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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P54098: Variant p.Gly268Ala

DNA polymerase subunit gamma-1
Gene: POLG
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Variant information Variant position: help 268 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 Glycine (G) to Alanine (A) at position 268 (G268A, p.Gly268Ala). 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 glycine (G) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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; sporadic case; displays mildly reduced exonuclease activity; does not affect the polymerization activity or 5'-end ligation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 268 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 EVPTGASSPTQRDWQEQLVV G HNVSFDRAHIREQYLIQGSR 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                         EVPTGASSPTQRDWQ--------EQLVVGHNVSFDRAHIREQYLIQGSR

Mouse                         GGSTSASSSTKQDGQ--------EQLVVGHNVSFDRAHIRE

Rat                           GVSASASSSTQQDWQ--------EQLVVGHNVSFDRAHIRE

Xenopus laevis                ETSMNCNYMTKNNWT--------ERLVVGHNVSFDRAHIKE

Drosophila                    DVDTDSERPHYTTDELIPLGTTGPGLVVGHNVSYDRARLKE
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
Motif 267 – 275 Exo II
Mutagenesis 274 – 274 D -> A. Unable to idle at the 5'-end of the nascent DNA strand. Continues DNA synthesis into double-stranded DNA past the 5'-end creating a flap structure that can not be ligated.
Beta strand 265 – 268



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; POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions.
Di Fonzo A.; Bordoni A.; Crimi M.; Sara G.; Del Bo R.; Bresolin N.; Comi G.P.;
Hum. Mutat. 22:498-499(2003)
Cited for: VARIANTS PEOB1 ILE-251; ALA-268; ARG-312; THR-467; GLN-562; LEU-587; PRO-807 AND TYR-932; 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.