Human DNA polymerase is composed of two subunits, a 140 kDa catalytic subunit encoded by the POLG on chromosome 15q25, and a 55kDa accessory subunit encoded by the POLG2 gene on chromosome 17q23-24.
A number of mutations have been mapped to the gene for the catalytic subunit of DNA polymerase, POLG, and found to be associated with mitochondrial diseases.
This database lists all known mutations in the coding region of the POLG gene and describes the associated disease. This list is maintained by the Mitochondrial DNA Replication Group at NIEHS.
The nucleotide changes are numbered from the initiation Methionine codon and are based on the cDNA (accession U60325.1) and gene sequence (accession AF497906.1).
All inquiries, additions to the list, and comments should be made to Bill Copeland.
Alignment Document (132 KB)
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Visual overview of the POLG mutations.
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Amino Acid Substitution: R3P
cDNA Position: 8 g→c (exon 2)
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| Disease | Genetics | Frequency | Reference |
| PEO | ar | (Van Goethem et al., 2001) reported 0 out of 229 control Individuals (<0.4%) | (Van Goethem et al., 2001) PubMed |
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Amino Acid Substitution: G11D
cDNA Position: 32 g→a (exon 2)
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| Disease | Genetics | Frequency | Reference |
| Ataxia Neuropathy | Found in cis with R627Q and in trans with R852C, and also found as a Heterozygous mutation with a failure to thrive | (Wong et al., 2008) PubMed |
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| Alpers | Found in cis w/ R852C and in trans w/ W748S. In a second pt. found in cis w/R852C and in trans w/ A467T. | (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed |
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| Alpers | Found in cis w/ R852C and in trans w/ A467T. In a 2nd pt., found in cis w/ R852C and in trans w/ W748S and E1143G | (Stewart et al., 2009) PubMed |
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| Leigh Syndrome | Found in cis with R852C and in trans with W748S | (Naess et al., 2009) PubMed |
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| Multiple system atrophy | Found with R852C in a 58 y.o. female with progressive cerebellar atrophy. Pt. had mtDNA deletions and mtDNA depletion. | (Mehta et al., 2011) PubMed |
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| Seizures and liver failure | Found in trans w/ A467T and in cis w/ R852C in an 8 mo. w/ seizures, liver failure, and lactic acidosis. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| Encephalopathy | Found in cis w/ R852C and in trans w/ R627Q in a 25 y.o. w/ dementia, encephalopathy, and stroke. | Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. | (Tang et al., 2011) PubMed |
| MDS | Found in a large cohort study. | (Hikmat et al., 2020) PubMed |
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| Alpers-Huttenlochers syndrome | Found as homozygous from the multicentric study among 22 children with POLG pathogenic variants in India. | 1 out of 22 patients with POLG variants | (Jha et al., 2022) PubMed |