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Aliases for LRRK2 Gene

Aliases for LRRK2 Gene

  • Leucine-Rich Repeat Kinase 2 2 3
  • PARK8 3 4 6
  • DARDARIN 3 4
  • Leucine-Rich Repeat Serine/Threonine-Protein Kinase 2 3
  • 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 lrrk2-related parkinson disease. Among its related pathways are MAPK signaling pathway and Neuroscience. GO annotations related to this gene include protein homodimerization activity and GTP binding. 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. LRRK2 is encoded by the PARK8 gene

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

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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

No data available for DME Specific Peptides for LRRK2 Gene

Domains for LRRK2 Gene

Gene Families for LRRK2 Gene

Suggested Antigen Peptide Sequences for LRRK2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q5S007

UniProtKB/Swiss-Prot:

LRRK2_HUMAN :
  • Q5S007
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:0000149 SNARE binding IPI 21307259
GO:0001948 glycoprotein binding IPI 21307259
GO:0003779 actin binding IPI 21307259
GO:0003924 GTPase activity IDA 21048939
GO:0004672 protein kinase activity IDA 16269541
genes like me logo Genes that share ontologies with LRRK2: view
genes like me logo Genes that share phenotypes with LRRK2: view

Animal Models for LRRK2 Gene

MGI Knock Outs for LRRK2:

miRNA for LRRK2 Gene

miRTarBase miRNAs that target LRRK2

No data available for Transcription Factor Targeting 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
mitochondrion 5
nucleus 3
cytoskeleton 2
lysosome 2
plasma membrane 2
vacuole 2
cytosol 1
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for LRRK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IDA 22664934
GO:0005622 intracellular --
GO:0005737 cytoplasm IDA 16321986
GO:0005739 mitochondrion IDA 21850687
GO:0005741 mitochondrial outer membrane ISS --
genes like me logo Genes that share ontologies with LRRK2: view

Pathways for LRRK2 Gene

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

Pathways by source for LRRK2 Gene

1 Cell Signaling Technology pathway for LRRK2 Gene
1 KEGG pathway for LRRK2 Gene

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:0000187 activation of MAPK activity IMP 21857923
GO:0001933 negative regulation of protein phosphorylation ISS --
GO:0001934 positive regulation of protein phosphorylation IMP 20659558
genes like me logo Genes that share ontologies with LRRK2: view

Compounds for LRRK2 Gene

(3) Tocris Compounds for LRRK2 Gene

Compound Action Cas Number
CZC 54252 hydrochloride Potent LRRK2 inhibitor; neuroprotective [1191911-27-9]
GSK2578215A Potent, selective LRRK2 inhibitor; brain penetrant [1285515-21-0]
LRRK2-IN-1 Potent and selective LRRK2 inhibitor [1234480-84-2]

(3) HMDB Compounds for LRRK2 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Guanosine triphosphate
  • 5'-GTP
86-01-1

(4) Novoseek inferred chemical compound relationships for LRRK2 Gene

Compound -log(P) Hits PubMed IDs
levodopa 35.6 2
gtp 35.3 9
dopamine 26.1 6
lipid 1.83 4
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 (12.1) and Lung (5.5).

Integrated Proteomics: protein expression 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 expressions with LRRK2: view

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 35
  • 90.39 (n)
  • 90.86 (a)
LRRK2 36
  • 91 (a)
OneToOne
dog
(Canis familiaris)
Mammalia LRRK2 35
  • 91.08 (n)
  • 91.77 (a)
LRRK2 36
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Lrrk2 35
  • 83.27 (n)
  • 86.69 (a)
Lrrk2 16
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 35
  • 55.71 (n)
  • 49.76 (a)
lrrk2 36
  • 47 (a)
OneToOne
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

Selected 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 MAF
rs715402 -- 40,337,412(+) TTTCT(A/G)TATGT intron-variant
rs715403 -- 40,337,381(+) ATAAA(A/C)CTTAT intron-variant
rs721709 -- 40,315,611(+) AATGA(A/T)GGCTT intron-variant
rs721710 Uncertain significance, Parkinson disease 8 (PARK8) 40,315,266(+) CTTTG(A/T)GGAAC missense, reference
rs721711 -- 40,315,526(+) ATACA(A/G)ATGTT intron-variant

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

Relevant External Links for LRRK2 Gene

HapMap Linkage Disequilibrium report
LRRK2
Human Gene Mutation Database (HGMD)
LRRK2
Locus Specific Mutation Databases (LSDB)
LRRK2

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

Disorders for LRRK2 Gene

(1) OMIM Diseases for LRRK2 Gene (609007)

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.

(18) Novoseek inferred disease relationships for LRRK2 Gene

Disease -log(P) Hits PubMed IDs
parkinson disease, autosomal dominant 95 27
parkinson disease 91.5 176
autosomal dominant parkinsonism 88.3 8
parkinsonism 87.1 62
lewy body disease 74.9 5

Relevant External Links for LRRK2

GeneTests
LRRK2
GeneReviews
LRRK2
Genetic Association Database (GAD)
LRRK2
Human Genome Epidemiology (HuGE) Navigator
LRRK2
genes like me logo Genes that share disorders with LRRK2: view

Publications for LRRK2 Gene

  1. A common LRRK2 mutation in idiopathic Parkinson's disease. (PMID: 15680457) Gilks W.P. … Wood N.W. (Lancet 2005) 3 4 23 48
  2. Clinical features of LRRK2-associated Parkinson's disease in central Norway. (PMID: 15852371) Aasly J.O. … Farrer M.J. (Ann. Neurol. 2005) 3 4 23 48
  3. LRRK2 mutations are not common in Alzheimer's disease. (PMID: 16087219) Toft M. … Farrer M.J. (Mech. Ageing Dev. 2005) 3 4 23 48
  4. 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
  5. A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations. (PMID: 16157909) Zabetian C.P. … Griffith A. (Neurology 2005) 3 4 23 48

Products for LRRK2 Gene

  • Addgene plasmids for LRRK2

Sources for LRRK2 Gene

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