LIG3

Summary

LIG3 (DNA ligase 3, HGNC:6600) is a protein-coding gene on chromosome 17q12, encoding DNA ligase 3 (P49916). Isoform 3 functions as a heterodimer with DNA-repair protein XRCC1 in the nucleus and can correct defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents.

This gene is a member of the DNA ligase family. Each member of this family encodes a protein that catalyzes the joining of DNA ends but they each have a distinct role in DNA metabolism. The protein encoded by this gene is involved in excision repair and is located in both the mitochondria and nucleus, with translation initiation from the upstream start codon allowing for transport to the mitochondria and translation initiation from a downstream start codon allowing for transport to the nucleus. Additionally, alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 3980 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 206 total — 7 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 68
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_013975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6600
Approved symbol	LIG3
Name	DNA ligase 3
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	LIG3alpha
Ensembl gene	ENSG00000005156
Ensembl biotype	protein_coding
OMIM	600940
Entrez	3980

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 16 protein_coding, 8 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000262327, ENST00000378526, ENST00000585370, ENST00000585740, ENST00000585941, ENST00000586058, ENST00000586119, ENST00000586407, ENST00000586435, ENST00000588109, ENST00000588713, ENST00000590181, ENST00000590630, ENST00000592244, ENST00000592690, ENST00000593099, ENST00000858900, ENST00000858901, ENST00000858902, ENST00000858903, ENST00000858904, ENST00000932519, ENST00000932520, ENST00000961393, ENST00000961394, ENST00000961395, ENST00000961396

RefSeq mRNA: 2 — MANE Select: NM_013975 NM_002311, NM_013975

CCDS: CCDS11284, CCDS11285

Canonical transcript exons

ENST00000378526 — 20 exons

Exon	Start	End
ENSE00000713836	35002668	35002789
ENSE00001106042	34991671	34991837
ENSE00001160722	34990963	34991114
ENSE00001429066	34980512	34980622
ENSE00002730758	35004273	35009743
ENSE00003461043	34994276	34994431
ENSE00003466925	34983002	34983552
ENSE00003473059	34996574	34996653
ENSE00003489703	34999307	34999449
ENSE00003500295	34999782	34999856
ENSE00003502587	34991958	34992035
ENSE00003520894	34985988	34986131
ENSE00003551872	34998219	34998296
ENSE00003577385	34989466	34989663
ENSE00003611786	34992524	34992692
ENSE00003632882	35001909	35002104
ENSE00003656802	35001257	35001403
ENSE00003659495	34996064	34996195
ENSE00003662710	34997738	34997825
ENSE00003682982	34998604	34998727

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.2099 / max 279.7789, expressed in 1802 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160326	20.8100	1802
160327	0.3999	211

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.52	gold quality
medial globus pallidus	UBERON:0002477	93.71	gold quality
globus pallidus	UBERON:0001875	91.79	gold quality
colonic epithelium	UBERON:0000397	91.26	gold quality
ganglionic eminence	UBERON:0004023	90.44	gold quality
sural nerve	UBERON:0015488	89.53	gold quality
body of uterus	UBERON:0009853	89.27	gold quality
right testis	UBERON:0004534	89.00	gold quality
left testis	UBERON:0004533	88.87	gold quality
ventricular zone	UBERON:0003053	88.86	gold quality
adrenal tissue	UBERON:0018303	88.80	gold quality
right uterine tube	UBERON:0001302	88.39	gold quality
tendon	UBERON:0000043	88.33	gold quality
oocyte	CL:0000023	88.21	gold quality
testis	UBERON:0000473	88.05	gold quality
ovary	UBERON:0000992	87.74	gold quality
left ovary	UBERON:0002119	87.61	gold quality
left uterine tube	UBERON:0001303	87.42	gold quality
prostate gland	UBERON:0002367	87.40	gold quality
right lobe of thyroid gland	UBERON:0001119	87.33	gold quality
right ovary	UBERON:0002118	87.23	gold quality
corpus callosum	UBERON:0002336	87.18	gold quality
bone marrow cell	CL:0002092	87.12	gold quality
vagina	UBERON:0000996	87.02	gold quality
stromal cell of endometrium	CL:0002255	86.95	gold quality
calcaneal tendon	UBERON:0003701	86.90	gold quality
tendon of biceps brachii	UBERON:0008188	86.90	gold quality
left lobe of thyroid gland	UBERON:0001120	86.82	gold quality
ectocervix	UBERON:0012249	86.77	gold quality
islet of Langerhans	UBERON:0000006	86.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, PARP1

miRNA regulators (miRDB)

41 targeting LIG3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-2276-3P	98.76	67.75	1384

Literature-anchored findings (GeneRIF, showing 37)

• PMID 10207110 showed that translation initiation at the first ATG in the cDNA can lead to a mitochondrially-targeted isoform of the protein. (PMID:10207110)
• calpain-mediated proteolysis of DNA ligase III plays an essential role in DNA damage-induced cell death in human cells (PMID:11994275)
• majority of single-strand DNA interruptions produced during the repair of alkylated DNA bases are repaired by the pathway mediated by Pol beta and either Lig I or Lig III (PMID:14627836)
• In response to DNA damage, DNA ligase IIIalpha translocate from centrosomes to chromosomes. (PMID:15653642)
• XRCC1 stimulates Pol beta strand displacement activity and releases inhibition of Pol beta by DNA-bound Lig III if ligation is prevented. (PMID:16442856)
• the interaction of DNA ligase III and DNA polymerase gamma is required for proper maintenance of the mammalian mitochondrial genome. (PMID:17054425)
• Results describe the activity requirements for DNA ligases III and IV in the pathways of non-homologous DNA end joining. (PMID:17492771)
• analysis of DNA-binding and nick recognition modules in human DNA ligase III (PMID:18238776)
• Data show that CHIP-mediated degradation and DNA damage-dependent stabilization regulate base excision repair proteins XRCC1, DNA polymerase beta, and DNA ligase III. (PMID:18313385)
• siRNA mediated down-regulation of DNA ligase III in human HTD114 cells led to impaired end joining that was mediated by 2-, 3- or 10-bp microhomology. (PMID:18440984)
• altered DNA double-strand break repair in CML cells is caused by the increased activity of an alternative nonhomologous end-joining repair pathway, involving DNA ligase IIIalpha and WRN (PMID:18524993)
• The interaction with Lig3alpha is promoted by serine 81 that is located within a putative S/TQ site in the N-terminus domain of TDP1. (PMID:20009512)
• The collective results support a “jackknife model” in which the ZnF loads ligase III onto nicked DNA and conformational changes deliver DNA into the active site. (PMID:20518483)
• results establish a role for Lig3 in mitochondria, but distinguish it from its interacting protein Xrcc1 (PMID:21390132)
• Using our cohort of 480 breast cancer patients, we provide replicated evidence that a polymorphism near the LIG3 gene is associated with acute skin toxicity following radiotherapy. (PMID:21620500)
• Human Mre11/human Rad50/Nbs1 and DNA ligase IIIalpha/XRCC1 protein complexes act together in an alternative nonhomologous end joining pathway. (PMID:21816818)
• data confirm previous work showing that Lig3 is required to maintain mtDNA integrity and function, and highlight a new function of ATM in regulating DNA Lig3 stability and consequently mtDNA repair (PMID:24342190)
• Results show that overexpression of DNA ligase III in mitochondria improves mitochondrial base excision repair and enhances cell survival after oxidative stress. (PMID:24674627)
• LIGIII plays a role in additional EJing repair pathway only in the absence of Ku. (PMID:24837021)
• there is an absolute requirement for fully functional DNA ligase III (LIG3), but not ligase IV (LIG4), to facilitate the escape from a telomere-driven crisis. (PMID:25127141)
• The g.29661G>A and g.29059C>T polymorphisms of LIG3 may play a role in the keratoconus and Fuchs endothelial corneal dystrophy pathogenesis and can be considered as markers in these diseases. (PMID:25817347)
• In the context of tyrosine kinase-activated leukemias, c-MYC contributes to aberrant DNA repair through downstream targets LIG3 and PARP1 up-regulation. (PMID:25828893)
• Domains constituting the LigIII catalytic core collaborate and are essential for formation of a DNA-bridging intermediate by adenylated LigIII that positions a pair of blunt-ended duplex DNAs for efficient and specific intermolecular ligation. (PMID:26130724)
• A computational approach to determine susceptibility to cancer by evaluating the deleterious effect of nsSNP in XRCC1 gene on binding interaction of XRCC1 protein with ligase III. (PMID:26449312)
• single-stranded break repair by human DNA ligase III isoforms reveal biochemical differences from DNA ligase I (PMID:28751376)
• MM express elevated MALAT1 and involve in alternative non-homozygous end joining (A-NHEJ) pathway by binding to PARP1 and LIG3, two key components of the A-NHEJ protein complex. (PMID:29632340)
• The homozygotes of rs1052536 TT were associated with an increased risk for NTDs than CC, and variants of rs1052536 T were associated with an increased risk of Neural Tube Defects. The stratified analysis showed that TT genotype of rs1052536 increased the risk of anencephaly and the T allele significantly increased the risk of cranial Neural Tube Defects. (PMID:30022792)
• High lig3 expression is associated with multiple myeloma. (PMID:30120376)
• Data report that polymorphisms in LIG3 gene are not associated with the susceptibility to gastric cancer. The study helps to provide novel insight into the role of LIG3 polymorphisms in gastric cancer risk. (PMID:31034940)
• Altered DNA ligase activity in human disease. (PMID:31630206)
• Human DNA ligases in replication and repair. (PMID:33087274)
• An atypical BRCT-BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIalpha within a flexible DNA repair complex. (PMID:33330937)
• Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy. (PMID:33855352)
• Direct interaction of DNA repair protein tyrosyl DNA phosphodiesterase 1 and the DNA ligase III catalytic domain is regulated by phosphorylation of its flexible N-terminus. (PMID:34181949)
• Rac GTPase activating protein 1 promotes gallbladder cancer via binding DNA ligase 3 to reduce apoptosis. (PMID:34239347)
• Human DNA ligases I and III have stand-alone end-joining capability, but differ in ligation efficiency and specificity. (PMID:36625284)
• Toxicity and therapy outcome associations in LIG3, SLCO1B3, ABCB1, OPRM1 and GSTP1 in high-grade serous ovarian cancer. (PMID:36988399)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	lig3	ENSDARG00000052553
mus_musculus	Lig3	ENSMUSG00000020697
rattus_norvegicus	Lig3	ENSRNOG00000021815
drosophila_melanogaster	DNAlig3	FBGN0286075
caenorhabditis_elegans		WBGENE00010626
caenorhabditis_elegans		WBGENE00022237

Paralogs (2): LIG1 (ENSG00000105486), LIG4 (ENSG00000174405)

Protein

Protein identifiers

DNA ligase 3 — P49916 (reviewed: P49916)

Alternative names: DNA ligase III, Polydeoxyribonucleotide synthase [ATP] 3

All UniProt accessions (6): P49916, K7EJR4, K7ELY6, K7ENR9, K7EQB6, K7ERZ5

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 3 functions as a heterodimer with DNA-repair protein XRCC1 in the nucleus and can correct defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents. Isoform 1 is targeted to mitochondria, where it functions as a DNA ligase in mitochondrial base-excision DNA repair.

Subunit / interactions. Isoform 3 interacts (via BRCT domain) with the nuclear DNA-repair protein XRCC1. Interacts with POLG. Interacts with POLB.

Subcellular location. Mitochondrion Mitochondrion Nucleus Nucleus.

Tissue specificity. Testis, thymus, prostate and heart.

Disease relevance. Mitochondrial DNA depletion syndrome 20, MNGIE type (MTDPS20) [MIM:619780] An autosomal recessive mitochondrial disorder characterized by severe gut dysmotility, muscle weakness and atrophy, neurological abnormalities including epilepsy, migraine, stroke-like episodes, learning difficulties or cognitive decline, and neurogenic bladder. Brain imaging usually shows diffuse leukoencephalopathy and may show cerebellar atrophy. Disease onset can range from infancy to the teenage years. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PARP-type zinc finger is required for DNA ligase activity.

Miscellaneous. Produced by alternative splicing. Produced by alternative splicing. Produced by alternative initiation of isoform 1. Produced by alternative initiation of isoform 2.

Similarity. Belongs to the ATP-dependent DNA ligase family.

Isoforms (4)

UniProt ID	Names	Canonical?
P49916-1	1	yes
P49916-2	2
P49916-3	3, Alpha
P49916-4	4, Beta

RefSeq proteins (2): NP_002302, NP_039269* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000977	DNA_ligase_ATP-dep	Family
IPR001357	BRCT_dom	Domain
IPR001510	Znf_PARP	Domain
IPR012308	DNA_ligase_ATP-dep_N	Domain
IPR012309	DNA_ligase_ATP-dep_C	Domain
IPR012310	DNA_ligase_ATP-dep_cent	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR016059	DNA_ligase_ATP-dep_CS	Conserved_site
IPR031916	LIG3_BRCT	Domain
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR036599	DNA_ligase_N_sf	Homologous_superfamily
IPR036957	Znf_PARP_sf	Homologous_superfamily
IPR050191	ATP-dep_DNA_ligase	Family

Pfam: PF00645, PF01068, PF04675, PF04679, PF16759

Enzyme classification (BRENDA):

• EC 6.5.1.1 — DNA ligase (ATP) (BRENDA: 129 organisms, 228 substrates, 149 inhibitors, 70 Km, 29 kcat entries)

Substrate kinetics (BRENDA)

21 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	—	33
DNA	—	7
DATP	0.0016–0.004	3
NICKED DNA	—	2
(2E,6E)-FARNESYL TRIPHOSPHATE	0.15	1
(DEOXYRIBONUCLEOTIDE)20	—	1
(DT)20	0.0001	1
(NICKED DOUBLE-STRANDED DNA)N	0.0001	1
(SINGLE-STRANDED DNA SPLINTED BY RNA)M	—	1
CLODRONATE	0.08	1
DIMETHYLALLYL DIPHOSPHATE	4	1
ETIDRONATE	0.73	1
FARNESYL DIPHOSPHATE	0.05	1
GERANYL DIPHOSPHATE	0.21	1
GERANYL TRIPHOSPHATE	0.31	1

UniProt features (118 total): helix 30, strand 30, sequence variant 13, binding site 12, turn 9, region of interest 6, modified residue 5, compositionally biased region 4, splice variant 2, mutagenesis site 2, transit peptide 1, chain 1, active site 1, domain 1, zinc finger region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
3PC7	X-RAY DIFFRACTION	1.65
3QVG	X-RAY DIFFRACTION	2.26
3PC8	X-RAY DIFFRACTION	2.31
6WH1	X-RAY DIFFRACTION	2.4
10YE	ELECTRON MICROSCOPY	2.5
10YH	ELECTRON MICROSCOPY	2.9
10YI	ELECTRON MICROSCOPY	2.9
3L2P	X-RAY DIFFRACTION	3
10YF	ELECTRON MICROSCOPY	3
10YG	ELECTRON MICROSCOPY	3.4
1IMO	SOLUTION NMR
1IN1	SOLUTION NMR
1UW0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49916-F1	76.11	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 508 (n6-amp-lysine intermediate)

Ligand- & substrate-binding residues (12): 105; 108; 139; 142; 506; 513; 528; 560; 655; 660; 671; 675

Post-translational modifications (5): 210, 216, 227, 242, 913

Mutagenesis-validated functional residues (2):

Position	Phenotype
410	nearly abolishes ligase activity with blunt-ended dna, but not with nicked dna.
414	abolishes ligase activity with blunt-ended dna, but not with nicked dna.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-110381	Resolution of AP sites via the single-nucleotide replacement pathway
R-HSA-5649702	APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway
R-HSA-5685939	HDR through MMEJ (alt-NHEJ)
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-9913635	Strand-asynchronous mitochondrial DNA replication

MSigDB gene sets: 315 (showing top): REACTOME_DNA_REPLICATION, GCM_GSPT1, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_MITOCHONDRIAL_DNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_DNA_STRAND_ELONGATION_INVOLVED_IN_DNA_REPLICATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, KAUFFMANN_DNA_REPAIR_GENES, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, PATIL_LIVER_CANCER, CHIBA_RESPONSE_TO_TSA_DN

GO Biological Process (16): double-strand break repair via homologous recombination (GO:0000724), lagging strand elongation (GO:0006273), base-excision repair (GO:0006284), base-excision repair, gap-filling (GO:0006287), double-strand break repair (GO:0006302), mitochondrion organization (GO:0007005), mitochondrial DNA repair (GO:0043504), cell division (GO:0051301), DNA biosynthetic process (GO:0071897), negative regulation of mitochondrial DNA replication (GO:0090298), double-strand break repair via alternative nonhomologous end joining (GO:0097681), DNA replication (GO:0006260), DNA repair (GO:0006281), DNA recombination (GO:0006310), DNA damage response (GO:0006974), negative regulation of DNA metabolic process (GO:0051053)

GO Molecular Function (9): DNA binding (GO:0003677), DNA ligase activity (GO:0003909), DNA ligase (ATP) activity (GO:0003910), ATP binding (GO:0005524), zinc ion binding (GO:0008270), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), DNA ligase III-XRCC1 complex (GO:0070421)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Resolution of Abasic Sites (AP sites)	2
Homology Directed Repair	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1
DNA Replication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	6
DNA repair	3
mitochondrion	2
intracellular membrane-bounded organelle	2
recombinational repair	1
double-strand break repair	1
DNA replication, synthesis of primer	1
DNA strand elongation involved in DNA replication	1
DNA replication, removal of RNA primer	1
base-excision repair	1
organelle organization	1
mitochondrial DNA metabolic process	1
cellular process	1
nucleic acid biosynthetic process	1
mitochondrial DNA replication	1
regulation of mitochondrial DNA replication	1
negative regulation of mitochondrial DNA metabolic process	1
negative regulation of DNA-templated DNA replication	1
double-strand break repair via nonhomologous end joining	1
DNA biosynthetic process	1
DNA damage response	1
cellular response to stress	1
negative regulation of macromolecule metabolic process	1
negative regulation of nucleobase-containing compound metabolic process	1
regulation of DNA metabolic process	1
nucleic acid binding	1
ligase activity, forming phosphoric ester bonds	1
catalytic activity, acting on DNA	1
DNA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIG3	XRCC1	P18887	999
LIG3	POLB	P06746	999
LIG3	PARP2	Q9UGN5	985
LIG3	PNKP	Q96T60	980
LIG3	PARP1	P09874	973
LIG3	XRCC6	P12956	970
LIG3	APEX1	P27695	968
LIG3	APTX	Q7Z2E3	960
LIG3	TDP1	Q9NUW8	955
LIG3	XRCC5	P13010	943
LIG3	XRCC4	Q13426	941
LIG3	OGG1	P78554	876
LIG3	APLF	Q8IW19	865
LIG3	PRKDC	P78527	806
LIG3	FEN1	P39748	786

IntAct

206 interactions, top by confidence:

A	B	Type	Score
MAX	MYC	psi-mi:“MI:0914”(association)	0.980
SPC24	NDC80	psi-mi:“MI:0914”(association)	0.920
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
POLB	XRCC1	psi-mi:“MI:0914”(association)	0.740
LIG3	XRCC1	psi-mi:“MI:0914”(association)	0.740
RPA4	RPA1	psi-mi:“MI:0914”(association)	0.740
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TDP1	XRCC1	psi-mi:“MI:0914”(association)	0.670
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
TDP1	POLB	psi-mi:“MI:0914”(association)	0.640
CSNK2B	RPS6KA4	psi-mi:“MI:0914”(association)	0.640
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
RNF166	MPDZ	psi-mi:“MI:0914”(association)	0.530
POLB	PARP1	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	SEC16A	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
H2AC20	PPM1G	psi-mi:“MI:0914”(association)	0.530
POLB	H2AC11	psi-mi:“MI:0914”(association)	0.530

BioGRID (316): LIG3 (Affinity Capture-RNA), LIG3 (Affinity Capture-RNA), LIG3 (Affinity Capture-MS), LIG3 (Affinity Capture-MS), LIG3 (Affinity Capture-MS), LIG3 (Affinity Capture-MS), TOP3A (Affinity Capture-MS), PREPL (Affinity Capture-MS), JMJD4 (Affinity Capture-MS), CLPX (Affinity Capture-MS), RSAD1 (Affinity Capture-MS), C7orf55 (Affinity Capture-MS), PSME3 (Affinity Capture-MS), NDUFS6 (Affinity Capture-MS), LIG3 (Affinity Capture-MS)

ESM2 similar proteins: A2AP18, A6QPL4, A8WFU8, F1QGZ6, F4JGP4, O75038, P28740, P49916, P70096, P79955, P97386, Q14680, Q14807, Q28GW8, Q2I6J1, Q2NL05, Q2R2P7, Q3B7N1, Q3V300, Q4KWH5, Q4KWH8, Q4R918, Q5E913, Q5I0E8, Q5REP4, Q5XI51, Q61846, Q62909, Q69Z98, Q6L512, Q6P3R1, Q6P549, Q6PCN7, Q6ZMV9, Q7SXA9, Q7ZYL5, Q86WJ1, Q8BYW1, Q8C0N1, Q8IWQ3

Diamond homologs: A0A7H0DNE6, A0RWD6, A4WH24, C0QSL7, D2CJS7, O57250, P04819, P0DOO3, P0DOO4, P12000, P16272, P18858, P20492, P37913, P49916, P51892, P97386, Q42572, Q4JAM1, Q54QM4, Q67480, Q869E1, Q976G4, Q9C1W9, Q9JHY8, Q9W1H4, Q9YD18, Q9YMV2, A0B7F9, A1RTK4, A1RXA6, A1RY72, A2BJX6, A2SR38, A3CWP1, A3DP49, A3MS62, A3PXE2, A4FY19, A4YD25

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK2	down-regulates	LIG3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 201 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by ALK	5	19.6×	1e-04
Downstream signal transduction	5	13.0×	5e-04
Transcriptional regulation of granulopoiesis	13	11.2×	8e-08
B-WICH complex positively regulates rRNA expression	13	10.8×	8e-08
FXIIa activates plasma kallikrein-kinin system	9	10.7×	1e-05
MAP kinase activation	5	10.6×	1e-03
Packaging Of Telomere Ends	7	10.5×	9e-05
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	8	10.1×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
base-excision repair	8	20.8×	2e-06
heterochromatin formation	10	14.2×	2e-06
double-strand break repair via nonhomologous end joining	6	14.0×	1e-03
intrinsic apoptotic signaling pathway in response to DNA damage	6	10.8×	3e-03
positive regulation of fibroblast proliferation	6	9.8×	4e-03
positive regulation of miRNA transcription	6	9.7×	5e-03
response to endoplasmic reticulum stress	8	7.4×	3e-03
nucleosome assembly	9	7.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

206 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	4
Uncertain significance	128
Likely benign	24
Benign	19

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1343935	NM_013975.4(LIG3):c.1611G>C (p.Lys537Asn)	Pathogenic
1343936	NM_013975.4(LIG3):c.2890G>C (p.Gly964Arg)	Pathogenic
1343937	NM_013975.4(LIG3):c.2996G>A (p.Cys999Tyr)	Pathogenic
1343939	NM_013975.4(LIG3):c.1826C>T (p.Pro609Leu)	Pathogenic
1343940	NM_013975.4(LIG3):c.2431C>T (p.Arg811Ter)	Pathogenic
1343941	NM_013975.4(LIG3):c.1611+209G>A	Pathogenic
1343942	NM_013975.4(LIG3):c.86G>A (p.Trp29Ter)	Pathogenic
1343938	NM_013975.4(LIG3):c.799C>T (p.Arg267Ter)	Likely pathogenic
1699182	NM_013975.4(LIG3):c.2653_2654del (p.Leu884_Ser885insTer)	Likely pathogenic
4056583	NM_013975.4(LIG3):c.535del (p.Gln179fs)	Likely pathogenic
4819568	NM_013975.4(LIG3):c.1684dup (p.Leu562fs)	Likely pathogenic

SpliceAI

4081 predictions. Top by Δscore:

Variant	Effect	Δscore
17:34983551:AGGTA:A	donor_loss	1.0000
17:34983552:GGTAA:G	donor_loss	1.0000
17:34983553:GT:G	donor_loss	1.0000
17:34986127:TTCAG:T	donor_loss	1.0000
17:34986128:TCAG:T	donor_loss	1.0000
17:34986129:CAG:C	donor_loss	1.0000
17:34986130:AGGTA:A	donor_loss	1.0000
17:34986131:GGT:G	donor_loss	1.0000
17:34986132:GTAAG:G	donor_loss	1.0000
17:34986133:T:A	donor_loss	1.0000
17:34989464:A:AG	acceptor_gain	1.0000
17:34989465:G:GC	acceptor_gain	1.0000
17:34989465:GC:G	acceptor_gain	1.0000
17:34989465:GCC:G	acceptor_gain	1.0000
17:34989465:GCCA:G	acceptor_gain	1.0000
17:34989465:GCCAA:G	acceptor_gain	1.0000
17:34989636:G:GT	donor_gain	1.0000
17:34989648:A:T	donor_gain	1.0000
17:34989652:GC:G	donor_gain	1.0000
17:34989661:G:GT	donor_gain	1.0000
17:34991824:G:GT	donor_gain	1.0000
17:34992031:CATGT:C	donor_gain	1.0000
17:34992034:GT:G	donor_gain	1.0000
17:34992036:G:GG	donor_gain	1.0000
17:34992513:C:G	acceptor_gain	1.0000
17:34992520:GCA:G	acceptor_loss	1.0000
17:34992521:CAG:C	acceptor_loss	1.0000
17:34992689:GTTG:G	donor_gain	1.0000
17:34992693:G:GG	donor_gain	1.0000
17:34994427:ACAAG:A	donor_loss	1.0000

AlphaMissense

6661 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:34983364:G:A	G120D	1.000
17:34983414:T:A	W137R	1.000
17:34983414:T:C	W137R	1.000
17:34994342:A:G	K508E	1.000
17:34994344:G:C	K508N	1.000
17:34994344:G:T	K508N	1.000
17:34994349:A:T	D510V	1.000
17:34994350:T:A	D510E	1.000
17:34994350:T:G	D510E	1.000
17:34994352:G:A	G511E	1.000
17:34994352:G:T	G511V	1.000
17:34994361:T:A	V514D	1.000
17:34994399:A:C	S527R	1.000
17:34994401:C:A	S527R	1.000
17:34994401:C:G	S527R	1.000
17:34994402:C:A	R528S	1.000
17:34994402:C:G	R528G	1.000
17:34994409:T:C	L530P	1.000
17:34994418:T:A	V533D	1.000
17:34996172:T:C	F574L	1.000
17:34996173:T:G	F574C	1.000
17:34996174:T:A	F574L	1.000
17:34996174:T:G	F574L	1.000
17:34996613:T:C	F595L	1.000
17:34996615:T:A	F595L	1.000
17:34996615:T:G	F595L	1.000
17:34998273:G:A	G656R	1.000
17:34998273:G:C	G656R	1.000
17:34998274:G:A	G656E	1.000
17:34998277:T:C	L657P	1.000

dbSNP variants (sampled 300 via entrez): RS1000039793 (17:34985716 G>A), RS1000125341 (17:34978523 C>T), RS1000196613 (17:35005931 G>A), RS1000216831 (17:34991916 A>G), RS1000555927 (17:34986123 G>T), RS1000587850 (17:35004165 T>A), RS1000719799 (17:34997221 T>C), RS1000781672 (17:34997410 A>T), RS1000832550 (17:35009778 T>G), RS1000904121 (17:35003732 C>T), RS1000944078 (17:34979912 T>C), RS1001032002 (17:35010271 C>T), RS1001117395 (17:34998093 T>C), RS1001401334 (17:35008724 C>A,T), RS1001452084 (17:35008456 C>A,T)

Disease associations

OMIM: gene MIM:600940 | disease phenotypes: MIM:619780

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial DNA depletion syndrome 20 (mngie type)	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (2): mitochondrial DNA depletion syndrome 20 (mngie type) (MONDO:0030696), cardiac rhythm disease (MONDO:0007263)

Orphanet (0):

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000044	Hypogonadotropic hypogonadism
HP:0000407	Sensorineural hearing impairment
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000544	External ophthalmoplegia
HP:0000597	Ophthalmoparesis
HP:0000608	Macular degeneration
HP:0000726	Dementia
HP:0000815	Hypergonadotropic hypogonadism
HP:0001155	Abnormality of the hand
HP:0001249	Intellectual disability
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001310	Dysmetria
HP:0001336	Myoclonus
HP:0001394	Cirrhosis
HP:0001403	Macrovesicular hepatic steatosis
HP:0001824	Weight loss
HP:0001903	Anemia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002018	Nausea
HP:0002020	Gastroesophageal reflux
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002352	Leukoencephalopathy
HP:0002401	Stroke-like episode

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000363_4	QT interval	6.000000e-12
GCST002500_19	QT interval	6.000000e-25
GCST003542_132	Night sleep phenotypes	2.000000e-07
GCST003542_133	Night sleep phenotypes	4.000000e-07
GCST006629_8	Pulse pressure	8.000000e-11
GCST007218_2	QT interval	3.000000e-13
GCST008388_2	Acute post-radiotherapy pain in breast cancer	2.000000e-06
GCST008436_2	Nonobstructive coronary artery disease	2.000000e-06
GCST010346_43	TPE interval (resting)	2.000000e-08
GCST010919_27	QT interval	2.000000e-21
GCST011010_23	Electrocardiographic traits (multivariate)	5.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0005763	pulse pressure measurement
EFO:1001483	non-obstructive coronary artery disease
EFO:0004644	TPE interval measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295773 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1052536	Toxicity	3	cisplatin;cyclophosphamide	Ovarian Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1052536	LIG3	3	1.88	1	cisplatin;cyclophosphamide

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.55	Kd	28.02	nM	CHEMBL5653589
7.55	ED50	28.02	nM	CHEMBL5653589
6.16	IC50	690	nM	MOLIBRESIB
5.05	IC50	9000	nM	CHEMBL4458668
5.00	IC50	1e+04	nM	CHEMBL4461698

PubChem BioAssay actives

4 with measured affinity, of 11 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148651: Binding affinity to human LIG3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0280	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178922: Inhibition of LIG3 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.6900	uM
6-amino-5-(benzylideneamino)-2-sulfanylidene-1H-pyrimidin-4-one	1540613: Competitive inhibition of human DNA ligase 3 using nicked DNA as substrate by high-throughput fluorescence energy transfer-based DNA joining assay	ic50	9.0000	uM
2-(3,5-dibromo-4-methylanilino)-N-[(E)-(2-hydroxy-5-nitrophenyl)methylideneamino]acetamide	1540613: Competitive inhibition of human DNA ligase 3 using nicked DNA as substrate by high-throughput fluorescence energy transfer-based DNA joining assay	ic50	10.0000	uM

CTD chemical–gene interactions

53 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects binding, decreases reaction, decreases expression, increases abundance	5
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	5
bisphenol A	decreases expression, decreases reaction	3
Arsenic	decreases expression, decreases reaction, increases abundance, increases expression	2
Smoke	increases abundance, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
trichostatin A	affects expression	1
potassium bromate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Acetaminophen	decreases expression	1
Glyphosate	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	affects expression, increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Curcumin	decreases expression, decreases reaction	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4142329	Binding	Inhibition of human Lig3beta at 10 uM using double strand nicked DNA as substrate at 3.125 to 50 uM after 30 mins in presence of ATP by acrylamide-based fluorescence-assay	Synthesis and bio-evaluation of indole-chalcone based benzopyrans as promising antiligase and antiproliferative agents. — Eur J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1R03	HCT116-LIG3(+/-)	Cancer cell line	Male
CVCL_KT71	HeLa SilenciX LigIII	Cancer cell line	Female
CVCL_SV53	HAP1 LIG3 (-) 1	Cancer cell line	Male
CVCL_SV54	HAP1 LIG3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

265 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00146822	PHASE4	COMPLETED	REFLEx Study (ENDOTAK RELIANCE G Evaluation of Handling and Electrical Performance
NCT00187239	PHASE4	COMPLETED	Reduce Ventricular Pacing in Dual Chamber Implantable Cardioverter Defibrillators Using AutoIntrinsic Conduction Search Study
NCT00247533	PHASE4	UNKNOWN	Cerebral Artery Stenosis, Coronary Artery Disease and Arrhythmia
NCT00282620	PHASE4	UNKNOWN	Magnesium to Reduce Implantable Cardioverter Defibrillator (ICD) Shocks and Improve Patient’s Quality of Life.
NCT00290056	PHASE4	UNKNOWN	Effect of Supplemental Intake of Omega-3 Polyunsaturated Fatty Acids on the Rate and Complexity of Spontaneously Occurring Ventricular and Supraventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillator (ICD) - A Randomized Clinical Trial
NCT00313443	PHASE4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00457340	PHASE4	COMPLETED	Atorvastatin For The Reduction Of Ventricular Arrhythmias
NCT00507390	PHASE4	WITHDRAWN	Omega 3 Polyunsaturated Fatty Acid Supplements (PUFAs) and Microvolt T Wave Alternans (TWA) in Patients With Ventricular Arrhythmia
NCT00575523	PHASE4	COMPLETED	Atropine for Prevention of Dysrhythmias Caused by Percutaneous Ethanol Instillation for Hepatoma Therapy
NCT00579098	PHASE4	COMPLETED	The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation
NCT01613092	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01628666	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01717469	PHASE4	UNKNOWN	Safety and the Effects of Isolated Left Ventricular Pacing in Patients With Bradyarrhythmias
NCT01819064	PHASE4	COMPLETED	Heart Rate Response to Atropine Doses Less Than 0.1mg IV to Anesthetized Infants
NCT01834872	PHASE4	UNKNOWN	Safety and Feasibility of Arrhythmia Ablation Using the Amigo Remote Robotic System as Compared With Manual Ablation
NCT01841242	PHASE4	COMPLETED	Comparison of Alcoholic Chlorhexidine 2% Versus Alcoholic Povidone Iodine for Infections Prevention With Cardiac Resynchronization Therapy Device Implantation
NCT01991223	PHASE4	UNKNOWN	Dexmedetomidine for Catheter-related Bladder Discomfort
NCT02045173	PHASE4	COMPLETED	Automate Detection of Sleep Apnea by ApneascanTM
NCT02203630	PHASE4	TERMINATED	Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
NCT02565069	PHASE4	COMPLETED	Identification for the Treatment of Complex Arrhythmias
NCT03273634	PHASE4	COMPLETED	The Effect of Proton Pump Inhibition on Palpitations
NCT03289429	PHASE4	UNKNOWN	Antiarrhythmic and Cardioprotective Effects of Atorvastatin Versus Magnesium Sulfate in Cardiac Valve Replacement Surgery
NCT03895411	PHASE4	UNKNOWN	Efficacy and Safety of Sotalol in Children With Arrhythmia
NCT05486377	PHASE4	COMPLETED	Remimazolam vs Desflurane for General Anesthesia for Ablation of Arrhythmia
NCT06574555	PHASE4	COMPLETED	Norepinephrine ED90 Bolus After Spinal Anesthesia in Cesarean Section
NCT00000464	PHASE3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000476	PHASE3	COMPLETED	Digitalis Investigation Group (DIG)
NCT00000480	PHASE3	COMPLETED	Multicenter Unsustained Tachycardia Trial (MUSTT)
NCT00000492	PHASE3	COMPLETED	Beta-Blocker Heart Attack Trial (BHAT)
NCT00000502	PHASE3	COMPLETED	Evaluation of SC-V Versus Conventional CPR
NCT00000517	PHASE3	COMPLETED	Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF)
NCT00000518	PHASE3	COMPLETED	Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM)
NCT00000531	PHASE3	COMPLETED	Antiarrhythmics Versus Implantable Defibrillators (AVID)
NCT00000540	PHASE3	COMPLETED	Coronary Artery Bypass Graft (CABG) Patch Trial
NCT00000556	PHASE3	COMPLETED	Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
NCT00000561	PHASE3	COMPLETED	Mode Selection Trial in Sinus Node Dysfunction (MOST)
NCT00000609	PHASE3	COMPLETED	Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
NCT00004559	PHASE3	COMPLETED	Fatty Acid Antiarrhythmia Trial (FAAT)
NCT00004560	PHASE3	COMPLETED	Public Access Defibrillation (PAD) Community Trial
NCT00035490	PHASE3	COMPLETED	Efficacy and Safety Evaluation of Azimilide Dihydrochloride in Patients With Implantable Cardioverter Defibrillators