LIG1 (DNA Ligase 1): Function, Mutations, and Disease Relevance
A comprehensive biomedical overview of the LIG1 gene, encoding DNA ligase 1, with emphasis on its role in DNA replication and repair, associated diseases, and mutation landscape.
Gene Information Card
| Symbol | LIG1 |
|---|---|
| Full Name | DNA ligase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 3978 ncbi.nlm.nih.gov/gene/3978 |
| Ensembl ID | ENSG00000105486 |
| UniProt ID | P18858 |
| OMIM ID | 126391 |
| HGNC ID | 6598 |
| Aliases | LIG1, DNA ligase I, Ligase I, DNA ligase 1, MGC11364 |
Description
The LIG1 gene encodes DNA ligase 1, a key enzyme involved in DNA replication and repair. It catalyzes the joining of Okazaki fragments during lagging strand DNA synthesis and participates in base excision repair and nucleotide excision repair pathways. LIG1 is essential for maintaining genomic stability, and its dysfunction is linked to immunodeficiency, developmental delay, and increased cancer susceptibility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency with developmental delay and facial dysmorphism | Loss-of-function mutations in LIG1 impair DNA ligation, leading to defective DNA replication and repair, causing immune deficiency and developmental abnormalities. | ClinVar, OMIM |
| LIG1 deficiency (rare autosomal recessive disorder) | Biallelic mutations reduce DNA ligase 1 activity, causing sensitivity to DNA damaging agents and clinical features like growth retardation and photosensitivity. | OMIM, PubMed |
| Cancer (various types) | Somatic mutations and altered expression of LIG1 may contribute to genomic instability and tumorigenesis, though direct causal evidence varies. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High expression in hematopoietic tissues |
| Lymph Node | High | High expression in immune tissues |
| Spleen | High | High expression in immune tissues |
| Testis | High | High expression in proliferative tissues |
| Small Intestine | Medium | Moderate expression |
| Colon | Medium | Moderate expression |
| Liver | Medium | Moderate expression |
| Brain | Low | Low expression in non-proliferative tissues |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | High | Myelogenous leukemia cell line |
| HeLa (cervical cancer) | High | Epithelial carcinoma cell line |
| A549 (lung cancer) | Medium | Lung carcinoma cell line |
| MCF7 (breast cancer) | Medium | Breast adenocarcinoma cell line |
| HepG2 (liver cancer) | Medium | Hepatocellular carcinoma cell line |
| IMR-90 (fibroblast) | Low | Normal lung fibroblast cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg771Trp | Missense | Rare | Reduced enzyme activity, associated with LIG1 deficiency |
| p.Gly595Arg | Missense | Rare | Impaired DNA ligation, linked to immunodeficiency |
| p.Arg582Trp | Missense | Rare | Decreased stability and activity |
| p.Glu346Lys | Missense | Rare | Potential impact on catalytic function |
| c.1738C>T (p.Arg580Ter) | Nonsense | Very rare | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most LIG1 mutations are loss-of-function, reducing or abolishing DNA ligase activity, leading to defective DNA replication and repair.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for LIG1.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type enzyme function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • DNA ligase activity |
| • ATP binding | • DNA replication |
| • DNA repair | • base-excision repair |
| • nucleotide-excision repair | • nucleus |
| • zinc ion binding |
Pathways
• DNA replication
• Base excision repair
• Nucleotide excision repair
• Mismatch repair
• Double-strand break repair via non-homologous end joining
Protein Summary
DNA ligase 1 is a 919-amino acid protein that catalyzes the formation of phosphodiester bonds between adjacent nucleotides in DNA. It contains an N-terminal regulatory domain and a C-terminal catalytic domain. The enzyme is essential for joining Okazaki fragments during DNA replication and for completing DNA repair processes. Its activity is regulated by phosphorylation and interaction with PCNA. Defects in LIG1 lead to genomic instability and disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OLIG1 Knockout HEK293 Cell Line | EDJ-KQ3768 | Human | 116448 | Details Get a Quote |
| LIG1 Knockout HEK293 Cell Line | EDJ-KQ5120 | Human | 3978 | Details Get a Quote |
| RLIG1 Knockout HEK293 Cell Line | EDJ-KQ15083 | Human | 91298 | Details Get a Quote |
| LIG1 Knockout A-549 Cell Line | EDJ-KQ28066 | Human | 3978 | Details Get a Quote |
| LIG1 Knockout HCT 116 Cell Line | EDJ-KQ28067 | Human | 3978 | Details Get a Quote |
| LIG1 Knockout HeLa Cell Line | EDJ-KQ28068 | Human | 3978 | Details Get a Quote |
| RLIG1 Knockout A-549 Cell Line | EDJ-KQ45651 | Human | 91298 | Details Get a Quote |
| RLIG1 Knockout HCT 116 Cell Line | EDJ-KQ45652 | Human | 91298 | Details Get a Quote |
| RLIG1 Knockout HeLa Cell Line | EDJ-KQ45653 | Human | 91298 | Details Get a Quote |
| OLIG1 Knockout HeLa Cell Line | EDJ-KQ57989 | Human | 116448 | Details Get a Quote |
| OLIG1 Knockout A-549 Cell Line | EDJ-KQ66475 | Human | 116448 | Details Get a Quote |
| OLIG1 Knockout HCT 116 Cell Line | EDJ-KQ74898 | Human | 116448 | Details Get a Quote |
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