POLG
Chr 15ARADDNA polymerase gamma, catalytic subunit
Also known as: MIRAS, MTDPS4A, MTDPS4B, PEO, POLG1, POLGA, PolG-alpha, SANDO
The encoded protein is the catalytic subunit of mitochondrial DNA polymerase, which replicates mitochondrial DNA. Mutations cause a spectrum of mitochondrial disorders including Alpers-Huttenlocher syndrome, progressive external ophthalmoplegia, sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO), and mitochondrial DNA depletion syndromes, inherited in both autosomal recessive and autosomal dominant patterns. The pathogenic mechanism involves defective mitochondrial DNA replication leading to mitochondrial DNA depletion or deletions.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
POLG · 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
Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
RECRUITINGThe Impact of Mitochondrial Dysfunction on Human Bone Cell Metabolism and Remodelling
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools