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... See more...

Aliases for LRRK2 Gene

Aliases for LRRK2 Gene

  • Leucine Rich Repeat Kinase 2 2 3 5
  • Leucine-Rich Repeat Serine/Threonine-Protein Kinase 2 3 4
  • Dardarin 2 4
  • PARK8 3 4
  • RIPK7 2 3
  • ROCO2 2 3
  • Parkinson Disease (Autosomal Dominant) 8 2
  • Augmented In Rheumatoid Arthritis 17 3
  • DKFZp434H2111 2
  • EC 2.7.11.1 4
  • EC 3.6.5.- 4
  • DARDARIN 3
  • FLJ45829 2
  • AURA17 3
  • LRRK2 5

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, Autosomal Dominant and Hereditary Late-Onset Parkinson Disease. Among its related pathways are Pathways of neurodegeneration - multiple diseases and Signaling by PTK6. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is KSR1.

UniProtKB/Swiss-Prot Summary for LRRK2 Gene

  • Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). 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 (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Independent of its kinase activity, inhibits the proteosomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29212815).

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 CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LRRK2 Gene

Genomics for LRRK2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for LRRK2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J040223 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 296.3 +28.2 28203 5.5 BCLAF1 SP1 ZNF600 ZNF580 ZNF10 ZIC2 ZBTB10 YY1 BCL11A CTCF LRRK2 LRRK2-DT NONHSAG010911.2 LINC02471 MN309549 MUC19
GH12J040197 Enhancer 0.3 Ensembl 250.7 +1.2 1157 0.2 MNT LRRK2 piR-35729-013 LRRK2-DT LINC02471 MUC19
GH12J040216 Enhancer 0.6 FANTOM5 dbSUPER 59.5 +20.4 20371 0.2 ATF2 SPI1 MYC PRDM1 LRRK2 LRRK2-DT LOC105369735 MUC19
GH12J040208 Enhancer 1 FANTOM5 ENCODE dbSUPER 27.9 +12.3 12335 1.8 CTCF TCF7L2 BHLHE40 SPI1 ELF1 IKZF1 NR2F1 NKRF ZNF217 IKZF2 LOC105369735 LRRK2 LINC02471 LRRK2-DT MUC19
GH12J040103 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 9.4 -91.0 -91044 4.6 SP1 ZNF654 ZNF600 IKZF1 ZNF592 NFIC POLR2A NONO CEBPB CTCF SLC2A13 LINC02555 LINC02471 LRRK2 LOC112268095 ABCD2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LRRK2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LRRK2

Top Transcription factor binding sites by QIAGEN in the LRRK2 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • GCNF-2
  • Ik-3
  • Meis-1
  • Meis-1a
  • Meis-1b
  • Nkx2-2
  • STAT5B

Genomic Locations for LRRK2 Gene

Latest Assembly
chr12:40,196,744-40,369,285
(GRCh38/hg38)
Size:
172,542 bases
Orientation:
Plus strand

Previous Assembly
chr12:40,618,799-40,763,087
(GRCh37/hg19 by Entrez Gene)
Size:
144,289 bases
Orientation:
Plus strand

chr12:40,590,546-40,763,087
(GRCh37/hg19 by Ensembl)
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
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homodimer (PubMed:22952686, PubMed:18230735, PubMed:30635421). Interacts with PRKN, PRDX3, and TPCN2 (PubMed:16352719, PubMed:21850687, PubMed:22012985). Interacts with VPS35 and RAB29 (PubMed:23395371). Interacts (via ROC domain) with SEC16A (PubMed:25201882). Interacts with APP; interaction promotes phosphorylation of 'Thr-743' of APP (PubMed:28720718). Interacts with MAPT (PubMed:26014385). Interacts with RAB8A, RAB10, and RAB12 (PubMed:26824392). Interacts with YWHAG; this interaction is dependent on phosphorylation of Ser-910 and either Ser-935 or Ser-1444 (PubMed:28202711). Interacts with SFN; this interaction is dependent on phosphorylation of Ser-910 and/or Ser-935 (PubMed:28202711).

    Three dimensional structures from OCA and Proteopedia for LRRK2 Gene

neXtProt entry for LRRK2 Gene

Post-translational modifications for LRRK2 Gene

  • Autophosphorylated (PubMed:28202711, PubMed:28720718, PubMed:29127255, PubMed:29212815, PubMed:30635421). Phosphorylation of Ser-910 and either Ser-935 or Ser-1444 facilitates interaction with YWHAG (PubMed:28202711). Phosphorylation of Ser-910 and/or Ser-935 facilitates interaction with SFN (PubMed:28202711).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibodies for research

  • Abcam antibodies for LRRK2

No data available for DME Specific Peptides for LRRK2 Gene

Domains & Families for LRRK2 Gene

Gene Families for LRRK2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for LRRK2 Gene

GenScript: Design optimal peptide antigens:
  • Augmented in rheumatoid arthritis 17 (A2VED2_HUMAN)
  • Dardarin (LRRK2_HUMAN)
  • Leucine-rich repeat kinase 2 (Q17RV3_HUMAN)

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 (PubMed:24687852). It also mediates homodimerization and regulates kinase activity (PubMed:30635421).
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Domain:
  • The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins (PubMed:24687852). It also mediates homodimerization and regulates kinase activity (PubMed:30635421).
  • The Roc domain mediates homodimerization and regulates kinase activity.
Family:
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
genes like me logo Genes that share domains with LRRK2: view

Function for LRRK2 Gene

Molecular function for LRRK2 Gene

UniProtKB/Swiss-Prot Function:
Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). 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 (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Independent of its kinase activity, inhibits the proteosomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29212815).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29212815};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Kinase activity is regulated by the GTPase activity of the ROC domain (PubMed:29212815, PubMed:18230735). GTP-bound LLRK2 kinase activity is stimulated by RAB29 (PubMed:29212815). Inhibited by small molecule inhibitor MLi-2 (PubMed:26824392, PubMed:29127255).

Enzyme Numbers (IUBMB) for LRRK2 Gene

Phenotypes From GWAS Catalog 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:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding IMP 28720718
GO:0003779 actin binding IPI 21307259
GO:0003924 GTPase activity IDA 21048939
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:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LRRK2

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

Cytoplasmic vesicle. Perikaryon. Golgi apparatus membrane. Peripheral membrane protein. Cell projection, axon. Cell projection, dendrite. Endoplasmic reticulum membrane. Peripheral membrane protein. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane. Endosome. Lysosome. Mitochondrion outer membrane. Peripheral membrane protein. Note=Colocalized with RAB29 along tubular structures emerging from Golgi apparatus (PubMed:23395371). Localizes to endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER) (PubMed:25201882). {ECO:0000269 PubMed:23395371, ECO:0000269 PubMed:25201882}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LRRK2 gene
Compartment Confidence
mitochondrion 5
nucleus 5
endoplasmic reticulum 5
cytosol 5
lysosome 5
plasma membrane 4
extracellular 4
endosome 4
golgi apparatus 4
cytoskeleton 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for LRRK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005615 extracellular space HDA 22664934
GO:0005737 cytoplasm IEA,IMP 26014385
GO:0005739 mitochondrion IEA,IDA 21850687
GO:0005741 mitochondrial outer membrane IBA,ISS --
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:0000187 activation of MAPK activity IMP 21857923
GO:0001933 negative regulation of protein phosphorylation IEA,ISS --
GO:0001934 positive regulation of protein phosphorylation IDA,IMP 20659558
genes like me logo Genes that share ontologies with LRRK2: view

Drugs & Compounds for LRRK2 Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Guanosine triphosphate Experimental Pharma 0
Leucine Investigational Nutra 184
ATP Investigational Nutra 0
CZC 54252 hydrochloride Pharma Potent LRRK2 inhibitor; neuroprotective 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
58-64-0
MLi-2
1627091-47-7

(5) 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
MLi-2 Potent and selective LRRK2 inhibitor 1627091-47-7
PF 06447475 Potent LRRK2 inhibitor; neuroprotective 1527473-33-1

(9) ApexBio Compounds for LRRK2 Gene

Compound Action Cas Number
CZC 54252 hydrochloride 1191911-27-9
CZC-25146 LRRK2 inhibitor 1191911-26-8
GNE0877 Potent and selective LRRK2 inhibitor 1374828-69-9
GNE-7915 Potent and selective LRRK2 inhibitor 1351761-44-8
GNE-9605 1536200-31-3
GSK2578215A 1285515-21-0
HG-10-102-01 LRRK2 inhibitor 1351758-81-0
LRRK2-IN-1 LRRK2 inhibitor,cell-permeable and ATP competitive 1234480-84-2
PF-06447475 1527473-33-1
genes like me logo Genes that share compounds with LRRK2: view

Drug products for research

Transcripts for LRRK2 Gene

mRNA/cDNA for LRRK2 Gene

1 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
21 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LRRK2

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

No ASD Table

Relevant External Links for LRRK2 Gene

GeneLoc Exon Structure for
LRRK2

Expression for LRRK2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE 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 and MOPED for LRRK2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LRRK2

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 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 in neutrophils (at protein level) (PubMed:29127255). Expressed in the brain. 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.

Evidence on tissue expression from TISSUES for LRRK2 Gene

  • Nervous system(4.6)
  • Liver(4.4)
  • Blood(2.8)
  • Kidney(2.8)
  • Lung(2.8)
  • Spleen(2.5)
  • Muscle(2.4)
  • Adrenal gland(2.4)
  • Skin(2.3)
  • Heart(2.3)
  • Intestine(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for LRRK2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • ear
  • eye
  • eyelid
  • face
  • head
  • mouth
  • olfactory bulb
  • pharynx
Thorax:
  • diaphragm
  • esophagus
  • heart
  • lung
Abdomen:
  • stomach
Pelvis:
  • urethra
  • urinary bladder
Limb:
  • foot
  • hand
  • lower limb
  • upper limb
General:
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with LRRK2: view

Primer products for research

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 29 30
  • 99.49 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 97 (a)
OneToMany
-- 30
  • 85 (a)
OneToMany
-- 30
  • 69 (a)
OneToMany
Dog
(Canis familiaris)
Mammalia LRRK2 29 30
  • 91.08 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia LRRK2 29 30
  • 90.39 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Lrrk2 29 16 30
  • 83.27 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Lrrk2 29
  • 83 (n)
Oppossum
(Monodelphis domestica)
Mammalia LRRK2 30
  • 78 (a)
OneToOne
Chicken
(Gallus gallus)
Aves LRRK2 29 30
  • 73.11 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia LRRK2 30
  • 72 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia lrrk2 29
  • 65.86 (n)
Zebrafish
(Danio rerio)
Actinopterygii lrrk2 29 30
  • 55.71 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Lrrk 30
  • 18 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea lrk-1 30
  • 16 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 35 (a)
OneToOne
Species where no ortholog for LRRK2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for LRRK2: view image
Alliance of Genome Resources:
Additional Orthologs for LRRK2

Paralogs for LRRK2 Gene

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

  • LRRK2_HUMAN
  • C9JBF0_HUMAN
  • E9PC85_HUMAN
  • H7C3B6_HUMAN
  • Q17RV3_HUMAN
genes like me logo Genes that share paralogs with LRRK2: view

Variants for LRRK2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LRRK2 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
1007154 Uncertain Significance: Parkinson disease 8, autosomal dominant 40,310,581(+) G/A
NM_198578.4(LRRK2):c.4468G>A (p.Ala1490Thr)
MISSENSE
1011348 Uncertain Significance: Parkinson disease 8, autosomal dominant 40,354,311(+) A/G
NM_198578.4(LRRK2):c.6589A>G (p.Ser2197Gly)
MISSENSE
1015545 Uncertain Significance: Parkinson disease 8, autosomal dominant 40,305,908(+) G/A
NM_198578.4(LRRK2):c.3901G>A (p.Glu1301Lys)
MISSENSE
1015784 Uncertain Significance: Parkinson disease 8, autosomal dominant 40,298,330(+) A/C
NM_198578.4(LRRK2):c.3184A>C (p.Asn1062His)
MISSENSE
1042541 Uncertain Significance: Parkinson disease 8, autosomal dominant 40,240,516(+) A/G
NM_198578.4(LRRK2):c.605A>G (p.Asn202Ser)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for LRRK2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

Variant ID Type Subtype PubMed ID
dgv186e201 CNV deletion 23290073
esv1215291 CNV deletion 17803354
esv2432211 CNV deletion 19546169
esv2454181 CNV insertion 19546169
esv2745783 CNV deletion 23290073
esv2745786 CNV deletion 23290073
esv2745787 CNV deletion 23290073
esv3304542 CNV mobile element insertion 20981092
esv3309569 CNV mobile element insertion 20981092
esv3399810 CNV insertion 20981092
esv3437009 CNV insertion 20981092
nsv1042967 CNV gain 25217958
nsv1048258 CNV gain 25217958
nsv1069657 CNV deletion 25765185
nsv1113477 CNV deletion 24896259
nsv1124724 CNV deletion 24896259
nsv1150510 CNV insertion 26484159
nsv558598 CNV loss 21841781
nsv819273 CNV gain 19587683
nsv832377 CNV gain 17160897

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)

Additional Variant Information for LRRK2 Gene

Human Gene Mutation Database (HGMD)
LRRK2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
LRRK2
Leiden Open Variation Database (LOVD)
LRRK2

SNP Genotyping and Copy Number Assays for research

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

Disorders for LRRK2 Gene

MalaCards: The human disease database

(61) MalaCards diseases for LRRK2 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- 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:16269541, ECO:0000269 PubMed:16272164, ECO:0000269 PubMed:16272257, ECO:0000269 PubMed:16298482, ECO:0000269 PubMed:16321986, ECO:0000269 PubMed:16333314, ECO:0000269 PubMed:16533964, ECO:0000269 PubMed:17114044, ECO:0000269 PubMed:18213618, ECO:0000269 PubMed:21850687, ECO:0000269 PubMed:22956510, ECO:0000269 PubMed:23395371, ECO:0000269 PubMed:25201882, ECO:0000269 PubMed:26824392, ECO:0000269 PubMed:28202711, ECO:0000269 PubMed:28720718, ECO:0000269 PubMed:29125462, ECO:0000269 PubMed:29127255, ECO:0000269 PubMed:29212815, ECO:0000269 PubMed:30398148, ECO:0000269 PubMed:30635421}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for LRRK2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
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 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance. (PMID: 16533964) Gaig C … Tolosa E (Archives of neurology 2006) 3 4 22 40 72
  2. A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations. (PMID: 16157909) Zabetian CP … Griffith A (Neurology 2005) 3 4 22 40 72
  3. Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease. (PMID: 18704525) Choi JM … Kim YJ (Neurogenetics 2008) 3 22 40 72
  4. Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls. (PMID: 18213618) Paisán-Ruíz C … Singleton AB (Human mutation 2008) 3 4 22 40
  5. LRRK2 exon 41 mutations in sporadic Parkinson disease in Europeans. (PMID: 17353388) Lesage S … Vérin M (Archives of neurology 2007) 3 22 40 72

Products for LRRK2 Gene

Sources for LRRK2 Gene