MCID: LG4001
MIFTS: 52

Lig4 Syndrome malady

Categories: Genetic diseases, Blood diseases, Rare diseases, Immune diseases

Aliases & Classifications for Lig4 Syndrome

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Sources:
11Disease Ontology, 12diseasecard, 13DISEASES, 24GeneTests, 26GTR, 30ICD10 via Orphanet, 36MedGen, 49Novoseek, 51OMIM, 53Orphanet, 67UMLS, 69UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Lig4 Syndrome:

Name: Lig4 Syndrome 51 11 24 53 69 12 49 67
Dna Ligase Iv Deficiency 11 53 13
 
Lig4s 69 26
Ligase 4 Syndrome 53

Characteristics:

Orphanet epidemiological data:

53
lig4 syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: young Adult

Classifications:



External Ids:

OMIM51 606593
Disease Ontology11 DOID:0060021
Orphanet53 ORPHA99812
ICD10 via Orphanet30 D81.1
MedGen36 C1847827

Summaries for Lig4 Syndrome

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Disease Ontology:11 A combined T cell and B cell immunodeficiency that has material basis in a mutation 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 based summary: Lig4 Syndrome, also known as dna ligase iv deficiency, is related to nijmegen breakage syndrome and omenn syndrome, and has symptoms including microcephaly, abnormality of chromosome stability and thin vermilion border. An important gene associated with Lig4 Syndrome is LIG4 (DNA Ligase 4), and among its related pathways are DNA Damage Induced 14-3-3Sigma Signaling and DNA damage_ATM/ATR regulation of G1/S checkpoint. Affiliated tissues include skin, b cells and t cells, and related mouse phenotypes are liver/biliary system and behavior/neurological.

UniProtKB/Swiss-Prot:69 LIG4 syndrome: Characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities.

Description from OMIM:51 606593

Related Diseases for Lig4 Syndrome

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Graphical network of diseases related to Lig4 Syndrome:



Diseases related to lig4 syndrome

Symptoms for Lig4 Syndrome

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Clinical features from OMIM:

606593

Human phenotypes related to Lig4 Syndrome:

 63 53 (show all 41)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 microcephaly63 53 hallmark (90%) Very frequent (99-80%) HP:0000252
2 abnormality of chromosome stability63 53 hallmark (90%) Very frequent (99-80%) HP:0003220
3 thin vermilion border63 53 typical (50%) Frequent (79-30%) HP:0000233
4 epicanthus63 53 typical (50%) Frequent (79-30%) HP:0000286
5 low anterior hairline63 53 typical (50%) Frequent (79-30%) HP:0000294
6 narrow forehead63 typical (50%) HP:0000341
7 micrognathia63 53 typical (50%) Frequent (79-30%) HP:0000347
8 wide nasal bridge63 53 typical (50%) Frequent (79-30%) HP:0000431
9 telecanthus63 53 typical (50%) Frequent (79-30%) HP:0000506
10 upslanted palpebral fissure63 53 typical (50%) Frequent (79-30%) HP:0000582
11 cutaneous photosensitivity63 53 typical (50%) Frequent (79-30%) HP:0000992
12 acute leukemia63 53 typical (50%) Frequent (79-30%) HP:0002488
13 abnormality of calvarial morphology63 typical (50%) HP:0002648
14 lymphoma63 53 typical (50%) Frequent (79-30%) HP:0002665
15 abnormal nasal morphology63 typical (50%) HP:0005105
16 bone marrow hypocellularity63 typical (50%) HP:0005528
17 cognitive impairment63 typical (50%) HP:0100543
18 cryptorchidism63 53 occasional (7.5%) Occasional (29-5%) HP:0000028
19 hypothyroidism63 53 occasional (7.5%) Occasional (29-5%) HP:0000821
20 leukocytosis63 53 occasional (7.5%) Occasional (29-5%) HP:0001974
21 malabsorption63 53 occasional (7.5%) Occasional (29-5%) HP:0002024
22 hepatomegaly63 53 occasional (7.5%) Occasional (29-5%) HP:0002240
23 lymphadenopathy63 53 occasional (7.5%) Occasional (29-5%) HP:0002716
24 clinodactyly of the 5th finger63 53 occasional (7.5%) Occasional (29-5%) HP:0004209
25 severe combined immunodeficiency63 53 occasional (7.5%) Frequent (79-30%) HP:0004430
26 type ii diabetes mellitus63 53 occasional (7.5%) Occasional (29-5%) HP:0005978
27 hypoplasia of penis63 53 occasional (7.5%) Occasional (29-5%) HP:0008736
28 telangiectasia of the skin63 occasional (7.5%) HP:0100585
29 brachycephaly53 Frequent (79-30%)
30 bird-like facies53 Very frequent (99-80%)
31 abnormality of the skeletal system53 Occasional (29-5%)
32 intellectual disability53 Frequent (79-30%)
33 global developmental delay53 Very frequent (99-80%)
34 growth delay53 Very frequent (99-80%)
35 pancytopenia53 Frequent (79-30%)
36 immunodeficiency53 Very frequent (99-80%)
37 large beaked nose53 Frequent (79-30%)
38 biparietal narrowing53 Frequent (79-30%)
39 abnormality of bone marrow cell morphology53 Frequent (79-30%)
40 erythema53 Frequent (79-30%)
41 teleangiectasia of the skin53 Occasional (29-5%)

Drugs & Therapeutics for Lig4 Syndrome

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Drugs for Lig4 Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1Sunscreening Agents113
2Radiation-Protective Agents466
3Protective Agents7190
4Dermatologic Agents5674

Interventional clinical trials:

idNameStatusNCT IDPhase
1Use of an SPF30 Sunscreen and an After-sun-lotion in Skin Cancer Risk PatientsCompletedNCT00555633

Search NIH Clinical Center for Lig4 Syndrome

Genetic Tests for Lig4 Syndrome

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Genetic tests related to Lig4 Syndrome:

id Genetic test Affiliating Genes
1 Lig4 Syndrome26 24 LIG4

Anatomical Context for Lig4 Syndrome

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MalaCards organs/tissues related to Lig4 Syndrome:

35
Skin, B cells, T cells, Bone marrow, Bone

Animal Models for Lig4 Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Lig4 Syndrome:

40 (show all 19)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053708.3ATR, LIG1, LIG4, NLRP3, PRKDC, RAG1
2MP:00053867.5ATM, ATR, LIG4, LRIG2, NBN, PRKDC
3MP:00053897.5ATM, ATR, LIG4, NBN, NLRP3, PRKDC
4MP:00053817.3ATR, LIG4, NLRP3, NOD2, PRKDC, RAG1
5MP:00053797.2ATM, ATR, DCLRE1C, LIG1, LIG4, NBN
6MP:00107717.0ATM, ATR, LIG1, LRIG2, NLRP3, PRKDC
7MP:00020066.5ATM, ATR, LIG1, LIG4, LRIG2, NBN
8MP:00036316.0ATM, ATR, LIG4, LRIG2, NBN, NLRP3
9MP:00053975.7ATM, ATR, DCLRE1C, LIG1, LIG4, NBN
10MP:00053765.5ATM, ATR, LIG1, LIG4, NBN, NHEJ1
11MP:00107685.4ATM, ATR, LIG1, LIG4, LRIG2, NBN
12MP:00053875.3ATM, ATR, DCLRE1C, LIG1, LIG4, LRIG2
13MP:00053785.1ATM, ATR, LIG1, LIG4, LRIG2, NBN
14MP:00053844.8ATM, ATR, DCLRE1C, LIG1, LIG4, LRIG2

Publications for Lig4 Syndrome

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Articles related to Lig4 Syndrome:

idTitleAuthorsYear
1
Two hits in one: whole genome sequencing unveils LIG4 syndrome and urofacial syndrome in a case report of a child with complex phenotype. (27855655)
2016
2
Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome. (20133615)
2010
3
Epstein-Barr virus-associated B-cell lymphoma in a patient with DNA ligase IV (LIG4) syndrome. (17345618)
2007
4
An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR-Seckel syndrome. (15279811)
2004
5
Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms. (15333585)
2004

Variations for Lig4 Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Lig4 Syndrome:

69
id Symbol AA change Variation ID SNP ID
1LIG4p.Arg278HisVAR_012774rs104894421
2LIG4p.Gly469GluVAR_012775rs104894420

Clinvar genetic disease variations for Lig4 Syndrome:

5
id Gene Variation Type Significance SNP ID Assembly Location
1LIG4NM_002312.3(LIG4): c.1312T> C (p.Tyr438His)SNVLikely pathogenicrs886037777GRCh37Chr 13, 108862305: 108862305
2LIG4NM_002312.3(LIG4): c.1751_1755delTAAGA (p.Ile584Argfs)deletionPathogenicrs770128720GRCh37Chr 13, 108861862: 108861866
3LIG4NM_002312.3(LIG4): c.1738C> T (p.Arg580Ter)SNVPathogenicrs104894418GRCh37Chr 13, 108861879: 108861879
4LIG4NM_002312.3(LIG4): c.2440C> T (p.Arg814Ter)SNVPathogenicrs104894419GRCh37Chr 13, 108861177: 108861177
5LIG4NM_002312.3(LIG4): c.1406G> A (p.Gly469Glu)SNVPathogenicrs104894420GRCh37Chr 13, 108862211: 108862211
6LIG4NM_002312.3(LIG4): c.833G> A (p.Arg278His)SNVPathogenicrs104894421GRCh37Chr 13, 108862784: 108862784
7LIG4NM_002312.3(LIG4): c.26C> T (p.Thr9Ile)SNVprotectivers1805388GRCh37Chr 13, 108863591: 108863591
8LIG4NM_002312.3(LIG4): c.1298_1300delAAC (p.Gln433del)deletionPathogenicrs587776663GRCh37Chr 13, 108862317: 108862319

Expression for genes affiliated with Lig4 Syndrome

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Search GEO for disease gene expression data for Lig4 Syndrome.

Pathways for genes affiliated with Lig4 Syndrome

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Pathways related to Lig4 Syndrome according to GeneCards Suite gene sharing:

(show all 19)
idSuper pathwaysScoreTop Affiliating Genes
19.9ATM, ATR
29.6ATM, ATR, NBN
3
Show member pathways
9.6ATM, ATR, NBN
49.6PRKDC, XRCC5, XRCC6
5
Show member pathways
9.6ATM, ATR, XRCC5
69.6ATM, NOD2
7
Show member pathways
9.5NBN, XRCC5, XRCC6
89.4ATM, ATR, PRKDC, XRCC4
99.4DCLRE1C, RAG1, RAG2
109.2ATM, NBN, XRCC5, XRCC6
11
Show member pathways
9.2LIG1, LIG4, XRCC4, XRCC5, XRCC6
12
Show member pathways
9.1ATM, ATR, NBN, XRCC2
13
Show member pathways
9.0NOD2, PRKDC, XRCC5, XRCC6
148.7ATM, ATR, NBN, PRKDC, XRCC5, XRCC6
158.6DCLRE1C, LIG4, NBN, PRKDC, XRCC4, XRCC5
16
Show member pathways
8.1ATM, DCLRE1C, LIG4, NBN, NHEJ1, PRKDC
178.1ATM, ATR, DCLRE1C, LIG4, NBN, NHEJ1
18
Show member pathways
8.0ATM, ATR, LIG1, LIG4, NBN, PRKDC
19
Show member pathways
7.1ATM, ATR, DCLRE1C, LIG1, LIG4, NBN

GO Terms for genes affiliated with Lig4 Syndrome

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Cellular components related to Lig4 Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1DNA ligase IV complexGO:003280710.7LIG4, XRCC4
2nuclear telomere cap complexGO:000078310.5XRCC5, XRCC6
3Ku70:Ku80 complexGO:004356410.5XRCC5, XRCC6
4DNA-dependent protein kinase-DNA ligase 4 complexGO:000595810.4LIG4, PRKDC, XRCC4
5replication forkGO:00056579.9NBN, XRCC2
6nonhomologous end joining complexGO:00704199.2DCLRE1C, LIG4, NHEJ1, PRKDC, XRCC4, XRCC5
7nuclear chromosome, telomeric regionGO:00007848.7ATM, ATR, DCLRE1C, LIG4, NBN, PRKDC
8nucleoplasmGO:00056546.2ATM, ATR, DCLRE1C, LIG1, LIG4, NBN

Biological processes related to Lig4 Syndrome according to GeneCards Suite gene sharing:

(show all 50)
idNameGO IDScoreTop Affiliating Genes
1pro-B cell differentiationGO:000232810.7LIG4, PRKDC
2nucleotide-excision repair, DNA gap fillingGO:000629710.7LIG1, LIG4
3positive regulation of ligase activityGO:005135110.7NHEJ1, XRCC4
4immunoglobulin V(D)J recombinationGO:003315210.7LIG4, PRKDC
5DNA ligationGO:000626610.6LIG4, XRCC6
6double-strand break repair via classical nonhomologous end joiningGO:009768010.6LIG4, XRCC6
7T cell receptor V(D)J recombinationGO:003315310.6LIG4, PRKDC
8cellular response to lithium ionGO:007128510.6LIG4, XRCC4
9establishment of macromolecular complex localization to telomereGO:009769510.5ATM, ATR
10establishment of RNA localization to telomereGO:009769410.5ATM, ATR
11positive regulation of telomerase catalytic core complex assemblyGO:190488410.5ATM, ATR
12isotype switchingGO:004519010.5LIG4, NBN
13chromosome organizationGO:005127610.5DCLRE1C, LIG4
14negative regulation of telomere cappingGO:190435410.5ATM, NBN
15cellular hyperosmotic salinity responseGO:007147510.5XRCC5, XRCC6
16replicative senescenceGO:009039910.4ATM, ATR
17DNA ligation involved in DNA repairGO:005110310.4LIG1, LIG4, XRCC4
18B cell lineage commitmentGO:000232610.4PRKDC, RAG2
19T cell lineage commitmentGO:000236010.4PRKDC, RAG2
20positive regulation of DNA damage response, signal transduction by p53 class mediatorGO:004351710.3ATM, ATR
21DNA double-strand break processingGO:000072910.2ATM, NBN
22response to X-rayGO:001016510.1LIG4, XRCC2, XRCC4
23establishment of integrated proviral latencyGO:007571310.1LIG4, XRCC4, XRCC5, XRCC6
24positive regulation of neurogenesisGO:005076910.0LIG4, XRCC2, XRCC5
25regulation of smooth muscle cell proliferationGO:004866010.0PRKDC, XRCC5, XRCC6
26peptidyl-serine phosphorylationGO:00181059.9ATM, ATR, PRKDC
27pre-B cell allelic exclusionGO:00023319.9ATM, RAG1, RAG2
28regulation of signal transduction by p53 class mediatorGO:19017969.9ATM, ATR, NBN
29double-strand break repair via homologous recombinationGO:00007249.9ATM, NBN, XRCC2
30response to gamma radiationGO:00103329.9LIG4, PRKDC, XRCC2
31positive regulation of type I interferon productionGO:00324819.8PRKDC, XRCC5, XRCC6
32cellular response to gamma radiationGO:00714809.8ATM, ATR, XRCC5, XRCC6
33DNA duplex unwindingGO:00325089.8NBN, XRCC5, XRCC6
34detection of biotic stimulusGO:00095959.7NLRP3, NOD2
35cellular response to X-rayGO:00714819.7ATM, XRCC5, XRCC6
36DNA synthesis involved in DNA repairGO:00007319.7ATM, NBN, XRCC2
37strand displacementGO:00007329.7ATM, NBN, XRCC2
38telomere maintenanceGO:00007239.6DCLRE1C, NBN, XRCC5, XRCC6
39B cell differentiationGO:00301839.6DCLRE1C, NHEJ1, RAG1, RAG2
40positive regulation of interleukin-1 beta secretionGO:00507189.6NLRP3, NOD2
41positive regulation of type 2 immune responseGO:00028309.6NLRP3, NOD2
42somitogenesisGO:00017569.6ATM, PRKDC, XRCC2
43T cell differentiation in thymusGO:00330779.5LIG4, PRKDC, RAG1, RAG2
44double-strand break repairGO:00063029.3DCLRE1C, LIG4, NBN, PRKDC, XRCC4, XRCC5
45brain developmentGO:00074209.3ATM, PRKDC, XRCC5, XRCC6
46DNA recombinationGO:00063109.2DCLRE1C, NHEJ1, RAG1, XRCC4, XRCC5, XRCC6
47DNA repairGO:00062819.0ATM, ATR, LIG1, LIG4, XRCC2
48V(D)J recombinationGO:00331518.8ATM, DCLRE1C, LIG1, LIG4, PRKDC, RAG1
49double-strand break repair via nonhomologous end joiningGO:00063038.6ATM, DCLRE1C, LIG4, NBN, NHEJ1, PRKDC
50response to ionizing radiationGO:00102128.4ATM, DCLRE1C, LIG4, NHEJ1, PRKDC, XRCC2

Molecular functions related to Lig4 Syndrome according to GeneCards Suite gene sharing:

(show all 14)
idNameGO IDScoreTop Affiliating Genes
1DNA ligase (ATP) activityGO:000391010.8LIG1, LIG4
2DNA ligase activityGO:000390910.8LIG1, LIG4
3DNA-dependent protein kinase activityGO:000467710.7ATM, PRKDC
4double-stranded telomeric DNA bindingGO:000369110.6XRCC5, XRCC6
55-deoxyribose-5-phosphate lyase activityGO:005157510.6XRCC5, XRCC6
6macromolecular complex bindingGO:004487710.6XRCC5, XRCC6
7ATP-dependent DNA helicase activityGO:000400310.1NBN, XRCC5, XRCC6
8damaged DNA bindingGO:00036849.9DCLRE1C, NBN, XRCC5, XRCC6
9protein C-terminus bindingGO:00080229.9LIG4, XRCC4, XRCC5, XRCC6
10peptidoglycan bindingGO:00428349.8NLRP3, NOD2
11double-stranded DNA bindingGO:00036909.6PRKDC, XRCC2, XRCC5, XRCC6
12DNA bindingGO:00036777.5ATM, ATR, LIG1, LIG4, NHEJ1, RAG1
13ATP bindingGO:00055247.0ATM, ATR, LIG1, LIG4, NLRP3, NOD2
14protein bindingGO:00055154.5ATM, ATR, COX5A, DCLRE1C, LIG4, NBN

Sources for Lig4 Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
26GTR
27HGMD
28HMDB
29ICD10
30ICD10 via Orphanet
31ICD9CM
32IUPHAR
33KEGG
36MedGen
38MeSH
39MESH via Orphanet
40MGI
43NCI
44NCIt
45NDF-RT
48NINDS
49Novoseek
51OMIM
52OMIM via Orphanet
56PubMed
57QIAGEN
62SNOMED-CT via Orphanet
66Tumor Gene Family of Databases
67UMLS
68UMLS via Orphanet