LIG3: DNA Ligase 3 – Key Player in Mitochondrial and Nuclear DNA Repair
Comprehensive gene card for LIG3, including genomic context, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | LIG3 |
|---|---|
| Full Name | DNA ligase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q12 |
| NCBI Gene ID | 3980 ncbi.nlm.nih.gov/gene/3980 |
| Ensembl ID | ENSG00000005156 |
| UniProt ID | P49916 |
| OMIM ID | 600940 |
| HGNC ID | 6600 |
| Aliases | LIG3alpha, LIG3beta, DNA ligase III, hLIG3 |
Description
LIG3 encodes DNA ligase 3, a key enzyme in DNA repair pathways including base excision repair (BER) and single-strand break repair (SSBR). It functions in both the nucleus and mitochondria, interacting with XRCC1 in the nucleus and with mitochondrial DNA. Alternative splicing produces nuclear (LIG3α) and mitochondrial (LIG3β) isoforms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial DNA depletion syndrome 11 (MTDPS11) | Defects in LIG3 impair mitochondrial DNA ligation, leading to mtDNA depletion and dysfunction. | ClinVar, OMIM #615084 |
| Breast cancer | LIG3 overexpression or altered activity may contribute to genomic instability and tumor progression. | COSMIC, NCBI PubMed |
| Lung cancer | Somatic mutations and altered expression of LIG3 have been reported in lung adenocarcinoma. | COSMIC, NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Heart | 10.8 | Medium |
| Brain | 7.5 | Low |
| Liver | 6.3 | Low |
| Kidney | 8.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.4 | Embryonic kidney cells |
| HeLa | 9.8 | Cervical cancer cells |
| A549 | 11.2 | Lung adenocarcinoma cells |
| MCF7 | 7.6 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; likely loss of function |
| c.1270C>T (p.Arg424Trp) | Missense | 0.02% | Impaired DNA binding; associated with MTDPS11 |
| c.1685G>A (p.Arg562Gln) | Missense | 0.01% | Reduced ligase activity; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg424Trp and p.Met1? reduce or abolish ligase activity, leading to mtDNA depletion and cellular dysfunction.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in LIG3.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by interfering with XRCC1 interaction, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA ligation (GO:0006266) | • DNA repair (GO:0006281) |
| • base-excision repair (GO:0006284) | • mitochondrion (GO:0005739) |
| • nucleus (GO:0005634) | • DNA binding (GO:0003677) |
| • ATP binding (GO:0005524) |
Pathways
• Base excision repair (BER) – Reactome R-HSA-73884
• Single-strand break repair (SSBR) – Reactome R-HSA-73928
• Mitochondrial DNA repair – Reactome R-HSA-159227
Protein Summary
DNA ligase 3 (LIG3) is a 922-amino acid protein (UniProt P49916) that catalyzes the joining of DNA strands during repair. It contains an N-terminal DNA-binding domain, a central catalytic domain, and a C-terminal XRCC1-binding region. The mitochondrial isoform lacks the nuclear localization signal and is essential for mtDNA maintenance. LIG3 is critical for genomic stability and cell survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OLIG3 Knockout HEK293 Cell Line | EDJ-KQ2909 | Human | 167826 | Details Get a Quote |
| LIG3 Knockout HEK293 Cell Line | EDJ-KQ5121 | Human | 3980 | Details Get a Quote |
| LIG3 Knockout HeLa Cell Line | EDJ-KQ28070 | Human | 3980 | Details Get a Quote |
| LIG3 Knockout HCT 116 Cell Line | EDJ-KQ26841 | Human | 3980 | Details Get a Quote |
| OLIG3 Knockout HeLa Cell Line | EDJ-KQ58907 | Human | 167826 | Details Get a Quote |
| LIG3 Knockout A-549 Cell Line | EDJ-KQ62272 | Human | 3980 | Details Get a Quote |
| OLIG3 Knockout A-549 Cell Line | EDJ-KQ67395 | Human | 167826 | Details Get a Quote |
| OLIG3 Knockout HCT 116 Cell Line | EDJ-KQ75789 | Human | 167826 | Details Get a Quote |
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