 8 | Standard | |
| Ensembl | ENSP00000497902.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fanconi anemia pathway - Homo sapiens (human)
- Fanconi Anemia Pathway
- DNA Repair
- role of brca1 brca2 and atr in cancer susceptibility
- brca1 dependent ub ligase activity
Biological Process
- interstrand cross-link repair
Molecular Function
- molecular_function
Cellular Component
- nucleus
- nucleoplasm
- Fanconi anaemia nuclear complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000229769
- Coding exons
- 10
- Length
- 14743
- Individuals with no LoFs
- 125686
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 62
- Defined
- 125748
- p
- 0.000247
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.129 | 238 | 244 | 0.977 | 0.0000136 | 3378 |
| Missense (PolyPhen) | 79 | 72.37 | 1.0916 | 1067 | ||
| Synonymous | 0.117 | 105 | 107 | 0.986 | 0.00000583 | 1158 |
| Loss of Function | 1.96 | 13 | 23.2 | 0.561 | 0.00000129 | 292 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00030 | 0.00030 | rare |
| South Asian | 0.00042 | 0.00042 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- 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}.;
- Disease
- DISEASE: Fanconi anemia complementation group E (FANCE) [MIM:600901]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269|PubMed:11001585, ECO:0000269|PubMed:17924555}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.476
Intolerance Scores
- LoFtool
- 0.818
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 32.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.624
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |