LIG4S
MCID: LG4001
MIFTS: 55

Lig4 Syndrome (LIG4S)

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

Aliases & Classifications for Lig4 Syndrome

MalaCards integrated aliases for Lig4 Syndrome:

Name: Lig4 Syndrome 57 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®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
closely resembles nijmegen breakage syndrome


HPO:

31
lig4 syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


Summaries for Lig4 Syndrome

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 nijmegen breakage syndrome and immune deficiency disease. 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 bone marrow, bone and brain, 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

Related Diseases for Lig4 Syndrome

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

(show top 50) (show all 63)
# Related Disease Score Top Affiliating Genes
1 nijmegen breakage syndrome 30.7 XRCC6 XRCC5 PRKDC NHEJ1 NBN LIG4
2 immune deficiency disease 29.6 RAG2 RAG1 NBN LIG4 DCLRE1C ATM
3 combined immunodeficiency 29.5 XRCC6 XRCC5 XRCC4 RAG2 RAG1 PRKDC
4 severe combined immunodeficiency 29.2 XRCC6 XRCC5 XRCC4 RAG2 RAG1 PRKDC
5 microcephaly 29.0 XRCC6 XRCC5 XRCC4 TP53BP1 RAG1 PRKDC
6 seckel syndrome 29.0 XRCC6 XRCC5 XRCC4 TP53BP1 PRKDC PNKP
7 fanconi anemia, complementation group a 28.2 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 RNF168
8 ataxia-telangiectasia 28.1 XRCC5 XRCC1 TP53BP1 RAG1 PRKDC NBN
9 hemangioma of subcutaneous tissue 10.3 XRCC5 PRKDC
10 autosomal recessive disease 10.3
11 pancytopenia 10.3
12 ocular motor apraxia 10.2 ATM APTX
13 lymphopenia 10.2
14 fibrosclerosis of breast 10.2 XRCC1 LIG4
15 t-b- severe combined immunodeficiency 10.2 RAG2 DCLRE1C
16 neonatal leukemia 10.2 RAG1 DCLRE1C
17 recombinase activating gene 1 deficiency 10.2 RAG2 RAG1
18 purine nucleoside phosphorylase deficiency 10.1 RAG1 NHEJ1 DCLRE1C
19 alpha-thalassemia/mental retardation syndrome, x-linked 10.1 XRCC6 XRCC5 PRKDC NBN
20 alpha-thalassemia 10.1 XRCC6 XRCC5 PRKDC NBN
21 ataxia-oculomotor apraxia 3 10.1 TDP1 APTX
22 dubowitz syndrome 10.0 XRCC4 PRKDC NHEJ1 LIG4 DCLRE1C
23 spinocerebellar ataxia, autosomal recessive 23 10.0 TDP1 PNKP
24 lymphoma, hodgkin, classic 10.0
25 lymphoma, non-hodgkin, familial 10.0
26 thrombocytopenia 10.0
27 agammaglobulinemia 10.0
28 rubella 10.0
29 dwarfism 10.0
30 hutchinson-gilford progeria syndrome 10.0 TP53BP1 PRKDC ATM
31 congenital nervous system abnormality 10.0 XRCC4 PNKP NHEJ1 NBN LIG4
32 sporadic breast cancer 10.0 XRCC1 NBN ATM
33 haverhill fever 10.0 RAG2 RAG1
34 werner syndrome 10.0 XRCC6 XRCC5 PRKDC NBN ATM
35 pigmentary disorder, reticulate, with systemic manifestations, x-linked 10.0 XRCC6 XRCC5 XRCC4 TP53BP1 ATM
36 combined cellular and humoral immune defects with granulomas 9.9 RAG2 RAG1
37 vesicoureteral reflux 1 9.9
38 urofacial syndrome 1 9.9
39 ataxia and polyneuropathy, adult-onset 9.9
40 myelodysplastic syndrome 9.9
41 inflammatory bowel disease 9.9
42 diffuse large b-cell lymphoma 9.9
43 lymphoma 9.9
44 human cytomegalovirus infection 9.9
45 bacterial infectious disease 9.9
46 neutropenia 9.9
47 leukemia 9.9
48 telangiectasis 9.9
49 b-cell lymphoma 9.9
50 bloom syndrome 9.9 XRCC6 LIG1 ATM

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



Diseases related to Lig4 Syndrome

Symptoms & Phenotypes for Lig4 Syndrome

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 biparietal narrowing 58 31 frequent (33%) Frequent (79-30%) HP:0004422
10 micrognathia 58 31 frequent (33%) Frequent (79-30%) HP:0000347
11 epicanthus 58 31 frequent (33%) Frequent (79-30%) HP:0000286
12 upslanted palpebral fissure 58 31 frequent (33%) Frequent (79-30%) HP:0000582
13 lymphoma 58 31 frequent (33%) Frequent (79-30%) HP:0002665
14 low anterior hairline 58 31 frequent (33%) Frequent (79-30%) HP:0000294
15 telecanthus 58 31 frequent (33%) Frequent (79-30%) HP:0000506
16 erythema 58 31 frequent (33%) Frequent (79-30%) HP:0010783
17 acute leukemia 58 31 frequent (33%) Frequent (79-30%) HP:0002488
18 cutaneous photosensitivity 58 31 frequent (33%) Frequent (79-30%) HP:0000992
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 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
24 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002240
25 type ii diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0005978
26 malabsorption 58 31 occasional (7.5%) Occasional (29-5%) HP:0002024
27 cryptorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000028
28 telangiectasia of the skin 58 31 occasional (7.5%) Occasional (29-5%) HP:0100585
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 failure to thrive 31 HP:0001508
35 delayed speech and language development 31 HP:0000750
36 immunodeficiency 58 Very frequent (99-80%)
37 abnormality of the skeletal system 58 Occasional (29-5%)
38 thrombocytopenia 31 HP:0001873
39 myelodysplasia 31 HP:0002863
40 micropenis 31 HP:0000054
41 hypotelorism 31 HP:0000601
42 abnormality of bone marrow cell morphology 58 Frequent (79-30%)
43 prominent nose 31 HP:0000448
44 psoriasiform dermatitis 31 HP:0003765
45 amenorrhea 31 HP:0000141
46 narrow forehead 31 HP:0000341

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
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 05-Mar-2021)

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 10.06 ATM LIG1 LIG4 PRKDC
2 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-2 10.06 ATM LIG1 LIG4 NBN TP53BP1
3 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 10.06 ATM LIG1 LIG4 NBN TDP1 TP53BP1
4 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.95 NBN TDP1 TP53BP1 XRCC1
5 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.95 ATM LIG1 LIG4 PRKDC TDP1 TP53BP1
6 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-3 9.95 ATM LIG1 NBN PRKDC TDP1 TP53BP1
7 Reduced mammosphere formation GR00396-S 9.5 ATM DCLRE1C PNKP PRKDC XRCC1 XRCC5

MGI Mouse Phenotypes related to Lig4 Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.45 APTX ATM DCLRE1C LIG1 LIG4 NBN
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 NBN NHEJ1
5 homeostasis/metabolism MP:0005376 10.27 APTX ATM LIG1 LIG4 NBN NHEJ1
6 immune system MP:0005387 10.22 ATM DCLRE1C LIG1 LIG4 NBN NHEJ1
7 mortality/aging MP:0010768 10.1 ATM LIG1 LIG4 NBN NHEJ1 PAXX
8 neoplasm MP:0002006 10.03 ATM LIG1 LIG4 NBN NHEJ1 PAXX
9 nervous system MP:0003631 9.8 ATM LIG4 NBN NHEJ1 PAXX PNKP
10 reproductive system MP:0005389 9.36 ATM LIG4 NBN POLM PRKDC RAG2

Drugs & Therapeutics for Lig4 Syndrome

Search Clinical Trials , NIH Clinical Center for Lig4 Syndrome

Genetic Tests for Lig4 Syndrome

Genetic tests related to Lig4 Syndrome:

# Genetic test Affiliating Genes
1 Lig4 Syndrome 29 LIG4

Anatomical Context for Lig4 Syndrome

MalaCards organs/tissues related to Lig4 Syndrome:

40
Bone Marrow, Bone, Brain, Kidney, Myeloid

Publications for Lig4 Syndrome

Articles related to Lig4 Syndrome:

(show all 50)
# Title Authors PMID Year
1
A new type of radiosensitive T-B-NK+ severe combined immunodeficiency caused by a LIG4 mutation. 61 54 57 6
16357942 2006
2
A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome. 6 57 54 61
16088910 2005
3
DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. 57 6
11779494 2001
4
Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome. 57 54 61
20133615 2010
5
Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms. 61 54 57
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. 54 61
17554302 2007
12
Epstein-Barr virus-associated B-cell lymphoma in a patient with DNA ligase IV (LIG4) syndrome. 61 54
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. 61 54
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. 54 61
12640452 2003
17
Hypomorphic mutations in human DNA ligase IV lead to compromised DNA binding efficiency, hydrophobicity and thermal stability. 61
33586762 2021
18
DNA Ligase IV Deficiency Identified by Chance Following Vaccine-Derived Rubella Virus Infection. 61
32914283 2020
19
Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations. 61
32534991 2020
20
LIG4 syndrome: clinical and molecular characterization in a Chinese cohort. 61
32471509 2020
21
Spatiotemporal Gradient of Cortical Neuron Death Contributes to Microcephaly in Knock-In Mouse Model of Ligase 4 Syndrome. 61
31541646 2019
22
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
23
Allogeneic hematopoietic stem cell transplantation in two brothers with DNA ligase IV deficiency: a case report and review of the literature. 61
31604460 2019
24
[LIG4 syndrome: a report of four cases and literature review]. 61
30818900 2019
25
A Novel Missense LIG4 Mutation in a Patient With a Phenotype Mimicking Behçet's Disease. 61
30617623 2019
26
LIG4 Syndrome Associated with Hypocellular Myeloid Dysplasia. 61
29491294 2018
27
Structures of DNA-bound human ligase IV catalytic core reveal insights into substrate binding and catalysis. 61
29980672 2018
28
Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature. 61
30719430 2018
29
Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders. 61
28392333 2018
30
DNA ligase IV deficiency: Immunoglobulin class deficiency depends on the genotype. 61
28039949 2017
31
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
32
DNA ligase IV syndrome; a review. 61
27717373 2016
33
Ligase-4 Deficiency Causes Distinctive Immune Abnormalities in Asymptomatic Individuals. 61
27063650 2016
34
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
35
Molecular and immunological characterization of DNA ligase IV deficiency. 61
26762768 2016
36
Integrating Gene Correction in the Reprogramming and Transdifferentiation Processes: A One-Step Strategy to Overcome Stem Cell-Based Gene Therapy Limitations. 61
28074097 2016
37
Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly-progressing radiosensitive-severe combined immunodeficiency. 61
26172957 2015
38
Reprint of "The clinical impact of deficiency in DNA non-homologous end-joining". 61
24780557 2014
39
The clinical impact of deficiency in DNA non-homologous end-joining. 61
24629483 2014
40
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
41
Structural insights into the role of domain flexibility in human DNA ligase IV. 61
22658747 2012
42
Nijmegen breakage syndrome (NBS). 61
22373003 2012
43
Requirement for DNA ligase IV during embryonic neuronal development. 61
21734301 2011
44
Ligase IV syndrome. 61
20687505 2010
45
Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure. 61
17224058 2007
46
Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. 61
16777961 2006
47
Cernunnos interacts with the XRCC4 x DNA-ligase IV complex and is homologous to the yeast nonhomologous end-joining factor Nej1. 61
16571728 2006
48
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
49
Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm. 61
11040211 2000
50
DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. 61
10911993 2000

Variations for Lig4 Syndrome

ClinVar genetic disease variations for Lig4 Syndrome:

6 (show top 50) (show all 206)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LIG4 NM_206937.2(LIG4):c.832C>G (p.Arg278Gly) SNV Pathogenic 978715 13:108862785-108862785 13:108210437-108210437
2 LIG4 NM_206937.2(LIG4):c.1738C>T (p.Arg580Ter) SNV Pathogenic 7672 rs104894418 13:108861879-108861879 13:108209531-108209531
3 LIG4 NM_206937.2(LIG4):c.1406G>A (p.Gly469Glu) SNV Pathogenic 7674 rs104894420 13:108862211-108862211 13:108209863-108209863
4 LIG4 NM_206937.2(LIG4):c.833G>A (p.Arg278His) SNV Pathogenic 7675 rs104894421 13:108862784-108862784 13:108210436-108210436
5 LIG4 NM_206937.2(LIG4):c.1295_1297AAC[1] (p.Gln433del) Microsatellite Pathogenic 7678 rs587776663 13:108862317-108862319 13:108209969-108209971
6 LIG4 NM_206937.2(LIG4):c.797_798AG[1] (p.Ser267fs) Microsatellite Pathogenic 567502 rs1566366148 13:108862817-108862818 13:108210469-108210470
7 LIG4 NM_206937.2(LIG4):c.1271_1275del (p.Lys424fs) Deletion Pathogenic 279838 rs772226399 13:108862342-108862346 13:108209994-108209998
8 LIG4 NM_206937.2(LIG4):c.1640_1641TA[1] (p.Tyr548fs) Microsatellite Pathogenic 638937 rs1594458526 13:108861974-108861975 13:108209626-108209627
9 LIG4 NM_206937.2(LIG4):c.2305dup (p.Thr769fs) Duplication Pathogenic 841699 13:108861311-108861312 13:108208963-108208964
10 LIG4 NM_206937.2(LIG4):c.1506_1507TC[3] (p.Arg505fs) Microsatellite Pathogenic 433156 rs759838407 13:108862104-108862105 13:108209756-108209757
11 LIG4 NM_206937.2(LIG4):c.1904del (p.Lys635fs) Deletion Pathogenic 418659 rs375554612 13:108861713-108861713 13:108209365-108209365
12 LIG4 NM_206937.2(LIG4):c.613del (p.Ser205fs) Deletion Pathogenic 521262 rs780879476 13:108863004-108863004 13:108210656-108210656
13 LIG4 NC_000013.11:g.(?_108208513)_(108211288_?)del Deletion Pathogenic 665646 13:108860861-108863636 13:108208513-108211288
14 LIG4 NM_206937.2(LIG4):c.2440C>T (p.Arg814Ter) SNV Pathogenic 7673 rs104894419 13:108861177-108861177 13:108208829-108208829
15 LIG4 NM_206937.2(LIG4):c.2440C>T (p.Arg814Ter) SNV Pathogenic/Likely pathogenic 7673 rs104894419 13:108861177-108861177 13:108208829-108208829
16 LIG4 NM_206937.2(LIG4):c.845A>T (p.His282Leu) SNV Likely pathogenic 845678 13:108862772-108862772 13:108210424-108210424
17 LIG4 NM_206937.2(LIG4):c.847A>G (p.Lys283Glu) SNV Likely pathogenic 694006 rs1594462950 13:108862770-108862770 13:108210422-108210422
18 LIG4 NM_206937.2(LIG4):c.1312T>C (p.Tyr438His) SNV Likely pathogenic 225274 rs886037777 13:108862305-108862305 13:108209957-108209957
19 LIG4 NM_206937.2(LIG4):c.2321T>C (p.Leu774Pro) SNV Likely pathogenic 397529 rs1060499662 13:108861296-108861296 13:108208948-108208948
20 LIG4 NM_206937.2(LIG4):c.879_883del (p.Asn294fs) Deletion Likely pathogenic 505512 rs751070095 13:108862734-108862738 13:108210386-108210390
21 LIG4 NM_206937.2(LIG4):c.2525C>A (p.Ala842Asp) SNV Conflicting interpretations of pathogenicity 310975 rs72660870 13:108861092-108861092 13:108208744-108208744
22 LIG4 NM_206937.2(LIG4):c.500T>G (p.Ile167Arg) SNV Conflicting interpretations of pathogenicity 310992 rs138021217 13:108863117-108863117 13:108210769-108210769
23 LIG4 NM_206937.2(LIG4):c.1983T>C (p.Asp661=) SNV Conflicting interpretations of pathogenicity 310980 rs199638675 13:108861634-108861634 13:108209286-108209286
24 LIG4 NM_206937.2(LIG4):c.1252T>C (p.Leu418=) SNV Conflicting interpretations of pathogenicity 310984 rs147181971 13:108862365-108862365 13:108210017-108210017
25 LIG4 NM_206937.2(LIG4):c.285G>A (p.Glu95=) SNV Conflicting interpretations of pathogenicity 435755 rs150146196 13:108863332-108863332 13:108210984-108210984
26 LIG4 NM_206937.2(LIG4):c.2222G>A (p.Arg741His) SNV Conflicting interpretations of pathogenicity 310979 rs143767581 13:108861395-108861395 13:108209047-108209047
27 LIG4 NM_206937.2(LIG4):c.-32C>T SNV Uncertain significance 310998 rs536441091 13:108866889-108866889 13:108214541-108214541
28 LIG4 NM_206937.2(LIG4):c.*56G>C SNV Uncertain significance 310969 rs886049947 13:108860825-108860825 13:108208477-108208477
29 LIG4 NM_206937.2(LIG4):c.2016C>G (p.Ser672Arg) SNV Uncertain significance 211374 rs142144659 13:108861601-108861601 13:108209253-108209253
30 LIG4 NM_206937.2(LIG4):c.*291A>G SNV Uncertain significance 881190 13:108860590-108860590 13:108208242-108208242
31 LIG4 NM_206937.2(LIG4):c.1710T>C (p.Tyr570=) SNV Uncertain significance 881301 13:108861907-108861907 13:108209559-108209559
32 LIG4 NM_206937.2(LIG4):c.1705A>G (p.Met569Val) SNV Uncertain significance 881302 13:108861912-108861912 13:108209564-108209564
33 LIG4 NM_206937.2(LIG4):c.*857T>C SNV Uncertain significance 881611 13:108860024-108860024 13:108207676-108207676
34 LIG4 NM_206937.2(LIG4):c.2435T>G (p.Met812Arg) SNV Uncertain significance 881240 13:108861182-108861182 13:108208834-108208834
35 LIG4 NM_206937.2(LIG4):c.1239A>G (p.Glu413=) SNV Uncertain significance 881753 13:108862378-108862378 13:108210030-108210030
36 LIG4 NM_206937.2(LIG4):c.1235A>G (p.Asn412Ser) SNV Uncertain significance 881754 13:108862382-108862382 13:108210034-108210034
37 LIG4 NM_206937.2(LIG4):c.*781A>G SNV Uncertain significance 882771 13:108860100-108860100 13:108207752-108207752
38 LIG4 NM_206937.2(LIG4):c.*736C>G SNV Uncertain significance 882772 13:108860145-108860145 13:108207797-108207797
39 LIG4 NM_206937.2(LIG4):c.1971T>C (p.Asn657=) SNV Uncertain significance 882854 13:108861646-108861646 13:108209298-108209298
40 LIG4 NM_206937.2(LIG4):c.968T>C (p.Ile323Thr) SNV Uncertain significance 882900 13:108862649-108862649 13:108210301-108210301
41 LIG4 NM_206937.2(LIG4):c.1882C>T (p.Arg628Trp) SNV Uncertain significance 577575 rs755708095 13:108861735-108861735 13:108209387-108209387
42 LIG4 NM_206937.2(LIG4):c.1094G>T (p.Cys365Phe) SNV Uncertain significance 533822 rs144322912 13:108862523-108862523 13:108210175-108210175
43 LIG4 NM_206937.2(LIG4):c.2525C>A (p.Ala842Asp) SNV Uncertain significance 310975 rs72660870 13:108861092-108861092 13:108208744-108208744
44 LIG4 NM_206937.2(LIG4):c.1882C>T (p.Arg628Trp) SNV Uncertain significance 577575 rs755708095 13:108861735-108861735 13:108209387-108209387
45 LIG4 NM_206937.2(LIG4):c.2425C>G (p.Pro809Ala) SNV Uncertain significance 647972 rs137899041 13:108861192-108861192 13:108208844-108208844
46 LIG4 NM_206937.2(LIG4):c.*525T>G SNV Uncertain significance 883558 13:108860356-108860356 13:108208008-108208008
47 LIG4 NM_206937.2(LIG4):c.*26C>G SNV Uncertain significance 883601 13:108860855-108860855 13:108208507-108208507
48 LIG4 NM_206937.2(LIG4):c.1830C>T (p.Leu610=) SNV Uncertain significance 883646 13:108861787-108861787 13:108209439-108209439
49 LIG4 NM_206937.2(LIG4):c.713T>C (p.Ile238Thr) SNV Uncertain significance 883697 13:108862904-108862904 13:108210556-108210556
50 LIG4 NM_206937.2(LIG4):c.*166G>C SNV Uncertain significance 310965 rs538355612 13:108860715-108860715 13:108208367-108208367

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

Expression for Lig4 Syndrome

Search GEO for disease gene expression data for Lig4 Syndrome.

Pathways for Lig4 Syndrome

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 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.63 XRCC6 XRCC5 XRCC4 XRCC1 PRKDC PNKP
2
Show member pathways
12.53 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
3
Show member pathways
12.33 XRCC6 XRCC5 XRCC4 TP53BP1 TDP1 RNF168
4 12.27 XRCC6 XRCC5 XRCC1 TP53BP1 TDP1 PRKDC
5
Show member pathways
11.64 TP53BP1 NBN ATM
6 11.55 XRCC6 XRCC5 NBN ATM
7 11.51 TP53BP1 RNF168 PRKDC NBN DCLRE1C ATM
8 11.43 XRCC6 XRCC5 PRKDC
9 11.29 XRCC6 XRCC5 XRCC4 PRKDC POLM PNKP
10 11.26 XRCC6 XRCC5 PRKDC NBN ATM
11 11.23 RAG2 RAG1 DCLRE1C
12
Show member pathways
11.01 XRCC6 XRCC5 NBN
13 10.99 XRCC4 PRKDC ATM
14
Show member pathways
10.74 NBN ATM

GO Terms for Lig4 Syndrome

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.26 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
2 nucleolus GO:0005730 10.08 XRCC6 XRCC5 XRCC1 PRKDC PNKP NBN
3 site of double-strand break GO:0035861 9.8 XRCC4 TP53BP1 RNF168 PAXX NBN
4 chromosome, telomeric region GO:0000781 9.76 XRCC6 XRCC5 XRCC1 TP53BP1 PRKDC NBN
5 protein-DNA complex GO:0032993 9.67 XRCC6 XRCC5 PRKDC
6 nucleoplasm GO:0005654 9.62 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
7 DNA-dependent protein kinase-DNA ligase 4 complex GO:0005958 9.61 XRCC4 PRKDC LIG4
8 nonhomologous end joining complex GO:0070419 9.56 XRCC6 XRCC5 XRCC4 PRKDC PAXX NHEJ1
9 Ku70:Ku80 complex GO:0043564 9.54 XRCC6 XRCC5 PAXX
10 nuclear telomere cap complex GO:0000783 9.52 XRCC6 XRCC5
11 DNA repair complex GO:1990391 9.51 TP53BP1 ATM
12 DNA ligase IV complex GO:0032807 9.5 XRCC4 NHEJ1 LIG4
13 DNA recombinase complex GO:0097519 9.46 RAG2 RAG1

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

(show all 47)
# Name GO ID Score Top Affiliating Genes
1 DNA recombination GO:0006310 10.02 XRCC6 XRCC5 XRCC4 RAG2 RAG1 PRKDC
2 double-strand break repair via nonhomologous end joining GO:0006303 10 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 RNF168
3 brain development GO:0007420 9.99 XRCC6 XRCC5 PRKDC ATM
4 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.97 TDP1 RAG1 PNKP DCLRE1C APTX
5 DNA replication GO:0006260 9.96 NBN LIG4 LIG1 ATM
6 double-strand break repair GO:0006302 9.96 XRCC5 XRCC4 TDP1 RNF168 PRKDC NHEJ1
7 response to ionizing radiation GO:0010212 9.91 RNF168 PRKDC NHEJ1 LIG4 DCLRE1C ATM
8 V(D)J recombination GO:0033151 9.91 RAG2 RAG1 PRKDC LIG4 LIG1 DCLRE1C
9 cellular response to DNA damage stimulus GO:0006974 9.91 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
10 B cell differentiation GO:0030183 9.89 RAG2 RAG1 NHEJ1 DCLRE1C
11 telomere maintenance GO:0000723 9.88 XRCC6 XRCC5 PRKDC NBN DCLRE1C ATM
12 DNA duplex unwinding GO:0032508 9.86 XRCC6 XRCC5 NBN
13 double-strand break repair via homologous recombination GO:0000724 9.86 XRCC1 NBN ATM
14 positive regulation of type I interferon production GO:0032481 9.86 XRCC6 XRCC5 PRKDC
15 T cell differentiation in thymus GO:0033077 9.86 RAG2 RAG1 PRKDC LIG4
16 thymus development GO:0048538 9.83 RAG1 PRKDC ATM
17 single strand break repair GO:0000012 9.83 XRCC1 TDP1 LIG4 APTX
18 DNA biosynthetic process GO:0071897 9.82 POLM LIG4 LIG1
19 DNA damage checkpoint GO:0000077 9.81 TP53BP1 NBN ATM
20 cellular response to X-ray GO:0071481 9.81 XRCC6 XRCC5 TP53BP1 ATM
21 establishment of integrated proviral latency GO:0075713 9.8 XRCC6 XRCC5 XRCC4 LIG4
22 positive regulation of telomere maintenance via telomerase GO:0032212 9.79 XRCC5 PNKP ATM
23 cellular response to gamma radiation GO:0071480 9.79 XRCC6 XRCC5 ATM
24 activation of innate immune response GO:0002218 9.78 XRCC6 XRCC5 PRKDC
25 DNA ligation GO:0006266 9.78 XRCC6 LIG4 LIG1 APTX
26 nucleotide-excision repair, DNA gap filling GO:0006297 9.77 XRCC1 LIG4 LIG1
27 isotype switching GO:0045190 9.76 RNF168 NBN LIG4
28 DNA ligation involved in DNA repair GO:0051103 9.76 XRCC4 PAXX LIG4 LIG1
29 regulation of smooth muscle cell proliferation GO:0048660 9.75 XRCC6 XRCC5 PRKDC
30 immunoglobulin V(D)J recombination GO:0033152 9.72 XRCC4 PRKDC LIG4
31 pre-B cell allelic exclusion GO:0002331 9.71 RAG2 RAG1 ATM
32 response to X-ray GO:0010165 9.7 XRCC4 LIG4
33 positive regulation of double-strand break repair via nonhomologous end joining GO:2001034 9.7 PRKDC PNKP
34 DNA double-strand break processing GO:0000729 9.7 NBN ATM
35 cellular response to lithium ion GO:0071285 9.69 XRCC4 LIG4
36 double-strand break repair via classical nonhomologous end joining GO:0097680 9.68 XRCC6 LIG4
37 T cell lineage commitment GO:0002360 9.68 RAG2 PRKDC
38 negative regulation of telomere capping GO:1904354 9.67 NBN ATM
39 positive regulation of lymphocyte differentiation GO:0045621 9.67 XRCC6 PRKDC
40 T cell receptor V(D)J recombination GO:0033153 9.67 PRKDC LIG4
41 B cell lineage commitment GO:0002326 9.66 RAG2 PRKDC
42 positive regulation of ligase activity GO:0051351 9.65 XRCC4 NHEJ1
43 pro-B cell differentiation GO:0002328 9.65 PRKDC LIG4
44 cellular hyperosmotic salinity response GO:0071475 9.63 XRCC6 XRCC5
45 small-subunit processome assembly GO:0034462 9.63 XRCC5 PRKDC
46 negative regulation of protein ADP-ribosylation GO:0010836 9.62 XRCC1 PNKP
47 DNA repair GO:0006281 9.58 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1

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

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.5 XRCC6 XRCC5 XRCC4 XRCC1 TP53BP1 TDP1
2 ATP binding GO:0005524 10.09 XRCC6 XRCC5 PRKDC PNKP LIG4 LIG1
3 protein C-terminus binding GO:0008022 9.78 XRCC6 XRCC5 XRCC4 LIG4
4 DNA binding GO:0003677 9.77 XRCC6 XRCC5 XRCC4 TP53BP1 RAG2 RAG1
5 protein N-terminus binding GO:0047485 9.73 NBN ATM APTX
6 endonuclease activity GO:0004519 9.71 RAG1 PNKP DCLRE1C
7 double-stranded DNA binding GO:0003690 9.63 XRCC6 XRCC5 TDP1 PRKDC PNKP APTX
8 U3 snoRNA binding GO:0034511 9.51 XRCC5 PRKDC
9 telomeric DNA binding GO:0042162 9.5 XRCC6 XRCC5 TP53BP1
10 double-stranded telomeric DNA binding GO:0003691 9.49 XRCC6 XRCC5
11 5'-deoxyribose-5-phosphate lyase activity GO:0051575 9.46 XRCC6 XRCC5
12 DNA-dependent protein kinase activity GO:0004677 9.43 PRKDC ATM
13 DNA end binding GO:0045027 9.43 XRCC6 XRCC5 NHEJ1
14 DNA ligase (ATP) activity GO:0003910 9.4 LIG4 LIG1
15 DNA ligase activity GO:0003909 9.37 LIG4 LIG1
16 damaged DNA binding GO:0003684 9.23 XRCC6 XRCC5 XRCC1 TP53BP1 PNKP NBN

Sources for Lig4 Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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