MCID: DNL001
MIFTS: 54

Dna Ligase Iv Deficiency malady

Blood diseases, Cancer diseases categories

Summaries for Dna Ligase Iv Deficiency

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8Disease Ontology, 46OMIM, 32MalaCards
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Disease Ontology:8 A combined t cell and b cell immunodeficiency that is caused by a mutatino in the lig4 gene, a dna ligase, encoding a protein essential for v(d)j recombination and dna double-strand break (dsb) repair through nonhomologous end joining (nhej). patients present with immunodeficiency and developmental and growth delay.

MalaCards: Dna Ligase Iv Deficiency, also known as lig4 syndrome, is related to seckel syndrome and nijmegen breakage syndrome, and has symptoms including lymphadenopathy/polyadenopathies, hepatomegaly/liver enlargement (excluding storage disease) and malabsorption/chronic diarrhea/steatorrhea. An important gene associated with Dna Ligase Iv Deficiency is LIG4 (ligase IV, DNA, ATP-dependent), and among its related pathways are Global Genomic NER (GG-NER) and Fanconi Anemia pathway. The compounds l189 and aphidicolin have been mentioned in the context of this disorder. Affiliated tissues include b cells, t cells and skin, and related mouse phenotypes are tumorigenesis and craniofacial.

Description from OMIM:46 606593

Aliases & Classifications for Dna Ligase Iv Deficiency

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8Disease Ontology, 9diseasecard, 20GeneTests, 22GTR, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 60UMLS, 26ICD10 via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Cancer diseases
Anatomical: Blood diseases


Characteristics (Orphanet epidemiological data):

48
lig4 syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy; Age of death: Young adult


Aliases & Descriptions:

dna ligase iv deficiency 8 10 48
lig4 syndrome 8 9 20 22 46 44 48 60
ligase 4 syndrome 48


External Ids:

Disease Ontology8 DOID:0060021
OMIM46 606593
ICD10 via Orphanet26 D81.1

Related Diseases for Dna Ligase Iv Deficiency

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17GeneCards, 18GeneDecks
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Graphical network of diseases related to Dna Ligase Iv Deficiency:



Diseases related to dna ligase iv deficiency

Clinical Features for Dna Ligase Iv Deficiency

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46OMIM, 48Orphanet
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Clinical features from OMIM:

606593

Symptoms:

48 (show all 34)
  • lymphadenopathy/polyadenopathies
  • hepatomegaly/liver enlargement (excluding storage disease)
  • malabsorption/chronic diarrhea/steatorrhea
  • telangiectasiae of the skin
  • insulin-independent/type 2 diabetes
  • clinodactyly of fifth finger
  • micropenis/small penis/agenesis
  • undescended/ectopic testes/cryptorchidia/unfixed testes
  • hypothyroidy
  • anomalies of bones/skeletal anomalies
  • severe combined immune deficiency syndrome/scid
  • hyperleukocytosis/leukocytosis
  • brachycephaly/flat occiput
  • acute leukemia
  • lymphoma
  • micrognathia/retrognathia/micrognathism/retrognathism
  • upslanted palpebral fissures/mongoloid slanting palpebral fissures
  • low hair line-front
  • narrow forehead
  • failure to thrive/difficulties for feeding in infancy/growth delay
  • chromosome breakage
  • autosomal recessive inheritance
  • immunodeficiency/increased susceptibility to infections/recurrent infections
  • epicanthic folds
  • telecanthus/canthal dystopy
  • bone marrow failure/pancytopenia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • erythema/erythematous lesions/erythroderma/polymorphous erythema
  • skin photosensitivity
  • anomalies of skin, subcutaneous tissue and mucosae
  • thin/retracted lips
  • broad nasal root
  • long/large/bulbous nose
  • microcephaly

Drugs & Therapeutics for Dna Ligase Iv Deficiency

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5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 60UMLS, 40NDF-RT
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Approved drugs:

Search CenterWatch for Dna Ligase Iv Deficiency

Drug clinical trials:

Search ClinicalTrials for Dna Ligase Iv Deficiency

Search NIH Clinical Center for Dna Ligase Iv Deficiency

Search CenterWatch for Dna Ligase Iv Deficiency

Genetic Tests for Dna Ligase Iv Deficiency

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20GeneTests, 22GTR
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Genetic tests related to Dna Ligase Iv Deficiency:

id Genetic test Affiliating Genes
1 Lig4 Syndrome20 22 LIG4

Anatomical Context for Dna Ligase Iv Deficiency

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32MalaCards
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MalaCards organs/tissues related to Dna Ligase Iv Deficiency:

32
B cells, T cells, Skin, Bone, Testes, Bone marrow, Liver

Animal Models for Dna Ligase Iv Deficiency or affiliated genes

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36MGI
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MGI Mouse Phenotypes related to Dna Ligase Iv Deficiency:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00020069.6LIG1, ATR
2MP:00053828.1XRCC4, XRCC2, ATR, LIG4
3MP:00107687.4LIG1, LIG4, ATR, XRCC2, XRCC4, XRCC5
4MP:00053787.3XRCC5, XRCC4, XRCC2, ATR, LIG4, LIG1
5MP:00053976.9XRCC5, XRCC4, ATR, DCLRE1C, LIG4, LIG1
6MP:00053876.9XRCC5, XRCC4, ATR, DCLRE1C, LIG4, LIG1
7MP:00053766.8XRCC5, XRCC4, XRCC2, ATR, LIG4, LIG1
8MP:00053846.6XRCC5, XRCC4, XRCC2, ATR, DCLRE1C, LIG4

Publications for Dna Ligase Iv Deficiency

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50PubMed
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Articles related to Dna Ligase Iv Deficiency:

idTitleAuthorsYear
1
A novel mutation in a family with DNA ligase IV deficiency syndrome. (19418549)
2009
2
DNA-ligase IV and DNA-protein kinase play a critical role in deficient caspases activation in apoptosis-resistant cancer cells by using doxorubicin. (18508926)
2008
3
Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure. (17224058)
2007
4
Ku80- and DNA ligase IV-deficient plants are sensitive to ionizing radiation and defective in T-DNA integration. (12753583)
2003
5
The embryonic lethality in DNA ligase IV-deficient mice is rescued by deletion of Ku: implications for unifying the heterogeneous phenotypes of NHEJ mutants. (12531011)
2002
6
Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm. (11040211)
2000
7
DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. (10911993)
2000

Genetic Variations for Dna Ligase Iv Deficiency

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62UniProtKB/Swiss-Prot
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Genetic disease variations for Dna Ligase Iv Deficiency:

62
id Symbol AA change Variation ID SNP ID
1LIG4p.Arg278HisVAR_012774
2LIG4p.Gly469GluVAR_012775

Expression for genes affiliated with Dna Ligase Iv Deficiency

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1BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Dna Ligase Iv Deficiency

Search GEO for disease gene expression data for Dna Ligase Iv Deficiency.

Pathways for genes affiliated with Dna Ligase Iv Deficiency

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53Reactome, 29KEGG, 51QIAGEN, 37NCBI BioSystems Database, 4Cell Signaling Technology, 12EMD Millipore
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Compounds for genes affiliated with Dna Ligase Iv Deficiency

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59Tocris Bioscience, 44Novoseek, 11DrugBank, 49PharmGKB, 28IUPHAR, 2BitterDB, 24HMDB
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Compounds related to Dna Ligase Iv Deficiency according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1l189599.8LIG1, LIG4
2aphidicolin449.3LIG1, ATR
3bleomycin44 1110.2LIG1, DCLRE1C, XRCC5
4camptothecin44 59 1111.1ATR, XRCC2, XRCC5
5cisplatin44 49 59 1112.1LIG1, XRCC2, XRCC5
6caffeine44 49 28 2 11 2414.1XRCC2, ATR, LIG1
7polynucleotide449.0LIG1, LIG4, XRCC4
8etoposide44 49 59 1111.8XRCC5, ATR, DCLRE1C, LIG1
9wortmannin448.5XRCC4, ATR, LIG4

GO Terms for genes affiliated with Dna Ligase Iv Deficiency

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16Gene Ontology
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Cellular components related to Dna Ligase Iv Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1chromosomeGO:0056949.4LIG1, ATR
2DNA ligase IV complexGO:0328079.4XRCC4, LIG4
3DNA-dependent protein kinase-DNA ligase 4 complexGO:0059589.4LIG4, XRCC4
4condensed chromosomeGO:0007939.2LIG4, XRCC4
5nonhomologous end joining complexGO:0704198.4NHEJ1, LIG4, XRCC4, XRCC5
6nucleoplasmGO:0056547.8XRCC5, XRCC4, ATR, LIG4, LIG1
7nucleusGO:0056346.6XRCC5, XRCC4, XRCC2, DCLRE1C, LIG4, LIG1

Biological processes related to Dna Ligase Iv Deficiency according to GeneCards/GeneDecks:

(show all 27)
idNameGO IDScoreTop Affiliating Genes
1lagging strand elongationGO:0062739.9LIG4, LIG1
2V(D)J recombinationGO:0331519.9LIG1, LIG4
3nucleotide-excision repair, DNA gap fillingGO:0062979.8LIG1, LIG4
4pro-B cell differentiationGO:0023289.6LIG4, XRCC4
5immunoglobulin V(D)J recombinationGO:0331529.6LIG4, XRCC4
6double-strand break repair via homologous recombinationGO:0007249.5LIG1, XRCC2
7cellular response to lithium ionGO:0712859.5LIG4, XRCC4
8isotype switchingGO:0451909.5XRCC4, LIG4
9response to ionizing radiationGO:0102129.5NHEJ1, DCLRE1C
10telomere maintenanceGO:0007239.4LIG1, DCLRE1C, XRCC5
11T cell differentiation in thymusGO:0330779.4LIG4, XRCC4
12positive regulation of fibroblast proliferationGO:0481469.4XRCC4, LIG4
13positive regulation of ligase activityGO:0513519.4XRCC4, NHEJ1
14DNA recombinationGO:0063109.3NHEJ1, DCLRE1C, XRCC5
15response to X-rayGO:0101659.2XRCC4, XRCC2, LIG4
16response to gamma radiationGO:0103329.2LIG4, XRCC2, XRCC4
17establishment of integrated proviral latencyGO:0757139.2LIG4, XRCC4, XRCC5
18B cell differentiationGO:0301839.2NHEJ1, DCLRE1C
19negative regulation of neuron apoptotic processGO:0435249.2XRCC4, XRCC2, LIG4
20DNA ligation involved in DNA repairGO:0511039.1XRCC4, LIG4, LIG1
21in utero embryonic developmentGO:0017019.0LIG4, XRCC2, XRCC4
22central nervous system developmentGO:0074178.9NHEJ1, LIG4, XRCC4
23positive regulation of neurogenesisGO:0507698.8LIG4, XRCC2, XRCC4, XRCC5
24viral processGO:0160328.8XRCC5, XRCC4, LIG4
25double-strand break repairGO:0063028.3XRCC5, XRCC4, DCLRE1C, LIG4, LIG1
26double-strand break repair via nonhomologous end joiningGO:0063038.1NHEJ1, LIG1, LIG4, XRCC4, XRCC5
27DNA repairGO:0062817.8XRCC5, XRCC4, XRCC2, ATR, LIG4, LIG1

Molecular functions related to Dna Ligase Iv Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1DNA ligase (ATP) activityGO:0039109.7LIG4, LIG1
2DNA ligase activityGO:0039099.6LIG4, LIG1
3ligase activityGO:0168749.3LIG4, XRCC4
4protein C-terminus bindingGO:0080228.8LIG4, XRCC4, XRCC5
5ATP bindingGO:0055247.9XRCC5, XRCC2, ATR, LIG4, LIG1
6DNA bindingGO:0036776.9NHEJ1, LIG1, LIG4, ATR, XRCC2, XRCC4

Products for genes affiliated with Dna Ligase Iv Deficiency

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Dna Ligase Iv Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet