The frequency of this variant in the general population is consistent with pathogenicity (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org). This variant has been identified in multiple individuals and families with Parkinson disease (PD) and has been reported as one of the most common pathogenic variants in the LRRK2 gene (PMID: 15541309, 18197194, 18337586, 21538529, 24496098, 32580205). This variant has been primarily identified in individuals with PD diagnosed after the age of 50 years. Early-onset cases have also been reported (PMID: 18197194, 18337586, 21538529, 25330418). Numerous individuals with Parkinson disease have been reported with missense changes at codon 1441, suggesting that this residue is important for protein function (PMID: 27111571). Assessment of experimental evidence suggests this variant results in abnormal protein function. Studies have shown that expression of this variant results in a reduction in GTPase activity and increased kinase activity (PMID: 17200152, 17442267, 17623048, 19781641, 21658387, 24351927, 30796162).
ClinVar Genomic variation as it relates to human health
NM_198578.4(LRRK2):c.4321C>T (p.Arg1441Cys)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(10)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
10
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_198578.4(LRRK2):c.4321C>T (p.Arg1441Cys)
Variation ID: 1938 Accession: VCV000001938.30
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 12q12 12: 40310434 (GRCh38) [ NCBI UCSC ] 12: 40704236 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Nov 24, 2024 Feb 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_198578.4:c.4321C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_940980.4:p.Arg1441Cys missense NC_000012.12:g.40310434C>T NC_000012.11:g.40704236C>T NG_011709.1:g.90424C>T Q5S007:p.Arg1441Cys - Protein change
- R1441C
- Other names
- -
- Canonical SPDI
- NC_000012.12:40310433:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Exome Aggregation Consortium (ExAC) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00003
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| LRRK2 | - | - |
GRCh38 GRCh37 |
3559 | 3584 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Oct 28, 2023 | RCV000002015.26 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV002472921.25 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jul 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant Parkinson disease 8
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV001652802.2
First in ClinVar: May 28, 2021 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Jan 03, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV004237764.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(May 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics
Accession: SCV002771473.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org). This variant has been … (more)
The frequency of this variant in the general population is consistent with pathogenicity (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org). This variant has been identified in multiple individuals and families with Parkinson disease (PD) and has been reported as one of the most common pathogenic variants in the LRRK2 gene (PMID: 15541309, 18197194, 18337586, 21538529, 24496098, 32580205). This variant has been primarily identified in individuals with PD diagnosed after the age of 50 years. Early-onset cases have also been reported (PMID: 18197194, 18337586, 21538529, 25330418). Numerous individuals with Parkinson disease have been reported with missense changes at codon 1441, suggesting that this residue is important for protein function (PMID: 27111571). Assessment of experimental evidence suggests this variant results in abnormal protein function. Studies have shown that expression of this variant results in a reduction in GTPase activity and increased kinase activity (PMID: 17200152, 17442267, 17623048, 19781641, 21658387, 24351927, 30796162). (less)
|
|
|
Pathogenic
(Oct 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant Parkinson disease 8
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004121779.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
Variant summary: LRRK2 c.4321C>T (p.Arg1441Cys) results in a non-conservative amino acid change located in the Small GTP-binding protein domain (IPR005225) of the encoded protein sequence. … (more)
Variant summary: LRRK2 c.4321C>T (p.Arg1441Cys) results in a non-conservative amino acid change located in the Small GTP-binding protein domain (IPR005225) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251116 control chromosomes. c.4321C>T has been reported in the literature in multiple individuals affected with Autosomal Dominant Parkinson Disease (example, Zimprich_2004, DiFonzo_2006). It has also been observed to segregate with disease in related individuals (Zimprich_2004). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. Decreased LRRK2 autophosphorylation, increased formation of inclusion bodies, cell death of neurons and neuronal cell lines after expression of this variant have been reported (Greggio_2006). The following publications have been ascertained in the context of this evaluation (PMID: 16633828, 16750377, 15541309). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Oct 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant Parkinson disease 8
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000640130.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1441 of the LRRK2 protein … (more)
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1441 of the LRRK2 protein (p.Arg1441Cys). This variant is present in population databases (rs33939927, gnomAD 0.01%). This missense change has been observed in individuals with Parkinson's disease (PMID: 15541309, 21538529, 24565865). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1938). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LRRK2 protein function. Experimental studies have shown that this missense change affects LRRK2 function (PMID: 16750377, 17200152, 21494637, 21658387, 23241745). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002821698.14
First in ClinVar: Jan 21, 2023 Last updated: Oct 20, 2024 |
Comment:
LRRK2: PP1:Strong, PS3, PM2, PM5, PS4:Moderate
Number of individuals with the variant: 2
|
|
|
Pathogenic
(Jul 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV005414071.1
First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024 |
Comment:
PP1, PM1, PM5, PS3, PS4
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Apr 20, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Autosomal dominant Parkinson disease 8
Affected status: yes
Allele origin:
germline
|
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare
Accession: SCV000599864.1
First in ClinVar: Oct 07, 2016 Last updated: Oct 07, 2016 |
|
|
|
Pathogenic
(Aug 25, 2009)
|
no assertion criteria provided
Method: literature only
|
PARKINSON DISEASE 8, AUTOSOMAL DOMINANT
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000022173.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 30, 2017 |
Comment on evidence:
In affected members of a family with autosomal dominant Parkinson disease (PARK8; 607060) originally reported by Wszolek et al. (1995), Zimprich et al. (2004) identified … (more)
In affected members of a family with autosomal dominant Parkinson disease (PARK8; 607060) originally reported by Wszolek et al. (1995), Zimprich et al. (2004) identified a heterozygous 4321C-T transition in the LRRK2 gene, resulting in an arg1441-to-cys (R1441C) substitution in the ROC (GTPase) domain. Affected members of another unrelated family also had the R1441C mutation. The mutation was not identified in more than 1,000 control individuals or 300 patients with sporadic PD. West et al. (2005) determined that the R1441C mutation, which lies within the GTPase domain of LRRK2, did not alter the steady-state level, turnover, or intracellular localization of the LRRK2 protein, but that R1441C appeared to enhance protein kinase activity. Tong et al. (2009) found that mutant knockin mice with expression of normal levels of the R1441C mutant protein appeared grossly normal and did not show any evidence of dopaminergic degeneration up to 2 years of age. However, knockin mice showed impaired augmentation of locomotor activity in response to amphetamine compared to wildtype, suggesting a defect in drug-induced dopamine release. Adrenal chromaffin cells derived from mutant mice showed a significant reduction in stimulus-induced catecholamine release compared to controls. Mutant mice also showed impaired dopamine D2 receptor (DRD2; 126450)-mediated functions, such as reduced response to the locomotor inhibitory effect of a DRD2 agonist and decreased cellular sensitivity to suppression by DRD2 agonists. Tong et al. (2009) suggested that these changes may represent pathogenic precursors to dopaminergic degeneration. (less)
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Autosomal dominant Parkinson disease 8
Affected status: not provided
Allele origin:
unknown
|
GeneReviews
Accession: SCV000056116.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
|
Comment:
Comment:
Variant summary: LRRK2 c.4321C>T (p.Arg1441Cys) results in a non-conservative amino acid change located in the Small GTP-binding protein domain (IPR005225) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251116 control chromosomes. c.4321C>T has been reported in the literature in multiple individuals affected with Autosomal Dominant Parkinson Disease (example, Zimprich_2004, DiFonzo_2006). It has also been observed to segregate with disease in related individuals (Zimprich_2004). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. Decreased LRRK2 autophosphorylation, increased formation of inclusion bodies, cell death of neurons and neuronal cell lines after expression of this variant have been reported (Greggio_2006). The following publications have been ascertained in the context of this evaluation (PMID: 16633828, 16750377, 15541309). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1441 of the LRRK2 protein (p.Arg1441Cys). This variant is present in population databases (rs33939927, gnomAD 0.01%). This missense change has been observed in individuals with Parkinson's disease (PMID: 15541309, 21538529, 24565865). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1938). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LRRK2 protein function. Experimental studies have shown that this missense change affects LRRK2 function (PMID: 16750377, 17200152, 21494637, 21658387, 23241745). For these reasons, this variant has been classified as Pathogenic.
Comment:
LRRK2: PP1:Strong, PS3, PM2, PM5, PS4:Moderate
Comment:
PP1, PM1, PM5, PS3, PS4
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org). This variant has been identified in multiple individuals and families with Parkinson disease (PD) and has been reported as one of the most common pathogenic variants in the LRRK2 gene (PMID: 15541309, 18197194, 18337586, 21538529, 24496098, 32580205). This variant has been primarily identified in individuals with PD diagnosed after the age of 50 years. Early-onset cases have also been reported (PMID: 18197194, 18337586, 21538529, 25330418). Numerous individuals with Parkinson disease have been reported with missense changes at codon 1441, suggesting that this residue is important for protein function (PMID: 27111571). Assessment of experimental evidence suggests this variant results in abnormal protein function. Studies have shown that expression of this variant results in a reduction in GTPase activity and increased kinase activity (PMID: 17200152, 17442267, 17623048, 19781641, 21658387, 24351927, 30796162).
Comment:
Variant summary: LRRK2 c.4321C>T (p.Arg1441Cys) results in a non-conservative amino acid change located in the Small GTP-binding protein domain (IPR005225) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251116 control chromosomes. c.4321C>T has been reported in the literature in multiple individuals affected with Autosomal Dominant Parkinson Disease (example, Zimprich_2004, DiFonzo_2006). It has also been observed to segregate with disease in related individuals (Zimprich_2004). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. Decreased LRRK2 autophosphorylation, increased formation of inclusion bodies, cell death of neurons and neuronal cell lines after expression of this variant have been reported (Greggio_2006). The following publications have been ascertained in the context of this evaluation (PMID: 16633828, 16750377, 15541309). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1441 of the LRRK2 protein (p.Arg1441Cys). This variant is present in population databases (rs33939927, gnomAD 0.01%). This missense change has been observed in individuals with Parkinson's disease (PMID: 15541309, 21538529, 24565865). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1938). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LRRK2 protein function. Experimental studies have shown that this missense change affects LRRK2 function (PMID: 16750377, 17200152, 21494637, 21658387, 23241745). For these reasons, this variant has been classified as Pathogenic.
Comment:
LRRK2: PP1:Strong, PS3, PM2, PM5, PS4:Moderate
Comment:
PP1, PM1, PM5, PS3, PS4
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| LRRK2 Parkinson Disease. | Adam MP | - | 2023 | PMID: 20301387 |
| Clinical Phenotype of LRRK2 R1441C in 2 Chinese Sisters. | Lim SY | Neuro-degenerative diseases | 2020 | PMID: 32580205 |
| Parkinson's disease-associated mutations in the GTPase domain of LRRK2 impair its nucleotide-dependent conformational dynamics. | Wu CX | The Journal of biological chemistry | 2019 | PMID: 30796162 |
| The discovery of LRRK2 p.R1441S, a novel mutation for Parkinson's disease, adds to the complexity of a mutational hotspot. | Mata IF | American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics | 2016 | PMID: 27111571 |
| (R1441C) LRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model. | Weng YH | Experimental neurology | 2016 | PMID: 26363496 |
| Pathogenic LRRK2 mutations, through increased kinase activity, produce enlarged lysosomes with reduced degradative capacity and increase ATP13A2 expression. | Henry AG | Human molecular genetics | 2015 | PMID: 26251043 |
| Glutaredoxin deficiency exacerbates neurodegeneration in C. elegans models of Parkinson's disease. | Johnson WM | Human molecular genetics | 2015 | PMID: 25355420 |
| Disease penetrance of late-onset parkinsonism: a meta-analysis. | Trinh J | JAMA neurology | 2014 | PMID: 25330418 |
| Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations. | Godena VK | Nature communications | 2014 | PMID: 25316291 |
| Conditional expression of Parkinson's disease-related R1441C LRRK2 in midbrain dopaminergic neurons of mice causes nuclear abnormalities without neurodegeneration. | Tsika E | Neurobiology of disease | 2014 | PMID: 25174890 |
| Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations. | Foo JN | Human molecular genetics | 2014 | PMID: 24565865 |
| Genetic screening for the LRRK2 R1441C and G2019S mutations in Parkinsonian patients from Campania. | De Rosa A | Journal of Parkinson's disease | 2014 | PMID: 24496098 |
| Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2 and disrupts its interaction with 14-3-3. | Muda K | Proceedings of the National Academy of Sciences of the United States of America | 2014 | PMID: 24351927 |
| Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations. | Sheng Z | Science translational medicine | 2012 | PMID: 23241745 |
| Phosphorylation of LRRK2 serines 955 and 973 is disrupted by Parkinson's disease mutations and LRRK2 pharmacological inhibition. | Doggett EA | Journal of neurochemistry | 2012 | PMID: 22004453 |
| LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: impairment of the kinase activity by Parkinson's disease-associated mutations. | Ohta E | FEBS letters | 2011 | PMID: 21658387 |
| The LRRK2 R1441C mutation is more frequent than G2019S in Parkinson's disease patients from southern Italy. | Criscuolo C | Movement disorders : official journal of the Movement Disorder Society | 2011 | PMID: 21538529 |
| Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. | Ramonet D | PloS one | 2011 | PMID: 21494637 |
| The R1441C mutation alters the folding properties of the ROC domain of LRRK2. | Li Y | Biochimica et biophysica acta | 2009 | PMID: 19781641 |
| R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. | Tong Y | Proceedings of the National Academy of Sciences of the United States of America | 2009 | PMID: 19667187 |
| Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease. | Haugarvoll K | Neurology | 2008 | PMID: 18337586 |
| Founder mutation p.R1441C in the leucine-rich repeat kinase 2 gene in Belgian Parkinson's disease patients. | Nuytemans K | European journal of human genetics : EJHG | 2008 | PMID: 18197194 |
| Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants. | Li X | Journal of neurochemistry | 2007 | PMID: 17623048 |
| The R1441C mutation of LRRK2 disrupts GTP hydrolysis. | Lewis PA | Biochemical and biophysical research communications | 2007 | PMID: 17442267 |
| Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. | West AB | Human molecular genetics | 2007 | PMID: 17200152 |
| Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. | Greggio E | Neurobiology of disease | 2006 | PMID: 16750377 |
| A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan. | Di Fonzo A | Neurogenetics | 2006 | PMID: 16633828 |
| Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. | West AB | Proceedings of the National Academy of Sciences of the United States of America | 2005 | PMID: 16269541 |
| Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. | Zimprich A | Neuron | 2004 | PMID: 15541309 |
| Western Nebraska family (family D) with autosomal dominant parkinsonism. | Wszolek ZK | Neurology | 1995 | PMID: 7898705 |
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Text-mined citations for rs33939927 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.