NM_007262.5(PARK7):c.497T>C (p.Leu166Pro) AND Autosomal recessive early-onset Parkinson disease 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 1, 2012
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000007480.4

Allele description [Variation Report for NM_007262.5(PARK7):c.497T>C (p.Leu166Pro)]

NM_007262.5(PARK7):c.497T>C (p.Leu166Pro)

Gene:

PARK7:Parkinsonism associated deglycase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.23

Genomic location:

Preferred name:

NM_007262.5(PARK7):c.497T>C (p.Leu166Pro)

HGVS:

NC_000001.11:g.7984981T>C
NG_008271.1:g.28328T>C
NM_001123377.2:c.497T>C
NM_007262.5:c.497T>CMANE SELECT
NP_001116849.1:p.Leu166Pro
NP_009193.2:p.Leu166Pro
NC_000001.10:g.8045041T>C
Q99497:p.Leu166Pro

Protein change:

L166P; LEU166PRO

Links:

UniProtKB: Q99497#VAR_020498; OMIM: 602533.0002; dbSNP: rs28938172

NCBI 1000 Genomes Browser:

rs28938172

Molecular consequence:

NM_001123377.2:c.497T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_007262.5:c.497T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive early-onset Parkinson disease 7
Synonyms:: Parkinson disease 7
Identifiers:: MONDO: MONDO:0011658; MedGen: C1853445; Orphanet: 2828; OMIM: 606324

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000027680	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2012)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 12446870, 20639397, 22492997

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000027680

OMIM

no assertion criteria provided

Pathogenic
(Jul 1, 2012)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.

Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P.

Science. 2003 Jan 10;299(5604):256-9. Epub 2002 Nov 21.

PubMed [citation]

PMID:: 12446870

Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics.

Irrcher I, Aleyasin H, Seifert EL, Hewitt SJ, Chhabra S, Phillips M, Lutz AK, Rousseaux MW, Bevilacqua L, Jahani-Asl A, Callaghan S, MacLaurin JG, Winklhofer KF, Rizzu P, Rippstein P, Kim RH, Chen CX, Fon EA, Slack RS, Harper ME, McBride HM, Mak TW, et al.

Hum Mol Genet. 2010 Oct 1;19(19):3734-46. doi: 10.1093/hmg/ddq288. Epub 2010 Jul 16.

PubMed [citation]

PMID:: 20639397

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000027680.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

In a consanguineous Italian family with autosomal recessive early-onset Parkinson disease (PARK7; 606324), Bonifati et al. (2003) identified a homozygous 497T-C transition in the DJ1 gene, resulting in a leu166-to-pro substitution (L166P) in the protein. The mutation showed cosegregation with the disease in 3 affected sibs and was absent in 320 chromosomes from the Italian population. A molecular model of the mutation was predicted to destabilize the terminal helix of the protein.

Irrcher et al. (2010) showed that the L166P mutation in DJ1 resulted in fragmented mitochondria and elevated markers of autophagy.

Im et al. (2012) found that DJ1 with the L166P substitution was unable to induce TRX1 (187700) expression or to protect transfected HeLa cells from H2O2-induced cytotoxicity. Wildtype, but not mutant DJ1, mediated H2O2-induced and DJ1-dependent expression and nuclear translocation of NRF2 (600492) and enhanced recruitment of NRF2 to the antioxidant response element in the TRX1 promoter region.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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