Affinage

FANCL

E3 ubiquitin-protein ligase FANCL · UniProt Q9NW38

Length
375 aa
Mass
42.9 kDa
Annotated
2026-06-09
51 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FANCL is the catalytic RING-type E3 ubiquitin ligase subunit of the Fanconi anemia core complex, partnering with the E2 enzyme UBE2T to monoubiquitinate FANCD2 and FANCI and thereby drive homologous-recombination repair of DNA interstrand crosslinks (PMID:19111657, PMID:17352736). Its crystal structure resolves a tripartite architecture in which the central DRWD/URD domain binds the FANCD2/FANCI substrate dimer while the C-terminal RING domain mediates E2 recruitment, and an extensive electrostatic/hydrophobic RING–UBE2T interface confers selective recruitment of UBE2T over other E2 enzymes (PMID:20154706, PMID:24389026). Reconstitution shows FANCL and UBE2T are sufficient to monoubiquitinate FANCD2, with FANCI both stimulating the reaction and restricting modification to the correct lysine (K561 on FANCD2; K523 on FANCI) (PMID:19111657, PMID:19589784); the N-terminal ELF domain additionally binds free ubiquitin via the Ile44 patch to promote efficient damage-induced FANCD2 monoubiquitination in cells (PMID:26149689). FANCL-dependent monoubiquitination is required for FANCD2 chromatin and nuclear-matrix association and for HR repair of induced chromosomal breaks, an epistatic relationship conserved from Drosophila to vertebrates (PMID:14712086, PMID:17352736, PMID:16860002). A catalytic-cysteine knock-in mouse establishes that loss of RING E3 ligase activity alone reproduces all major Fanconi anemia phenotypes, and FANCL variants causing protein destabilization or cytoplasmic mislocalization underlie premature ovarian insufficiency (PMID:41259745, PMID:32048394). Beyond DNA repair, FANCL extends K11-linked non-proteolytic ubiquitin chains on β-catenin to enhance Wnt target transcription in hematopoietic stem/progenitor cells (PMID:22653977), supports Parkin-mediated mitophagy through a ubiquitin ligase-independent mitochondrial function (PMID:35644338), and is required for primordial germ cell proliferation and oocyte survival through meiosis (PMID:12417526, PMID:20661450).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2002 Medium

    Before its biochemical role was known, the FANCL ortholog was shown to be developmentally essential, establishing a germ-cell function distinct from any later-defined enzymatic activity.

    Evidence Targeted Pog knockout mice with primordial germ cell counting across developmental time points

    PMID:12417526

    Open questions at the time
    • Molecular mechanism of the proliferation defect not defined
    • No link to ubiquitination established at this stage
  2. 2003 Medium

    Identification of GGN1/GGN3 as POG interactors that relocalize the protein addressed where and with what partners FANCL acts during gametogenesis.

    Evidence Yeast two-hybrid and HeLa co-expression with localization readout, plus Pog-knockout spermatogenesis analysis

    PMID:12574169

    Open questions at the time
    • Functional consequence of GGN binding for ligase activity unknown
    • Interactions not validated in germ cells in vivo
  3. 2004 Medium

    The question of which factor monoubiquitinates FANCD2 was narrowed to FANCL, linking its activity to FANCD2 chromatin localization.

    Evidence Subcellular fractionation of FANCL- vs BRCA1-mutant cells plus evolutionary co-existence analysis

    PMID:14712086

    Open questions at the time
    • No reconstitution showing direct ligase activity
    • E2 partner not identified
  4. 2006 Medium

    Domain dissection separated FANCL's structural role in the core complex from its catalytic role, and Drosophila epistasis placed FANCL upstream of FANCD2 in a linear repair pathway.

    Evidence Domain-deletion/point mutants in FANCL-deficient cells with co-IP, in vitro ubiquitination, MMC complementation; RNAi epistasis in Drosophila

    PMID:16474167 PMID:16860002

    Open questions at the time
    • E2 enzyme identity unresolved
    • Atomic basis of substrate vs core-complex binding not defined
  5. 2007 High

    Genetic and physical evidence established FANCL as required for FANCD2 monoubiquitination, focus formation, and HR repair, quantitatively coupling its activity to recombination outcome.

    Evidence Yeast two-hybrid, co-IP, FANCL disruption in DT40 cells, I-SceI HR assay, focus formation

    PMID:17352736

    Open questions at the time
    • Reconstitution with defined components still lacking
    • Site specificity of modification unaddressed
  6. 2008 High

    Minimal reconstitution proved FANCL plus UBE2T are sufficient to monoubiquitinate FANCD2, and that FANCI confers site specificity — defining the core catalytic logic of the FA pathway.

    Evidence In vitro reconstitution with purified UBE2T and FANCL; FANCI addition to assess K561 site restriction

    PMID:19111657

    Open questions at the time
    • Structural basis of E2 and substrate selection not yet resolved
    • Mechanism of FANCI-driven site restriction not defined
  7. 2009 High

    FANCI was shown to be a direct second substrate of the UBE2T–FANCL pair, broadening the enzyme's targets within the ID complex.

    Evidence In vitro ubiquitination with purified UBE2T/FANCL on FANCI K523; branched DNA binding assay

    PMID:19589784

    Open questions at the time
    • Order/coordination of FANCD2 vs FANCI modification in vivo unclear
    • Role of DNA binding in substrate positioning not directly tested
  8. 2010 High

    The crystal structure assigned distinct molecular functions to FANCL's three domains, defining DRWD as the substrate-binding module and RING as the E2-interaction module.

    Evidence X-ray crystallography at 3.2 Å with domain-deletion binding assays

    PMID:20154706

    Open questions at the time
    • Determinants of E2 selectivity not resolved at residue level
    • Role of ELF domain undefined
  9. 2010 Medium

    A non-canonical E2 (UBE2W) acting on FANCL's PHD domain was found to regulate FANCD2 monoubiquitination via a UV-specific route distinct from UBE2T.

    Evidence Co-IP domain mapping, in vitro ubiquitination, and siRNA knockdown with FANCD2 readout

    PMID:21229326

    Open questions at the time
    • Physiological significance of FANCL PHD monoubiquitination unclear
    • Single-lab finding not independently reproduced
  10. 2010 High

    Zebrafish work revealed FANCL safeguards germ cell survival through meiosis by suppressing Tp53-dependent apoptosis, mechanistically explaining its sex-determination role.

    Evidence fancl mutant zebrafish, caspase-3 assay, tp53;fancl double-mutant epistasis, fertility assay

    PMID:20661450

    Open questions at the time
    • Whether germ-cell role depends on ligase activity not tested here
    • Connection to ICL repair in germ cells not established
  11. 2011 High

    Structure and mutagenesis of the central DRWD/URD domain pinpointed the residues for FANCD2/FANCI binding versus UBE2T binding, refining the substrate-recognition map.

    Evidence X-ray crystallography of the central domain with mutagenesis and binding assays

    PMID:21775430

    Open questions at the time
    • Dynamics of substrate handoff to the RING-bound E2 unresolved
  12. 2012 Medium

    FANCL was shown to extend atypical K11-linked, non-proteolytic chains on β-catenin, defining a DNA-repair-independent role in Wnt signaling and HSC progenitor expansion.

    Evidence Co-IP, in vitro ubiquitination, LEF/TCF reporter, and FANCL knockdown in CD34+ cells

    PMID:22653977

    Open questions at the time
    • E2 partner for β-catenin chains not identified
    • In vivo relevance to leukemogenesis not established
  13. 2013 Medium

    FANCL's own stability was placed under post-translational control, with K48-linked degradation modulated by phosphorylation and the Akt/GSK-3β/axin1 axis.

    Evidence Proteasome inhibition, K48-linkage ubiquitination assay, N-terminal deletions, axin1/GSK-3β co-IP, 2D-PAGE, active Akt expression

    PMID:23783032

    Open questions at the time
    • Responsible E3 for FANCL K48 chains not identified
    • Physiological trigger for FANCL turnover unclear
  14. 2014 High

    The RING–UBE2T co-crystal structure explained how FANCL selectively recruits its cognate E2 through interactions beyond the generic E3–E2 interface.

    Evidence X-ray crystallography of FANCL RING–UBE2T with interface mutagenesis and E2 selectivity assays

    PMID:24389026

    Open questions at the time
    • Conformational activation of the E2~Ub for transfer not resolved
  15. 2015 High

    The ELF domain's non-covalent ubiquitin binding was assigned a regulatory role specifically enabling efficient damage-induced FANCD2 monoubiquitination in cells.

    Evidence NMR/binding assays, Ile44-patch mutagenesis, in vitro ubiquitination, and cellular complementation

    PMID:26149689

    Open questions at the time
    • Source of the bound ubiquitin in vivo not identified
    • Mechanism coupling ubiquitin binding to enhanced catalysis unclear
  16. 2017 Medium

    Direct arsenite binding to the PHD/RING domain was shown to inhibit FANCL catalysis, providing a chemical mechanism by which an environmental toxin disrupts the FA pathway.

    Evidence In vitro arsenite-binding assay plus cellular FANCD2 monoubiquitination, chromatin recruitment, and clonogenic survival

    PMID:28535027

    Open questions at the time
    • Exact cysteines coordinating arsenite not mapped
    • In vivo relevance to arsenic toxicity not established
  17. 2019 Medium

    A small-molecule inhibitor of UBE2T/FANCL catalysis validated the pair as a druggable target for sensitizing cells to crosslinking chemotherapy.

    Evidence High-throughput biochemical screen with in vitro and cellular ubiquitylation assays and carboplatin clonogenic survival

    PMID:31525021

    Open questions at the time
    • Binding site of the inhibitor on FANCL not defined
    • Selectivity over other E3 ligases not characterized
  18. 2020 Medium

    Systematic characterization of URD-domain cancer variants separated destabilizing from catalysis-impairing mutations, mapping genotype to FA-pathway dysfunction, while POI frameshift variants linked FANCL mislocalization to human reproductive disease.

    Evidence Thermal shift, FANCD2 interaction, and in vitro ubiquitination with ICL sensitivity for URD variants; immunofluorescence and ligase activity for POI patient variants

    PMID:32048394 PMID:32420600

    Open questions at the time
    • Causality in POI not proven beyond cellular assays
    • In vivo consequences of individual URD variants untested
  19. 2022 Medium

    A CRISPR knockout combined with catalytic-mutant rescue revealed FANCL has a ubiquitin ligase-independent mitochondrial function supporting Parkin-mediated mitophagy.

    Evidence Mitochondrial fractionation, CRISPR KO, mitophagy assay, and rescue with WT and catalytically dead C307A FANCL

    PMID:35644338

    Open questions at the time
    • Molecular role of FANCL at mitochondria undefined
    • Physiological relevance beyond Parkin-overexpressing cells unknown
  20. 2026 High

    A catalytic-cysteine knock-in mouse with genetic correction demonstrated that loss of RING E3 ligase activity alone explains all major Fanconi anemia phenotypes, formally separating catalysis from structural roles in disease.

    Evidence CRISPR knock-in mouse, FANCD2 monoubiquitination assay, phenotyping, and CRISPR/prime-editing correction with functional rescue

    PMID:41259745

    Open questions at the time
    • Whether non-catalytic FANCL functions contribute to any residual phenotype not addressed
    • Translatability of gene correction to human HSCs untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FANCL's ligase-dependent DNA-repair role, its non-proteolytic Wnt/β-catenin signaling activity, and its ligase-independent mitochondrial function are integrated within single cell types remains unresolved.
  • No unified model linking the three activities
  • E2 partners for non-FANCD2 substrates incompletely defined
  • Mitochondrial molecular mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0031386 protein tag activity 3
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-1474165 Reproduction 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-162582 Signal Transduction 1 R-HSA-9612973 Autophagy 1
Partners
AXIN1CTNNB1FANCD2FANCIGGNUBE2TUBE2W
Complex memberships
Fanconi anemia core complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 FANCL acts as an E3 ubiquitin ligase that, together with the E2-conjugating enzyme Ube2t, is sufficient to monoubiquitinate FANCD2 in a minimal reconstituted system. A conserved RWD-like domain in FANCL stimulates monoubiquitination, and addition of FANCI enhances the reaction and restricts it to the correct in vivo lysine residue on FANCD2 (K561). In vitro reconstitution of monoubiquitination with purified Ube2t and FANCL; addition of FANCI to assess site restriction Molecular cell High 19111657
2004 FANCL (PHF9), but not BRCA1, is the likely E3 ubiquitin ligase responsible for FANCD2 monoubiquitination. In FANCL-mutant cells, monoubiquitinated FANCD2 is absent from chromatin and nuclear matrix fractions, whereas non-ubiquitinated FANCD2 resides in the soluble fraction, demonstrating that FANCL-dependent monoubiquitination is required for FANCD2 chromatin association. Subcellular fractionation of FANCL-mutant vs. BRCA1-mutant cell lines; evolutionary co-existence analysis of FANCL and FANCD2 Cell cycle (Georgetown, Tex.) Medium 14712086
2010 Crystal structure of FANCL at 3.2 Å reveals three domains: an N-terminal E2-like fold (ELF domain), a novel double-RWD (DRWD) domain, and a C-terminal RING domain. Binding assays show the DRWD domain (not ELF) is responsible for substrate (FANCD2/FANCI) binding, while the RING domain mediates E2 (Ube2T) interaction. X-ray crystallography at 3.2 Å; domain-deletion binding assays Nature structural & molecular biology High 20154706
2014 Crystal structure of the FANCL RING domain in complex with Ube2T reveals an extensive network of specific electrostatic and hydrophobic interactions beyond the generic E3–E2 interface, and mutagenesis shows these specific interactions are required for selective recruitment of Ube2T over other E2 enzymes by FANCL. X-ray crystallography of FANCL RING–Ube2T complex; site-directed mutagenesis of interface residues; E2 selectivity assays Structure (London, England : 1993) High 24389026
2011 Structure of the central (DRWD/URD) domain of human FANCL confirms conservation with Drosophila FANCL. Mutational analysis identifies residues in the DRWD domain required for binding FANCD2 and FANCI substrates, and a separate region required for Ube2T binding. X-ray crystallography of central domain; mutagenesis; binding assays with FANCD2, FANCI, and Ube2T The Journal of biological chemistry High 21775430
2006 The WD40 repeats (not the PHD/RING domain) of FANCL are required for interaction with other FA core complex subunits. The PHD domain is dispensable for core complex incorporation but is required for FANCD2 monoubiquitination; a conserved tryptophan in the PHD analogous to the c-CBL RING finger is required for in vitro auto-ubiquitination and in vivo FANCD2 monoubiquitination. Domain-deletion and point-mutation constructs expressed in FANCL-deficient cells; co-immunoprecipitation; in vitro ubiquitination assay; MMC resistance complementation The Journal of biological chemistry High 16474167
2007 FANCL physically interacts with FANCD2 via its PHD domain (co-immunoprecipitation in 293T cells and yeast two-hybrid). FANCL is required for FANCD2 monoubiquitination and focus formation in DT40 cells, and loss of FANCL (or FANCD2 monoubiquitination) causes quantitatively identical defects in homologous recombination repair of I-SceI-induced chromosomal breaks. Yeast two-hybrid; co-immunoprecipitation; FANCL gene disruption in DT40 cells; I-SceI HR repair assay; focus formation immunoassay Genes to cells : devoted to molecular & cellular mechanisms High 17352736
2009 The UBE2T–FANCL pair can monoubiquitinate FANCI on Lys-523 in vitro. FANCI binds branched DNA structures through its C-terminal fragment, a binding activity that likely positions it as a substrate. In vitro ubiquitination assay with purified UBE2T and FANCL; DNA binding assay with branched DNA substrates The Journal of biological chemistry High 19589784
2010 UBE2W interacts with the PHD domain of FANCL (the PHD domain is necessary and sufficient for this interaction) and catalyzes monoubiquitination of the FANCL PHD domain in vitro. UBE2W overexpression promotes FANCD2 monoubiquitination in cells, and UBE2W knockdown reduces UV-induced (but not MMC-induced) FANCD2 monoubiquitination, indicating UBE2W regulates FANCD2 monoubiquitination through FANCL by a mechanism distinct from UBE2T. Co-immunoprecipitation; domain-deletion mapping; in vitro ubiquitination assay; siRNA knockdown with FANCD2 monoubiquitination readout Molecules and cells Medium 21229326
2015 The N-terminal ELF domain of FANCL mediates a non-covalent interaction with ubiquitin via the canonical Ile44 patch on ubiquitin. This interaction is not required for FANCD2 monoubiquitination in vitro, nor for core complex recognition or Ube2T binding, but is required for efficient DNA damage-induced FANCD2 monoubiquitination in vertebrate cells, indicating a regulatory in vivo function for ubiquitin binding by the ELF domain. NMR/binding assays for ELF–ubiquitin interaction; mutagenesis of ubiquitin Ile44 patch and corresponding FANCL patch; in vitro ubiquitination assay; cellular complementation assay for damage-induced FANCD2 monoubiquitination The Journal of biological chemistry High 26149689
2012 FANCL ubiquitinates β-catenin with atypical lysine-11 ubiquitin chain extension (non-proteolytic), enhancing β-catenin nuclear activity and transcription of Wnt targets c-Myc and Cyclin D1. FANCL-deficient cells show diminished β-catenin activation, and suppression of FANCL in human CD34+ stem/progenitor cells reduces β-catenin-active cells and inhibits multilineage progenitor expansion. Co-immunoprecipitation; in vitro ubiquitination assay; LEF/TCF reporter assay; immunofluorescence; FANCL knockdown in human CD34+ cells with colony/progenitor readout Blood Medium 22653977
2013 FANCL protein is constitutively targeted for proteasomal degradation via K48-linked polyubiquitination. The ELF (E2-like fold) domain may direct this polyubiquitination. FANCL is stabilized in a complex with axin1 when GSK-3β is overexpressed, and constitutively active Akt (myristoylated) increases FANCL steady-state levels by reducing K48-linked polyubiquitination. Phosphorylated (acidic) forms of FANCL are not subject to polyubiquitination. Proteasome inhibitor treatment; K48-linkage-specific ubiquitination assay; N-terminal deletion constructs; co-immunoprecipitation with axin1/GSK-3β; 2D-PAGE phospho-FANCL analysis; constitutively active Akt expression Molecular biology of the cell Medium 23783032
2017 Arsenite (As3+) binds directly to the PHD/RING finger domain of FANCL both in vitro and in cells. This binding compromises FANCL-mediated FANCD2 ubiquitination in cells, reduces FANCD2 chromatin recruitment to DNA damage sites, and renders cells more sensitive to DNA interstrand cross-linking agents. In vitro binding assay (recombinant FANCL PHD/RING + arsenite); cellular As3+ treatment with FANCD2 monoubiquitination and chromatin recruitment readout; clonogenic survival assay ACS chemical biology Medium 28535027
2019 A small-molecule inhibitor identified by high-throughput screening inhibits UBE2T/FANCL-mediated FANCD2 monoubiquitylation and sensitizes cells to the DNA cross-linking agent carboplatin, validating the UBE2T–FANCL catalytic pair as a druggable target in the FA pathway. High-throughput biochemical screen; in vitro ubiquitylation assay; cellular FANCD2 monoubiquitylation assay; clonogenic survival with carboplatin ACS chemical biology Medium 31525021
2022 FANCL protein localizes to mitochondria (in both basal and mitochondrial stress conditions), and its ubiquitin ligase activity is not required for this mitochondrial localization. CRISPR/Cas9 knockout of FANCL in parkin-overexpressing HeLa cells impairs clearance of damaged mitochondria (mitophagy) upon oligomycin/antimycin treatment; this defect is rescued by reintroduction of either wild-type FANCL or the catalytically dead FANCL(C307A) mutant, demonstrating a ubiquitin ligase-independent role in supporting Parkin-mediated mitophagy. Subcellular fractionation/mitochondrial localization; CRISPR/Cas9 KO; mitophagy assay (mitochondrial clearance upon OA stress); complementation with WT and C307A catalytic mutant Biochimica et biophysica acta. Molecular basis of disease Medium 35644338
2006 In Drosophila, FANCL is necessary for monoubiquitination of FANCD2, and epistasis analysis places FANCL upstream of FANCD2 in a linear DNA repair pathway. Knockdown of either FANCL or FANCD2 confers hypersensitivity to cross-linking agents. RNAi knockdown in Drosophila; cross-linking agent sensitivity assay; FANCD2 monoubiquitination Western blot; genetic epistasis DNA repair Medium 16860002
2002 Mouse Pog (the ortholog of FANCL) is necessary for primordial germ cell (PGC) proliferation between E9.5 and E10.25 dpc. Deletion of Pog causes the germ-cell-deficient (gcd) phenotype with reduced PGC numbers and adult sterility; the proliferation defect rather than aberrant migration is responsible. Targeted Pog knockout mice; PGC counting at multiple developmental time points; comparison with gcd insertional mutant Human molecular genetics Medium 12417526
2003 POG (FANCL ortholog) interacts with GGN1 and GGN3 (gametogenetin isoforms) via yeast two-hybrid and co-expression in HeLa cells. Co-expression of POG with GGN1 or GGN3 relocalizes POG to the perinuclear region or nucleoli, respectively, and Pog-deficient mice show impaired meiosis during spermatogenesis. Yeast two-hybrid; co-expression in HeLa cells with localization readout; Pog-knockout mouse spermatogenesis analysis The Journal of biological chemistry Medium 12574169
2010 In zebrafish, fancl is expressed in developing germ cells at the critical time of sexual fate determination. Loss of fancl causes Tp53-mediated germ cell apoptosis (demonstrated by caspase-3 immunoassay), compromises oocyte survival through meiosis, and results in female-to-male sex reversal. Introduction of a tp53 mutation into fancl mutants rescues sex reversal by reducing germ cell apoptosis. fancl mutant zebrafish; caspase-3 immunoassay; cyp19a1a and amh expression analysis; tp53;fancl double mutant genetic epistasis; fertility assay PLoS genetics High 20661450
2020 Two heterozygous frameshift mutations in FANCL (c.1048_1051delGTCT and c.739dupA) identified in POI patients cause cytoplasmic retention of mutant FANCL protein (whereas wild-type FANCL is nuclear), impaired ubiquitin-ligase activity, and compromised DNA repair after mitomycin C treatment. Subcellular localization of mutant vs. WT FANCL by immunofluorescence; in vitro ubiquitin ligase activity assay; MMC DNA repair assay in patient-derived cells Human mutation Medium 32048394
2026 A murine FanclTATΔ allele removing the catalytic cysteine in the RING domain generates a core complex that retains structural integrity but lacks FANCD2 monoubiquitination activity. Homozygous mice phenocopy human FA (infertility, craniofacial anomalies, DNA damage hypersensitivity, progressive HSC loss). CRISPR-Cas9 or prime editing correction of the mutation restores FANCD2 monoubiquitination and DNA damage resistance in myeloid cells, demonstrating that loss of RING E3 ligase activity alone explains all major FA phenotypes. CRISPR knock-in mouse model; biochemical FANCD2 monoubiquitination assay; mouse phenotyping; CRISPR-Cas9 and prime editing correction with functional rescue Blood advances High 41259745
2020 Analysis of 17 FANCL URD-domain variants from patient cancer cells shows that mutations I136V, L154S, W212A, L214A, R221W, R221C, and V287G destabilize FANCL, while E217K, T224K, M247V, and the hydrophobic patch mutants (L248A, F252A, L254A, I265A) impair catalytic function without destabilizing the fold. N270K and E289Q specifically destabilize the C-terminal helices of the URD domain. These functional defects correlate with cellular sensitivity to an interstrand cross-linking agent. Recombinant expression; thermal shift assay; FANCD2 interaction assay; in vitro ubiquitination assay; cellular ICL sensitivity assay Bioscience reports Medium 32420600

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481. Blood 199 16469874
2010 Sex reversal in zebrafish fancl mutants is caused by Tp53-mediated germ cell apoptosis. PLoS genetics 169 20661450
2008 Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI. Molecular cell 158 19111657
2011 Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404). Blood 135 21474675
2002 A novel gene, Pog, is necessary for primordial germ cell proliferation in the mouse and underlies the germ cell deficient mutation, gcd. Human molecular genetics 105 12417526
2004 FANCL replaces BRCA1 as the likely ubiquitin ligase responsible for FANCD2 monoubiquitination. Cell cycle (Georgetown, Tex.) 80 14712086
2009 FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL. The Journal of biological chemistry 72 19589784
2014 Structure of the human FANCL RING-Ube2T complex reveals determinants of cognate E3-E2 selection. Structure (London, England : 1993) 66 24389026
2008 Outcomes of the POG 9340/9341/9342 trials for children with high-risk neuroblastoma: a report from the Children's Oncology Group. Pediatric blood & cancer 63 18704922
2010 The structure of the catalytic subunit FANCL of the Fanconi anemia core complex. Nature structural & molecular biology 59 20154706
1997 Therapeutic trial for infant acute lymphoblastic leukemia: the Pediatric Oncology Group experience (POG 8493). Journal of pediatric hematology/oncology 45 9065717
2006 The WD40 repeats of FANCL are required for Fanconi anemia core complex assembly. The Journal of biological chemistry 43 16474167
2011 Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia pathway. The Journal of biological chemistry 41 21775430
2020 FANCL gene mutations in premature ovarian insufficiency. Human mutation 40 32048394
2001 The effect of cisplatin dose and surgical resection in children with malignant germ cell tumors at the sacrococcygeal region: a pediatric intergroup trial (POG 9049/CCG 8882). Journal of pediatric surgery 39 11150431
2003 Mouse GGN1 and GGN3, two germ cell-specific proteins from the single gene Ggn, interact with mouse POG and play a role in spermatogenesis. The Journal of biological chemistry 34 12574169
2003 Late onset of spermatogenesis and gain of fertility in POG-deficient mice indicate that POG is not necessary for the proliferation of spermatogonia. Biology of reproduction 33 12606378
2008 Hypermethylation of the FANCC and FANCL promoter regions in sporadic acute leukaemia. Cellular oncology : the official journal of the International Society for Cellular Oncology 32 18607065
2006 Drosophila homologs of FANCD2 and FANCL function in DNA repair. DNA repair 32 16860002
2012 FANCL ubiquitinates β-catenin and enhances its nuclear function. Blood 31 22653977
2007 A requirement of FancL and FancD2 monoubiquitination in DNA repair. Genes to cells : devoted to molecular & cellular mechanisms 29 17352736
2019 Small-Molecule Inhibition of UBE2T/FANCL-Mediated Ubiquitylation in the Fanconi Anemia Pathway. ACS chemical biology 28 31525021
2015 Loss-of-Function FANCL Mutations Associate with Severe Fanconi Anemia Overlapping the VACTERL Association. Human mutation 28 25754594
2009 Mutational analysis of FANCL, FANCM and the recently identified FANCI suggests that among the 13 known Fanconi Anemia genes, only FANCD1/BRCA2 plays a major role in high-risk breast cancer predisposition. Carcinogenesis 28 19737859
2015 The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL. The Journal of biological chemistry 26 26149689
2010 UBE2W interacts with FANCL and regulates the monoubiquitination of Fanconi anemia protein FANCD2. Molecules and cells 26 21229326
2006 Altered expression of FANCL confers mitomycin C sensitivity in Calu-6 lung cancer cells. Cancer biology & therapy 26 17106252
2009 Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation group. Human mutation 24 19405097
2017 Arsenite Binds to the RING Finger Domain of FANCL E3 Ubiquitin Ligase and Inhibits DNA Interstrand Crosslink Repair. ACS chemical biology 22 28535027
2003 Phase 2 study of idarubicin in pediatric brain tumors: Pediatric Oncology Group study POG 9237. Neuro-oncology 21 14565163
2006 Antimetabolite-based therapy in childhood T-cell acute lymphoblastic leukemia: a report of POG study 9296. Pediatric blood & cancer 17 16007607
1994 A new monoclonal antibody (POG-1) detects a differentiation antigen of porcine granulosa and thecal cells and indicates heterogeneity of thecal-stromal cells. Endocrinology 14 8119152
1994 Presenting characteristics of trisomy 8 as the primary cytogenetic abnormality associated with childhood acute lymphoblastic leukemia. A Pediatric Oncology Group (POG) Study (8600/8493). Cancer genetics and cytogenetics 12 8039165
2022 FANCL supports Parkin-mediated mitophagy in a ubiquitin ligase-independent manner. Biochimica et biophysica acta. Molecular basis of disease 11 35644338
2011 Evaluation of Fanconi anaemia genes FANCA, FANCC and FANCL in cervical cancer susceptibility. Gynecologic oncology 11 21543111
2019 A founder variant in the South Asian population leads to a high prevalence of FANCL Fanconi anemia cases in India. Human mutation 10 31513304
2013 The PI3K/Akt1 pathway enhances steady-state levels of FANCL. Molecular biology of the cell 9 23783032
2012 Switch of FANCL, a key FA-BRCA component, between tumor suppressor and promoter by alternative splicing. Cell cycle (Georgetown, Tex.) 9 22918243
2020 Characterization of FANCL variants observed in patient cancer cells. Bioscience reports 8 32420600
2017 Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a Chinese girl with Fanconi Anemia. European journal of medical genetics 8 28419882
2013 Treatment of relapsed precursor-B acute lymphoblastic leukemia with intensive chemotherapy: POG (Pediatric Oncology Group) study 9411 (SIMAL 9). Journal of pediatric hematology/oncology 8 23887024
2021 Quantitative Proteomics Reveals a Novel Role of the E3 Ubiquitin-Protein Ligase FANCL in the Activation of the Innate Immune Response through Regulation of TBK1 Phosphorylation during Peste des Petits Ruminants Virus Infection. Journal of proteome research 7 34289691
2025 Deficient FANCL Predisposes to Endothelial Damage: A New Therapeutic Target for Pulmonary Hypertension. American journal of respiratory and critical care medicine 3 40479584
2020 Poly(POG)n loaded with recombinant human bone morphogenetic protein-2 accelerates new bone formation in a critical-sized bone defect mouse model. Journal of orthopaedic surgery and research 3 33054796
2005 [Functions of FANCL in primordial germ cell formation and Fanconi anemia]. Yi chuan xue bao = Acta genetica Sinica 3 16201245
2012 No evidence for translation of pog, a predicted overlapping gene of Solenopsis invicta virus 1. Virus genes 2 22528643
1996 Monoclonal antibody PHF-9 recognizes phosphorylated serine 404 of tau protein and labels paired helical filaments. Journal of neuroscience research 2 8892109
2026 Fancl-mutant mice reveal central role of monoubiquitination in Fanconi anemia and a model for therapeutic gene editing. Blood advances 0 41259745
2025 Piperine Targets the FANCL/UBE2T Complex to Inhibit the FA Pathway and Sensitize Bladder Cancer to Cisplatin. Dose-response : a publication of International Hormesis Society 0 41306722
2025 Ginsenoside Rh2 Suppresses the Fanconi Anemia Pathway by Inhibiting NF-κB-Mediated FANCL Transcription in Bladder Cancer. Dose-response : a publication of International Hormesis Society 0 41425456
2023 An acquired BMF with FANCL gene heterozygous mutation: Case report. Medicine 0 37327301

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