UniProtKB/Swiss-Prot Q9BXM7: Variant p.Cys388Arg

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

Variant position:  388
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Cysteine (C) to Arginine (R) at position 388 (C388R, p.Cys388Arg).
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 medium size and polar (C) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

Involvement in disease:  Parkinson disease 6 (PARK6) [MIM:605909]: An early-onset form of Parkinson disease, a neurodegenerative disorder characterized by parkinsonian signs such as rigidity, resting tremor and bradykinesia. A subset of patients manifest additional symptoms including hyperreflexia, autonomic instability, dementia and psychiatric disturbances. Symptoms show diurnal fluctuation and can improve after sleep. PARK6 pathogenesis involves respiratory complex I deficiency causing mitochondrial depolarization and dysfunction. Inheritance is autosomal recessive. {ECO:0000269|PubMed:15087508, ECO:0000269|PubMed:15349860, ECO:0000269|PubMed:15349870, ECO:0000269|PubMed:15505171, ECO:0000269|PubMed:15596610, ECO:0000269|PubMed:15955953, ECO:0000269|PubMed:15970950, ECO:0000269|PubMed:16009891, ECO:0000269|PubMed:16207217, ECO:0000269|PubMed:16207731, ECO:0000269|PubMed:16257123, ECO:0000269|PubMed:16401616, ECO:0000269|PubMed:16482571, ECO:0000269|PubMed:16632486, ECO:0000269|PubMed:16966503, ECO:0000269|PubMed:17030667, ECO:0000269|PubMed:18286320, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22043288, ECO:0000269|PubMed:22956510, ECO:0000269|PubMed:24652937, ECO:0000269|PubMed:24784582}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PARK6.
Any additional useful information about the variant.



Sequence information

Variant position:  388
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:   ILVELDPDGCPWLVIADFGC  C LADESIGLQLPFSSWYVDRG
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                         ILVELD-PDGCPWLVIADFGCCLADESIGLQLPFSSWYVDRG

Mouse                         ILVEWD-SDGCPWLVISDFGCCLADQHVGLRLPFNSSSVER

Caenorhabditis elegans        ILLEYDFDDEIPQLVVADFGCALACDN--WQVDYESDEVSL

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
Modified residue 402 – 402 Phosphoserine; by autocatalysis
Mutagenesis 384 – 384 D -> A. Abolishes MFN2 phosphorylation and interaction with PRKN; when associated with ALA-219 and ALA-362.


Literature citations

Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism.
Li Y.; Tomiyama H.; Sato K.; Hatano Y.; Yoshino H.; Atsumi M.; Kitaguchi M.; Sasaki S.; Kawaguchi S.; Miyajima H.; Toda T.; Mizuno Y.; Hattori N.;
Neurology 64:1955-1957(2005)
Cited for: VARIANT PARK6 ARG-388;

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.