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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

LIG4 Gene

protein-coding   GIFtS: 72
GCID: GC13M108859

Ligase IV, DNA, ATP-Dependent

Microbiology & Infectious Diseases Congress
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at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Ligase IV, DNA, ATP-Dependent1 2     sealase1 2
Polydeoxyribonucleotide Synthase [ATP] 41 2 3     DNA Ligase IV2 3
DNA Joinase1 2     EC 6.5.1.13 8
DNA Repair Enzyme1 2     DNA Ligase 42
Polynucleotide Ligase1 2     

External Ids:    HGNC: 66011   Entrez Gene: 39812   Ensembl: ENSG000001744057   OMIM: 6018375   UniProtKB: P499173   

Export aliases for LIG4 gene to outside databases

Previous GC identifers: GC13M107220 GC13M103247 GC13M107696 GC13M106558 GC13M107657 GC13M089450


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for LIG4 Gene:
The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded
polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA
double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the
X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase
(DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by
this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively
spliced transcript variants encoding the same protein have been observed. (provided by RefSeq, Jul 2008)

GeneCards Summary for LIG4 Gene: 
LIG4 (ligase IV, DNA, ATP-dependent) is a protein-coding gene. Diseases associated with LIG4 include dna ligase iv deficiency, and multiple myeloma, resistance to, and among its related super-pathways are Non-homologous end joining and Integration of provirus. GO annotations related to this gene include DNA ligase activity and protein C-terminus binding. An important paralog of this gene is LIG3.

UniProtKB/Swiss-Prot: DNLI4_HUMAN, P49917
Function: Efficiently joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent
reaction. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J
recombination. The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining
activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent
protein kinase complex DNA-PK to these DNA ends

summary for LIG4 Gene:
Ligases catalyze the joining of two molecules with concomitant hydrolysis of the diphosphate bond in ATP or
a similar triphosphate. They belong to the E.C. 6 class, which also includes synthases and carboxylases. DNA
ligases play an integral role in DNA repair and replication: they catalyze the formation of phosphodiester
bonds, using ATP as a co-factor. These enzymes are divided into three classes: DNA ligase I, III and IV. DNA
ligase I links Okazaki fragments to form a continuous strand of DNA. DNA ligase III is involved in base
excision repair. Finally, DNA ligase IV is involved in the repair of DNA double-strand breaks by
non-homologous end joining (NHEJ).

Gene Wiki entry for LIG4 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000013.10  NT_009952.14  NC_018924.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the LIG4 gene promoter:
         RP58   p300   ZID   NF-AT1   NF-AT   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 5): LIG4 promoter sequence
   Search SABiosciences Chromatin IP Primers for LIG4

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat LIG4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 13q33-q34   Ensembl cytogenetic band:  13q33.3   HGNC cytogenetic band: 13q33-q34

LIG4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
LIG4 gene location

GeneLoc information about chromosome 13         GeneLoc Exon Structure

GeneLoc location for GC13M108859:  view genomic region     (about GC identifiers)

Start:
108,859,787 bp from pter      End:
108,870,716 bp from pter
Size:
10,930 bases      Orientation:
minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: DNLI4_HUMAN, P49917 (See protein sequence)
Recommended Name: DNA ligase 4  
Size: 911 amino acids; 103971 Da
Cofactor: Magnesium (By similarity)
Subunit: Binds to XRCC4. The LIG4-XRCC4 complex has probably a 1:2 stoichiometry. The LIG4-XRCC4 heteromer
associates in a DNA-dependent manner with the DNA-dependent protein kinase complex DNA-PK, formed by the Ku
p70/p86 dimer (G22P1/G22P2) and PRKDC. Interacts with APLF
Subcellular location: Nucleus
Sequence caution: Sequence=AAL77435.1; Type=Erroneous initiation; Sequence=CAA58467.1; Type=Erroneous initiation;
6/9 PDB 3D structures from and Proteopedia for LIG4 (see all 9):
1IK9 (3D)        2E2W (3D)        3II6 (3D)        3VNN (3D)        3W1B (3D)        3W1G (3D)    
Secondary accessions: Q8IY66 Q8TEU5

Explore the universe of human proteins at neXtProt for LIG4: NX_P49917

Explore proteomics data for LIG4 at MOPED 

Post-translational modifications:

  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P49917

  • 4/10 DME Specific Peptides for LIG4 (P49917) (see all 10)
     DGERMQMH  TQTFMQKG  FYPAMRLI  ILCGTEKPE 

    LIG4 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    LIG4 Protein Expression
    REFSEQ proteins (3 alternative transcripts): 
    NP_001091738.1  NP_002303.2  NP_996820.1  

    ENSEMBL proteins: 
     ENSP00000349393   ENSP00000385955   ENSP00000402030  
    Reactome Protein details: P49917
    Human Recombinant Protein Products for LIG4: 
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    Novus Biologicals LIG4 Protein
    Novus Biologicals LIG4 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for LIG4 

    Gene Ontology (GO): 5/10 cellular component terms (GO ID links to tree view) (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000793condensed chromosome IDA12589063
    GO:0005634nucleus IDA--
    GO:0005654nucleoplasm TAS--
    GO:0005730NOT nucleolus IDA--
    GO:0005737cytoplasm IDA--

    LIG4 for ontologies           About GeneDecksing



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    Cloud-Clone Corp. ELISAs for LIG4 
    Cloud-Clone Corp. CLIAs for LIG4


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    5/8 InterPro protein domains (see all 8):
     IPR012340 NA-bd_OB-fold
     IPR012308 DNA_ligase_ATP-dep_N
     IPR012310 DNA_ligase_ATP-dep_cent
     IPR021536 DNA_ligase_IV
     IPR016059 DNA_ligase_ATP-dep_CS

    Graphical View of Domain Structure for InterPro Entry P49917

    ProtoNet protein and cluster: P49917

    2 Blocks protein domains:
    IPB001357 BRCT domain
    IPB012308 DNA ligase


    UniProtKB/Swiss-Prot: DNLI4_HUMAN, P49917
    Similarity: Belongs to the ATP-dependent DNA ligase family
    Similarity: Contains 2 BRCT domains


    LIG4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: DNLI4_HUMAN, P49917
    Function: Efficiently joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent
    reaction. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J
    recombination. The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining
    activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent
    protein kinase complex DNA-PK to these DNA ends
    Catalytic activity: ATP + (deoxyribonucleotide)(n) + (deoxyribonucleotide)(m) = AMP + diphosphate +
    (deoxyribonucleotide)(n+m)

         Genatlas biochemistry entry for LIG4:
    DNA ligase IV,ATP-dependent,96kDa,the ligation responsible for DNA double-strand breaks repair by end joining (non
    homologous recombination) and V(D)J recombination

         Enzyme Number (IUBMB): EC 6.5.1.11 2

         Gene Ontology (GO): 5/8 molecular function terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003677DNA binding IDA8798671
    GO:0003909DNA ligase activity TAS--
    GO:0003910DNA ligase (ATP) activity IDA8798671
    GO:0005515protein binding IPI16439205
    GO:0005524ATP binding IEA--
         
    LIG4 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for LIG4:
     Increased homologous recombina 

         13 MGI mutant phenotypes (inferred from 6 alleles(MGI details for Lig4):
     behavior/neurological  cellular  craniofacial  digestive/alimentary  growth/size 
     hematopoietic system  homeostasis/metabolism  immune system  liver/biliary system  mortality/aging 
     nervous system  reproductive system  tumorigenesis 

    LIG4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for LIG4: Lig4tm1Fwa Lig4tm1Icrf

       inGenious Targeting Laboratory - Custom generated mouse model solutions for LIG4 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for LIG4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for LIG4 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for LIG4 

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    hsa-miR-548am hsa-miR-548x hsa-miR-4282
    SwitchGear 3'UTR luciferase reporter plasmidLIG4 3' UTR sequence
    Inhib. RNA
    Products:
        
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for LIG4


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for LIG4 About   (see all 9)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Non-homologous end-joining
    Non-homologous end-joining0.46
    DNA damage NHEJ mechanisms of DSBs repair0.37
    2Integration of provirus
    Integration of provirus0.88
    Early Phase of HIV Life Cycle0.73
    2-LTR circle formation0.88
    3HIV Life Cycle
    HIV Life Cycle0.92
    HIV Infection0.61
    4Homologous Recombination Repair
    Double-Strand Break Repair0.71
    5Processing of DNA ends prior to end rejoining
    Nonhomologous End-joining (NHEJ)0.67

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 EMD Millipore Pathway for LIG4
        DNA damage NHEJ mechanisms of DSBs repair

    2 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for LIG4
        DNA Repair Mechanisms
    Nucleotide Excision Repair Pathway

    1 GeneGo (Thomson Reuters) Pathway for LIG4
        DNA damage NHEJ mechanisms of DSBs repair


    5/9        Reactome Pathways for LIG4 (see all 9)
        DNA Repair
    Nonhomologous End-joining (NHEJ)
    Early Phase of HIV Life Cycle
    Disease
    HIV Life Cycle


    1         Kegg Pathway  (Kegg details for LIG4):
        Non-homologous end-joining


    LIG4 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for LIG4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/48 Interacting proteins for LIG4 (P499171, 2, 3 ENSP000003493934) via UniProtKB, MINT, STRING, and/or I2D (see all 48)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    NHEJ1Q9H9Q41, 3, ENSP000003493134EBI-847896,EBI-847807 I2D: score=3 STRING: ENSP00000349313
    APLFQ8IW192, 3, ENSP000003070044MINT-4790271 MINT-8412696 I2D: score=3 STRING: ENSP00000307004
    XRCC4Q134262, 3, ENSP000003420114MINT-8412696 I2D: score=4 STRING: ENSP00000342011
    PES1O005413, ENSP000003467254I2D: score=4 STRING: ENSP00000346725
    PRKDCP785273, ENSP000003134204I2D: score=3 STRING: ENSP00000313420
    About this table

    Gene Ontology (GO): 5/34 biological process terms (GO ID links to tree view) (see all 34):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000012single strand break repair IDA8798671
    GO:0001701in utero embryonic development ISS--
    GO:0002328pro-B cell differentiation ISS--
    GO:0006260DNA replication ----
    GO:0006266DNA ligation IDA12517771

    LIG4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    LIG4 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Compounds for LIG4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    L189 DNA ligase I, III and IV inhibitor [64232-83-3]

    4 HMDB Compounds for LIG4    About this table
    CompoundSynonyms CAS #PubMed Ids
    Adenosine monophosphate5'-AMP (see all 28)61-19-8--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    Phosphoric acidacide phosphorique (FRENCH) (see all 20)7664-38-2--
    Pyrophosphate(4-)Diphosphoric acid ion (see all 10)14000-31-8--

    7 Novoseek inferred chemical compound relationships for LIG4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    polynucleotide 72.3 8 2144612 (1), 8559059 (1), 18644470 (1), 18262407 (1) (see all 8)
    wortmannin 34.2 1 11292837 (1)
    alanine 3.59 2 15194694 (1)
    nacl 0 2 8798671 (1)
    phosphatidylinositol 0 1 10608806 (1)
    aspartate 0 1 12904551 (1)
    glutamate 0 1 12904551 (1)

    Search CenterWatch for drugs/clinical trials and news about LIG4 / DNLI4

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for LIG4 gene (3 alternative transcripts): 
    NM_001098268.1  NM_002312.3  NM_206937.1  

    Unigene Cluster for LIG4:

    Ligase IV, DNA, ATP-dependent
    Hs.166091  [show with all ESTs]
    Unigene Representative Sequence: NM_002312
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000356922(uc010agg.1) ENST00000405925(uc001vqn.3 uc001vqo.3 uc010agf.3 uc001vqp.3)
    ENST00000442234
    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Additional mRNA sequence: 

    AK292419.1 AK314844.1 BC037491.2 BX648833.1 X83441.1 

    4 DOTS entries:

    DT.212191  DT.212190  DT.101975916  DT.92419742 

    24/56 AceView cDNA sequences (see all 56):

    AA831460 NM_002312 NM_206937 AA687734 BU167518 X83441 AA772198 BC037491 
    CR618195 Z42891 AI469486 AA084590 BX474719 BI546008 BQ575639 R54358 
    AW439586 AI969600 Z39019 BM803759 AI809944 CB044764 H79100 BX480593 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for LIG4    About this scheme

    ExUns: 1 ^ 2a · 2b · 2c ^ 3a · 3b · 3c ^ 4a · 4b · 4c · 4d
    SP1:                          -                                       
    SP2:                                                                  
    SP3:                          -           -                           
    SP4:        -     -     -     -     -     -                           


    ECgene alternative splicing isoforms for LIG4

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    LIG4 expression in normal human tissues (normalized intensities)      LIG4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CGATACTATG
    LIG4 Expression
    About this image


    LIG4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/26 selected tissues (see all 26) fully expand
     
     Brain (Nervous System)    fully expand to see all 6 entries
             Cerebral Cortex
             posterior singulate   
     
     Testis (Reproductive System)    fully expand to see all 4 entries
             Leydig Cells Testis Interstitium
             seminal vesicle ; glandular cells   
     
     Uterus (Reproductive System)    fully expand to see all 4 entries
             uterus, post-menopause ; glandular cells   
     
     Lung (Respiratory System)    fully expand to see all 3 entries
             lung ; pneumocytes   
     
     Breast
             breast ; myoepithelial cells   

    See LIG4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for LIG4

    SOURCE GeneReport for Unigene cluster: Hs.166091

    UniProtKB/Swiss-Prot: DNLI4_HUMAN, P49917
    Tissue specificity: Testis, thymus, prostate and heart

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of eukaryotes.

    Orthologs for LIG4 gene from 9/21 species (see all 21)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Lig41 , 5 ligase IV, DNA, ATP-dependent1, 5 82.58(n)1
    87.05(a)1
      8 (4.52 cM)5
    3195831  NM_176953.31  NP_795927.21 
     99700205 
    chicken
    (Gallus gallus)
    Aves LIG41 ligase IV, DNA, ATP-dependent 75.04(n)
    77.11(a)
      418764  NM_001030816.1  NP_001025987.1 
    lizard
    (Anolis carolinensis)
    Reptilia LIG46
    DNA ligase
    76(a)
    1 ↔ 1
    1(137058376-137061096)
    African clawed frog
    (Xenopus laevis)
    Amphibia lig4-A2 ligase IV, DNA, ATP-dependent 78.21(n)    AF393656.1 
    zebrafish
    (Danio rerio)
    Actinopterygii lig41 ligase IV, DNA, ATP-dependent 65.85(n)
    64.99(a)
      569525  NM_001103123.1  NP_001096593.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta ligase43
    Lig41
    DNA ligase (ATP)3
    Ligase41
    31(a)3
    45.21(n)1
    33.63(a)1
      12B23
    323221  NM_132679.21  NP_572907.11 
    worm
    (Caenorhabditis elegans)
    Secernentea lig-46
    Protein LIG-4
    19(a)
    possible ortholog
    III(7521463-7524836)
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes DNL4(YOR005C)4
    DNL41
    DNA ligase required for nonhomologous end-joining (NHEJ), more4
    Dnl4p1
    44.78(n)1
    29.73(a)1
      15(337343-334509)4
    8541661, 4  NP_014647.11, 4 
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons ATLIG41 DNA ligase 4 46.05(n)
    34.1(a)
      835822  NM_125098.3  NP_568851.2 


    ENSEMBL Gene Tree for LIG4 (if available)
    TreeFam Gene Tree for LIG4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for LIG4 gene
    LIG32  

    LIG4 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/318 SNPs in LIG4 are shown (see all 318)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 13 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0127744
    LIG4 syndrome (LIG4S)4--see VAR_0127742 R H mis40--------
    VAR_0127754
    LIG4 syndrome (LIG4S)4--see VAR_0127752 G E mis40--------
    rs1048944191,2
    Cpathogenic1108861177(-) TGTTTC/TGACGC 6 R * stg10--------
    rs1048944181,2
    Cpathogenic1108861879(-) TTCCAC/TGAATT 6 R * stg10--------
    rs1048944201,2
    Cpathogenic1108862211(-) TGGAGA/GATATT 6 E G mis10--------
    rs1048944211,2
    Cpathogenic1108862784(-) TGAACA/GTATGC 6 H R mis10--------
    rs18053881,2,4
    C,F,O,Hpathogenic1108863591(-) ACAAAC/TTGTTG 6 T I mis140Minor allele frequency- N:0.00NA NS EA MN WA CSA EU 8920
    rs18053891,2,4
    C,F,Hpathogenic1108863609(-) GGCTGC/TCTCAC 6 A V mis1 ese324Minor allele frequency- T:0.04NA NS MN EA EU 6587
    rs1117964841,2
    F--89450090(+) CACGAG/TATCAG 3 -- int11Minor allele frequency- T:0.50CSA 2
    rs1135547261,2
    F--89450091(+) ACGAGG/ATCAGG 3 -- int11Minor allele frequency- A:0.50CSA 2

    HapMap Linkage Disequilibrium report for LIG4 (108859787 - 108870716 bp)

    Structural Variations
          Database of Genomic Variants (DGV) variations for LIG4: --

    Human Gene Mutation Database (HGMD): LIG4

    Locus Specific Mutation Databases (LSDB): LIG4
    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 601837   
    OMIM disorders: 606593  254500  
    UniProtKB/Swiss-Prot: DNLI4_HUMAN, P49917
  • LIG4 syndrome (LIG4S) [MIM:606593]: Characterized by immunodeficiency and developmental and growth delay.
    Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and
    various skin abnormalities. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive
    with sensitivity to ionizing radiation (RSSCID) [MIM:602450]: A form of severe combined immunodeficiency, a
    genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both
    humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy
    with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID
    is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by
    RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J
    recombination. A subset of cells from such patients show increased radiosensitivity. Note=The disease is caused
    by mutations affecting the gene represented in this entry

  • 20/60 diseases for LIG4 (see all 60):    About MalaCards
    dna ligase iv deficiency    multiple myeloma, resistance to    severe combined immunodeficiency with sensitivity to ionizing radiation    acoustic neuroma
    nijmegen breakage syndrome    multiple myeloma    omenn syndrome    primary immunodeficiency disease
    seckel syndrome    neuroma    severe combined immunodeficiency    pancytopenia
    stomach cancer    ataxia telangiectasia    microcephaly    leukopenia
    follicular lymphoma    sporadic breast cancer    xeroderma pigmentosum    lynch syndrome

    5 diseases from the University of Copenhagen DISEASES database for LIG4:
    Primary immunodeficiency disease     Vaccinia     Dubowitz Syndrome     Microcephaly
    Autosomal recessive disease

    LIG4 for disorders           About GeneDecksing

    10/20 Novoseek inferred disease relationships for LIG4 gene (see all 20)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    lig4 syndrome 97.4 38 15333585 (4), 16735143 (3), 17345618 (3), 19418549 (3) (see all 13)
    nijmegen breakage syndrome 76.5 6 16088910 (2), 15966765 (1), 12640452 (1), 18568480 (1)
    seckel syndrome 68.9 1 12640452 (1)
    omenn syndrome 66.4 1 18845326 (1)
    ataxia telangiectasia 65.8 11 16971555 (1), 17224058 (1), 19008195 (1), 15966765 (1) (see all 5)
    severe combined immunodeficiency 64.3 3 16358361 (1), 16357942 (1), 18568480 (1)
    microcephaly 56.7 8 16358361 (3), 20133615 (1), 16088910 (1), 19418549 (1)
    fanconis anemia 52.3 1 15966765 (1)
    growth retardation 46.4 8 20133615 (1), 19451691 (1), 16088910 (1), 17554302 (1) (see all 5)
    developmental delay 44.6 6 20133615 (1), 11779494 (1), 16358361 (1), 15333585 (1) (see all 5)

    Genetic Association Database (GAD): LIG4
    Human Genome Epidemiology (HuGE) Navigator: LIG4 (56 documents)

    Export disorders for LIG4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for LIG4 gene, integrated from 9 sources (see all 247):
    (articles sorted by number of sources associating them with LIG4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination. (PubMed id 7760816)1, 2, 3 Wei Y.-F.... Lindahl T. (1995)
    2. DNA ligase IV from HeLa cell nuclei. (PubMed id 8798671)1, 2, 9 Robins P. and Lindahl T. (1996)
    3. A new type of radiosensitive T-B-NK(+) severe combined immunodeficiency caused by a LIG4 mutation. (PubMed id 16357942)1, 2, 9 van der Burg M.... van Gent D.C. (2006)
    4. Polymorphisms of LIG4 and XRCC4 involved in the NHEJ pathway interact to modify risk of glioma. (PubMed id 18165945)1, 4, 9 Liu Y....Zhou L. (2008)
    5. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. (PubMed id 11779494)1, 2, 9 O'Driscoll M.... Concannon P. (2001)
    6. Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes: a multiple genotype-phenotype study. (PubMed id 19408343)1, 4, 9 Tseng R.C....Wang Y.C. (2009)
    7. Association between total immunoglobulin E and antibo dy responses to naturally acquired Ascaris lumbricoides infection and polymorph isms of immune system-related LIG4, TNFSF13B and IRS2 genes. (PubMed id 19604268)1, 4, 9 Acevedo N....Caraballo L. (2009)
    8. DNA ligase IV is essential for V(D)J recombination and DNA double- strand break repair in human precursor lymphocytes. (PubMed id 9809069)1, 2, 9 Grawunder U.... Lieber M.R. (1998)
    9. Association of DNA repair and steroid metabolism gene polymorphisms with clinical late toxicity in patients treated with conformal radiotherapy for prostate cancer. (PubMed id 16638864)1, 4, 9 Damaraju S....Parliament M. (2006)
    10. Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity. (PubMed id 11349135)1, 2, 9 Riballo E.... Kysela B. (2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 3981 HGNC: 6601 AceView: LIG4 Ensembl:ENSG00000174405 euGenes: HUgn3981
    ECgene: LIG4 Kegg: 3981 H-InvDB: LIG4

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for LIG4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for LIG4 Genetics and Cytogenetics in Oncology and Haematology
    LIG4basehttp://bioinf.uta.fi/LIG4base/
    NIEHS-SNPshttp://egp.gs.washington.edu/data/lig4/
    Wikipedia http://en.wikipedia.org/wiki/DNA_ligase

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for LIG4 gene:
    Search GeneIP for patents involving LIG4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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