LIG3
Chr 17ARDNA ligase 3
Also known as: LIG2, LIG3alpha, MTDPS20
LIG3 encodes DNA ligase III, which catalyzes the joining of DNA ends during excision repair in both the nucleus (as part of the XRCC1 complex) and mitochondria. Mutations cause mitochondrial DNA depletion syndrome 20 (MNGIE type) with autosomal recessive inheritance. The gene is highly constrained against loss-of-function mutations, reflecting its essential role in DNA repair across cellular compartments.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
LIG3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools