DNA polymerase gamma, catalytic subunit
Annotations refreshed 1 month ago.
Diagnostic Grade (Green)
Acute rhabdomyolysis
BOTH monoallelic and biallelic, autosomal or pseudoautosomalAdult onset neurodegenerative disorder
BOTH monoallelic and biallelic, autosomal or pseudoautosomalAtaxia and cerebellar anomalies - narrow panel
BOTH monoallelic and biallelic, autosomal or pseudoautosomalBilateral congenital or childhood onset cataracts
BOTH monoallelic and biallelic, autosomal or pseudoautosomalCholestasis
BIALLELIC, autosomal or pseudoautosomalDDG2P
BIALLELIC, autosomal or pseudoautosomalEarly onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomalGastrointestinal neuromuscular disorders
BIALLELIC, autosomal or pseudoautosomal+24 more panels — install the extension to see the full list inline on any page.
mitochondrial DNA depletion syndrome 4a
sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1
mitochondrial neurogastrointestinal encephalomyopathy
Sensory ataxic neuropathy - dysarthria - ophthalmoparesis
progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1
Alpers syndrome
spinocerebellar ataxia with epilepsy
mitochondrial DNA depletion syndrome
autosomal dominant progressive external ophthalmoplegia
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
DNA polymerase subunit gamma-1
Catalytic subunit of DNA polymerase gamma solely responsible for replication of mitochondrial DNA (mtDNA). Replicates both heavy and light strands of the circular mtDNA genome using a single-stranded DNA template, RNA primers and the four deoxyribonucleoside triphosphates as substrates (PubMed:11477093, PubMed:11897778, PubMed:15917273, PubMed:19837034, PubMed:9558343). Has 5' -> 3' polymerase activity. Functionally interacts with TWNK and SSBP1 at the replication fork to form a highly processive replisome, where TWNK unwinds the double-stranded DNA template prior to replication and SSBP1 covers the parental heavy strand to enable continuous replication of the entire mitochondrial genome. A single nucleotide incorporation cycle includes binding of the incoming nucleotide at the insertion site, a phosphodiester bond formation reaction that extends the 3'-end of the primer DNA, and translocation of the primer terminus to the post-insertion site. After completing replication of a mtDNA strand, mediates 3' -> 5' exonucleolytic degradation at the nick to enable proper ligation (PubMed:11477093, PubMed:11897778, PubMed:15167897, PubMed:15917273, PubMed:19837034, PubMed:26095671, PubMed:9558343). Highly accurate due to high nucleotide selectivity and 3' -> 5' exonucleolytic proofreading. Proficiently corrects base substitutions, single-base additions and deletions in non-repetitive sequences and short repeats, but displays lower proofreading activity when replicating longer homopolymeric stretches. Exerts exonuclease activity toward single-stranded DNA and double-stranded DNA containing 3'-terminal mispairs. When a misincorporation occurs, transitions from replication to a pro-nucleolytic editing mode and removes the missincorporated nucleoside in the exonuclease active site. Proceeds via an SN2 nucleolytic mechanism in which Asp-198 catalyzes phosphodiester bond hydrolysis and Glu-200 stabilizes the leaving group. As a result the primer strand becomes one nucleotide shorter and is positioned in the post-insertion site, ready to resume DNA synthesis (PubMed:10827171, PubMed:11477094, PubMed:11504725, PubMed:37202477). Exerts 5'-deoxyribose phosphate (dRP) lyase activity and mediates repair-associated mtDNA synthesis (gap filling) in base-excision repair pathway. Catalyzes the release of the 5'-terminal 2-deoxyribose-5-phosphate sugar moiety from incised apurinic/apyrimidinic (AP) sites to produce a substrate for DNA ligase. The dRP lyase reaction does not require divalent metal ions and likely proceeds via a Schiff base intermediate in a beta-elimination reaction mechanism (PubMed:9770471)
POLG · P54098
Mean pLDDT
78.9/ 100
Confident
1,239 residues
Confidence breakdown
AlphaFold (Jumper et al., 2021) · CC BY 4.0
