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Aliases for LRRK2 Gene

Aliases for LRRK2 Gene

  • Leucine-Rich Repeat Kinase 2 2 3 5
  • DARDARIN 3 4
  • PARK8 3 4
  • Parkinson Disease (Autosomal Dominant) 8 2
  • Augmented In Rheumatoid Arthritis 17 3
  • EC 2.7.11.1 4
  • AURA17 3
  • RIPK7 3
  • ROCO2 3

External Ids for LRRK2 Gene

Previous HGNC Symbols for LRRK2 Gene

  • PARK8

Previous GeneCards Identifiers for LRRK2 Gene

  • GC00U914055
  • GC12P038908
  • GC12P040590
  • GC12P037646

Summaries for LRRK2 Gene

Entrez Gene Summary for LRRK2 Gene

  • This gene is a member of the leucine-rich repeat kinase family and encodes a protein with an ankryin repeat region, a leucine-rich repeat (LRR) domain, a kinase domain, a DFG-like motif, a RAS domain, a GTPase domain, a MLK-like domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. Mutations in this gene have been associated with Parkinson disease-8. [provided by RefSeq, Jul 2008]

GeneCards Summary for LRRK2 Gene

LRRK2 (Leucine-Rich Repeat Kinase 2) is a Protein Coding gene. Diseases associated with LRRK2 include parkinson disease 8 and parkinson disease, late-onset. Among its related pathways are Signaling by GPCR and MAPK signaling pathway. GO annotations related to this gene include protein homodimerization activity and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is LRRK1.

UniProtKB/Swiss-Prot for LRRK2 Gene

  • Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease.

Tocris Summary for LRRK2 Gene

  • Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin, is a large multidomain protein kinase that includes leucine-rich repeats and a GTPase domain. Mutations in LRRK2 are commonly associated with late-onset Parkinson's disease (PD).

Gene Wiki entry for LRRK2 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for LRRK2 Gene

Genomics for LRRK2 Gene

Regulatory Elements for LRRK2 Gene

Genomic Location for LRRK2 Gene

Chromosome:
12
Start:
40,196,744 bp from pter
End:
40,369,285 bp from pter
Size:
172,542 bases
Orientation:
Plus strand

Genomic View for LRRK2 Gene

Genes around LRRK2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LRRK2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LRRK2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LRRK2 Gene

Proteins for LRRK2 Gene

  • Protein details for LRRK2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q5S007-LRRK2_HUMAN
    Recommended name:
    Leucine-rich repeat serine/threonine-protein kinase 2
    Protein Accession:
    Q5S007
    Secondary Accessions:
    • A6NJU2
    • Q6ZS50
    • Q8NCX9

    Protein attributes for LRRK2 Gene

    Size:
    2527 amino acids
    Molecular mass:
    286103 Da
    Quaternary structure:
    • Homodimer. Interacts with PARK2, PRDX3, RAB29, TPCN2 and VPS35.

    Three dimensional structures from OCA and Proteopedia for LRRK2 Gene

neXtProt entry for LRRK2 Gene

Proteomics data for LRRK2 Gene at MOPED

Post-translational modifications for LRRK2 Gene

Other Protein References for LRRK2 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for LRRK2 (LRRK2)

No data available for DME Specific Peptides for LRRK2 Gene

Domains & Families for LRRK2 Gene

Gene Families for LRRK2 Gene

Suggested Antigen Peptide Sequences for LRRK2 Gene

Graphical View of Domain Structure for InterPro Entry

Q5S007

UniProtKB/Swiss-Prot:

LRRK2_HUMAN :
  • The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins.
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
  • Contains 12 LRR (leucine-rich) repeats.
Domain:
  • The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins.
  • The Roc domain mediates homodimerization and regulates kinase activity.
  • Contains 1 protein kinase domain.
  • Contains 1 Roc domain.
Family:
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Similarity:
  • Contains 12 LRR (leucine-rich) repeats.
  • Contains 7 WD repeats.
genes like me logo Genes that share domains with LRRK2: view

Function for LRRK2 Gene

Molecular function for LRRK2 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot Function:
Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease.

Enzyme Numbers (IUBMB) for LRRK2 Gene

Gene Ontology (GO) - Molecular Function for LRRK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005524 ATP binding IEA --
GO:0030276 clathrin binding IPI 21307259
GO:0044325 ion channel binding IPI 21370995
genes like me logo Genes that share ontologies with LRRK2: view
genes like me logo Genes that share phenotypes with LRRK2: view

Human Phenotype Ontology for LRRK2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for LRRK2 Gene

MGI Knock Outs for LRRK2:

Animal Model Products

miRNA for LRRK2 Gene

No data available for Transcription Factor Targets and HOMER Transcription for LRRK2 Gene

Localization for LRRK2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LRRK2 Gene

Membrane; Peripheral membrane protein. Cytoplasm. Perikaryon. Mitochondrion. Golgi apparatus. Cell projection, axon. Cell projection, dendrite. Endoplasmic reticulum. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Peripheral membrane protein; Cytoplasmic side. Endosome. Lysosome. Mitochondrion outer membrane. Mitochondrion inner membrane. Mitochondrion matrix. Note=Predominantly associated with intracytoplasmic vesicular and membranous structures (By similarity). Localized in the cytoplasm and associated with cellular membrane structures. Predominantly associated with the mitochondrial outer membrane of the mitochondria. Colocalized with RAB29 along tubular structures emerging from Golgi apparatus. Localizes in intracytoplasmic punctate structures of neuronal perikarya and dendritic and axonal processes. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for LRRK2 Gene COMPARTMENTS Subcellular localization image for LRRK2 gene
Compartment Confidence
cytosol 5
endoplasmic reticulum 5
endosome 5
extracellular 5
golgi apparatus 5
lysosome 5
mitochondrion 5
vacuole 5
plasma membrane 4
nucleus 3
cytoskeleton 2

Gene Ontology (GO) - Cellular Components for LRRK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IDA 22664934
GO:0005739 mitochondrion IDA 21850687
GO:0005759 mitochondrial matrix IEA,ISS --
GO:0005829 cytosol IDA,TAS --
GO:0005901 caveola IDA 19640926
genes like me logo Genes that share ontologies with LRRK2: view

Pathways & Interactions for LRRK2 Gene

genes like me logo Genes that share pathways with LRRK2: view

Pathways by source for LRRK2 Gene

SIGNOR curated interactions for LRRK2 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for LRRK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IDA 17200152
GO:0000186 activation of MAPKK activity IDA 19302196
GO:0001933 negative regulation of protein phosphorylation IEA,ISS --
GO:0001934 positive regulation of protein phosphorylation IMP 20659558
GO:0006468 protein phosphorylation IEA,IMP 23628791
genes like me logo Genes that share ontologies with LRRK2: view

Drugs & Compounds for LRRK2 Gene

(11) Drugs for LRRK2 Gene - From: Novoseek, HMDB, DGIdb, ApexBio, and ClinicalTrials

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
Guanosine triphosphate Experimental Pharma 0
Cola Nutra 1768
leucine Nutra 103
GNE0877 Pharma Potent and selective LRRK2 inhibitor 0

(7) Additional Compounds for LRRK2 Gene - From: HMDB, Novoseek, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
CZC 54252 hydrochloride
1191911-27-9
GSK2578215A
1285515-21-0
LRRK2-IN-1
1234480-84-2
PF 06447475
1527473-33-1
genes like me logo Genes that share compounds with LRRK2: view

Transcripts for LRRK2 Gene

Unigene Clusters for LRRK2 Gene

Leucine-rich repeat kinase 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for LRRK2 Gene

No ASD Table

Relevant External Links for LRRK2 Gene

GeneLoc Exon Structure for
LRRK2
ECgene alternative splicing isoforms for
LRRK2

Expression for LRRK2 Gene

mRNA expression in normal human tissues for LRRK2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for LRRK2 Gene

This gene is overexpressed in Whole Blood (x12.1) and Lung (x5.5).

Protein differential expression in normal tissues from HIPED for LRRK2 Gene

This gene is overexpressed in Adrenal (45.6) and Kidney (10.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for LRRK2 Gene



SOURCE GeneReport for Unigene cluster for LRRK2 Gene Hs.187636

mRNA Expression by UniProt/SwissProt for LRRK2 Gene

Q5S007-LRRK2_HUMAN
Tissue specificity: Expressed in the brain. Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level). Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas.
genes like me logo Genes that share expression patterns with LRRK2: view

Primer Products

In Situ Assay Products

No data available for Protein tissue co-expression partners for LRRK2 Gene

Orthologs for LRRK2 Gene

This gene was present in the common ancestor of animals.

Orthologs for LRRK2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LRRK2 35
  • 99.49 (n)
  • 99.21 (a)
LRRK2 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia LRRK2 36
  • 91 (a)
OneToOne
LRRK2 35
  • 90.39 (n)
  • 90.86 (a)
dog
(Canis familiaris)
Mammalia LRRK2 35
  • 91.08 (n)
  • 91.77 (a)
LRRK2 36
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Lrrk2 16
Lrrk2 35
  • 83.27 (n)
  • 86.69 (a)
Lrrk2 36
  • 87 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia LRRK2 36
  • 78 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 97 (a)
OneToMany
-- 36
  • 85 (a)
OneToMany
-- 36
  • 69 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Lrrk2 35
  • 83 (n)
  • 86.65 (a)
chicken
(Gallus gallus)
Aves LRRK2 35
  • 73.11 (n)
  • 72.73 (a)
LRRK2 36
  • 71 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia LRRK2 36
  • 72 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia lrrk2 35
  • 65.86 (n)
  • 63.5 (a)
zebrafish
(Danio rerio)
Actinopterygii lrrk2 36
  • 47 (a)
OneToOne
lrrk2 35
  • 55.71 (n)
  • 49.76 (a)
fruit fly
(Drosophila melanogaster)
Insecta Lrrk 36
  • 18 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea lrk-1 36
  • 16 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 35 (a)
OneToOne
Species with no ortholog for LRRK2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for LRRK2 Gene

ENSEMBL:
Gene Tree for LRRK2 (if available)
TreeFam:
Gene Tree for LRRK2 (if available)

Paralogs for LRRK2 Gene

Paralogs for LRRK2 Gene

(3) SIMAP similar genes for LRRK2 Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with LRRK2: view

Variants for LRRK2 Gene

Sequence variations from dbSNP and Humsavar for LRRK2 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type
VAR_040678 An ovarian mucinous carcinoma sample
VAR_040679 An ovarian serous carcinoma sample
rs28365226 - 40,308,632(+) AAAGA(A/C)TGGCC downstream-variant-500B, reference, missense
rs56108242 - 40,240,594(+) GCATT(C/G)TTTAC reference, missense
VAR_054741 Parkinson disease 8 (PARK8)

Structural Variations from Database of Genomic Variants (DGV) for LRRK2 Gene

Variant ID Type Subtype PubMed ID
dgv205e201 CNV Deletion 23290073
esv2745783 CNV Deletion 23290073
esv2745786 CNV Deletion 23290073
esv1215291 CNV Deletion 17803354
esv2745787 CNV Deletion 23290073
nsv819273 CNV Gain 19587683
esv2454181 CNV Insertion 19546169
esv273841 CNV Insertion 20981092
esv268820 CNV Insertion 20981092
nsv832377 CNV Gain 17160897
nsv899032 CNV Loss 21882294
esv2432211 CNV Deletion 19546169
nsv899033 CNV Loss 21882294
esv274613 CNV Insertion 20981092

Variation tolerance for LRRK2 Gene

Residual Variation Intolerance Score: 6.56% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.25; 92.50% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for LRRK2 Gene

HapMap Linkage Disequilibrium report
LRRK2
Human Gene Mutation Database (HGMD)
LRRK2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LRRK2 Gene

Disorders for LRRK2 Gene

MalaCards: The human disease database

(26) MalaCards diseases for LRRK2 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
parkinson disease 8
  • autosomal dominant parkinson disease 8
parkinson disease, late-onset
  • parkinson disease
lrrk2-related parkinson disease
  • lrrk2-associated parkinson disease
hereditary late-onset parkinson disease
  • autosomal dominant late-onset parkinson disease
essential tremor
  • benign essential tremor
- elite association - COSMIC cancer census association via MalaCards
Search LRRK2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

LRRK2_HUMAN
  • Parkinson disease 8 (PARK8) [MIM:607060]: A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients. {ECO:0000269 PubMed:15541308, ECO:0000269 PubMed:15541309, ECO:0000269 PubMed:15680455, ECO:0000269 PubMed:15680456, ECO:0000269 PubMed:15680457, ECO:0000269 PubMed:15726496, ECO:0000269 PubMed:15732108, ECO:0000269 PubMed:15811454, ECO:0000269 PubMed:15852371, ECO:0000269 PubMed:15880653, ECO:0000269 PubMed:15925109, ECO:0000269 PubMed:15929036, ECO:0000269 PubMed:16102999, ECO:0000269 PubMed:16157901, ECO:0000269 PubMed:16157908, ECO:0000269 PubMed:16157909, ECO:0000269 PubMed:16172858, ECO:0000269 PubMed:16240353, ECO:0000269 PubMed:16247070, ECO:0000269 PubMed:16250030, ECO:0000269 PubMed:16251215, ECO:0000269 PubMed:16272164, ECO:0000269 PubMed:16272257, ECO:0000269 PubMed:16298482, ECO:0000269 PubMed:16333314, ECO:0000269 PubMed:16533964, ECO:0000269 PubMed:18213618, ECO:0000269 PubMed:22956510}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for LRRK2

Genetic Association Database (GAD)
LRRK2
Human Genome Epidemiology (HuGE) Navigator
LRRK2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
LRRK2
genes like me logo Genes that share disorders with LRRK2: view

No data available for Genatlas for LRRK2 Gene

Publications for LRRK2 Gene

  1. LRRK2 gene in Parkinson disease: mutation analysis and case control association study. (PMID: 16157901) Paisan-Ruiz C. … Rogaeva E. (Neurology 2005) 3 4 23 48 67
  2. Mutations in the Parkinson's disease genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), are not associated with essential tremor. (PMID: 19527940) Clark L.N. … Louis E.D. (Parkinsonism Relat. Disord. 2010) 3 23
  3. A comparative study of LRRK2, PINK1 and genetically undefined familial Parkinson's disease. (PMID: 19726410) Nishioka K. … Hentati F. (J. Neurol. Neurosurg. Psychiatr. 2010) 3 23
  4. GTPase activity plays a key role in the pathobiology of LRRK2. (PMID: 20386743) Xiong Y. … Moore D.J. (PLoS Genet. 2010) 3 23
  5. Leucine-rich repeat kinase 2 gene-associated disease: redefining genotype-phenotype correlation. (PMID: 20197701) Wider C. … Wszolek Z.K. (Neurodegener Dis 2010) 3 23

Products for LRRK2 Gene

Sources for LRRK2 Gene

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