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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q96RR1: Variant p.Trp315Leu

Twinkle mtDNA helicase
Gene: TWNK
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Variant information Variant position: help 315 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 Leucine (L) at position 315 (W315L, p.Trp315Leu). 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 medium size and hydrophobic (L) 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 PEOA3; reduced single-strand DNA binding; increased heptamer oligomerization; increased stability of the closed or 'compacted' conformation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 315 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 684 The length of the canonical sequence.
Location on the sequence: help LPYLEQFRRIVFWLGDDLRS W EAAKLFARKLNPKRCFLVRP 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                         LPYLEQFRRIVFWLG-DDLRSWEAAKLFARKLNPKRCFLVRP

Mouse                         LPYLEQFRRIVFWLG-DDLRSWEAAKLFARKLNPKRCSLVR

Chicken                       LPYLEQFRRVTLWLG-DDLRSWEASKLFARKLNPKRCSLVQ

Drosophila                    LPALERFKELIFWLHYDASHSWDAARAFALKLDERRCLLIR
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 32 – 684 Twinkle mtDNA helicase
Region 121 – 372 Required for hexamers formation and DNA helicase activity
Region 215 – 335 Primase-like domain



Literature citations
Human mitochondrial DNA deletions associated with mutations in the gene for Twinkle, a phage T7 gene 4-like protein localized in mitochondria.
Spelbrink J.N.; Li F.-Y.; Tiranti V.; Nikali K.; Yuan Q.-P.; Tariq M.; Wanrooij S.; Garrido N.; Comi G.; Morandi L.; Santoro L.; Toscano A.; Fabrizi G.-M.; Somer H.; Croxen R.; Beeson D.; Poulton J.; Suomalainen A.; Jacobs H.T.; Zeviani M.; Larsson C.;
Nat. Genet. 28:223-231(2001)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2); TISSUE SPECIFICITY; SUBCELLULAR LOCATION; VARIANT ILE-368; VARIANTS PEOA3 LEU-315; PRO-354; THR-359; THR-367; PRO-369; GLN-374; PRO-381; CYS-474 AND PRO-475; Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling.
Goffart S.; Cooper H.M.; Tyynismaa H.; Wanrooij S.; Suomalainen A.; Spelbrink J.N.;
Hum. Mol. Genet. 18:328-340(2009)
Cited for: FUNCTION (ISOFORM 1); CATALYTIC ACTIVITY (ISOFORM 1); SUBUNIT (ISOFORM 1); SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS LEU-315; GLU-319; THR-359; PRO-369; GLN-374 AND CYS-474; Structural insight and characterization of human Twinkle helicase in mitochondrial disease.
Riccio A.A.; Bouvette J.; Perera L.; Longley M.J.; Krahn J.M.; Williams J.G.; Dutcher R.; Borgnia M.J.; Copeland W.C.;
Proc. Natl. Acad. Sci. U.S.A. 119:e2207459119-e2207459119(2022)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.8 ANGSTROMS) OF 1-684 OF VARIANT LEU-315; CATALYTIC ACTIVITY; SUBUNIT; CHARACTERIZATION OF VARIANT LEU-315;
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.