Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	3981
Gene name	DNA ligase 4
Gene symbol	LIG4
Synonyms (NCBI Gene)	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

Show/Hide all (25)

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

Show/Hide all (20)

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

Show/Hide all (97)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000012	Process	Single strand break repair	IDA	8798671
GO:0000166	Function	Nucleotide binding	IEA
GO:0000287	Function	Magnesium ion binding	IDA	29980672
GO:0000781	Component	Chromosome, telomeric region	IC	23275564
GO:0000793	Component	Condensed chromosome	IDA	12589063
GO:0001701	Process	In utero embryonic development	IEA
GO:0001701	Process	In utero embryonic development	ISS
GO:0002328	Process	Pro-B cell differentiation	IEA
GO:0002328	Process	Pro-B cell differentiation	ISS
GO:0003677	Function	DNA binding	IBA
GO:0003677	Function	DNA binding	IDA	8798671, 29980672
GO:0003677	Function	DNA binding	IEA
GO:0003909	Function	DNA ligase activity	IDA	12517771, 17290226, 19589734
GO:0003909	Function	DNA ligase activity	IEA
GO:0003909	Function	DNA ligase activity	TAS
GO:0003910	Function	DNA ligase (ATP) activity	IBA
GO:0003910	Function	DNA ligase (ATP) activity	IDA	8798671, 22192310, 23523427, 29980672
GO:0003910	Function	DNA ligase (ATP) activity	IEA
GO:0003910	Function	DNA ligase (ATP) activity	IMP	29980672
GO:0005515	Function	Protein binding	IPI	9242410, 9259561, 9809069, 11702069, 12589063, 16439205, 17290226, 17389648, 17396150, 19589734, 21070942, 22529269, 22658747, 23178593, 23219551, 23523427, 25416956, 25910212, 25934149, 28514442, 31548606, 32296183, 33961781
GO:0005524	Function	ATP binding	IBA
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IDA	25934149
GO:0005634	Component	Nucleus	IDA	8798671, 12589063
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	IBA
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	IDA	15194694, 34352203
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	IEA
GO:0005958	Component	DNA-dependent protein kinase-DNA ligase 4 complex	ISS
GO:0006281	Process	DNA repair	IEA
GO:0006281	Process	DNA repair	IEA
GO:0006284	Process	Base-excision repair	IDA	19589734
GO:0006297	Process	Nucleotide-excision repair, DNA gap filling	IBA
GO:0006297	Process	Nucleotide-excision repair, DNA gap filling	IDA	12517771, 17290226
GO:0006302	Process	Double-strand break repair	IDA	9242410, 19589734
GO:0006302	Process	Double-strand break repair	IEA
GO:0006302	Process	Double-strand break repair	ISS
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IBA
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IDA	12517771, 17290226
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IEA
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IEA
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	TAS
GO:0006310	Process	DNA recombination	IEA
GO:0006974	Process	DNA damage response	IEA
GO:0007417	Process	Central nervous system development	IEA
GO:0007417	Process	Central nervous system development	ISS
GO:0008283	Process	Cell population proliferation	ISS
GO:0010165	Process	Response to X-ray	IMP	9809069
GO:0010212	Process	Response to ionizing radiation	IEA
GO:0010212	Process	Response to ionizing radiation	IEA
GO:0010332	Process	Response to gamma radiation	IEA
GO:0010332	Process	Response to gamma radiation	ISS
GO:0016208	Function	AMP binding	IEA
GO:0016874	Function	Ligase activity	IDA	9242410
GO:0016874	Function	Ligase activity	IEA
GO:0022008	Process	Neurogenesis	IEA
GO:0032807	Component	DNA ligase IV complex	IBA
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:0033151	Process	V(D)J recombination	IEA
GO:0033151	Process	V(D)J recombination	IEA
GO:0033152	Process	Immunoglobulin V(D)J recombination	IBA
GO:0033152	Process	Immunoglobulin V(D)J recombination	IEA
GO:0033153	Process	T cell receptor V(D)J recombination	IEA
GO:0033153	Process	T cell receptor V(D)J recombination	ISS
GO:0035019	Process	Somatic stem cell population maintenance	IEA
GO:0035019	Process	Somatic stem cell population maintenance	ISS
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0043524	Process	Negative regulation of neuron apoptotic process	ISS
GO:0045190	Process	Isotype switching	IEA
GO:0045190	Process	Isotype switching	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0048144	Process	Fibroblast proliferation	IEA
GO:0048146	Process	Positive regulation of fibroblast proliferation	IEA
GO:0048146	Process	Positive regulation of fibroblast proliferation	ISS
GO:0050769	Process	Positive regulation of neurogenesis	IEA
GO:0050769	Process	Positive regulation of neurogenesis	ISS
GO:0051276	Process	Chromosome organization	IEA
GO:0051276	Process	Chromosome organization	ISS
GO:0051301	Process	Cell division	IEA
GO:0051402	Process	Neuron apoptotic process	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:0072089	Process	Stem cell proliferation	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:1904155	Process	DN2 thymocyte differentiation	IEA
GO:2001252	Process	Positive regulation of chromosome organization	IMP	23275564

MIM	HGNC	e!Ensembl
601837	6601	ENSG00000174405

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

Interactions

View interactions

	KEGG		Reactome
	Non-homologous end-joining		2-LTR circle formation Nonhomologous End-Joining (NHEJ)

840

Show/Hide Causal Diseases (6)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
DNA ligase IV deficiency	Pathogenic; Likely pathogenic	rs750080610, rs759838407, rs759829934, rs2138967445, rs2138974645, rs373938258, rs752339466, rs2138974907, rs2138978299, rs767195999, rs753883369, rs1286797317, rs2138978193, rs777008519, rs1386691031 View all (66 more)	RCV001320593 RCV001885359 RCV001389935 RCV001533455 RCV001824262 RCV001844574 RCV001870931 RCV001952014 RCV001928912 RCV002004863 RCV002002469 RCV001972494 RCV001880861 RCV003058425 RCV002770223 RCV003011582 RCV003048117 RCV003045012 RCV000008111 RCV000008112 RCV000008113 RCV000008114 RCV000008117 RCV000241548 RCV000768258 RCV003232906 RCV003619668 RCV003509855 RCV003510453 RCV003510582 RCV003510586 RCV003510476 RCV003510532 RCV003511407 RCV003511078 RCV003511059 RCV003511144 RCV003509001 RCV003509002 RCV003509003 RCV003509004 RCV003511455 RCV003509314 RCV003509403 RCV003509970 RCV003510210 RCV003510355 RCV003510423 RCV003510427 RCV003619902 RCV003620106 RCV003620057 RCV003620691 RCV003620802 RCV003620900 RCV003620996 RCV003621178 RCV003621018 RCV003620982 RCV003621156 RCV003621288 RCV003621332 RCV003621304 RCV003621261 RCV003621425 RCV003619347 RCV003620240 RCV003619636 RCV003864278 RCV003881400 RCV000449526 RCV000641087 RCV001204413 RCV000704058 RCV000601286 RCV000690275 RCV001860490 RCV000687607 RCV003509606 RCV000791619 RCV001007660 RCV001070391 RCV001043969 RCV001048790 RCV001257441 RCV001297827
LIG4-related disorder	Likely pathogenic; Pathogenic	rs104894419, rs772226399, rs2501600808, rs375554612, rs765317127	RCV004532308 RCV000267680 RCV004540864 RCV004535497 RCV001535528
Multiple myeloma	Likely pathogenic; Pathogenic	rs759829934, rs752339466, rs2138978299, rs104894418, rs104894419, rs772226399, rs104894421, rs1317409403, rs948441067, rs375554612, rs759838407, rs751070095, rs780879476	RCV005005244 RCV005005322 RCV005002677 RCV005007834 RCV000763320 RCV002494809 RCV005013036 RCV005013049 RCV005013102 RCV005010384 RCV005004193 RCV005004268 RCV005010594
Papillary thyroid carcinoma	Likely pathogenic	rs751409106	RCV000761169
prenatal LIG4 syndrome with aqueductal stenosis	Likely pathogenic; Pathogenic	rs104894419, rs1131691430, rs759838407	RCV003483426 RCV003483638 RCV003483642
Severe combined immunodeficiency disease	Pathogenic	rs104894421, rs765317127, rs777008519	RCV005417421 RCV004690433 RCV005239131 RCV002240198

Show/Hide Unknown Diseases (3)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Acute myeloid leukemia	Likely benign	rs138936350	RCV005900203
Multiple myeloma, resistance to	Benign; Likely benign	rs1805389, rs1805388	RCV000008115 RCV000008116
Severe combined immunodeficiency due to DCLRE1C deficiency	Benign; Uncertain significance; Likely benign; Conflicting classifications of pathogenicity	rs1805386, rs142144659, rs61731910, rs3093764, rs1805389, rs1805388, rs10131, rs146506306, rs3093770, rs112171260, rs543340651, rs886049944, rs886049945, rs886049946, rs538355612 View all (69 more)	RCV000270912 RCV001110887 RCV001114247 RCV000260838 RCV000284646 RCV000382071 RCV000393586 RCV000307154 RCV000294191 RCV000295533 RCV000407379 RCV000358708 RCV000405916 RCV000315918 RCV000295209 RCV000340359 RCV000377962 RCV000279874 RCV000372834 RCV000306941 RCV000301406 RCV000334340 RCV000260627 RCV000312266 RCV000325177 RCV000285774 RCV000294082 RCV000393068 RCV000347931 RCV000408025 RCV000327105 RCV000349632 RCV000366537 RCV000322139 RCV000373686 RCV000320202 RCV000330338 RCV000381307 RCV000283269 RCV000305552 RCV000403577 RCV000273441 RCV000383863 RCV000337673 RCV000312009 RCV000393677 RCV000315847 RCV000302024 RCV000403085 RCV000356462 RCV000295813 RCV000332802 RCV000314664 RCV000323207 RCV000289099 RCV000308642 RCV000321510 RCV000386052 RCV000330885 RCV000354752 RCV000275436 RCV000282783 RCV000374994 RCV001111061 RCV001112971 RCV001112888 RCV001110886 RCV001112885 RCV001110747 RCV001112729 RCV001112732 RCV001112733 RCV001114084 RCV001110044 RCV001114163 RCV001110130 RCV001112887 RCV001114246 RCV001114248 RCV001110225 RCV001110972 RCV001110973 RCV001112972 RCV001114333

Show/Hide Text Mining Associations (71)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
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

LIG4 (DNA ligase 4)