FANCL
MCID: FNC028
MIFTS: 41

Fanconi Anemia, Complementation Group L (FANCL)

Categories: Blood diseases, Bone 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 58 30 13 6 41 74
Fanconi Anemia Complementation Group L 12 76 15
Fancl 58 12 76

Characteristics:

OMIM:

58
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:

33
fanconi anemia, complementation group l:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Fanconi Anemia, Complementation Group L

OMIM : 58 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 b. 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 Olaparib and Durvalumab have been mentioned in the context of this disorder. Affiliated tissues include bone and bone marrow, 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 : 76 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 a family:

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 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 17)
# Related Disease Score Top Affiliating Genes
1 fanconi anemia, complementation group a 32.6 FANCD2 FANCL UBE2T
2 fanconi anemia, complementation group b 31.7 FANCD2 FANCL
3 fanconi anemia, complementation group j 31.6 FANCD2 FANCL
4 congenital hypoplastic anemia 31.4 FANCD2 FANCL
5 fanconi anemia, complementation group r 31.3 FANCD2 FANCL UBE2T
6 fanconi anemia, complementation group t 31.3 FANCD2 FANCL UBE2T
7 squamous cell carcinoma, head and neck 11.2
8 western equine encephalitis 11.2
9 extraosseous ewing's sarcoma 11.2
10 breast cancer 10.1
11 vater/vacterl association 10.1
12 lung cancer 10.1
13 cervical cancer 10.1
14 vacterl association 10.1
15 fanconi anemia, complementation group u 9.9 FANCD2 UBE2T
16 fanconi anemia, complementation group v 9.7 FANCD2 UBE2T
17 fanconi anemia, complementation group q 9.7 FANCD2 FANCL UBE2T

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:

33 (show all 21)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 33 occasional (7.5%) HP:0000316
2 short neck 33 occasional (7.5%) HP:0000470
3 hydrocephalus 33 occasional (7.5%) HP:0000238
4 depressed nasal bridge 33 occasional (7.5%) HP:0005280
5 wide nasal bridge 33 occasional (7.5%) HP:0000431
6 abnormal facial shape 33 occasional (7.5%) HP:0001999
7 microtia 33 occasional (7.5%) HP:0008551
8 cleft palate 33 occasional (7.5%) HP:0000175
9 bone marrow hypocellularity 33 occasional (7.5%) HP:0005528
10 intrauterine growth retardation 33 occasional (7.5%) HP:0001511
11 microphthalmia 33 occasional (7.5%) HP:0000568
12 anal atresia 33 occasional (7.5%) HP:0002023
13 renal hypoplasia 33 occasional (7.5%) HP:0000089
14 tracheoesophageal fistula 33 occasional (7.5%) HP:0002575
15 esophageal atresia 33 occasional (7.5%) HP:0002032
16 micropenis 33 occasional (7.5%) HP:0000054
17 absent thumb 33 occasional (7.5%) HP:0009777
18 global developmental delay 33 HP:0001263
19 anemia 33 HP:0001903
20 cafe-au-lait spot 33 HP:0000957
21 chromosome breakage 33 HP:0040012

Symptoms via clinical synopsis from OMIM:

58
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:

27
# 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 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Olaparib Approved Phase 1 763113-22-0 23725625
2
Durvalumab Approved, Investigational Phase 1 1428935-60-7
3 Immunoglobulins Phase 1
4 Antibodies, Monoclonal Phase 1
5 Antineoplastic Agents, Immunological Phase 1
6 Immunoglobulin G Phase 1
7 Antibodies Phase 1
8 Immunologic Factors Phase 1
9 Poly(ADP-ribose) Polymerase Inhibitors Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Copanlisib, Olaparib, and Durvalumab in Treating Patients With Metastatic or Unresectable Solid Tumors Not yet recruiting NCT03842228 Phase 1 Copanlisib;Copanlisib Hydrochloride;Olaparib

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 30 FANCL

Anatomical Context for Fanconi Anemia, Complementation Group L

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

42
Bone, Bone Marrow

Publications for Fanconi Anemia, Complementation Group L

Variations for Fanconi Anemia, Complementation Group L

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

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 FANCL NM_018062.3(FANCL): c.268delC (p.Leu90Phefs) deletion Pathogenic rs869320684 GRCh37 Chromosome 2, 58453868: 58453868
2 FANCL NM_018062.3(FANCL): c.268delC (p.Leu90Phefs) deletion Pathogenic rs869320684 GRCh38 Chromosome 2, 58226733: 58226733
3 FANCL NM_018062.3(FANCL): c.430delT (p.Ser144Leufs) deletion Pathogenic rs869320685 GRCh38 Chromosome 2, 58204171: 58204171
4 FANCL NM_018062.3(FANCL): c.430delT (p.Ser144Leufs) deletion Pathogenic rs869320685 GRCh37 Chromosome 2, 58431306: 58431306
5 FANCL NM_001114636.1(FANCL): c.1111_1114dupATTA (p.Thr372Asnfs) duplication Conflicting interpretations of pathogenicity rs759217526 GRCh37 Chromosome 2, 58386929: 58386932
6 FANCL NM_001114636.1(FANCL): c.1111_1114dupATTA (p.Thr372Asnfs) duplication Conflicting interpretations of pathogenicity rs759217526 GRCh38 Chromosome 2, 58159794: 58159797
7 FANCL NM_018062.3(FANCL): c.822-15_822-9delins177 indel Pathogenic GRCh37 Chromosome 2, 58390091: 58390097
8 FANCL NM_018062.3(FANCL): c.822-15_822-9delins177 indel Pathogenic GRCh38 Chromosome 2, 58162956: 58162962
9 FANCL FANCL, 3-BP DEL, 1007TAT deletion Pathogenic
10 FANCL FANCL, 4-BP DUP, 1095AATT duplication Pathogenic
11 FANCL NM_018062.3(FANCL): c.1007_1009delTAT (p.Ile336_Cys337delinsSer) deletion Conflicting interpretations of pathogenicity rs747253294 GRCh37 Chromosome 2, 58388668: 58388670
12 FANCL NM_018062.3(FANCL): c.1007_1009delTAT (p.Ile336_Cys337delinsSer) deletion Conflicting interpretations of pathogenicity rs747253294 GRCh38 Chromosome 2, 58161533: 58161535

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 FANCL UBE2W
2
Show member pathways
11.24 FANCD2 FANCL
3 10.9 FANCD2 FANCL
4 10.77 FANCD2 FANCL UBE2T
5 10.62 FANCD2 FANCL
6 10.42 UBE2T UBE2W

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 8.92 FANCD2 GGN UBE2T UBE2W

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 FANCD2 FANCL UBE2T UBE2W
2 protein ubiquitination GO:0016567 9.61 FANCL UBE2T UBE2W
3 DNA repair GO:0006281 9.56 FANCD2 FANCL UBE2T UBE2W
4 cellular response to oxidative stress GO:0034599 9.4 FANCD2 VRK2
5 protein K11-linked ubiquitination GO:0070979 9.37 UBE2T UBE2W
6 interstrand cross-link repair GO:0036297 9.33 FANCD2 FANCL UBE2T
7 protein monoubiquitination GO:0006513 9.13 FANCL UBE2T UBE2W
8 gamete generation GO:0007276 8.8 FANCD2 FANCL GGN

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 FANCL UBE2T UBE2W VRK2
2 ubiquitin-protein transferase activity GO:0004842 9.33 FANCL UBE2T UBE2W
3 ubiquitin conjugating enzyme activity GO:0061631 8.96 UBE2T UBE2W
4 ubiquitin protein ligase binding GO:0031625 8.92 FANCL GGN UBE2T UBE2W

Sources for Fanconi Anemia, Complementation Group L

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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