LIG4 (DNA ligase 4)

Gene

• Entrez ID: 3981
• Gene name: DNA ligase 4
• Gene symbol: LIG4
• Synonyms (NCBI Gene): LIG4S
• Disease Acronyms (UniProt): LIG4S
• Chromosome: 13
• Chromosome location: 13q33.3
• Summary: 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 nonh

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs72660870	G>C,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs104894418	G>A,C	Pathogenic	Stop gained, missense variant, coding sequence variant
rs104894419	G>A	Pathogenic-likely-pathogenic, pathogenic	Stop gained, coding sequence variant
rs104894420	C>T	Pathogenic	Missense variant, coding sequence variant
rs104894421	C>A,T	Pathogenic	Missense variant, coding sequence variant
rs142957638	T>C	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs201176444	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs375554612	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs587776663	GTT>-	Pathogenic	Inframe deletion, coding sequence variant
rs748385144	C>T	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs751070095	ATTTC>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs751409106	T>C,G	Likely-pathogenic	Missense variant, coding sequence variant
rs759838407	AG>-,AGAG	Pathogenic	Frameshift variant, coding sequence variant
rs770128720	ATCTT>-	Pathogenic	Frameshift variant, coding sequence variant
rs772226399	CTTTT>-	Pathogenic	Frameshift variant, coding sequence variant
rs780504243	C>A	Pathogenic	Coding sequence variant, missense variant
rs780879476	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs886037777	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1060499662	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1131691430	C>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1246940345	AG>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1555305016	CTCTT>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1566366148	CT>-	Pathogenic	Coding sequence variant, frameshift variant
rs1594458526	TA>-	Pathogenic	Frameshift variant, coding sequence variant
rs1594462950	T>C	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT021742	hsa-miR-132-3p	Microarray	17612493
MIRT028768	hsa-miR-26b-5p	Microarray	19088304
MIRT051082	hsa-miR-16-5p	CLASH	23622248
MIRT2030346	hsa-miR-1279	CLIP-seq
MIRT2561080	hsa-miR-1	CLIP-seq
MIRT2561081	hsa-miR-1243	CLIP-seq
MIRT2561082	hsa-miR-1257	CLIP-seq
MIRT2561083	hsa-miR-129-5p	CLIP-seq
MIRT2561084	hsa-miR-206	CLIP-seq
MIRT2561085	hsa-miR-2113	CLIP-seq
MIRT2561086	hsa-miR-3163	CLIP-seq
MIRT2561087	hsa-miR-3611	CLIP-seq
MIRT2561088	hsa-miR-3654	CLIP-seq
MIRT2561089	hsa-miR-3673	CLIP-seq
MIRT2561090	hsa-miR-4272	CLIP-seq
MIRT2561091	hsa-miR-4496	CLIP-seq
MIRT2561092	hsa-miR-4668-3p	CLIP-seq
MIRT2561093	hsa-miR-577	CLIP-seq
MIRT2561094	hsa-miR-613	CLIP-seq
MIRT2561095	hsa-miR-758	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000012	Process	Single strand break repair	IDA	8798671
GO:0000781	Component	Chromosome, telomeric region	IC	23275564
GO:0000793	Component	Condensed chromosome	IDA	12589063
GO:0001701	Process	In utero embryonic development	ISS
GO:0002328	Process	Pro-B cell differentiation	ISS
GO:0003677	Function	DNA binding	IBA	21873635
GO:0003677	Function	DNA binding	IDA	8798671
GO:0003909	Function	DNA ligase activity	IDA	12517771
GO:0003909	Function	DNA ligase activity	TAS
GO:0003910	Function	DNA ligase (ATP) activity	IBA	21873635
GO:0003910	Function	DNA ligase (ATP) activity	IDA	8798671, 22192310
GO:0005515	Function	Protein binding	IPI	9242410, 9259561, 9809069, 11702069, 16439205, 17389648, 17396150, 21070942, 22529269, 22658747, 23178593, 23219551, 25416956, 25910212, 28514442, 32296183
GO:0005524	Function	ATP binding	IBA	21873635
GO:0005634	Component	Nucleus	IDA	8798671, 12589063
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	IBA	21873635
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	IDA	15194694
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	ISS
GO:0006260	Process	DNA replication	IEA
GO:0006266	Process	DNA ligation	IDA	12517771
GO:0006297	Process	Nucleotide-excision repair, DNA gap filling	IBA	21873635
GO:0006297	Process	Nucleotide-excision repair, DNA gap filling	IDA	12517771
GO:0006302	Process	Double-strand break repair	IDA	9242410, 19589734
GO:0006302	Process	Double-strand break repair	ISS
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IBA	21873635
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IDA	12517771
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IGI	23275564
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IMP	9809069
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	ISS
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	TAS
GO:0007049	Process	Cell cycle	IEA
GO:0007417	Process	Central nervous system development	ISS
GO:0008022	Function	Protein C-terminus binding	IPI	12589063
GO:0008283	Process	Cell population proliferation	ISS
GO:0010165	Process	Response to X-ray	IMP	9809069
GO:0010332	Process	Response to gamma radiation	ISS
GO:0016874	Function	Ligase activity	IDA	9242410
GO:0032807	Component	DNA ligase IV complex	IBA	21873635
GO:0032807	Component	DNA ligase IV complex	IMP	9809069
GO:0033077	Process	T cell differentiation in thymus	ISS
GO:0033151	Process	V(D)J recombination	IDA	9809069
GO:0033152	Process	Immunoglobulin V(D)J recombination	IBA	21873635
GO:0033153	Process	T cell receptor V(D)J recombination	ISS
GO:0035019	Process	Somatic stem cell population maintenance	ISS
GO:0036464	Component	Cytoplasmic ribonucleoprotein granule	IDA
GO:0043524	Process	Negative regulation of neuron apoptotic process	ISS
GO:0045190	Process	Isotype switching	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0048146	Process	Positive regulation of fibroblast proliferation	ISS
GO:0050769	Process	Positive regulation of neurogenesis	ISS
GO:0051102	Process	DNA ligation involved in DNA recombination	ISS
GO:0051103	Process	DNA ligation involved in DNA repair	IBA	21873635
GO:0051103	Process	DNA ligation involved in DNA repair	IDA	12517771
GO:0051103	Process	DNA ligation involved in DNA repair	ISS
GO:0051276	Process	Chromosome organization	ISS
GO:0051301	Process	Cell division	IEA
GO:0051402	Process	Neuron apoptotic process	ISS
GO:0070419	Component	Nonhomologous end joining complex	IDA	20383123, 25941166
GO:0071285	Process	Cellular response to lithium ion	IEA
GO:0071479	Process	Cellular response to ionizing radiation	IGI	29463814
GO:0071897	Process	DNA biosynthetic process	IEA
GO:0075713	Process	Establishment of integrated proviral latency	TAS
GO:0097680	Process	Double-strand break repair via classical nonhomologous end joining	IMP	24837021
GO:2001252	Process	Positive regulation of chromosome organization	IMP	23275564

Other IDs

• MIM: 601837
• HGNC: 6601
• e!Ensembl: ENSG00000174405

Protein

• UniProt ID: P49917
• Protein name: DNA ligase 4 (EC 6.5.1.1) (DNA ligase IV) (Polydeoxyribonucleotide synthase [ATP] 4)
• Protein function: DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:12517771, PubMed:17290226, PubMed:23523427, PubMed:29980672, PubMed:33586762, PubMed:8798671, PubMed:9242
• PDB: 1IK9, 2E2W, 3II6, 3VNN, 3W1B, 3W1G, 3W5O, 4HTO, 4HTP, 6BKF, 6BKG, 7D9K, 7D9Y, 7LSY, 7LT3, 7NFC, 7NFE, 8BH3, 8BHV, 8BHY, 8BOT, 8EZA, 8EZB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04675	DNA_ligase_A_N	15 → 208	DNA ligase N terminus	Family
  PF01068	DNA_ligase_A_M	248 → 451	ATP dependent DNA ligase domain	Domain
  PF04679	DNA_ligase_A_C	476 → 588		Family
  PF00533	BRCT	654 → 730	BRCA1 C Terminus (BRCT) domain	Family
  PF11411	DNA_ligase_IV	750 → 783	DNA ligase IV	Family
  PF00533	BRCT	813 → 898	BRCA1 C Terminus (BRCT) domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Testis, thymus, prostate and heart. {ECO:0000269|PubMed:7760816}.
• Sequence:

  MAASQTSQTVASHVPFADLCSTLERIQKSKGRAEKIRHFREFLDSWRKFHDALHKNHKDV
  TDSFYPAMRLILPQLERERMAYGIKETMLAKLYIELLNLPRDGKDALKLLNYRTPTGTHG
  DAGDFAMIAYFVLKPRCLQKGSLTIQQVNDLLDSIASNNSAKRKDLIKKSLLQLITQSSA
  LEQKWLIRMIIKDLKLGVSQQTIFSVFHNDAAELHNVTTDLEKVCRQLHDPSVGLSDISI
  TLFSAFKPMLAAIADIEHIEKDMKHQSFYIETKLDGERMQMHKDGDVYKYFSRNGYNYTD
  QFGASPTEGSLTPFIHNAFKADIQICILDGEMMAYNPNTQTFMQKGTKFDIKRMVEDSDL
  QTCYCVFDVLMVNNKKLGHETLRKRYEILSSIFTPIPGRIEIVQKTQAHTKNEVIDALNE
  AIDKREEGIMVKQPLSIYKPDKRGEGWLKIKPEYVSGLMDELDILIVGGYWGKGSRGGMM
  SHFLCAVAEKPPPGEKPSVFHTLSRVGSGCTMKELYDLGLKLAKYWKPFHRKAPPSSILC
  GTEKPEVYIEPCNSVIVQIKAAEIVPSDMYKTGCTLRFPRIEKIRDDKEWHECMTLDDLE
  QLRGKASGKLASKHLYIGGDDEPQEKKRKAAPKMKKVIGIIEHLKAPNLTNVNKISNIFE
  DVEFCVMSGTDSQPKPDLENRIAEFGGYIVQNPGPDTYCVIAGSENIRVKNIILSNKHDV
  VKPAWLLECFKTKSFVPWQPRFMIHMCPSTKEHFAREYDCYGDSYFIDTDLNQLKEVFSG
  IKNSNEQTPEEMASLIADLEYRYSWDCSPLSMFRRHTVYLDSYAVINDLSTKNEGTRLAI
  KALELRFHGAKVVSCLAEGVSHVIIGEDHSRVADFKAFRRTFKRKFKILKESWVTDSIDK
  CELQEENQYLI

• Sequence length: 911

Associated diseases

Unknown
Disease term	Disease name	Evidence	References	Source
Dubowitz Syndrome	Dubowitz syndrome			GenCC
Omenn Syndrome	Omenn syndrome			GenCC
Irritable Bowel Syndrome	Irritable Bowel Syndrome			GWAS
Dementia	Dementia			GWAS
Diabetes	Diabetes			GWAS

Associations from Text Mining
Disease Name	Relationship Type	References
Acquired Immunodeficiency Syndrome	Associate	36312587
Agammaglobulinemia	Associate	27063650, 35592332, 37004747
Alzheimer Disease	Associate	37333771
Autoimmune Diseases	Associate	37004747
Bone Marrow Failure Disorders	Associate	24123394, 25239263
Breast Neoplasms	Associate	20496270
Carcinoma Non Small Cell Lung	Associate	19408343, 21717429
Cell Transformation Neoplastic	Associate	25563294
Central Nervous System Neoplasms	Associate	28976792
Colorectal Neoplasms	Associate	31243170
Cyclic neutropenia	Associate	24123394
Death	Associate	20368557
Developmental Disabilities	Associate	11779494, 16358361, 27063650, 38351293
DNA Virus Infections	Associate	11779494, 36221079, 37004747
Drug Related Side Effects and Adverse Reactions	Inhibit	36048168
Dubowitz syndrome	Associate	23372718, 24892279, 27612988
Dyskeratosis Congenita	Associate	24892279, 27612988
Ectodermal Dysplasia	Associate	27612988
Erythema	Associate	24027040
Evans Syndrome	Associate	35655776
Fanconi Anemia	Associate	11124945, 15199173
Genetic Diseases Inborn	Associate	16358361, 35655776
Glioblastoma	Associate	20368557, 35440003
Glioma	Associate	23663450, 25973104
Graft vs Host Disease	Associate	24027040
Growth Disorders	Associate	11779494, 23722522, 24123394, 25728776, 27063650, 27612988, 37437665, 38351293
Heart defects limb shortening	Associate	37004747
HIV Infections	Associate	36312587
Hydrocephalus	Associate	38351293
IgA Deficiency	Associate	32471509
Immune System Diseases	Associate	27063650
Immunologic Deficiency Syndromes	Associate	11779494, 16358361, 23722522, 24123394, 29980672, 36221079, 37004747, 38351293
Inflammatory Bowel Diseases	Associate	32471509
Leukemia	Associate	11349135, 16358361
Leukemia Myelogenous Chronic BCR ABL Positive	Associate	18524993
Leukemia Myeloid Acute	Associate	36308385
Leukemia T Cell	Associate	23722522
LIG4 Syndrome	Inhibit	17224058
LIG4 Syndrome	Associate	23722522, 24027040, 32471509, 32534991, 34630384, 36221079, 37437665
LIG4 Syndrome	Stimulate	36221079, 38351293
Lung Neoplasms	Associate	19408343
Lymphopenia	Associate	35592332
Malformations of Cortical Development Group I	Associate	31067307
Microcephaly	Associate	16358361, 23722522, 24123394, 32471509, 32534991, 38351293
Mouth Neoplasms	Associate	34528560
Multiple Myeloma	Associate	12471202
Myelodysplastic Syndromes	Associate	25239263, 27497341, 32471509, 36221079
Nasopharyngeal Neoplasms	Associate	25605214
Neoplasms	Associate	12471202, 18508926, 28976792, 36048168, 37004747
Neuroblastoma	Associate	25563294
Neurologic Manifestations	Associate	24027040
Neutropenia	Associate	27612988
Nijmegen Breakage Syndrome	Associate	11779494
Opportunistic Infections	Associate	37004747
Ovarian Neoplasms	Associate	19127255, 20386703
Pancreatic Neoplasms	Associate	19147782
Pancytopenia	Associate	25728776, 27063650, 36221079, 37437665
Prostatic Neoplasms	Associate	23936089, 30271587
Radiation Injuries	Associate	38351293
Radiation Pneumonitis	Associate	21717429
Renal Insufficiency	Associate	24123394, 25728776
Retinoblastoma	Associate	29415984
Rothmund Thomson Syndrome	Associate	27612988
Seckel syndrome 1	Associate	24123394, 25728776
Severe Combined Immunodeficiency	Associate	16358361, 21721379, 24123394, 35303369, 40457861
Squamous Cell Carcinoma of Head and Neck	Associate	34528560
Succinate Coa Ligase Deficiency	Inhibit	17224058
Succinate Coa Ligase Deficiency	Associate	24123394, 27063650, 35592332
Syndrome	Associate	27612988
Thrombocytopenia	Associate	24123394
X Linked Combined Immunodeficiency Diseases	Associate	16358361, 16585603, 27063650, 32471509