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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P54098: Variant p.Trp748Ser

DNA polymerase subunit gamma-1
Gene: POLG
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Variant information Variant position: help 748 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 Tryptophan (W) to Serine (S) at position 748 (W748S, p.Trp748Ser). 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 large size and aromatic (W) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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 SANDO, SCAE and MTDPS4A; pathogenic. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 748 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 TQPSYHHGNGPYNDVDIPGC W FFKLPHKDGNSCNVGSPFAK 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                         TQPSYHHGNGP-YNDVDIPGCWFFKLPHKDGNSCNVGSPFAK

Mouse                         SQPTYHHGNGP-YNDVNIPGCWFFKLPHKDGNNYNVGSPFA

Rat                           SQPTYHHGNGP-YNDVDIPGCWFFKLPHKDGNNYNVGSPFA

Xenopus laevis                SLPDNHHGNSP-CGDVNVSGCWFYKLPHKDGNANNVGSPFA

Drosophila                    ---TQYQGSGVWCNKVLDDCCFFLKLPHKNGPSFRVGNPLS

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 754 – 754
Binding site 763 – 763
Binding site 768 – 768
Beta strand 747 – 751



Literature citations
POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.
Van Goethem G.; Luoma P.; Rantamaeki M.; Al-Memar A.; Kaakkola S.; Hackman P.; Krahe R.; Loefgren A.; Martin J.-J.; De Jonghe P.; Suomalainen A.; Udd B.; Van Broeckhoven C.;
Neurology 63:1251-1257(2004)
Cited for: VARIANT PEOB1 THR-467; VARIANT SANDO SER-748; VARIANT GLY-1143; Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin.
Hakonen A.H.; Heiskanen S.; Juvonen V.; Lappalainen I.; Luoma P.T.; Rantamaeki M.; Van Goethem G.; Loefgren A.; Hackman P.; Paetau A.; Kaakkola S.; Majamaa K.; Varilo T.; Udd B.; Kaeaeriaeinen H.; Bindoff L.A.; Suomalainen A.;
Am. J. Hum. Genet. 77:430-441(2005)
Cited for: VARIANT SANDO SER-748; VARIANT GLY-1143; POLG mutations and Alpers syndrome.
Davidzon G.; Mancuso M.; Ferraris S.; Quinzii C.; Hirano M.; Peters H.L.; Kirby D.; Thorburn D.R.; DiMauro S.;
Ann. Neurol. 57:921-923(2005)
Cited for: VARIANTS MTDPS4A SER-748 AND SER-848; Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-gammaA.
Ferrari G.; Lamantea E.; Donati A.; Filosto M.; Briem E.; Carrara F.; Parini R.; Simonati A.; Santer R.; Zeviani M.;
Brain 128:723-731(2005)
Cited for: VARIANTS MTDPS4A GLY-232; PRO-244; ILE-251; THR-467; LEU-587; SER-748; SER-848 AND PRO-957; VARIANT GLY-1143; Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations.
Winterthun S.; Ferrari G.; He L.; Taylor R.W.; Zeviani M.; Turnbull D.M.; Engelsen B.A.; Moen G.; Bindoff L.A.;
Neurology 64:1204-1208(2005)
Cited for: VARIANTS SANDO THR-467; HIS-497 AND SER-748; 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; Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion.
Taanman J.-W.; Rahman S.; Pagnamenta A.T.; Morris A.A.M.; Bitner-Glindzicz M.; Wolf N.I.; Leonard J.V.; Clayton P.T.; Schapira A.H.V.;
Hum. Mutat. 30:248-254(2009)
Cited for: VARIANTS LS HIS-232 AND SER-848; VARIANTS MTDPS4A ILE-251; THR-467; LEU-587; SER-748; CYS-831; SER-848; PRO-914; TYR-1110; ARG-1134 AND LYS-1136; VARIANTS GLY-1143 AND HIS-1236; Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.
Tzoulis C.; Neckelmann G.; Moerk S.J.; Engelsen B.E.; Viscomi C.; Moen G.; Ersland L.; Zeviani M.; Bindoff L.A.;
Brain 133:1428-1437(2010)
Cited for: VARIANTS SCAE THR-467 AND SER-748; VARIANTS MTDPS4A ARG-303; THR-467 AND SER-848; Alpers syndrome with mutations in POLG: clinical and investigative features.
Hunter M.F.; Peters H.; Salemi R.; Thorburn D.; Mackay M.T.;
Pediatr. Neurol. 45:311-318(2011)
Cited for: VARIANTS MTDPS4A ARG-305; THR-467; SER-748; SER-848; CYS-852 AND ARG-966; PRICKLE2 mutations might not be involved in epilepsy.
Sandford E.; Bird T.D.; Li J.Z.; Burmeister M.;
Am. J. Hum. Genet. 98:588-589(2016)
Cited for: INVOLVEMENT IN SCAE; VARIANTS SCAE THR-467; HIS-497 AND SER-748;
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.