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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P54098: Variant p.Leu304Arg

DNA polymerase subunit gamma-1
Gene: POLG
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Variant information Variant position: help 304 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Leucine (L) to Arginine (R) at position 304 (L304R, p.Leu304Arg). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from medium size and hydrophobic (L) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In PEOB1 and SANDO; results in loss of exonuclease activity and formation of an unligatable 5'-flap; displays low polymerization activity and reduced DNA-binding affinity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 304 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1239 The length of the canonical sequence.
Location on the sequence: help IQGSRMRFLDTMSMHMAISG L SSFQRSLWIAAKQGKHKVQP The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         IQGSRMRFLDTMSMHMAISGLSSFQRSLWIAAKQGKHKVQP

Mouse                         IQDSRMRFLDTMSMHMAISGLSSFQRSLWMGAKQGKHKNPA

Rat                           IQGSRMRFLDTMSMHMAISGLSSFQRSLWMGAKQGKHKTQH

Xenopus laevis                IKGSKTRFMDTMSMHMAISGLTGFQRTLWMASKYGKKKGLQ

Drosophila                    TEDTGTRFVDTMSLHMCVSGVTSYQRAMLKSKKE-------
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 1239 DNA polymerase subunit gamma-1
Binding site 306 – 306



Literature citations
The exonuclease activity of DNA polymerase gamma is required for ligation during mitochondrial DNA replication.
Macao B.; Uhler J.P.; Siibak T.; Zhu X.; Shi Y.; Sheng W.; Olsson M.; Stewart J.B.; Gustafsson C.M.; Falkenberg M.;
Nat. Commun. 6:7303-7303(2015)
Cited for: FUNCTION; CATALYTIC ACTIVITY; MUTAGENESIS OF ASP-274; CHARACTERIZATION OF VARIANT LS HIS-232; CHARACTERIZATION OF VARIANTS PEOB1 ALA-268 AND ARG-304; CHARACTERIZATION OF VARIANTS GLN-275; LEU-277; ARG-303 AND ARG-305; Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions.
Van Goethem G.; Dermaut B.; Loefgren A.; Martin J.-J.; Van Broeckhoven C.;
Nat. Genet. 28:211-212(2001)
Cited for: VARIANTS PEOB1 PRO-3; ARG-304; THR-467 AND CYS-955; Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.
Van Goethem G.; Martin J.-J.; Dermaut B.; Loefgren A.; Wibail A.; Ververken D.; Tack P.; Dehaene I.; Van Zandijcke M.; Moonen M.; Ceuterick C.; De Jonghe P.; Van Broeckhoven C.;
Neuromuscul. Disord. 13:133-142(2003)
Cited for: VARIANTS SANDO PRO-3; ARG-304; THR-467; TRP-627 AND CYS-955; Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay.
Naiemi M.; Bannwarth S.; Procaccio V.; Pouget J.; Desnuelle C.; Pellissier J.-F.; Roetig A.; Munnich A.; Calvas P.; Richelme C.; Jonveaux P.; Castelnovo G.; Simon M.; Clanet M.; Wallace D.; Paquis-Flucklinger V.;
Eur. J. Hum. Genet. 14:917-922(2006)
Cited for: VARIANTS PEOB1 ARG-304; ASP-380 AND THR-467; VARIANT SANDO SER-748; VARIANT MTDPS4A PRO-914; VARIANTS GLY-1143 AND HIS-1236;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.