FANCL
MCID: FNC028
MIFTS: 48

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 56 29 13 6 39 71
Fanconi Anemia Complementation Group L 12 73 15
Fancl 56 12 73

Characteristics:

OMIM:

56
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:

31
fanconi anemia, complementation group l:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Fanconi Anemia, Complementation Group L

OMIM : 56 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 vacterl association and fanconi anemia, complementation group a. An important gene associated with Fanconi Anemia, Complementation Group L is FANCL (FA Complementation Group L), and among its related pathways/superpathways are DNA damage_ATM/ATR regulation of G1/S checkpoint and Fanconi anemia pathway. The drugs Talazoparib and Silicon 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 : 73 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 32)
# Related Disease Score Top Affiliating Genes
1 vacterl association 32.2 FANCL FANCI
2 fanconi anemia, complementation group a 32.2 VRK2 UBE2T FANCL FANCI FANCD2
3 fanconi anemia, complementation group b 32.0 FANCL FANCD2
4 fanconi anemia, complementation group c 31.8 FANCL FANCI FANCD2
5 fanconi anemia, complementation group j 31.8 FANCL FANCI FANCD2
6 fanconi anemia, complementation group d1 31.5 UBE2T FANCL FANCI FANCD2
7 fanconi anemia, complementation group n 31.5 UBE2T FANCL FANCI FANCD2
8 esophageal atresia 31.4 FANCL FANCI FANCD2
9 fanconi anemia, complementation group o 31.3 FANCL FANCI FANCD2
10 fanconi anemia, complementation group p 31.3 FANCL FANCI FANCD2
11 fanconi anemia, complementation group u 31.0 UBE2T FANCL FANCI FANCD2
12 fanconi anemia, complementation group v 31.0 UBE2T FANCL FANCI FANCD2
13 fanconi anemia, complementation group r 31.0 UBE2T FANCL FANCI FANCD2
14 fanconi anemia, complementation group t 31.0 UBE2T FANCL FANCI FANCD2
15 fanconi anemia, complementation group q 31.0 UBE2T FANCL FANCI FANCD2
16 congenital hypoplastic anemia 30.9 UBE2T FANCL FANCI FANCD2
17 fanconi anemia, complementation group i 30.5 FANCI FANCD2
18 fanconi anemia, complementation group d2 30.3 FANCI FANCD2
19 fanconi anemia, complementation group e 11.6
20 squamous cell carcinoma, head and neck 11.2
21 bartholin's gland carcinoma 11.1
22 bartholin's gland disease 11.1
23 bartholin's gland adenocarcinoma 11.1
24 deficiency anemia 10.5
25 aplastic anemia 10.2
26 pulmonary fibrosis and/or bone marrow failure, telomere-related, 2 10.2
27 autosomal recessive disease 10.2
28 breast cancer 10.1
29 cervical cancer 10.1
30 allergic hypersensitivity disease 10.1
31 acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22) 10.1
32 interstitial nephritis, karyomegalic 9.8 FANCI 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:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 31 occasional (7.5%) HP:0000316
2 short neck 31 occasional (7.5%) HP:0000470
3 hydrocephalus 31 occasional (7.5%) HP:0000238
4 depressed nasal bridge 31 occasional (7.5%) HP:0005280
5 wide nasal bridge 31 occasional (7.5%) HP:0000431
6 abnormal facial shape 31 occasional (7.5%) HP:0001999
7 microtia 31 occasional (7.5%) HP:0008551
8 intrauterine growth retardation 31 occasional (7.5%) HP:0001511
9 cleft palate 31 occasional (7.5%) HP:0000175
10 bone marrow hypocellularity 31 occasional (7.5%) HP:0005528
11 tracheoesophageal fistula 31 occasional (7.5%) HP:0002575
12 microphthalmia 31 occasional (7.5%) HP:0000568
13 micropenis 31 occasional (7.5%) HP:0000054
14 anal atresia 31 occasional (7.5%) HP:0002023
15 renal hypoplasia 31 occasional (7.5%) HP:0000089
16 esophageal atresia 31 occasional (7.5%) HP:0002032
17 absent thumb 31 occasional (7.5%) HP:0009777
18 global developmental delay 31 HP:0001263
19 cafe-au-lait spot 31 HP:0000957
20 anemia 31 HP:0001903
21 chromosome breakage 31 HP:0040012

Symptoms via clinical synopsis from OMIM:

56
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)

Genitourinary Kidneys:
renal hypoplasia (in some patients)

Growth Other:
intrauterine growth retardation (in some patients)

Cardiovascular Heart:
cardiac malformations (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:
developmental delay (in some patients)
hydrocephalus (in some patients)

Genitourinary External Genitalia Male:
micropenis (in some patients)

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

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 viability with MLN4924 (a NAE inhibitor) GR00250-A-3 8.92 FANCD2 FANCI FANCL UBE2T

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
Silicon Approved, Investigational Phase 2 7440-21-3 4082203
3
Titanium dioxide Approved Phase 2 13463-67-7
4
Mannitol Approved, Investigational Phase 2 69-65-8 453 6251
5
Iron Approved, Experimental Phase 2 7439-89-6, 15438-31-0 23925 27284
6
Olaparib Approved Phase 2 763113-22-0 23725625
7
Bevacizumab Approved, Investigational Phase 2 216974-75-3
8
Irinotecan Approved, Investigational Phase 2 97682-44-5, 100286-90-6 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
5 A Study on the Homologous Recombination Deficiency Status in Chinese Population With Epithelial Ovarian Cancer Recruiting NCT04190667

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:

40
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 126)
# Title Authors PMID Year
1
Loss-of-Function FANCL Mutations Associate with Severe Fanconi Anemia Overlapping the VACTERL Association. 61 56 6
25754594 2015
2
Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation group. 61 56 6
19405097 2009
3
A novel ubiquitin ligase is deficient in Fanconi anemia. 61 56 6
12973351 2003
4
Fanconi anemia: at the crossroads of DNA repair. 56
21568838 2011
5
ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. 6
19888064 2009
6
Esophageal Atresia/Tracheoesophageal Fistula Overview 6
20301753 2009
7
Carrier screening in individuals of Ashkenazi Jewish descent. 6
18197057 2008
8
Fanconi Anemia 6
20301575 2002
9
Dataset of allele and genotype frequencies of five polymorphisms candidate genes analyzed for association with body mass index in Russian women. 61
31890803 2020
10
A founder variant in the South Asian population leads to a high prevalence of FANCL Fanconi anemia cases in India. 61
31513304 2020
11
Analysis of polymorphisms in genes associated with the FA/BRCA pathway in three patients with multiple primary malignant neoplasms. 61
30942098 2019
12
Allosteric mechanism for site-specific ubiquitination of FANCD2. 61
31873223 2019
13
Structure of the Fanconi anaemia monoubiquitin ligase complex. 61
31666700 2019
14
Small-Molecule Inhibition of UBE2T/FANCL-Mediated Ubiquitylation in the Fanconi Anemia Pathway. 61
31525021 2019
15
Efficacy of Radium-223 in Bone-metastatic Castration-resistant Prostate Cancer with and Without Homologous Repair Gene Defects. 61
30293905 2019
16
Prevalence of DNA repair gene mutations in localized prostate cancer according to clinical and pathologic features: association of Gleason score and tumor stage. 61
30171229 2019
17
CCNE1 amplification is associated with poor prognosis in patients with triple negative breast cancer. 61
30665374 2019
18
Genomic alterations important for the prognosis in patients with follicular lymphoma treated in SWOG study S0016. 61
30446494 2019
19
The Interplay Between the DNA Damage Response, RNA Processing and Extracellular Vesicles. 61
32010626 2019
20
Multiplexed CRISPR/Cas9-mediated knockout of 19 Fanconi anemia pathway genes in zebrafish revealed their roles in growth, sexual development and fertility. 61
30540754 2018
21
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings. 61
30306255 2018
22
Roles of Figla/figla in Juvenile Ovary Development and Follicle Formation During Zebrafish Gonadogenesis. 61
30184072 2018
23
Prenatal diagnosis of a 3.2-Mb 2p16.1-p15 duplication associated with familial intellectual disability. 61
30122582 2018
24
Germline deleterious mutations in genes other than BRCA2 are infrequent in male breast cancer. 61
29335925 2018
25
Somatic mutations in early onset luminal breast cancer. 61
29854292 2018
26
The HEM Lines: A New Library of Homozygous Arabidopsis thaliana EMS Mutants and its Potential to Detect Meiotic Phenotypes. 61
30283471 2018
27
Case study: patient-derived clear cell adenocarcinoma xenograft model longitudinally predicts treatment response. 61
30202792 2018
28
Penetrance of Polygenic Obesity Susceptibility Loci across the Body Mass Index Distribution. 61
29220676 2017
29
Constitutive role of the Fanconi anemia D2 gene in the replication stress response. 61
29021208 2017
30
Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50. 61
28678401 2017
31
Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene. 61
28881617 2017
32
Arsenite Binds to the RING Finger Domain of FANCL E3 Ubiquitin Ligase and Inhibits DNA Interstrand Crosslink Repair. 61
28535027 2017
33
Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a Chinese girl with Fanconi Anemia. 61
28419882 2017
34
Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer. 61
28050010 2017
35
Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells. 61
28926637 2017
36
The FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2. 61
27986592 2017
37
Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway. 61
27986371 2017
38
The functional status of DNA repair pathways determines the sensitization effect to cisplatin in non-small cell lung cancer cells. 61
27473273 2016
39
Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma. 61
27835906 2016
40
Leukemic survival factor SALL4 contributes to defective DNA damage repair. 61
27132514 2016
41
Hereditary truncating mutations of DNA repair and other genes in BRCA1/BRCA2/PALB2-negatively tested breast cancer patients. 61
26822949 2016
42
Frameshift variant FANCL*c.1096_1099dupATTA is not associated with high breast cancer risk. 61
27506598 2016
43
RE: frameshift variant FANCL*c.1096_1099dupATTA is not associated with high breast cancer risk. 61
27659787 2016
44
Mutations of myelodysplastic syndromes (MDS): An update. 61
27543316 2016
45
Fanconi Anemia Proteins Function in Mitophagy and Immunity. 61
27133164 2016
46
Determining the frequency of pathogenic germline variants from exome sequencing in patients with castrate-resistant prostate cancer. 61
27084275 2016
47
Profiling Fanconi Anemia Gene Mutations among Iranian Patients. 61
27041517 2016
48
Molecular and Cellular Mechanisms of Myelodysplastic Syndrome: Implications on Targeted Therapy. 61
27023522 2016
49
The Simple Chordate Ciona intestinalis Has a Reduced Complement of Genes Associated with Fanconi Anemia. 61
27279728 2016
50
Exposure to fluorescent light triggers down regulation of genes involved with mitotic progression in Xiphophorus skin. 61
26334372 2015

Variations for Fanconi Anemia, Complementation Group L

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

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FANCL NM_018062.3(FANCL):c.822-15_822-9delins177indel Pathogenic 2535 2:58390091-58390097 2:58162956-58162962
2 FANCL FANCL, 3-BP DEL, 1007TATdeletion Pathogenic 30701
3 FANCL FANCL, 4-BP DUP, 1095AATTduplication Pathogenic 30702
4 FANCL NM_001114636.1(FANCL):c.268del (p.Leu90fs)deletion Pathogenic 209076 rs869320684 2:58453868-58453868 2:58226733-58226733
5 FANCL NM_001114636.1(FANCL):c.430del (p.Ser144fs)deletion Pathogenic 209077 rs869320685 2:58431306-58431306 2:58204171-58204171
6 FANCL NM_001114636.1(FANCL):c.1111_1114dup (p.Thr372fs)duplication Conflicting interpretations of pathogenicity 210988 rs759217526 2:58386928-58386929 2:58159793-58159794
7 FANCL NM_001114636.1(FANCL):c.1022_1024del (p.Ile341_Cys342delinsSer)deletion Conflicting interpretations of pathogenicity 241247 rs747253294 2:58388668-58388670 2:58161533-58161535
8 FANCL NM_001114636.1(FANCL):c.947dup (p.Tyr316Ter)duplication Uncertain significance 336654 rs529201454 2:58388744-58388745 2:58161609-58161610
9 FANCL NM_001114636.1(FANCL):c.563_565TAA[1] (p.Ile189del)short repeat Uncertain significance 625940 2:58392997-58392999 2:58165862-58165864
10 FANCL NM_001114636.1(FANCL):c.147_148delinsTT (p.Lys49_Asn50delinsAsnTyr)indel Uncertain significance 625941 rs1558825558 2:58459196-58459197 2:58232061-58232062

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 10.97 FANCL FANCD2
2 10.89 UBE2T FANCL FANCI FANCD2
3 10.78 UBE2T FANCI
4 10.62 UBE2W UBE2T
5 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 nuclear envelope GO:0005635 8.8 VRK2 NUP43 FANCL

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 9.65 UBE2W UBE2T FANCL FANCI FANCD2
2 protein K11-linked ubiquitination GO:0070979 9.37 UBE2W UBE2T
3 DNA repair GO:0006281 9.35 UBE2W UBE2T FANCL FANCI FANCD2
4 protein monoubiquitination GO:0006513 9.33 UBE2W UBE2T FANCL
5 gamete generation GO:0007276 9.32 FANCL FANCD2
6 interstrand cross-link repair GO:0036297 8.92 UBE2T FANCL FANCI FANCD2

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

# Name GO ID Score Top Affiliating Genes
1 ubiquitin protein ligase binding GO:0031625 9.43 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 DNA polymerase binding GO:0070182 8.62 FANCI FANCD2

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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