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LIG4S
MCID: LG4001
MIFTS: 57

Lig4 Syndrome (LIG4S)

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

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MalaCards integrated aliases for Lig4 Syndrome:

Name: Lig4 Syndrome 57 11 58 73 12 53 38 71 75
Dna Ligase Iv Deficiency 11 58 28 5 14
Ligase 4 Syndrome 58
Lig4s 73

Characteristics:


Inheritance:

Autosomal recessive 58 57

Prevelance:

<1/1000000 (Worldwide) 58

Age Of Onset:

Infancy,Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
closely resembles nijmegen breakage syndrome


Classifications:

MalaCards categories:
Global: Genetic diseases Fetal diseases Rare diseases
Anatomical: Neuronal diseases Blood diseases Immune diseases Skin diseases Mental diseases
See all MalaCards categories (disease lists)
ICD10: 32
Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis
Rare immunological diseases


Sources

Summaries for Lig4 Syndrome

About this section

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 telangiectasis. An important gene associated with Lig4 Syndrome is LIG4 (DNA Ligase 4), and among its related pathways/superpathways are Homology Directed Repair and DNA Damage. Affiliated tissues include skin, bone marrow and bone, and related phenotypes are global developmental delay and microcephaly

Orphanet: 58 LIG4 syndrome is a hereditary disorder associated with impaired DNA double-strand break repair mechanisms and characterized by microcephaly, unusual facial features, growth and developmental delay, skin anomalies, and pancytopenia, which is associated with combined immunodeficiency (CID).

UniProtKB/Swiss-Prot: 73 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: 75 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 70)
# Related Disease Score Top Affiliating Genes
1 nijmegen breakage syndrome 30.3 XRCC6 XRCC5 XRCC4 TP53BP1 PRKDC NHEJ1
2 telangiectasis 30.0 NBN ERCC6 ATM
3 aplastic anemia 29.7 XRCC6 XRCC5 XRCC4 TP53BP1 PRKDC NBN
4 immune deficiency disease 29.6 RAG2 RAG1 NBN LIG4 DCLRE1C ATM
5 microcephaly 29.4 XRCC6 XRCC5 XRCC4 PRKDC PNKP NHEJ1
6 combined immunodeficiency 29.4 XRCC6 XRCC5 XRCC4 RAG2 RAG1 PRKDC
7 severe combined immunodeficiency 29.3 XRCC6 XRCC5 XRCC4 RAG2 RAG1 PRKDC
8 severe combined immunodeficiency with sensitivity to ionizing radiation 28.7 XRCC6 XRCC5 XRCC4 RAG2 RAG1 PRKDC
9 seckel syndrome 28.3 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 PRKDC
10 fanconi anemia, complementation group a 28.2 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 RNF168
11 ataxia-telangiectasia 27.6 XRCC6 XRCC5 XRCC1 TP53BP1 TDP1 RAG2
12 pancytopenia 10.3
13 hemangioma of subcutaneous tissue 10.2 XRCC5 PRKDC
14 lymphopenia 10.2
15 reticular dysgenesis 10.1 RAG1 NHEJ1 DCLRE1C
16 dubowitz syndrome 10.1 XRCC4 NHEJ1 LIG4 DCLRE1C
17 aneurysm, intracranial berry, 12 10.1 DCLRE1C ATM
18 janus kinase-3 deficiency 10.1 RAG2 LIG4
19 recombinase activating gene 1 deficiency 10.1 RAG2 RAG1
20 diamond-blackfan anemia 11 10.1 NBN ATM
21 immunodeficiency with hyper-igm, type 5 10.1 PAXX ERCC6 APTX
22 ataxia-oculomotor apraxia 3 10.1 PNKP APTX
23 riddle syndrome 10.1 TP53BP1 RNF168 ERCC6
24 lymphoma, hodgkin, classic 10.0
25 agammaglobulinemia, x-linked 10.0
26 lymphoma, non-hodgkin, familial 10.0
27 thrombocytopenia 10.0
28 agammaglobulinemia 10.0
29 rubella 10.0
30 viral infectious disease 10.0
31 monosomy 7 predisposition syndromes 10.0
32 purine-pyrimidine metabolic disorder 10.0 RAG2 RAG1 ERCC6
33 spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 10.0 PNKP ATM APTX
34 sporadic breast cancer 10.0 XRCC1 ERCC6 ATM
35 cockayne syndrome a 10.0 XRCC4 XRCC1 ERCC6
36 cornelia de lange syndrome 10.0 RNF168 NBN ERCC6 ATM
37 purine nucleoside phosphorylase deficiency 9.9 RAG2 RAG1 NHEJ1 DCLRE1C
38 spinocerebellar ataxia, autosomal recessive 26 9.9 XRCC1 PNKP APTX
39 xeroderma pigmentosum, complementation group a 9.9 XRCC6 XRCC1 ERCC6 ATM
40 burkitt lymphoma 9.9
41 urofacial syndrome 1 9.9
42 congenital hemidysplasia with ichthyosiform erythroderma and limb defects 9.9
43 myelodysplastic syndrome 9.9
44 diffuse large b-cell lymphoma 9.9
45 lymphoma 9.9
46 human cytomegalovirus infection 9.9
47 leukemia 9.9
48 thymus cancer 9.9
49 b-cell lymphoma 9.9
50 vesicoureteral reflux 9.9

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

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Endocrine Features:
hypothyroidism

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)

Head And Neck Head:
microcephaly

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 (Updated 08-Dec-2022)

GenomeRNAi Phenotypes related to Lig4 Syndrome according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 10.45 ERCC6 NBN TDP1 TP53BP1 XRCC1
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 10.45 ATM ERCC6 LIG4 PRKDC TDP1 TP53BP1
3 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-3 10.45 ATM ERCC6 NBN PRKDC TDP1 TP53BP1
4 Reduced mammosphere formation GR00396-S 9.17 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 nervous system MP:0003631 10.41 APTX ATM ERCC6 LIG4 NBN NHEJ1
2 neoplasm MP:0002006 10.4 APTX ATM ERCC6 LIG4 NBN NHEJ1
3 homeostasis/metabolism MP:0005376 10.39 APTX ATM ERCC6 LIG4 NBN NHEJ1
4 growth/size/body region MP:0005378 10.39 APTX ATM DCLRE1C ERCC6 LIG4 NBN
5 cellular MP:0005384 10.35 APTX ATM DCLRE1C ERCC6 LIG4 NBN
6 endocrine/exocrine gland MP:0005379 10.28 ATM DCLRE1C LIG4 NBN NHEJ1 PAXX
7 immune system MP:0005387 10.19 APTX ATM DCLRE1C ERCC6 LIG4 NBN
8 behavior/neurological MP:0005386 10.17 APTX ATM ERCC6 LIG4 NBN PAXX
9 reproductive system MP:0005389 9.97 ATM LIG4 NBN PAXX POLM PRKDC
10 hematopoietic system MP:0005397 9.89 APTX ATM DCLRE1C ERCC6 LIG4 NBN
11 mortality/aging MP:0010768 9.5 APTX ATM ERCC6 LIG4 NBN NHEJ1
Sources

Drugs & Therapeutics for Lig4 Syndrome

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Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Primordial Registry at Nemours/Alfred I. duPont Hospital for Children Recruiting NCT04569149

Search 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 Dna Ligase Iv Deficiency 28 LIG4
Sources

Anatomical Context for Lig4 Syndrome

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Organs/tissues related to Lig4 Syndrome:

MalaCards : Skin, Bone Marrow, Bone, Myeloid, Kidney, Brain
ODiseA: Blood And Bone Marrow
Sources

Publications for Lig4 Syndrome

About this section

Articles related to Lig4 Syndrome:

(show top 50) (show all 66)
# Title Authors PMID Year
1
A new type of radiosensitive T-B-NK+ severe combined immunodeficiency caused by a LIG4 mutation. 53 62 57 5
16357942 2006
2
A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome. 53 62 57 5
16088910 2005
3
DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. 57 5
11779494 2001
4
Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome. 53 62 57
20133615 2010
5
Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms. 53 62 57
15333585 2004
6
Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations. 62 5
32534991 2020
7
Allogeneic hematopoietic stem cell transplantation in two brothers with DNA ligase IV deficiency: a case report and review of the literature. 62 5
31604460 2019
8
Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature. 62 5
30719430 2018
9
DNA ligase IV deficiency: Immunoglobulin class deficiency depends on the genotype. 62 5
28039949 2017
10
Two hits in one: whole genome sequencing unveils LIG4 syndrome and urofacial syndrome in a case report of a child with complex phenotype. 62 5
27855655 2016
11
Ligase-4 Deficiency Causes Distinctive Immune Abnormalities in Asymptomatic Individuals. 62 5
27063650 2016
12
Characterization of a Cohort of Patients With LIG4 Deficiency Reveals the Founder Effect of p.R278L, Unique to the Chinese Population. 5
34630384 2021
13
A landscape of germ line mutations in a cohort of inherited bone marrow failure patients. 5
29146883 2018
14
Unique heterozygous presentation in an infant with DNA ligase IV syndrome. 5
28866308 2017
15
Late-onset combined immune deficiency due to LIGIV mutations in a 12-year-old patient. 5
27893162 2017
16
Marked overlap of four genetic syndromes with dyskeratosis congenita confounds clinical diagnosis. 5
27612988 2016
17
Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity. 5
25239263 2015
18
Extreme growth failure is a common presentation of ligase IV deficiency. 5
24123394 2014
19
Dubowitz syndrome is a complex comprised of multiple, genetically distinct and phenotypically overlapping disorders. 5
24892279 2014
20
Clinical spectrum of LIG4 deficiency is broadened with severe dysmaturity, primordial dwarfism, and neurological abnormalities. 5
24027040 2013
21
Identification of the DNA repair defects in a case of Dubowitz syndrome. 5
23372718 2013
22
Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency. 5
21664875 2011
23
[Diagnosis and treatment of hypertension. Individual aims, flexible control]. 5
16358631 2005
24
Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity. 5
11349135 2001
25
Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient. 5
10395545 1999
26
Ligase IV syndrome. 53 62
19467349 2009
27
A novel mutation in a family with DNA ligase IV deficiency syndrome. 53 62
19418549 2009
28
CsA can induce DNA double-strand breaks: implications for BMT regimens particularly for individuals with defective DNA repair. 53 62
18278071 2008
29
DNA repair is limiting for haematopoietic stem cells during ageing. 53 62
17554302 2007
30
Epstein-Barr virus-associated B-cell lymphoma in a patient with DNA ligase IV (LIG4) syndrome. 53 62
17345618 2007
31
Identification of a novel motif in DNA ligases exemplified by DNA ligase IV. 53 62
16735143 2006
32
Structure of an Xrcc4-DNA ligase IV yeast ortholog complex reveals a novel BRCT interaction mode. 53 62
16388993 2006
33
An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR-Seckel syndrome. 53 62
15279811 2004
34
A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. 53 62
12640452 2003
35
DNA ligase IV mutations confer shorter lifespan and increased sensitivity to nutrient stress in Drosophila melanogaster. 62
34817771 2022
36
Case Report: Wide Spectrum of Manifestations of Ligase IV Deficiency: Report of 3 Cases. 62
35592332 2022
37
A case report of an adolescent with ligase-4 deficiency and the potential dangers of ionizing radiation in this rare patient population. 62
34401020 2021
38
Genetic disorders with symptoms mimicking rheumatologic diseases: A single-center retrospective study. 62
33662637 2021
39
Hypomorphic mutations in human DNA ligase IV lead to compromised DNA binding efficiency, hydrophobicity and thermal stability. 62
33586762 2021
40
DNA Ligase IV Deficiency Identified by Chance Following Vaccine-Derived Rubella Virus Infection. 62
32914283 2020
41
LIG4 syndrome: clinical and molecular characterization in a Chinese cohort. 62
32471509 2020
42
Spatiotemporal Gradient of Cortical Neuron Death Contributes to Microcephaly in Knock-In Mouse Model of Ligase 4 Syndrome. 62
31541646 2019
43
Correction to: Allogeneic hematopoietic stem cell transplantation in two brothers with DNA ligase IV deficiency: a case report and review of the literature. 62
31791281 2019
44
[LIG4 syndrome: a report of four cases and literature review]. 62
30818900 2019
45
A Novel Missense LIG4 Mutation in a Patient With a Phenotype Mimicking Behçet's Disease. 62
30617623 2019
46
Structures of DNA-bound human ligase IV catalytic core reveal insights into substrate binding and catalysis. 62
29980672 2018
47
LIG4 Syndrome Associated with Hypocellular Myeloid Dysplasia. 62
29491294 2018
48
Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders. 62
28392333 2018
49
DNA ligase IV syndrome; a review. 62
27717373 2016
50
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. 62
26774591 2016
Sources

Variations for Lig4 Syndrome

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ClinVar genetic disease variations for Lig4 Syndrome:

5 (show top 50) (show all 379)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LIG4 NM_206937.2(LIG4):c.1406G>A (p.Gly469Glu) SNV Pathogenic
 7674 rs104894420 GRCh37: 13:108862211-108862211
GRCh38: 13:108209863-108209863
2 LIG4 NM_206937.2(LIG4):c.1295AAC[1] (p.Gln433del) MICROSAT Pathogenic
 7678 rs587776663 GRCh37: 13:108862317-108862319
GRCh38: 13:108209969-108209971
3 LIG4 NC_000013.11:g.(?_108208513)_(108211288_?)del DEL Pathogenic
 665646 GRCh37: 13:108860861-108863636
GRCh38: 13:108208513-108211288
4 LIG4 NM_206937.2(LIG4):c.597_600del (p.Gln200fs) DEL Pathogenic
 1370122 GRCh37: 13:108863017-108863020
GRCh38: 13:108210669-108210672
5 LIG4 NM_206937.2(LIG4):c.724_725del (p.Leu242fs) DEL Pathogenic
 1423545 GRCh37: 13:108862892-108862893
GRCh38: 13:108210544-108210545
6 LIG4 NM_206937.2(LIG4):c.613del (p.Ser205fs) DEL Pathogenic
 521262 rs780879476 GRCh37: 13:108863004-108863004
GRCh38: 13:108210656-108210656
7 LIG4 NC_000013.10:g.(?_108860881)_(108863616_?)del DEL Pathogenic
 1459476 GRCh37: 13:108860881-108863616
GRCh38:
8 LIG4 NM_206937.2(LIG4):c.1904del (p.Lys635fs) DEL Pathogenic
 418659 rs375554612 GRCh37: 13:108861713-108861713
GRCh38: 13:108209365-108209365
9 LIG4 NM_206937.2(LIG4):c.832C>G (p.Arg278Gly) SNV Pathogenic
 978715 rs574912936 GRCh37: 13:108862785-108862785
GRCh38: 13:108210437-108210437
10 LIG4 NM_206937.2(LIG4):c.799_800del (p.Ser267fs) MICROSAT Pathogenic
 567502 rs1566366148 GRCh37: 13:108862817-108862818
GRCh38: 13:108210469-108210470
11 LIG4 NM_206937.2(LIG4):c.1642_1643del (p.Tyr548fs) MICROSAT Pathogenic
 638937 rs1594458526 GRCh37: 13:108861974-108861975
GRCh38: 13:108209626-108209627
12 LIG4 NM_206937.2(LIG4):c.1512_1513del (p.Arg505fs) MICROSAT Pathogenic
 433156 rs759838407 GRCh37: 13:108862104-108862105
GRCh38: 13:108209756-108209757
13 LIG4 NM_206937.2(LIG4):c.2305dup (p.Thr769fs) DUP Pathogenic
 841699 rs1878251067 GRCh37: 13:108861311-108861312
GRCh38: 13:108208963-108208964
14 LIG4 NM_206937.2(LIG4):c.1746_1750del (p.Glu582fs) DEL Pathogenic
 1076150 GRCh37: 13:108861867-108861871
GRCh38: 13:108209519-108209523
15 LIG4 NM_206937.2(LIG4):c.845A>T (p.His282Leu) SNV Pathogenic
 845678 rs777008519 GRCh37: 13:108862772-108862772
GRCh38: 13:108210424-108210424
16 LIG4 NM_206937.2(LIG4):c.1144_1145del (p.Leu382fs) MICROSAT Pathogenic
 523952 rs1246940345 GRCh37: 13:108862472-108862473
GRCh38: 13:108210124-108210125
17 LIG4 NM_206937.2(LIG4):c.1512_1513dup (p.Arg505fs) MICROSAT Pathogenic
 1338655 rs759838407 GRCh37: 13:108862103-108862104
GRCh38: 13:108209755-108209756
18 LIG4 NM_206937.2(LIG4):c.1246_1250dup (p.Leu418fs) DUP Pathogenic
 1418233 GRCh37: 13:108862366-108862367
GRCh38: 13:108210018-108210019
19 LIG4 NM_206937.2(LIG4):c.1475del (p.Pro492fs) DEL Pathogenic
 1450499 GRCh37: 13:108862142-108862142
GRCh38: 13:108209794-108209794
20 LIG4 NM_206937.2(LIG4):c.2175del (p.Trp725fs) DEL Pathogenic
 1456881 GRCh37: 13:108861442-108861442
GRCh38: 13:108209094-108209094
21 LIG4 NM_206937.2(LIG4):c.73C>T (p.Arg25Ter) SNV Pathogenic
 1453558 GRCh37: 13:108863544-108863544
GRCh38: 13:108211196-108211196
22 LIG4 NM_206937.2(LIG4):c.1738C>T (p.Arg580Ter) SNV Pathogenic
 7672 rs104894418 GRCh37: 13:108861879-108861879
GRCh38: 13:108209531-108209531
23 LIG4 NM_206937.2(LIG4):c.833G>A (p.Arg278His) SNV Pathogenic
 7675 rs104894421 GRCh37: 13:108862784-108862784
GRCh38: 13:108210436-108210436
24 LIG4 NM_206937.2(LIG4):c.2440C>T (p.Arg814Ter) SNV Pathogenic
Pathogenic/Likely Pathogenic
 7673 rs104894419 GRCh37: 13:108861177-108861177
GRCh38: 13:108208829-108208829
25 LIG4 NM_206937.2(LIG4):c.1271_1275del (p.Lys424fs) DEL Pathogenic
 279838 rs772226399 GRCh37: 13:108862342-108862346
GRCh38: 13:108209994-108209998
26 LIG4 NM_206937.2(LIG4):c.2094C>G (p.Tyr698Ter) SNV Pathogenic/Likely Pathogenic
 1343557 GRCh37: 13:108861523-108861523
GRCh38: 13:108209175-108209175
27 LIG4 NM_206937.2(LIG4):c.879_883del (p.Asn294fs) DEL Pathogenic/Likely Pathogenic
 505512 rs751070095 GRCh37: 13:108862734-108862738
GRCh38: 13:108210386-108210390
28 LIG4 NM_206937.2(LIG4):c.2401_2410del (p.Tyr801fs) DEL Likely Pathogenic
 1177531 GRCh37: 13:108861207-108861216
GRCh38: 13:108208859-108208868
29 LIG4 NM_206937.2(LIG4):c.1282G>C (p.Gly428Arg) SNV Likely Pathogenic
 1339553 GRCh37: 13:108862335-108862335
GRCh38: 13:108209987-108209987
30 LIG4 NM_206937.2(LIG4):c.847A>G (p.Lys283Glu) SNV Likely Pathogenic
 694006 rs1594462950 GRCh37: 13:108862770-108862770
GRCh38: 13:108210422-108210422
31 LIG4 NM_206937.2(LIG4):c.2321T>C (p.Leu774Pro) SNV Likely Pathogenic
 397529 rs1060499662 GRCh37: 13:108861296-108861296
GRCh38: 13:108208948-108208948
32 LIG4 NM_206937.2(LIG4):c.1312T>C (p.Tyr438His) SNV Likely Pathogenic
 225274 rs886037777 GRCh37: 13:108862305-108862305
GRCh38: 13:108209957-108209957
33 LIG4 NM_206937.2(LIG4):c.68T>C (p.Leu23Ser) SNV Likely Pathogenic
 1706526 GRCh37: 13:108863549-108863549
GRCh38: 13:108211201-108211201
34 LIG4 NM_206937.2(LIG4):c.2525C>A (p.Ala842Asp) SNV Conflicting Interpretations Of Pathogenicity
Uncertain Significance
 310975 rs72660870 GRCh37: 13:108861092-108861092
GRCh38: 13:108208744-108208744
35 LIG4 NM_206937.2(LIG4):c.500T>G (p.Ile167Arg) SNV Conflicting Interpretations Of Pathogenicity
 310992 rs138021217 GRCh37: 13:108863117-108863117
GRCh38: 13:108210769-108210769
36 LIG4 NM_206937.2(LIG4):c.2499T>C (p.Asn833=) SNV Conflicting Interpretations Of Pathogenicity
 310977 rs769297575 GRCh37: 13:108861118-108861118
GRCh38: 13:108208770-108208770
37 LIG4 NM_206937.2(LIG4):c.1983T>C (p.Asp661=) SNV Conflicting Interpretations Of Pathogenicity
 310980 rs199638675 GRCh37: 13:108861634-108861634
GRCh38: 13:108209286-108209286
38 LIG4 NM_206937.2(LIG4):c.2274T>C (p.Tyr758=) SNV Conflicting Interpretations Of Pathogenicity
 310978 rs529756815 GRCh37: 13:108861343-108861343
GRCh38: 13:108208995-108208995
39 LIG4 NM_206937.2(LIG4):c.1252T>C (p.Leu418=) SNV Conflicting Interpretations Of Pathogenicity
 310984 rs147181971 GRCh37: 13:108862365-108862365
GRCh38: 13:108210017-108210017
40 LIG4 NM_206937.2(LIG4):c.2222G>A (p.Arg741His) SNV Conflicting Interpretations Of Pathogenicity
 310979 rs143767581 GRCh37: 13:108861395-108861395
GRCh38: 13:108209047-108209047
41 LIG4 NM_206937.2(LIG4):c.1710T>C (p.Tyr570=) SNV Conflicting Interpretations Of Pathogenicity
 881301 rs763222026 GRCh37: 13:108861907-108861907
GRCh38: 13:108209559-108209559
42 LIG4 NM_206937.2(LIG4):c.1830C>T (p.Leu610=) SNV Conflicting Interpretations Of Pathogenicity
 883646 rs768563098 GRCh37: 13:108861787-108861787
GRCh38: 13:108209439-108209439
43 LIG4 NM_206937.2(LIG4):c.1242A>C (p.Val414=) SNV Conflicting Interpretations Of Pathogenicity
 827984 rs150828164 GRCh37: 13:108862375-108862375
GRCh38: 13:108210027-108210027
44 LIG4 NM_206937.2(LIG4):c.285G>A (p.Glu95=) SNV Conflicting Interpretations Of Pathogenicity
 435755 rs150146196 GRCh37: 13:108863332-108863332
GRCh38: 13:108210984-108210984
45 LIG4 NM_206937.2(LIG4):c.2197A>G (p.Lys733Glu) SNV Uncertain Significance
 834564 rs762817407 GRCh37: 13:108861420-108861420
GRCh38: 13:108209072-108209072
46 LIG4 NM_206937.2(LIG4):c.691C>T (p.Pro231Ser) SNV Uncertain Significance
 834697 rs3093765 GRCh37: 13:108862926-108862926
GRCh38: 13:108210578-108210578
47 LIG4 NM_206937.2(LIG4):c.2468A>G (p.Tyr823Cys) SNV Uncertain Significance
 835493 rs751149500 GRCh37: 13:108861149-108861149
GRCh38: 13:108208801-108208801
48 LIG4 NM_206937.2(LIG4):c.2320C>G (p.Leu774Val) SNV Uncertain Significance
 837865 rs760371875 GRCh37: 13:108861297-108861297
GRCh38: 13:108208949-108208949
49 LIG4 NM_206937.2(LIG4):c.230G>A (p.Arg77Lys) SNV Uncertain Significance
 844794 rs199707115 GRCh37: 13:108863387-108863387
GRCh38: 13:108211039-108211039
50 LIG4 NM_206937.2(LIG4):c.689A>T (p.Asp230Val) SNV Uncertain Significance
 844865 rs1388798970 GRCh37: 13:108862928-108862928
GRCh38: 13:108210580-108210580

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 GeneCards Suite gene sharing:

(show all 19)
# Super pathways Score Top Affiliating Genes
1
Homology Directed Repair 66
Show member pathways
 13.16 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
2
DNA Damage 3
12.64 XRCC6 XRCC5 XRCC1 TP53BP1 TDP1 PRKDC
3
Chks in Checkpoint Regulation 64
Show member pathways
 12.63 ATM ERCC6 LIG4 NBN PNKP PRKDC
4
DNA Double Strand Break Response 66
Show member pathways
 12.54 PRKDC POLM NHEJ1 NBN LIG4 DCLRE1C
5
DNA repair pathways, full network 74
Show member pathways
 12.53 ATM DCLRE1C ERCC6 LIG4 NBN NHEJ1
6
DNA IR-double strand breaks and cellular response via ATM 74
Show member pathways
 11.96 ATM DCLRE1C NBN PRKDC TP53BP1 XRCC4
7
DNA IR-damage and cellular response via ATR 74
11.86 XRCC5 TP53BP1 TDP1 PRKDC NBN ATM
8
ATM Pathway 64
Show member pathways
 11.66 TP53BP1 NBN ATM
9
Regulation of Telomerase 61
11.64 XRCC6 XRCC5 NBN ATM
10
ATM signaling in development and disease 74
11.56 TP53BP1 RNF168 PRKDC NBN DCLRE1C ATM
11
Coregulation of Androgen receptor activity 61
11.5 XRCC6 XRCC5 PRKDC
12
BARD1 signaling events 61
11.32 XRCC6 XRCC5 PRKDC NBN ATM
13
Telomere Extension by Telomerase 64
Show member pathways
 11.08 XRCC6 XRCC5 NBN
14
Gemtuzumab ozogamicin Pathway, Pharmacokinetics/Pharmacodynamics 60
11.06 XRCC4 PRKDC ATM
15
DNA-PK pathway in nonhomologous end joining 61
10.77 APTX DCLRE1C LIG4 NHEJ1 PNKP POLM
16
DNA damage_NHEJ mechanisms of DSBs repair 22
10.66 DCLRE1C LIG4 NBN PNKP POLM PRKDC
17
SMC1/SMC3 role in DNA damage - Cornelia de Lange Syndrome 74
10.62 NBN ATM
18
NIPBL role in DNA damage - Cornelia de Lange syndrome 74
10.46 RNF168 ATM
19
DDX1 as a regulatory component of the Drosha microprocessor 74
10.39 NBN 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 14)
# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.74 APTX ATM DCLRE1C ERCC6 LIG4 NBN
2 nucleoplasm GO:0005654 10.26 APTX ATM DCLRE1C ERCC6 LIG4 NBN
3 chromosome, telomeric region GO:0000781 10.16 XRCC6 XRCC5 XRCC1 TP53BP1 PRKDC NBN
4 chromosome GO:0005694 10.08 NBN NHEJ1 PAXX PNKP TP53BP1 XRCC4
5 protein-DNA complex GO:0032993 10 XRCC6 XRCC5 PRKDC
6 site of double-strand break GO:0035861 10 NBN NHEJ1 PAXX PNKP RNF168 TP53BP1
7 site of DNA damage GO:0090734 9.99 XRCC5 XRCC1 ERCC6
8 DNA-dependent protein kinase complex GO:0070418 9.91 XRCC6 XRCC5 PRKDC
9 DNA-dependent protein kinase-DNA ligase 4 complex GO:0005958 9.88 XRCC4 PRKDC LIG4
10 DNA ligase IV complex GO:0032807 9.85 XRCC4 NHEJ1 LIG4
11 nuclear telomere cap complex GO:0000783 9.84 XRCC6 XRCC5
12 DNA recombinase complex GO:0097519 9.8 RAG2 RAG1
13 Ku70:Ku80 complex GO:0043564 9.72 PAXX XRCC5 XRCC6
14 nonhomologous end joining complex GO:0070419 9.53 XRCC6 XRCC5 XRCC4 PRKDC PAXX NHEJ1

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

(show all 43)
# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 10.35 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
2 nucleic acid phosphodiester bond hydrolysis GO:0090305 10.27 APTX DCLRE1C PNKP RAG1 TDP1
3 telomere maintenance GO:0000723 10.22 XRCC6 XRCC5 PRKDC NBN DCLRE1C ATM
4 B cell differentiation GO:0030183 10.21 RAG2 RAG1 NHEJ1 DCLRE1C
5 T cell differentiation in thymus GO:0033077 10.17 RAG2 RAG1 PRKDC LIG4
6 neurogenesis GO:0022008 10.16 XRCC5 LIG4 ERCC6
7 DNA duplex unwinding GO:0032508 10.16 XRCC6 XRCC5 NBN
8 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008630 10.16 PRKDC ERCC6 ATM
9 DNA damage checkpoint signaling GO:0000077 10.16 TP53BP1 NBN ERCC6 ATM
10 DNA repair GO:0006281 10.16 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
11 response to ionizing radiation GO:0010212 10.13 RNF168 PRKDC NHEJ1 LIG4 DCLRE1C ATM
12 positive regulation of telomere maintenance via telomerase GO:0032212 10.11 XRCC5 PNKP ATM
13 activation of innate immune response GO:0002218 10.11 XRCC6 XRCC5 PRKDC
14 cellular response to X-ray GO:0071481 10.11 ATM TP53BP1 XRCC5 XRCC6
15 V(D)J recombination GO:0033151 10.11 ATM DCLRE1C LIG4 PRKDC RAG1 RAG2
16 cellular response to gamma radiation GO:0071480 10.1 XRCC6 XRCC5 ATM
17 immunoglobulin V(D)J recombination GO:0033152 10.1 XRCC4 PRKDC NHEJ1 LIG4
18 single strand break repair GO:0000012 10.1 XRCC1 TDP1 LIG4 ERCC6 APTX
19 DNA recombination GO:0006310 10.1 XRCC6 XRCC5 XRCC4 RAG2 RAG1 PRKDC
20 response to gamma radiation GO:0010332 10.09 PRKDC LIG4 ERCC6
21 response to X-ray GO:0010165 10.08 XRCC4 LIG4 ERCC6
22 isotype switching GO:0045190 10.07 RNF168 NBN LIG4
23 regulation of smooth muscle cell proliferation GO:0048660 10.06 XRCC6 XRCC5 PRKDC
24 DNA ligation involved in DNA repair GO:0051103 10.06 LIG4 NHEJ1 PNKP XRCC4
25 DNA ligation GO:0006266 10.02 APTX LIG4 XRCC6
26 double-strand break repair via classical nonhomologous end joining GO:0097680 10.01 XRCC6 LIG4 ERCC6
27 pre-B cell allelic exclusion GO:0002331 10 RAG2 RAG1 ATM
28 T cell lineage commitment GO:0002360 9.98 RAG2 PRKDC
29 recombinational repair GO:0000725 9.97 XRCC5 XRCC6
30 B cell lineage commitment GO:0002326 9.97 PRKDC RAG2
31 T cell receptor V(D)J recombination GO:0033153 9.97 LIG4 PRKDC
32 negative regulation of telomere capping GO:1904354 9.96 ATM NBN
33 pro-B cell differentiation GO:0002328 9.96 LIG4 PRKDC
34 negative regulation of protein ADP-ribosylation GO:0010836 9.96 PNKP XRCC1
35 double-strand break repair GO:0006302 9.96 XRCC5 XRCC4 TDP1 RNF168 PRKDC NHEJ1
36 positive regulation of lymphocyte differentiation GO:0045621 9.95 PRKDC XRCC6
37 positive regulation of ligase activity GO:0051351 9.95 NHEJ1 XRCC4
38 DN2 thymocyte differentiation GO:1904155 9.94 LIG4 RAG2
39 small-subunit processome assembly GO:0034462 9.92 PRKDC XRCC5
40 double-strand break repair via nonhomologous end joining GO:0006303 9.74 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 PRKDC
41 regulation of cellular response to stress GO:0080135 9.69 PRKDC ATM
42 positive regulation of response to stimulus GO:0048584 9.68 PRKDC ATM
43 regulation of nucleobase-containing compound metabolic process GO:0019219 9.62 ATM PRKDC

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

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 10.18 APTX ATM ERCC6 LIG4 NHEJ1 POLM
2 hydrolase activity GO:0016787 10.08 APTX DCLRE1C ERCC6 PNKP RAG1 TDP1
3 protein N-terminus binding GO:0047485 10.06 NBN ERCC6 ATM APTX
4 double-stranded DNA binding GO:0003690 10.03 XRCC6 XRCC5 TDP1 PRKDC PNKP APTX
5 protein C-terminus binding GO:0008022 10.02 ERCC6 LIG4 XRCC4 XRCC5 XRCC6
6 endonuclease activity GO:0004519 10.01 RAG1 PNKP DCLRE1C
7 ATP-dependent activity, acting on DNA GO:0008094 9.91 XRCC6 XRCC5 ERCC6
8 DNA helicase activity GO:0003678 9.89 XRCC6 XRCC5 ERCC6
9 U3 snoRNA binding GO:0034511 9.85 XRCC5 PRKDC
10 telomeric DNA binding GO:0042162 9.85 XRCC6 XRCC5 TP53BP1
11 double-stranded telomeric DNA binding GO:0003691 9.83 XRCC6 XRCC5
12 5'-deoxyribose-5-phosphate lyase activity GO:0051575 9.81 XRCC6 XRCC5
13 DNA-dependent protein kinase activity GO:0004677 9.71 PRKDC ATM
14 damaged DNA binding GO:0003684 9.5 XRCC6 XRCC5 XRCC1 TP53BP1 PNKP NBN
15 DNA end binding GO:0045027 9.43 XRCC6 XRCC5 NHEJ1
Sources

Sources for Lig4 Syndrome

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2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
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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