UniProtKB/Swiss-Prot Q9BXM7: Variant p.Gly309Asp

Serine/threonine-protein kinase PINK1, mitochondrial
Gene: PINK1
Chromosomal location: 1p36
Variant information

Variant position:  309
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Glycine (G) to Aspartate (D) at position 309 (G309D, p.Gly309Asp).
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:  Change from glycine (G) to medium size and acidic (D)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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:  In PARK6; fails to maintain mitochondrial membrane potential; has reduced autophosphorylation activity compared to wild-type; strongly reduces interaction with PARK2.
Any additional useful information about the variant.



Sequence information

Variant position:  309
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  581
The length of the canonical sequence.

Location on the sequence:   PGALVDYPDVLPSRLHPEGL  G HGRTLFLVMKNYPCTLRQYL
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         PGALVDYPDVL-PSRLHPEGLGHGRTLFLVMKNYPCTLRQYL

Mouse                         PGALADYPDML-PPHYYPEGLGHGRTLFLVMKNYPCTLRQY

Caenorhabditis elegans        PDAIERYPDALHTARWYESIASEPKTMYVVMRRYRQTLHEY

Sequence annotation in neighborhood:  
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 78 – 581 Serine/threonine-protein kinase PINK1, mitochondrial
Topological domain 111 – 581 Cytoplasmic
Domain 156 – 511 Protein kinase
Alternative sequence 308 – 320 LGHGRTLFLVMKN -> MCGSQRPSPLSTS. In isoform 2.


Literature citations

The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations.
Geisler S.; Holmstrom K.M.; Treis A.; Skujat D.; Weber S.S.; Fiesel F.C.; Kahle P.J.; Springer W.;
Autophagy 6:871-878(2010)
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY; SUBCELLULAR LOCATION; INTERACTION WITH PARK2; CHARACTERIZATION OF VARIANTS PARK6 PRO-126; ASP-309 AND PRO-347;

Hereditary early-onset Parkinson's disease caused by mutations in PINK1.
Valente E.M.; Abou-Sleiman P.M.; Caputo V.; Muqit M.M.K.; Harvey K.; Gispert S.; Ali Z.; Del Turco D.; Bentivoglio A.R.; Healy D.G.; Albanese A.; Nussbaum R.; Gonzalez-Maldonado R.; Deller T.; Salvi S.; Cortelli P.; Gilks W.P.; Latchman D.S.; Harvey R.J.; Dallapiccola B.; Auburger G.; Wood N.W.;
Science 304:1158-1160(2004)
Cited for: VARIANT PARK6 ASP-309; CHARACTERIZATION OF VARIANT PARK6 ASP-309; FUNCTION; SUBCELLULAR LOCATION;

Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism.
Silvestri L.; Caputo V.; Bellacchio E.; Atorino L.; Dallapiccola B.; Valente E.M.; Casari G.;
Hum. Mol. Genet. 14:3477-3492(2005)
Cited for: CHARACTERIZATION OF VARIANTS PARK6 PRO-168 AND ASP-309;

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.