NM_032409.2(PINK1):c.1196C>T (p.Pro399Leu) AND Parkinson disease, autosomal recessive early-onset, digenic, PINK1/DJ1

Clinical significance:Pathogenic (Last evaluated: Jun 1, 2006)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000002518.2

Allele description [Variation Report for NM_032409.2(PINK1):c.1196C>T (p.Pro399Leu)]

NM_032409.2(PINK1):c.1196C>T (p.Pro399Leu)

Genes:
PINK1-AS:PINK1 antisense RNA [Gene - HGNC]
PINK1:PTEN induced putative kinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.12
Genomic location:
Preferred name:
NM_032409.2(PINK1):c.1196C>T (p.Pro399Leu)
HGVS:
  • NC_000001.11:g.20648577C>T
  • NG_008164.1:g.20123C>T
  • NM_032409.2:c.1196C>T
  • NP_115785.1:p.Pro399Leu
  • NC_000001.10:g.20975070C>T
  • Q9BXM7:p.Pro399Leu
Protein change:
P399L; PRO399LEU
Links:
UniProtKB: Q9BXM7#VAR_062777; OMIM: 608309.0014; dbSNP: 119451946
GMAF:
0.0002(T), 119451946
NCBI 1000 Genomes Browser:
rs119451946
Allele Frequency:
NaN
Molecular consequence:
  • NM_032409.2:c.1196C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Parkinson disease, autosomal recessive early-onset, digenic, PINK1/DJ1
Identifiers:
MedGen: C2751533

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000022676OMIMno assertion criteria providedPathogenic
(Jun 1, 2006)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.

Tang B, Xiong H, Sun P, Zhang Y, Wang D, Hu Z, Zhu Z, Ma H, Pan Q, Xia JH, Xia K, Zhang Z.

Hum Mol Genet. 2006 Jun 1;15(11):1816-25.

PubMed [citation]
PMID:
16632486

Details of each submission

From OMIM, SCV000022676.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 2 Chinese sibs with early-onset Parkinson disease (see 605909), Tang et al. (2006) identified compound heterozygosity for 2 mutations in 2 different genes: a 1196C-T transition in exon 6 of the PINK1 gene resulting in a pro399-to-leu (P399L) substitution in the predicted kinase domain, and an A39S mutation (602533.0007) in the DJ1 gene. The DJ1 and PINK1 mutations were not observed in 240 and 568 control chromosomes, respectively, and both were located in highly conserved residues. The findings were consistent with digenic inheritance of Parkinson disease. A 42-year-old unaffected family member also carried both mutations, suggesting incomplete penetrance. Coimmunoprecipitation studies showed that both wildtype and mutant PINK1 interacted with both wildtype and mutant DJ1. Expression of wildtype DJ1 increased steady-state levels of both mutant and wildtype PINK1, but mutant DJ1 decreased steady-state levels of both mutant and wildtype PINK1, suggesting that wildtype DJ1 can enhance PINK1 stability. Human neuroblastoma cells expressing either mutant PINK1 or DJ1 showed reduced viability following oxidative challenge with MPP compared to control cells, indicating that both proteins protect against cell stress. Coexpression of both wildtype proteins resulted in a synergistic increase in cell viability against MPP-induced stress. In addition, coexpression of both mutant proteins significantly increased susceptibility of cells to death, compared to either mutant alone. These findings indicated that DJ1 and PINK1 function collaboratively.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 6, 2016