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LIG4S
MCID: LG4001
MIFTS: 56

Lig4 Syndrome (LIG4S)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes
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Aliases & Classifications for Lig4 Syndrome

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MalaCards integrated aliases for Lig4 Syndrome:

Name: Lig4 Syndrome 56 12 58 73 36 29 13 54 6 71
Dna Ligase Iv Deficiency 12 58 15
Ligase 4 Syndrome 58
Syndrome, Lig4 39
Lig4s 73

Characteristics:

Orphanet epidemiological data:

58
lig4 syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: young Adult;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
closely resembles nijmegen breakage syndrome


HPO:

31
lig4 syndrome:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Blood diseases Immune diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare immunological diseases


Sources

Summaries for Lig4 Syndrome

About this section
KEGG : 36 LIG4 syndrome is an extremely rare autosomal recessive condition caused by mutations in the LIG4 gene which encodes DNA ligase IV. The clinical phenotype closely resembles that of Nijmegen breakage syndrome (NBS), and is characterized by microcephaly, characteristic facial features, growth retardation, developmental delay, and immunodeficiency.

MalaCards based summary : Lig4 Syndrome, also known as dna ligase iv deficiency, is related to dubowitz syndrome and nijmegen breakage syndrome. An important gene associated with Lig4 Syndrome is LIG4 (DNA Ligase 4), and among its related pathways/superpathways are Non-homologous end-joining and Chks in Checkpoint Regulation. Affiliated tissues include b cells, skin and t cells, and related phenotypes are global developmental delay and microcephaly

Disease Ontology : 12 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.

UniProtKB/Swiss-Prot : 73 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.

Wikipedia : 74 LIG4 syndrome (also known as Ligase IV syndrome) is an extremely rare condition caused by mutations in... more...

More information from OMIM: 606593
Sources

Related Diseases for Lig4 Syndrome

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Diseases related to Lig4 Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 89)
# Related Disease Score Top Affiliating Genes
1 dubowitz syndrome 32.0 XRCC4 PRKDC NHEJ1 LIG4 DCLRE1C
2 nijmegen breakage syndrome 31.0 XRCC6 XRCC5 NHEJ1 NBN MRE11 LIG4
3 immune deficiency disease 29.7 RAG2 RAG1 NBN LIG4 DCLRE1C ATM
4 severe combined immunodeficiency 29.2 XRCC6 XRCC5 XRCC4 RAG2 RAG1 PRKDC
5 microcephaly 28.7 XRCC6 XRCC5 XRCC4 TP53BP1 PRKDC PNKP
6 ataxia-telangiectasia 28.6 XRCC5 TP53BP1 PRKDC NBN MRE11 LIG1
7 seckel syndrome 28.4 XRCC6 XRCC5 XRCC4 TP53BP1 PRKDC PNKP
8 fanconi anemia, complementation group a 27.6 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 RNF168
9 severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 11.2
10 hemangioma of subcutaneous tissue 10.4 XRCC5 PRKDC
11 immunodeficiency with hyper-igm, type 4 10.4 NHEJ1 LIG4
12 t-b- severe combined immunodeficiency 10.3 RAG2 DCLRE1C
13 janus kinase-3 deficiency 10.3 RAG2 LIG4
14 purine nucleoside phosphorylase deficiency 10.3 RAG1 NHEJ1 DCLRE1C
15 recombinase activating gene 1 deficiency 10.2 RAG2 RAG1
16 reticular dysgenesis 10.2 RAG1 NHEJ1 DCLRE1C
17 glioma 10.2
18 glial tumor 10.2
19 neonatal leukemia 10.2 RAG1 DCLRE1C
20 autosomal recessive disease 10.2
21 pancytopenia 10.2
22 ataxia-telangiectasia-like disorder 1 10.2 NBN MRE11
23 lung cancer 10.1
24 congenital nervous system abnormality 10.1 XRCC4 PNKP NHEJ1 NBN
25 lymphopenia 10.1
26 ataxia-oculomotor apraxia 3 10.1 TDP1 APTX
27 bloom syndrome 10.0 XRCC6 LIG1 ATM
28 hutchinson-gilford progeria syndrome 10.0 XRCC5 TP53BP1 PRKDC ATM
29 sporadic breast cancer 10.0 XRCC1 NBN ATM
30 spinocerebellar ataxia, autosomal recessive 23 10.0 TDP1 PNKP
31 combined cellular and humoral immune defects with granulomas 10.0 RAG2 RAG1
32 immunodeficiency 17 10.0 RAG2 NHEJ1
33 vesicoureteral reflux 1 10.0
34 urofacial syndrome 1 10.0
35 ataxia and polyneuropathy, adult-onset 10.0
36 myelodysplastic syndrome 10.0
37 inflammatory bowel disease 10.0
38 diffuse large b-cell lymphoma 10.0
39 lymphoma 10.0
40 bacterial infectious disease 10.0
41 neutropenia 10.0
42 leukemia 10.0
43 telangiectasis 10.0
44 b-cell lymphoma 10.0
45 cytomegalovirus infection 10.0
46 ige responsiveness, atopic 10.0
47 systemic lupus erythematosus 10.0
48 small cell cancer of the lung 10.0
49 suppressor of tumorigenicity 3 10.0
50 corpus callosum, agenesis of 10.0

Graphical network of the top 20 diseases related to Lig4 Syndrome:



Diseases related to Lig4 Syndrome
Sources

Symptoms & Phenotypes for Lig4 Syndrome

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Human phenotypes related to Lig4 Syndrome:

58 31 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
2 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
3 growth delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001510
4 abnormality of chromosome stability 58 31 hallmark (90%) Very frequent (99-80%) HP:0003220
5 bird-like facies 58 31 hallmark (90%) Very frequent (99-80%) HP:0000320
6 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
7 wide nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000431
8 brachycephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000248
9 cutaneous photosensitivity 58 31 frequent (33%) Frequent (79-30%) HP:0000992
10 erythema 58 31 frequent (33%) Frequent (79-30%) HP:0010783
11 biparietal narrowing 58 31 frequent (33%) Frequent (79-30%) HP:0004422
12 micrognathia 58 31 frequent (33%) Frequent (79-30%) HP:0000347
13 epicanthus 58 31 frequent (33%) Frequent (79-30%) HP:0000286
14 upslanted palpebral fissure 58 31 frequent (33%) Frequent (79-30%) HP:0000582
15 lymphoma 58 31 frequent (33%) Frequent (79-30%) HP:0002665
16 low anterior hairline 58 31 frequent (33%) Frequent (79-30%) HP:0000294
17 telecanthus 58 31 frequent (33%) Frequent (79-30%) HP:0000506
18 acute leukemia 58 31 frequent (33%) Frequent (79-30%) HP:0002488
19 thin vermilion border 58 31 frequent (33%) Frequent (79-30%) HP:0000233
20 pancytopenia 58 31 frequent (33%) Frequent (79-30%) HP:0001876
21 large beaked nose 58 31 frequent (33%) Frequent (79-30%) HP:0003683
22 severe combined immunodeficiency 58 31 frequent (33%) Frequent (79-30%) HP:0004430
23 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002240
24 type ii diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0005978
25 malabsorption 58 31 occasional (7.5%) Occasional (29-5%) HP:0002024
26 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
27 telangiectasia of the skin 58 31 occasional (7.5%) Occasional (29-5%) HP:0100585
28 cryptorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000028
29 clinodactyly of the 5th finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0004209
30 hypoplasia of penis 58 31 occasional (7.5%) Occasional (29-5%) HP:0008736
31 lymphadenopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002716
32 leukocytosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001974
33 telangiectasia 31 very rare (1%) HP:0001009
34 delayed speech and language development 31 HP:0000750
35 failure to thrive 31 HP:0001508
36 immunodeficiency 58 Very frequent (99-80%)
37 psoriasiform dermatitis 31 HP:0003765
38 abnormality of the skeletal system 58 Occasional (29-5%)
39 thrombocytopenia 31 HP:0001873
40 myelodysplasia 31 HP:0002863
41 micropenis 31 HP:0000054
42 hypotelorism 31 HP:0000601
43 abnormality of bone marrow cell morphology 58 Frequent (79-30%)
44 prominent nose 31 HP:0000448
45 amenorrhea 31 HP:0000141
46 narrow forehead 31 HP:0000341

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
microcephaly

Genitourinary Internal Genitalia Male:
cryptorchidism

Genitourinary External Genitalia Male:
micropenis

Head And Neck Nose:
prominent nose

Head And Neck Face:
narrow forehead

Neurologic Central Nervous System:
delayed speech
developmental delay, global

Neoplasia:
t-cell acute lymphoblastic leukemia (in 1 patient)

Endocrine Features:
hypothyroidism

Hematology:
thrombocytopenia
myelodysplasia
pancytopenia

Head And Neck Eyes:
hypotelorism

Genitourinary Internal Genitalia Female:
amenorrhea

Skin Nails Hair Skin:
psoriasis
photosensitivity
telangiectasia (1 patient)

Growth Other:
failure to thrive growth retardation

Laboratory Abnormalities:
radiosensitivity, severe

Clinical features from OMIM:

606593

GenomeRNAi Phenotypes related to Lig4 Syndrome 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-1 10.09 ATM LIG1 LIG4 PRKDC
2 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-2 10.09 ATM LIG1 LIG4 NBN TP53BP1
3 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 10.09 ATM LIG1 LIG4 MRE11 NBN TDP1
4 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.99 MRE11 NBN TDP1 TP53BP1 XRCC1
5 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.99 ATM LIG1 LIG4 MRE11 PRKDC TDP1
6 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-3 9.99 ATM LIG1 MRE11 NBN PRKDC TDP1
7 Reduced mammosphere formation GR00396-S 9.5 ATM DCLRE1C PNKP PRKDC XRCC1 XRCC5

MGI Mouse Phenotypes related to Lig4 Syndrome:

45 (show all 11)
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.48 APTX ATM DCLRE1C LIG1 LIG4 MRE11
2 growth/size/body region MP:0005378 10.36 ATM DCLRE1C LIG1 LIG4 NBN NHEJ1
3 endocrine/exocrine gland MP:0005379 10.33 ATM DCLRE1C LIG1 LIG4 NBN NHEJ1
4 hematopoietic system MP:0005397 10.31 ATM DCLRE1C LIG1 LIG4 MRE11 NBN
5 homeostasis/metabolism MP:0005376 10.3 APTX ATM LIG1 LIG4 MRE11 NBN
6 behavior/neurological MP:0005386 10.24 ATM LIG4 MRE11 NBN PRKDC RAG1
7 immune system MP:0005387 10.22 ATM DCLRE1C LIG1 LIG4 MRE11 NBN
8 mortality/aging MP:0010768 10.13 ATM LIG1 LIG4 MRE11 NBN NHEJ1
9 neoplasm MP:0002006 10.06 ATM LIG1 LIG4 MRE11 NBN NHEJ1
10 nervous system MP:0003631 9.83 ATM LIG4 MRE11 NBN NHEJ1 PAXX
11 reproductive system MP:0005389 9.36 ATM LIG4 MRE11 NBN PRKDC RAG2
Sources

Drugs & Therapeutics for Lig4 Syndrome

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Search Clinical Trials , NIH Clinical Center for Lig4 Syndrome

Sources

Genetic Tests for Lig4 Syndrome

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Genetic tests related to Lig4 Syndrome:

# Genetic test Affiliating Genes
1 Lig4 Syndrome 29 LIG4
Sources

Anatomical Context for Lig4 Syndrome

About this section

MalaCards organs/tissues related to Lig4 Syndrome:

40
B Cells, Skin, T Cells, Bone Marrow, Bone, Brain, Kidney
Sources

Publications for Lig4 Syndrome

About this section

Articles related to Lig4 Syndrome:

(show all 48)
# Title Authors PMID Year
1
A new type of radiosensitive T-B-NK+ severe combined immunodeficiency caused by a LIG4 mutation. 61 54 6 56
16357942 2006
2
A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome. 61 54 56 6
16088910 2005
3
DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. 56 6
11779494 2001
4
Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome. 54 56 61
20133615 2010
5
Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms. 61 54 56
15333585 2004
6
Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity. 6
11349135 2001
7
Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient. 6
10395545 1999
8
Ligase IV syndrome. 61 54
19467349 2009
9
A novel mutation in a family with DNA ligase IV deficiency syndrome. 61 54
19418549 2009
10
CsA can induce DNA double-strand breaks: implications for BMT regimens particularly for individuals with defective DNA repair. 54 61
18278071 2008
11
DNA repair is limiting for haematopoietic stem cells during ageing. 61 54
17554302 2007
12
Epstein-Barr virus-associated B-cell lymphoma in a patient with DNA ligase IV (LIG4) syndrome. 54 61
17345618 2007
13
Identification of a novel motif in DNA ligases exemplified by DNA ligase IV. 61 54
16735143 2006
14
Structure of an Xrcc4-DNA ligase IV yeast ortholog complex reveals a novel BRCT interaction mode. 54 61
16388993 2006
15
An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR-Seckel syndrome. 54 61
15279811 2004
16
A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. 61 54
12640452 2003
17
Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations. 61
32534991 2020
18
LIG4 syndrome: clinical and molecular characterization in a Chinese cohort. 61
32471509 2020
19
Spatiotemporal Gradient of Cortical Neuron Death Contributes to Microcephaly in Knock-In Mouse Model of Ligase 4 Syndrome. 61
31541646 2019
20
Correction to: Allogeneic hematopoietic stem cell transplantation in two brothers with DNA ligase IV deficiency: a case report and review of the literature. 61
31791281 2019
21
Allogeneic hematopoietic stem cell transplantation in two brothers with DNA ligase IV deficiency: a case report and review of the literature. 61
31604460 2019
22
[LIG4 syndrome: a report of four cases and literature review]. 61
30818900 2019
23
A Novel Missense LIG4 Mutation in a Patient With a Phenotype Mimicking Behçet's Disease. 61
30617623 2019
24
Structures of DNA-bound human ligase IV catalytic core reveal insights into substrate binding and catalysis. 61
29980672 2018
25
LIG4 Syndrome Associated with Hypocellular Myeloid Dysplasia. 61
29491294 2018
26
Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders. 61
28392333 2018
27
Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature. 61
30719430 2018
28
DNA ligase IV deficiency: Immunoglobulin class deficiency depends on the genotype. 61
28039949 2017
29
Two hits in one: whole genome sequencing unveils LIG4 syndrome and urofacial syndrome in a case report of a child with complex phenotype. 61
27855655 2016
30
DNA ligase IV syndrome; a review. 61
27717373 2016
31
Ligase-4 Deficiency Causes Distinctive Immune Abnormalities in Asymptomatic Individuals. 61
27063650 2016
32
Molecular and immunological characterization of DNA ligase IV deficiency. 61
26762768 2016
33
Next generation sequencing revealed DNA ligase IV deficiency in a "developmentally normal" patient with massive brain Epstein-Barr virus-positive diffuse large B-cell lymphoma. 61
26774591 2016
34
Integrating Gene Correction in the Reprogramming and Transdifferentiation Processes: A One-Step Strategy to Overcome Stem Cell-Based Gene Therapy Limitations. 61
28074097 2016
35
Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly-progressing radiosensitive-severe combined immunodeficiency. 61
26172957 2015
36
Reprint of "The clinical impact of deficiency in DNA non-homologous end-joining". 61
24780557 2014
37
The clinical impact of deficiency in DNA non-homologous end-joining. 61
24629483 2014
38
A human iPSC model of Ligase IV deficiency reveals an important role for NHEJ-mediated-DSB repair in the survival and genomic stability of induced pluripotent stem cells and emerging haematopoietic progenitors. 61
23722522 2013
39
Structural insights into the role of domain flexibility in human DNA ligase IV. 61
22658747 2012
40
Nijmegen breakage syndrome (NBS). 61
22373003 2012
41
Requirement for DNA ligase IV during embryonic neuronal development. 61
21734301 2011
42
Ligase IV syndrome. 61
20687505 2010
43
Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure. 61
17224058 2007
44
Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. 61
16777961 2006
45
Cernunnos interacts with the XRCC4 x DNA-ligase IV complex and is homologous to the yeast nonhomologous end-joining factor Nej1. 61
16571728 2006
46
The embryonic lethality in DNA ligase IV-deficient mice is rescued by deletion of Ku: implications for unifying the heterogeneous phenotypes of NHEJ mutants. 61
12531011 2002
47
Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm. 61
11040211 2000
48
DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. 61
10911993 2000
Sources

Variations for Lig4 Syndrome

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ClinVar genetic disease variations for Lig4 Syndrome:

6 (show top 50) (show all 172) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LIG4 NM_002312.3(LIG4):c.1904del (p.Lys635fs)deletion Pathogenic 418659 rs375554612 13:108861713-108861713 13:108209365-108209365
2 LIG4 NM_002312.3(LIG4):c.613del (p.Ser205fs)deletion Pathogenic 521262 rs780879476 13:108863004-108863004 13:108210656-108210656
3 LIG4 NM_206937.2(LIG4):c.797_798AG[1] (p.Ser267fs)short repeat Pathogenic 567502 rs1566366148 13:108862817-108862818 13:108210469-108210470
4 LIG4 NM_206937.2(LIG4):c.1640_1641TA[1] (p.Tyr548fs)short repeat Pathogenic 638937 13:108861974-108861975 13:108209626-108209627
5 LIG4 NC_000013.11:g.(?_108208513)_(108211288_?)deldeletion Pathogenic 665646 13:108860861-108863636 13:108208513-108211288
6 LIG4 NM_002312.3(LIG4):c.2305dup (p.Thr769fs)duplication Pathogenic 841699 13:108861311-108861312 13:108208963-108208964
7 LIG4 NM_002312.3(LIG4):c.1406G>A (p.Gly469Glu)SNV Pathogenic 7674 rs104894420 13:108862211-108862211 13:108209863-108209863
8 LIG4 NM_002312.3(LIG4):c.833G>A (p.Arg278His)SNV Pathogenic 7675 rs104894421 13:108862784-108862784 13:108210436-108210436
9 LIG4 NM_206937.2(LIG4):c.1295_1297AAC[1] (p.Gln433del)short repeat Pathogenic 7678 rs587776663 13:108862317-108862319 13:108209969-108209971
10 LIG4 NM_002312.3(LIG4):c.1738C>T (p.Arg580Ter)SNV Pathogenic 7672 rs104894418 13:108861879-108861879 13:108209531-108209531
11 LIG4 NM_002312.3(LIG4):c.1271_1275del (p.Lys424fs)deletion Pathogenic 279838 rs772226399 13:108862342-108862346 13:108209994-108209998
12 LIG4 NM_002312.3(LIG4):c.2440C>T (p.Arg814Ter)SNV Pathogenic/Likely pathogenic 7673 rs104894419 13:108861177-108861177 13:108208829-108208829
13 LIG4 NM_002312.3(LIG4):c.1312T>C (p.Tyr438His)SNV Likely pathogenic 225274 rs886037777 13:108862305-108862305 13:108209957-108209957
14 LIG4 NM_002312.3(LIG4):c.847A>G (p.Lys283Glu)SNV Likely pathogenic 694006 13:108862770-108862770 13:108210422-108210422
15 LIG4 NM_002312.3(LIG4):c.845A>T (p.His282Leu)SNV Likely pathogenic 845678 13:108862772-108862772 13:108210424-108210424
16 LIG4 NM_002312.3(LIG4):c.2321T>C (p.Leu774Pro)SNV Likely pathogenic 397529 rs1060499662 13:108861296-108861296 13:108208948-108208948
17 LIG4 NM_002312.3(LIG4):c.879_883del (p.Asn294fs)deletion Likely pathogenic 505512 rs751070095 13:108862734-108862738 13:108210386-108210390
18 LIG4 NM_002312.3(LIG4):c.285G>A (p.Glu95=)SNV Conflicting interpretations of pathogenicity 435755 rs150146196 13:108863332-108863332 13:108210984-108210984
19 LIG4 NM_002312.3(LIG4):c.2525C>A (p.Ala842Asp)SNV Conflicting interpretations of pathogenicity 310975 rs72660870 13:108861092-108861092 13:108208744-108208744
20 LIG4 NM_002312.3(LIG4):c.2222G>A (p.Arg741His)SNV Conflicting interpretations of pathogenicity 310979 rs143767581 13:108861395-108861395 13:108209047-108209047
21 LIG4 NM_002312.3(LIG4):c.1983T>C (p.Asp661=)SNV Conflicting interpretations of pathogenicity 310980 rs199638675 13:108861634-108861634 13:108209286-108209286
22 LIG4 NM_002312.3(LIG4):c.1252T>C (p.Leu418=)SNV Conflicting interpretations of pathogenicity 310984 rs147181971 13:108862365-108862365 13:108210017-108210017
23 LIG4 NM_002312.3(LIG4):c.563G>A (p.Arg188Gln)SNV Conflicting interpretations of pathogenicity 310990 rs748385144 13:108863054-108863054 13:108210706-108210706
24 LIG4 NM_002312.3(LIG4):c.500T>G (p.Ile167Arg)SNV Conflicting interpretations of pathogenicity 310992 rs138021217 13:108863117-108863117 13:108210769-108210769
25 LIG4 NM_002312.3(LIG4):c.1473C>G (p.Pro491=)SNV Conflicting interpretations of pathogenicity 211372 rs189319839 13:108862144-108862144 13:108209796-108209796
26 LIG4 NM_002312.3(LIG4):c.686A>G (p.His229Arg)SNV Conflicting interpretations of pathogenicity 211376 rs142957638 13:108862931-108862931 13:108210583-108210583
27 LIG4 NM_002312.3(LIG4):c.2016C>G (p.Ser672Arg)SNV Uncertain significance 211374 rs142144659 13:108861601-108861601 13:108209253-108209253
28 LIG4 NM_002312.3(LIG4):c.1242A>C (p.Val414=)SNV Uncertain significance 827984 13:108862375-108862375 13:108210027-108210027
29 LIG4 NM_002312.3(LIG4):c.2595del (p.Ile865fs)deletion Uncertain significance 863425 13:108861022-108861022 13:108208674-108208674
30 LIG4 NM_002312.3(LIG4):c.2468A>G (p.Tyr823Cys)SNV Uncertain significance 835493 13:108861149-108861149 13:108208801-108208801
31 LIG4 NM_002312.3(LIG4):c.2675G>T (p.Ser892Ile)SNV Uncertain significance 860567 13:108860942-108860942 13:108208594-108208594
32 LIG4 NM_002312.3(LIG4):c.2320C>G (p.Leu774Val)SNV Uncertain significance 837865 13:108861297-108861297 13:108208949-108208949
33 LIG4 NM_002312.3(LIG4):c.*486A>GSNV Uncertain significance 310959 rs543340651 13:108860395-108860395 13:108208047-108208047
34 LIG4 NM_002312.3(LIG4):c.*352A>CSNV Uncertain significance 310960 rs886049944 13:108860529-108860529 13:108208181-108208181
35 LIG4 NM_002312.3(LIG4):c.*306A>GSNV Uncertain significance 310961 rs886049945 13:108860575-108860575 13:108208227-108208227
36 LIG4 NM_002312.3(LIG4):c.*242A>GSNV Uncertain significance 310963 rs886049946 13:108860639-108860639 13:108208291-108208291
37 LIG4 NM_002312.3(LIG4):c.*166G>CSNV Uncertain significance 310965 rs538355612 13:108860715-108860715 13:108208367-108208367
38 LIG4 NM_002312.3(LIG4):c.*56G>CSNV Uncertain significance 310969 rs886049947 13:108860825-108860825 13:108208477-108208477
39 LIG4 NM_002312.3(LIG4):c.2274T>C (p.Tyr758=)SNV Uncertain significance 310978 rs529756815 13:108861343-108861343 13:108208995-108208995
40 LIG4 NM_002312.3(LIG4):c.1198A>C (p.Ile400Leu)SNV Uncertain significance 310985 rs886049949 13:108862419-108862419 13:108210071-108210071
41 LIG4 NM_002312.3(LIG4):c.-32C>TSNV Uncertain significance 310998 rs536441091 13:108866889-108866889 13:108214541-108214541
42 LIG4 NM_002312.3(LIG4):c.*285A>GSNV Uncertain significance 310962 rs748776641 13:108860596-108860596 13:108208248-108208248
43 LIG4 NM_002312.3(LIG4):c.2549C>T (p.Ala850Val)SNV Uncertain significance 310974 rs188422094 13:108861068-108861068 13:108208720-108208720
44 LIG4 NM_002312.3(LIG4):c.2499T>C (p.Asn833=)SNV Uncertain significance 310977 rs769297575 13:108861118-108861118 13:108208770-108208770
45 LIG4 NM_002312.3(LIG4):c.607A>G (p.Ile203Val)SNV Uncertain significance 310989 rs778278351 13:108863010-108863010 13:108210662-108210662
46 LIG4 NM_002312.3(LIG4):c.13C>A (p.Gln5Lys)SNV Uncertain significance 310995 rs143590752 13:108863604-108863604 13:108211256-108211256
47 LIG4 NM_002312.3(LIG4):c.560T>C (p.Ile187Thr)SNV Uncertain significance 310991 rs199854013 13:108863057-108863057 13:108210709-108210709
48 LIG4 NM_002312.3(LIG4):c.1756G>T (p.Asp586Tyr)SNV Uncertain significance 310981 rs753492255 13:108861861-108861861 13:108209513-108209513
49 LIG4 NM_002312.3(LIG4):c.-260G>CSNV Uncertain significance 311001 rs886049950 13:108867117-108867117 13:108214769-108214769
50 LIG4 NM_002312.3(LIG4):c.*738G>ASNV Uncertain significance 310953 rs567294082 13:108860143-108860143 13:108207795-108207795

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

73
# Symbol AA change Variation ID SNP ID
1 LIG4 p.Arg278His VAR_012774 rs104894421
2 LIG4 p.Gly469Glu VAR_012775 rs104894420

Sources

Expression for Lig4 Syndrome

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Search GEO for disease gene expression data for Lig4 Syndrome.
Sources

Pathways for Lig4 Syndrome

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Pathways related to Lig4 Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Non-homologous end-joining hsa03450

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

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Chks in Checkpoint Regulation 63
Show member pathways
 12.71 XRCC6 XRCC5 XRCC4 XRCC1 PRKDC PNKP
2
DNA Double-Strand Break Repair 65
Show member pathways
 12.53 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
3
Cell Cycle Checkpoints 65
Show member pathways
 12.5 TP53BP1 RNF168 NBN MRE11 ATM
4
Cytosolic sensors of pathogen-associated DNA 65
Show member pathways
 12.38 XRCC6 XRCC5 PRKDC MRE11
5
DNA Double Strand Break Response 65
Show member pathways
 12.33 XRCC6 XRCC5 XRCC4 TP53BP1 TDP1 RNF168
6
DNA Damage 4
12.3 XRCC6 XRCC5 XRCC1 TP53BP1 TDP1 PRKDC
7
DNA Damage Response 1
Show member pathways
 12.23 PRKDC NBN MRE11 ATM
8
ATM Pathway 63
Show member pathways
 11.74 TP53BP1 NBN MRE11 ATM
9
BRCA1 Pathway 63
Show member pathways
 11.66 NBN MRE11 ATM
10
Regulation of Telomerase 1
11.65 XRCC6 XRCC5 NBN MRE11 ATM
11
ATM Signaling Network in Development and Disease 1
11.53 TP53BP1 RNF168 PRKDC NBN MRE11 DCLRE1C
12
Coregulation of Androgen receptor activity 1
11.48 XRCC6 XRCC5 PRKDC
13
BARD1 signaling events 1
11.34 XRCC6 XRCC5 PRKDC NBN MRE11 ATM
14
DNA damage_NHEJ mechanisms of DSBs repair 22
11.29 XRCC6 XRCC5 XRCC4 PRKDC PNKP NBN
15
Primary immunodeficiency 36
11.28 RAG2 RAG1 DCLRE1C
16
Telomere Extension by Telomerase 63
Show member pathways
 11.1 XRCC6 XRCC5 NBN MRE11
17
Gemtuzumab ozogamicin Pathway, Pharmacokinetics/Pharmacodynamics 60
11.05 XRCC4 PRKDC ATM
18
DDX1 as a regulatory component of the Drosha microprocessor 1
Show member pathways
 10.84 NBN MRE11 ATM
Sources

GO Terms for Lig4 Syndrome

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

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.26 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
2 nucleolus GO:0005730 10.11 XRCC6 XRCC5 XRCC1 PRKDC PNKP NBN
3 chromosome GO:0005694 9.97 XRCC6 XRCC5 TP53BP1 NBN MRE11
4 chromosome, telomeric region GO:0000781 9.76 TP53BP1 NBN MRE11 ATM
5 nonhomologous end joining complex GO:0070419 9.76 XRCC6 XRCC5 XRCC4 PRKDC PAXX NHEJ1
6 site of double-strand break GO:0035861 9.72 TP53BP1 RNF168 PAXX NBN MRE11
7 protein-DNA complex GO:0032993 9.7 XRCC6 XRCC5 PRKDC
8 replication fork GO:0005657 9.67 TP53BP1 NBN MRE11
9 nuclear chromosome, telomeric region GO:0000784 9.65 XRCC6 XRCC5 XRCC1 TP53BP1 PRKDC NBN
10 nucleoplasm GO:0005654 9.62 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
11 DNA-dependent protein kinase-DNA ligase 4 complex GO:0005958 9.61 XRCC4 PRKDC LIG4
12 Ku70:Ku80 complex GO:0043564 9.58 XRCC6 XRCC5 PAXX
13 nuclear telomere cap complex GO:0000783 9.56 XRCC6 XRCC5
14 Mre11 complex GO:0030870 9.55 NBN MRE11
15 DNA repair complex GO:1990391 9.54 TP53BP1 ATM
16 DNA ligase IV complex GO:0032807 9.54 XRCC4 NHEJ1 LIG4
17 DNA recombinase complex GO:0097519 9.48 RAG2 RAG1

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

(show top 50) (show all 51)
# Name GO ID Score Top Affiliating Genes
1 DNA recombination GO:0006310 10.02 XRCC6 XRCC5 XRCC4 RAG2 RAG1 PRKDC
2 nucleic acid phosphodiester bond hydrolysis GO:0090305 10.01 TDP1 RAG1 PNKP MRE11 DCLRE1C APTX
3 brain development GO:0007420 10 XRCC6 XRCC5 PRKDC ATM
4 double-strand break repair GO:0006302 10 XRCC5 XRCC4 TDP1 RNF168 PRKDC NHEJ1
5 double-strand break repair via nonhomologous end joining GO:0006303 10 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 RNF168
6 DNA replication GO:0006260 9.99 NBN MRE11 LIG4 LIG1 ATM
7 cell proliferation GO:0008283 9.98 XRCC5 NBN MRE11 LIG4
8 telomere maintenance GO:0000723 9.95 XRCC6 XRCC5 PRKDC NBN MRE11 DCLRE1C
9 double-strand break repair via homologous recombination GO:0000724 9.92 XRCC1 NBN MRE11 ATM
10 DNA duplex unwinding GO:0032508 9.92 XRCC6 XRCC5 NBN MRE11
11 B cell differentiation GO:0030183 9.91 RAG2 RAG1 NHEJ1 DCLRE1C
12 response to ionizing radiation GO:0010212 9.91 RNF168 PRKDC NHEJ1 LIG4 DCLRE1C ATM
13 V(D)J recombination GO:0033151 9.91 RAG2 RAG1 PRKDC LIG4 LIG1 DCLRE1C
14 cellular response to DNA damage stimulus GO:0006974 9.91 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
15 positive regulation of type I interferon production GO:0032481 9.88 XRCC6 XRCC5 PRKDC MRE11
16 T cell differentiation in thymus GO:0033077 9.87 RAG2 RAG1 PRKDC LIG4
17 thymus development GO:0048538 9.85 RAG1 PRKDC ATM
18 DNA damage checkpoint GO:0000077 9.84 TP53BP1 NBN ATM
19 single strand break repair GO:0000012 9.83 XRCC1 TDP1 LIG4 APTX
20 positive regulation of telomere maintenance via telomerase GO:0032212 9.82 XRCC5 PNKP ATM
21 chromosome organization GO:0051276 9.82 MRE11 LIG4 DCLRE1C
22 cellular response to gamma radiation GO:0071480 9.81 XRCC6 XRCC5 ATM
23 activation of innate immune response GO:0002218 9.81 XRCC6 XRCC5 PRKDC
24 cellular response to X-ray GO:0071481 9.81 XRCC6 XRCC5 TP53BP1 ATM
25 nucleotide-excision repair, DNA gap filling GO:0006297 9.8 XRCC1 LIG4 LIG1
26 establishment of integrated proviral latency GO:0075713 9.8 XRCC6 XRCC5 XRCC4 LIG4
27 isotype switching GO:0045190 9.78 RNF168 NBN LIG4
28 DNA ligation involved in DNA repair GO:0051103 9.78 XRCC4 PAXX LIG4 LIG1
29 DNA double-strand break processing GO:0000729 9.77 NBN MRE11 ATM
30 DNA ligation GO:0006266 9.76 XRCC6 LIG4 LIG1 APTX
31 regulation of smooth muscle cell proliferation GO:0048660 9.75 XRCC6 XRCC5 PRKDC
32 immunoglobulin V(D)J recombination GO:0033152 9.73 XRCC4 PRKDC LIG4
33 pre-B cell allelic exclusion GO:0002331 9.72 RAG2 RAG1 ATM
34 mitotic G2 DNA damage checkpoint GO:0007095 9.71 NBN MRE11
35 response to X-ray GO:0010165 9.71 XRCC4 LIG4
36 positive regulation of double-strand break repair via nonhomologous end joining GO:2001034 9.71 PRKDC PNKP
37 cellular response to lithium ion GO:0071285 9.7 XRCC4 LIG4
38 positive regulation of telomere maintenance GO:0032206 9.7 NBN MRE11
39 double-strand break repair via classical nonhomologous end joining GO:0097680 9.7 XRCC6 LIG4
40 T cell lineage commitment GO:0002360 9.69 RAG2 PRKDC
41 negative regulation of telomere capping GO:1904354 9.69 NBN ATM
42 positive regulation of lymphocyte differentiation GO:0045621 9.69 XRCC6 PRKDC
43 T cell receptor V(D)J recombination GO:0033153 9.68 PRKDC LIG4
44 B cell lineage commitment GO:0002326 9.68 RAG2 PRKDC
45 positive regulation of ligase activity GO:0051351 9.67 XRCC4 NHEJ1
46 telomeric 3' overhang formation GO:0031860 9.67 NBN MRE11
47 pro-B cell differentiation GO:0002328 9.67 PRKDC LIG4
48 cellular hyperosmotic salinity response GO:0071475 9.66 XRCC6 XRCC5
49 small-subunit processome assembly GO:0034462 9.65 XRCC5 PRKDC
50 negative regulation of protein ADP-ribosylation GO:0010836 9.65 XRCC1 PNKP

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

(show all 22)
# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.38 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
2 hydrolase activity GO:0016787 10.16 XRCC6 XRCC5 TDP1 RAG1 PNKP MRE11
3 ATP binding GO:0005524 10.15 XRCC6 XRCC5 PRKDC PNKP LIG4 LIG1
4 DNA binding GO:0003677 9.97 XRCC6 XRCC5 XRCC4 TP53BP1 RAG2 RAG1
5 nuclease activity GO:0004518 9.83 TDP1 RAG1 MRE11 DCLRE1C
6 protein N-terminus binding GO:0047485 9.77 NBN ATM APTX
7 exonuclease activity GO:0004527 9.72 TDP1 MRE11 DCLRE1C
8 protein C-terminus binding GO:0008022 9.72 XRCC6 XRCC5 XRCC4 MRE11 LIG4
9 endonuclease activity GO:0004519 9.67 RAG1 PNKP MRE11 DCLRE1C
10 telomeric DNA binding GO:0042162 9.61 XRCC6 XRCC5 TP53BP1
11 5'-3' exonuclease activity GO:0008409 9.59 MRE11 DCLRE1C
12 U3 snoRNA binding GO:0034511 9.58 XRCC5 PRKDC
13 double-stranded telomeric DNA binding GO:0003691 9.58 XRCC6 XRCC5
14 single-stranded DNA endodeoxyribonuclease activity GO:0000014 9.57 MRE11 DCLRE1C
15 DNA helicase activity GO:0003678 9.56 XRCC6 XRCC5 NBN MRE11
16 5'-deoxyribose-5-phosphate lyase activity GO:0051575 9.54 XRCC6 XRCC5
17 DNA-dependent protein kinase activity GO:0004677 9.51 PRKDC ATM
18 double-stranded DNA binding GO:0003690 9.5 XRCC6 XRCC5 TDP1 PRKDC PNKP MRE11
19 DNA ligase (ATP) activity GO:0003910 9.49 LIG4 LIG1
20 DNA ligase activity GO:0003909 9.48 LIG4 LIG1
21 DNA end binding GO:0045027 9.46 XRCC5 NHEJ1
22 damaged DNA binding GO:0003684 9.23 XRCC6 XRCC5 XRCC1 TP53BP1 PNKP NBN
Sources

Sources for Lig4 Syndrome

About this section
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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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