FANCL
MCID: FNC028
MIFTS: 47

Fanconi Anemia, Complementation Group L (FANCL)

Categories: Blood diseases, Bone diseases, Cancer diseases, Fetal diseases, Genetic diseases, Immune diseases, Nephrological diseases, Rare diseases, Skin diseases

Aliases & Classifications for Fanconi Anemia, Complementation Group L

MalaCards integrated aliases for Fanconi Anemia, Complementation Group L:

Name: Fanconi Anemia, Complementation Group L 57 29 13 6 40 72
Fanconi Anemia Complementation Group L 12 74 15
Fancl 57 12 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
four unrelated patients have been reported (last curated september 2015)
two unrelated patients had multiple congenital anomalies and died in early infancy


HPO:

32
fanconi anemia, complementation group l:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0111082
MeSH 44 D005199
UMLS 72 C3469528

Summaries for Fanconi Anemia, Complementation Group L

OMIM : 57 Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011). For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650. (614083)

MalaCards based summary : Fanconi Anemia, Complementation Group L, also known as fanconi anemia complementation group l, is related to fanconi anemia, complementation group a and fanconi anemia, complementation group j. An important gene associated with Fanconi Anemia, Complementation Group L is FANCL (FA Complementation Group L), and among its related pathways/superpathways are Ubiquitin mediated proteolysis and BRCA1 Pathway. The drugs Talazoparib and Olaparib have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and breast, and related phenotypes are hypertelorism and short neck

Disease Ontology : 12 A Fanconi anemia that has material basis in homozygous or compound heterozygous mutation in the PHF9 gene on chromosome 2p16.

UniProtKB/Swiss-Prot : 74 Fanconi anemia complementation group L: 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.

Related Diseases for Fanconi Anemia, Complementation Group L

Diseases in the Fanconi Anemia, Complementation Group C family:

Fanconi Anemia, Complementation Group D2 Fanconi Anemia, Complementation Group a
Fanconi Anemia, Complementation Group B Fanconi Anemia, Complementation Group E
Fanconi Anemia, Complementation Group F Fanconi Anemia, Complementation Group D1
Fanconi Anemia, Complementation Group I Fanconi Anemia, Complementation Group J
Fanconi Anemia, Complementation Group N Fanconi Anemia, Complementation Group O
Fanconi Anemia, Complementation Group P Fanconi Anemia, Complementation Group G
Fanconi Anemia, Complementation Group L Fanconi Anemia, Complementation Group Q
Fanconi Anemia, Complementation Group T Fanconi Anemia, Complementation Group V
Fanconi Anemia, Complementation Group R Fanconi Anemia, Complementation Group U
Fanconi Anemia, Complementation Group W Fanconi Anemia, Complementation Group S

Diseases related to Fanconi Anemia, Complementation Group L via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 27)
# Related Disease Score Top Affiliating Genes
1 fanconi anemia, complementation group a 32.5 UBE2T FANCL FANCD2
2 fanconi anemia, complementation group j 32.4 FANCL FANCD2
3 fanconi anemia, complementation group b 32.3 FANCL FANCD2
4 congenital hypoplastic anemia 31.4 FANCL FANCD2
5 fanconi anemia, complementation group e 11.6
6 squamous cell carcinoma, head and neck 11.3
7 extraosseous ewing sarcoma 11.3
8 fanconi anemia, complementation group d2 10.7
9 deficiency anemia 10.5
10 fanconi anemia, complementation group i 10.4
11 fanconi anemia, complementation group c 10.4
12 fanconi anemia, complementation group d1 10.2
13 aplastic anemia 10.2
14 pulmonary fibrosis and/or bone marrow failure, telomere-related, 2 10.2
15 autosomal recessive disease 10.2
16 breast cancer 10.1
17 lung cancer 10.1
18 cervical cancer 10.1
19 fanconi anemia, complementation group n 10.1
20 allergic hypersensitivity disease 10.1
21 vacterl association 10.1
22 acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22) 10.1
23 fanconi anemia, complementation group u 9.8 UBE2T FANCD2
24 fanconi anemia, complementation group v 9.6 UBE2T FANCD2
25 fanconi anemia, complementation group q 9.5 UBE2T FANCL FANCD2
26 fanconi anemia, complementation group r 9.5 UBE2T FANCL FANCD2
27 fanconi anemia, complementation group t 9.5 UBE2T FANCL FANCD2

Graphical network of the top 20 diseases related to Fanconi Anemia, Complementation Group L:



Diseases related to Fanconi Anemia, Complementation Group L

Symptoms & Phenotypes for Fanconi Anemia, Complementation Group L

Human phenotypes related to Fanconi Anemia, Complementation Group L:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 occasional (7.5%) HP:0000316
2 short neck 32 occasional (7.5%) HP:0000470
3 hydrocephalus 32 occasional (7.5%) HP:0000238
4 depressed nasal bridge 32 occasional (7.5%) HP:0005280
5 wide nasal bridge 32 occasional (7.5%) HP:0000431
6 abnormal facial shape 32 occasional (7.5%) HP:0001999
7 microtia 32 occasional (7.5%) HP:0008551
8 cleft palate 32 occasional (7.5%) HP:0000175
9 bone marrow hypocellularity 32 occasional (7.5%) HP:0005528
10 tracheoesophageal fistula 32 occasional (7.5%) HP:0002575
11 intrauterine growth retardation 32 occasional (7.5%) HP:0001511
12 microphthalmia 32 occasional (7.5%) HP:0000568
13 micropenis 32 occasional (7.5%) HP:0000054
14 anal atresia 32 occasional (7.5%) HP:0002023
15 renal hypoplasia 32 occasional (7.5%) HP:0000089
16 esophageal atresia 32 occasional (7.5%) HP:0002032
17 absent thumb 32 occasional (7.5%) HP:0009777
18 global developmental delay 32 HP:0001263
19 anemia 32 HP:0001903
20 cafe-au-lait spot 32 HP:0000957
21 chromosome breakage 32 HP:0040012

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
microphthalmia (in some patients)
hypertelorism (in some patients)

Head And Neck Neck:
short neck (in some patients)

Laboratory Abnormalities:
increased chromosomal breakage

Head And Neck Face:
dysmorphic facial features (in some patients)

Respiratory Airways:
tracheoesophageal fistula (in some patients)

Head And Neck Ears:
microtia (in some patients)

Head And Neck Nose:
depressed nasal root (in some patients)
broad nasal root (in some patients)

Genitourinary Kidneys:
renal hypoplasia (in some patients)

Skeletal Limbs:
radial ray defects (in some patients)

Head And Neck Mouth:
cleft palate (in some patients)

Hematology:
bone marrow failure (in some patients)

Neurologic Central Nervous System:
hydrocephalus (in some patients)
developmental delay (in some patients)

Genitourinary External Genitalia Male:
micropenis (in some patients)

Abdomen Gastrointestinal:
esophageal atresia (in some patients)
anal atresia (in some patients)

Growth Other:
intrauterine growth retardation (in some patients)

Cardiovascular Heart:
cardiac malformations (in some patients)

Skeletal Spine:
vertebral abnormalities (in some patients)

Skeletal Hands:
absent thumbs (in some patients)

Clinical features from OMIM:

614083

GenomeRNAi Phenotypes related to Fanconi Anemia, Complementation Group L according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased cell death HMECs cells GR00103-A-0 8.8 FANCL UBE2T VRK2

Drugs & Therapeutics for Fanconi Anemia, Complementation Group L

Drugs for Fanconi Anemia, Complementation Group L (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Talazoparib Approved, Investigational Phase 2 1207456-01-6 135565082
2
Olaparib Approved Phase 2 763113-22-0 23725625
3
Mannitol Approved, Investigational Phase 2 69-65-8 453 6251
4
Silicon Approved, Investigational Phase 2 7440-21-3 4082203
5
Titanium dioxide Approved Phase 2 13463-67-7
6
Iron Approved, Experimental Phase 2 15438-31-0, 7439-89-6 23925 27284
7
Bevacizumab Approved, Investigational Phase 2 216974-75-3
8
Irinotecan Approved, Investigational Phase 2 100286-90-6, 97682-44-5 60838
9 Poly(ADP-ribose) Polymerase Inhibitors Phase 2
10 Ferrosoferric Oxide Phase 2
11 topoisomerase I inhibitors Phase 2
12 Topoisomerase Inhibitors Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase II Clinical Trial of the PARP Inhibitor Talazoparib in BRCA1 and BRCA2 Wild Type Patients With Advanced Triple Negative Breast Cancer and Homologous Recombination Deficiency or Advanced HER2 Negative Breast Cancer or Other Solid Tumors With a Mutation in Homologous Recombination Pathway Genes Recruiting NCT02401347 Phase 2 Talazoparib Tosylate
2 Phase II Study of Olaparib in Metastatic Renal Cell Carcinoma Patients Harboring a BAP-1 or Other DNA Repair Gene Mutations (ORCHID) Recruiting NCT03786796 Phase 2 Olaparib
3 Phase II Study of Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis Recruiting NCT03047135 Phase 2 Olaparib
4 A Phase 2 Single-Arm Study of M6620 in Combination With Irinotecan in Patients With Progressive TP53 Mutant Gastric and Gastro-Esophageal Junction Cancer Not yet recruiting NCT03641313 Phase 2 ATR Kinase Inhibitor M6620;Irinotecan

Search NIH Clinical Center for Fanconi Anemia, Complementation Group L

Genetic Tests for Fanconi Anemia, Complementation Group L

Genetic tests related to Fanconi Anemia, Complementation Group L:

# Genetic test Affiliating Genes
1 Fanconi Anemia, Complementation Group L 29 FANCL

Anatomical Context for Fanconi Anemia, Complementation Group L

MalaCards organs/tissues related to Fanconi Anemia, Complementation Group L:

41
Bone, Bone Marrow, Breast, Prostate, Lung, Testes, Ovary

Publications for Fanconi Anemia, Complementation Group L

Articles related to Fanconi Anemia, Complementation Group L:

(show top 50) (show all 120)
# Title Authors PMID Year
1
Loss-of-Function FANCL Mutations Associate with Severe Fanconi Anemia Overlapping the VACTERL Association. 38 8 71
25754594 2015
2
Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation group. 38 8 71
19405097 2009
3
A novel ubiquitin ligase is deficient in Fanconi anemia. 38 8 71
12973351 2003
4
Fanconi anemia: at the crossroads of DNA repair. 8
21568838 2011
5
ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. 71
19888064 2009
6
Esophageal Atresia/Tracheoesophageal Fistula Overview 71
20301753 2009
7
Carrier screening in individuals of Ashkenazi Jewish descent. 71
18197057 2008
8
Fanconi Anemia 71
20301575 2002
9
Analysis of polymorphisms in genes associated with the FA/BRCA pathway in three patients with multiple primary malignant neoplasms. 38
30942098 2019
10
Efficacy of Radium-223 in Bone-metastatic Castration-resistant Prostate Cancer with and Without Homologous Repair Gene Defects. 38
30293905 2019
11
Prevalence of DNA repair gene mutations in localized prostate cancer according to clinical and pathologic features: association of Gleason score and tumor stage. 38
30171229 2019
12
CCNE1 amplification is associated with poor prognosis in patients with triple negative breast cancer. 38
30665374 2019
13
Genomic alterations important for the prognosis in patients with follicular lymphoma treated in SWOG study S0016. 38
30446494 2019
14
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings. 38
30306255 2018
15
Multiplexed CRISPR/Cas9-mediated knockout of 19 Fanconi anemia pathway genes in zebrafish revealed their roles in growth, sexual development and fertility. 38
30540754 2018
16
Roles of Figla/figla in Juvenile Ovary Development and Follicle Formation During Zebrafish Gonadogenesis. 38
30184072 2018
17
Prenatal diagnosis of a 3.2-Mb 2p16.1-p15 duplication associated with familial intellectual disability. 38
30122582 2018
18
Germline deleterious mutations in genes other than BRCA2 are infrequent in male breast cancer. 38
29335925 2018
19
Somatic mutations in early onset luminal breast cancer. 38
29854292 2018
20
The HEM Lines: A New Library of Homozygous Arabidopsis thaliana EMS Mutants and its Potential to Detect Meiotic Phenotypes. 38
30283471 2018
21
Case study: patient-derived clear cell adenocarcinoma xenograft model longitudinally predicts treatment response. 38
30202792 2018
22
Penetrance of Polygenic Obesity Susceptibility Loci across the Body Mass Index Distribution. 38
29220676 2017
23
Constitutive role of the Fanconi anemia D2 gene in the replication stress response. 38
29021208 2017
24
Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50. 38
28678401 2017
25
Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene. 38
28881617 2017
26
Arsenite Binds to the RING Finger Domain of FANCL E3 Ubiquitin Ligase and Inhibits DNA Interstrand Crosslink Repair. 38
28535027 2017
27
Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a Chinese girl with Fanconi Anemia. 38
28419882 2017
28
Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer. 38
28050010 2017
29
Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway. 38
27986371 2017
30
Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells. 38
28926637 2017
31
The FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2. 38
27986592 2017
32
The functional status of DNA repair pathways determines the sensitization effect to cisplatin in non-small cell lung cancer cells. 38
27473273 2016
33
Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma. 38
27835906 2016
34
Leukemic survival factor SALL4 contributes to defective DNA damage repair. 38
27132514 2016
35
Hereditary truncating mutations of DNA repair and other genes in BRCA1/BRCA2/PALB2-negatively tested breast cancer patients. 38
26822949 2016
36
RE: frameshift variant FANCL*c.1096_1099dupATTA is not associated with high breast cancer risk. 38
27659787 2016
37
Frameshift variant FANCL*c.1096_1099dupATTA is not associated with high breast cancer risk. 38
27506598 2016
38
Mutations of myelodysplastic syndromes (MDS): An update. 38
27543316 2016
39
Fanconi Anemia Proteins Function in Mitophagy and Immunity. 38
27133164 2016
40
Determining the frequency of pathogenic germline variants from exome sequencing in patients with castrate-resistant prostate cancer. 38
27084275 2016
41
Profiling Fanconi Anemia Gene Mutations among Iranian Patients. 38
27041517 2016
42
Molecular and Cellular Mechanisms of Myelodysplastic Syndrome: Implications on Targeted Therapy. 38
27023522 2016
43
The Simple Chordate Ciona intestinalis Has a Reduced Complement of Genes Associated with Fanconi Anemia. 38
27279728 2016
44
Exposure to fluorescent light triggers down regulation of genes involved with mitotic progression in Xiphophorus skin. 38
26334372 2015
45
Identification of point mutations and large intragenic deletions in Fanconi anemia using next-generation sequencing technology. 38
26740942 2015
46
Functional analyses of ATM, ATR and Fanconi anemia proteins in lung carcinoma : ATM, ATR and FA in lung carcinoma. 38
26438152 2015
47
Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy. 38
26296701 2015
48
RNA interferences targeting the Fanconi anemia/BRCA pathway upstream genes reverse cisplatin resistance in drug-resistant lung cancer cells. 38
26385482 2015
49
The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL. 38
26149689 2015
50
Deficiency of UBE2T, the E2 Ubiquitin Ligase Necessary for FANCD2 and FANCI Ubiquitination, Causes FA-T Subtype of Fanconi Anemia. 38
26119737 2015

Variations for Fanconi Anemia, Complementation Group L

ClinVar genetic disease variations for Fanconi Anemia, Complementation Group L:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 FANCL FANCL, 3-BP DEL, 1007TAT deletion Pathogenic
2 FANCL FANCL, 4-BP DUP, 1095AATT duplication Pathogenic
3 FANCL NM_018062.3(FANCL): c.822-15_822-9delins177 indel Pathogenic 2:58390091-58390097 2:58162956-58162962
4 FANCL NM_018062.3(FANCL): c.430del (p.Ser144fs) deletion Pathogenic rs869320685 2:58431306-58431306 2:58204171-58204171
5 FANCL NM_018062.3(FANCL): c.268del (p.Leu90fs) deletion Pathogenic rs869320684 2:58453868-58453868 2:58226733-58226733
6 FANCL NM_018062.3(FANCL): c.1096_1099dup (p.Thr367fs) duplication Conflicting interpretations of pathogenicity rs759217526 2:58386929-58386932 2:58159794-58159797
7 FANCL NM_018062.3(FANCL): c.1007_1009del (p.Ile336_Cys337delinsSer) deletion Conflicting interpretations of pathogenicity rs747253294 2:58388668-58388670 2:58161533-58161535
8 FANCL NM_018062.3(FANCL): c.548_550TAA[1] (p.Ile184del) short repeat Uncertain significance 2:58392997-58392999 2:58165862-58165864
9 FANCL NM_018062.3(FANCL): c.147_148delinsTT (p.Lys49_Asn50delinsAsnTyr) indel Uncertain significance 2:58459196-58459197 2:58232061-58232062
10 FANCL NM_018062.3(FANCL): c.932dup (p.Tyr311Ter) duplication Uncertain significance rs529201454 2:58388745-58388745 2:58161610-58161610

Expression for Fanconi Anemia, Complementation Group L

Search GEO for disease gene expression data for Fanconi Anemia, Complementation Group L.

Pathways for Fanconi Anemia, Complementation Group L

Pathways related to Fanconi Anemia, Complementation Group L according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.5 UBE2W FANCL
2
Show member pathways
11.24 FANCL FANCD2
3 10.9 FANCL FANCD2
4 10.77 UBE2T FANCL FANCD2
5 10.62 UBE2W UBE2T
6 10.42 FANCL FANCD2

GO Terms for Fanconi Anemia, Complementation Group L

Cellular components related to Fanconi Anemia, Complementation Group L according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleolus GO:0005730 8.8 UBE2W UBE2T FANCD2

Biological processes related to Fanconi Anemia, Complementation Group L according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.62 UBE2W UBE2T FANCL FANCD2
2 protein ubiquitination GO:0016567 9.61 UBE2W UBE2T FANCL
3 DNA repair GO:0006281 9.56 UBE2W UBE2T FANCL FANCD2
4 cellular response to oxidative stress GO:0034599 9.4 VRK2 FANCD2
5 protein K11-linked ubiquitination GO:0070979 9.37 UBE2W UBE2T
6 interstrand cross-link repair GO:0036297 9.33 UBE2T FANCL FANCD2
7 protein monoubiquitination GO:0006513 9.13 UBE2W UBE2T FANCL
8 gamete generation GO:0007276 8.8 GGN FANCL FANCD2

Molecular functions related to Fanconi Anemia, Complementation Group L according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.56 VRK2 UBE2W UBE2T FANCL
2 ubiquitin-protein transferase activity GO:0004842 9.33 UBE2W UBE2T FANCL
3 ubiquitin conjugating enzyme activity GO:0061631 8.96 UBE2W UBE2T
4 ubiquitin protein ligase binding GO:0031625 8.92 UBE2W UBE2T GGN FANCL

Sources for Fanconi Anemia, Complementation Group L

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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