LIG4 (DNA ligase 4)

Gene

• Entrez ID: 3981
• Gene name: DNA ligase 4
• Gene symbol: LIG4
• Synonyms: 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

• Sequence:

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

• Sequence length: 911