FANCL: Fanconi Anemia Complementation Group L (E3 Ubiquitin Ligase)
Key regulator of the Fanconi anemia pathway and DNA interstrand crosslink repair
Gene Information Card
| Symbol | FANCL |
|---|---|
| Full Name | Fanconi anemia complementation group L |
| Gene Type | Protein coding |
| Chromosomal Location | 2p16.1 |
| NCBI Gene ID | 55120 ncbi.nlm.nih.gov/gene/55120 |
| Ensembl ID | ENSG00000115392 |
| UniProt ID | Q9NW38 |
| OMIM ID | 608111 |
| HGNC ID | 20748 |
| Aliases | FAAP43, PHF9, POG |
Description
FANCL encodes a protein that functions as the catalytic E3 ubiquitin ligase subunit of the Fanconi anemia (FA) core complex. This complex is essential for the monoubiquitination of FANCD2 and FANCI, a key step in the DNA interstrand crosslink (ICL) repair pathway. FANCL is required for genome stability and hematopoietic stem cell maintenance. Loss-of-function mutations cause Fanconi anemia complementation group L, characterized by bone marrow failure, congenital abnormalities, and cancer predisposition.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fanconi anemia complementation group L | Loss-of-function mutations in FANCL impair FANCD2 monoubiquitination, disrupting ICL repair and leading to genomic instability | OMIM #608111; ClinVar |
| Acute myeloid leukemia (AML) | Biallelic FANCL mutations predispose to AML due to defective DNA repair and clonal hematopoiesis | COSMIC; NCBI Gene |
| Breast cancer | Heterozygous FANCL variants may increase risk of breast cancer via haploinsufficiency in DNA repair | ClinVar; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Testis | 18.3 | Medium |
| Lymph node | 9.8 | Low |
| Brain | 6.2 | Low |
| Liver | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.4 | Embryonic kidney; moderate expression |
| HeLa | 11.2 | Cervical carcinoma; moderate expression |
| K562 | 8.9 | Leukemia; low expression |
| HepG2 | 7.6 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1091C>T (p.Pro364Leu) | Missense | Rare | Loss of E3 ligase activity; associated with Fanconi anemia |
| c.853_854del (p.Glu285fs) | Frameshift | Rare | Loss of function; truncation of protein |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of translation; Fanconi anemia |
Mutation functional classification
Loss of Function (LOF)
Most FANCL mutations are loss-of-function, leading to defective FANCD2 monoubiquitination and ICL repair.
Gain of Function (GOF)
No gain-of-function mutations reported in FANCL.
Dominant Negative (DN)
No dominant-negative mutations described; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Fanconi anemia pathway (KEGG hsa03460)
• DNA interstrand crosslink repair (Reactome R-HSA-5696399)
• Ubiquitin-mediated proteolysis (KEGG hsa04120)
Protein Summary
FANCL is a 375-amino acid protein containing a RING finger domain that confers E3 ubiquitin ligase activity. It is the catalytic subunit of the FA core complex, which monoubiquitinates FANCD2 and FANCI at lysine residues. This modification recruits downstream repair factors to sites of DNA damage. FANCL also contains a PHD finger domain that may mediate protein-protein interactions. The protein is predominantly nuclear and expressed in tissues with high proliferative capacity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FANCL Knockout HEK293 Cell Line | EDJ-KQ13448 | Human | 55120 | Details Get a Quote |
| FANCL Knockout A-549 Cell Line | EDJ-KQ43003 | Human | 55120 | Details Get a Quote |
| FANCL Knockout HCT 116 Cell Line | EDJ-KQ43004 | Human | 55120 | Details Get a Quote |
| FANCL Knockout HeLa Cell Line | EDJ-KQ43005 | Human | 55120 | Details Get a Quote |
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