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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

LRRK2 Gene

protein-coding GIFtS: 66
GCID: GC12P040590

leucine-rich repeat kinase 2

(Previous name: Parkinson disease (autosomal dominant) 8 )
(Previous symbol: PARK8)

Explore 31 diseases affiliated with
LRRK2 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Leucine-Rich Repeat Kinase 2¹ ²		AURA17²
PARK8¹ ² ³ ⁵		DARDARIN²
RIPK7¹ ²		Augmented In Rheumatoid Arthritis 17²
ROCO2¹ ²		Leucine-Rich Repeat Serine/Threonine-Protein Kinase 2²
DKFZp434H2111¹		Dardarin³
FLJ45829¹		EC 2.7.11.1³
Parkinson Disease (Autosomal Dominant) 8¹

External Ids:	HGNC: 18618¹	Entrez Gene: 120892²	Ensembl: ENSG00000188906⁷	OMIM: 609007⁵	UniProtKB: Q5S007³

Export aliases for LRRK2 gene to outside databases

Previous GC identifers: GC00U914055 GC12P038908 GC12P037646

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for LRRK2:

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)

UniProtKB/Swiss-Prot: LRRK2_HUMAN, Q5S007

Function: May play a role in the phosphorylation of proteins central to Parkinson disease. Phosphorylates PRDX3. May

also have GTPase activity. 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

summary for LRRK2:

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. Autosomal dominant

missense mutations in LRRK2 are commonly associated with late-onset Parkinson's disease (PD); they are also

evident in a smaller percentage of familial Parkinson's disease cases, of which they are the most common

cause. The discovery of LRRK2 mutations helped strengthen a genetic link to Parkinson's disease, which had

previously been obscured by unusual inheritance patterns - in particular, incomplete/decreased penetrance

and variable age of onset. Mutations associated with PD have been isolated within the enzymatic domains of

LRRK2, namely its kinase and GTPase domains. The most frequent mutation is a substitution of the Gly2019

residue in the kinase domain with a serine residue, resulting in a kinase that exhibits 2- to 3-fold greater

catalytic activity. Pathogenic mutations within the Roc (Ras of complex) GTPase domain and COR

(carboxy-terminal of Roc) sequence have been shown to decrease GTPase activity, which is thought to

counteract LRRK2 activity and restore it to basal levels. Inhibitors of LRRK2 kinase activity have therefore

been of therapeutic interest in the treatment of LRRK2-linked PD. LRRK2 also contains protein-protein

interaction domains. Proteins thought to interact with LRRK2 include dishevelled proteins, MAPK kinase 6

(MKK6) and 14-3-3 proteins. Studies have shown that certain members of the 14-3-3 family bind and influence

the cytoplasmic localization of LRRK2. PD-associated mutants and a truncated form of LRRK2 show a decreased

ability to bind 14-3-3, suggesting that this interaction is important in the pathogenesis of PD.

Gene Wiki entry for LRRK2

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000012.11 NC_018923.1 NT_029419.12

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the LRRK2 gene promoter:
STAT5B AP-1 Nkx2-2 ATF-2 Ik-3 Meis-1b c-Jun Meis-1a GCNF-2 Meis-1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: LRRK2 promoter sequence

Search SABiosciences Chromatin IP Primers for LRRK2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat LRRK2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12q12 Ensembl cytogenetic band: 12q12 HGNC cytogenetic band: 12q12

LRRK2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
LRRK2 gene location

GeneLoc information about chromosome 12 GeneLoc Exon Structure

GeneLoc location for GC12P040590: view genomic region (about GC identifiers)

Start:	40,590,546 bp from pter	End:	40,763,087 bp from pter
Size:	172,542 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: LRRK2_HUMAN, Q5S007 (See protein sequence)

Recommended Name: Leucine-rich repeat serine/threonine-protein kinase 2

Size: 2527 amino acids; 286103 Da

Subunit: Homodimer. Interacts with PARK2. Interacts with PRDX3. Interacts with TPCN2

Subcellular location: Cytoplasm. Membrane; Peripheral membrane protein. Mitochondrion. Note=Localized in the cytoplasm

and associated with cellular membrane structures. Associates with the mitochondrial outer membrane

2 PDB 3D structures from and Proteopedia for LRRK2:

2ZEJ (3D)

3D6T (3D)

Secondary accessions: A6NJU2 Q6ZS50 Q8NCX9

Explore the universe of human proteins at neXtProt for LRRK2: NX_Q5S007

Post-translational modifications:

Autophosphorylated¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q5S007

LRRK2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_940980.3

ENSEMBL proteins:

ENSP00000398726 ENSP00000341930 ENSP00000298910 ENSP00000410821

Human Recombinant Protein Products for LRRK2:

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	Novus Biologicals LRRK2 Proteins
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	Browse ProSpec Recombinant Proteins
	Uscn Proteins for LRRK2

Gene Ontology (GO): 5/11 cellular component terms (GO ID links to tree view) (see all 11): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005622	intracellular	--	--
GO:0005737	cytoplasm	IDA	16352719
GO:0005739	mitochondrion	IDA	--
GO:0005802	trans-Golgi network	IEA	--
GO:0005886	plasma membrane	IEA	--

LRRK2 for ontologies About GeneDecksing

LRRK2 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of LRRK2
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	Cell Signaling Technology (CST) Antibodies for LRRK2
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	Uscn Antibodies for LRRK2
	ThermoFisher Antibody for LRRK2

Assay Products for LRRK2:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
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	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for LRRK2

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

LRRK2 for domains About GeneDecksing

5/17 InterPro domains/families (see all 17):

IPR017441 Protein_kinase_ATP_BS

IPR011989 ARM-like

IPR001611 Leu-rich_rpt

IPR025875 Leu-rich_rpt_4

IPR013684 MIRO-like

Graphical View of Domain Structure for InterPro Entry Q5S007

ProtoNet protein and cluster: Q5S007

2 Blocks protein families:

IPB000408 Regulator of chromosome condensation

IPB013684 Miro-like

UniProtKB/Swiss-Prot: LRRK2_HUMAN, Q5S007

Similarity: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family

Similarity: Contains 12 LRR (leucine-rich) repeats

Similarity: Contains 1 protein kinase domain

Similarity: Contains 1 Roc domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: LRRK2_HUMAN, Q5S007

Function: May play a role in the phosphorylation of proteins central to Parkinson disease. Phosphorylates PRDX3. May

also have GTPase activity. 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

Catalytic activity: ATP + a protein = ADP + a phosphoprotein

Enzyme Number (IUBMB): EC 2.7.11.1¹

Gene Ontology (GO): 5/14 molecular function terms (GO ID links to tree view) (see all 14): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003924	GTPase activity	IDA	--
GO:0004672	protein kinase activity	IDA	--
GO:0004674	protein serine/threonine kinase activity	IDA	--
GO:0004708	MAP kinase kinase activity	IDA	19302196
GO:0005096	GTPase activator activity	IDA	17442267

LRRK2 for ontologies About GeneDecksing

Phenotypes:
2 GenomeRNAi human phenotypes for LRRK2:

Decreased viability with pacli

Upregulation of Wnt/beta-caten

14 MGI mutant phenotypes (inferred from 12 alleles) (MGI details for Lrrk2):

behavior/neurological	cardiovascular system	cellular	endocrine/exocrine gland	hematopoietic system
homeostasis/metabolism	immune system	integument	mortality/aging	nervous system
no phenotypic analysis	pigmentation	renal/urinary system	respiratory system

LRRK2 for phenotypes           About GeneDecksing

Animal Models:
     Mouse knock-outs for LRRK2: Lrrk2^tm1Mjfa Lrrk2^tm1.1Cai Lrrk2^tm1Tmd Lrrk2^tm2.1Shn Lrrk2^tm1.1Mjff Lrrk2^tm1.1Npa
                                               Lrrk2^tm1Arte Lrrk2^tm3.1Shn

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for LRRK2

miRNA Products:		OriGene 3'-UTR Clone: LRRK2 Browse MicroRNA Expression Plasmids
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		8/17 QIAGEN miScript miRNA Assays for microRNAs that regulate LRRK2 (see all 17):
		hsa-miR-607 hsa-miR-181c hsa-miR-301a hsa-miR-130b hsa-miR-181b hsa-miR-301b hsa-miR-205 hsa-miR-181a

		SwitchGear 3'UTR luciferase reporter plasmid: LRRK2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for LRRK2 (see all 4) OriGene shRNA RFP: LRRK2 OriGene siRNA: LRRK2
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		Sirion Biotech Custom design and validation of potent shRNA sequences against LRRK2

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for LRRK2
			Sirion Biotech Customized adenovirus for potent knockdown of LRRK2

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for LRRK2 (see all 2) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for LRRK2 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: LRRK2 (NM_198578)
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		Sirion Biotech Customized stable knockdown cell line services for LRRK2 Sirion Biotech Customized inducible knockdown cell line services for LRRK2

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for LRRK2

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Neuroscience

Neuroscience

1.00

MAPK signaling pathway

MAPK signaling pathway

1.00

Parkinsons Disease Pathway

Parkinsons Disease Pathway

1.00

Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.

Parkinson's disease

0.61

Wnt Signaling Pathway

Wnt Signaling Pathway and Pluripotency

0.55

Pathway sources
See GeneCards unified pathways
Show all pathways

1 Cell Signaling Technology (CST) Pathway for LRRK2

Neuroscience

3 BioSystems Pathways for LRRK2

	MAPK signaling pathway
	Wnt Signaling Pathway and Pluripotency
	Parkinsons Disease Pathway

1 Kegg Pathway (Kegg details for LRRK2):

Parkinson's disease

LRRK2 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for LRRK2

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

47/67 Interacting proteins for LRRK2 (Q5S007^{1, 2, 3} ENSP00000298910⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 67) (see top 5)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PARK2	O60260¹^,³, ENSP00000355865⁴	EBI-5323863,EBI-716346 I2D: score=1 STRING: ENSP00000355865
AKT1	P31749²^,³, ENSP00000270202⁴	MINT-8177975 MINT-8177865 MINT-8177888 MINT-8177907 MINT-8177924 MINT-8177954 I2D: score=1 STRING: ENSP00000270202
CALM1	P62158³	I2D: score=1
CALM2	P62158³	I2D: score=1
CALM3	P62158³	I2D: score=1
STUB1	Q9UNE7³, ENSP00000219548⁴	I2D: score=2 STRING: ENSP00000219548
CAPZA1	P52907³, ENSP00000263168⁴	I2D: score=1 STRING: ENSP00000263168
CAPZA2	P47755³, ENSP00000354947⁴	I2D: score=1 STRING: ENSP00000354947
DBN1	Q16643³, ENSP00000292385⁴	I2D: score=1 STRING: ENSP00000292385
LIMA1	Q9UHB6³, ENSP00000378400⁴	I2D: score=1 STRING: ENSP00000378400
PPP1R12A	O14974³, ENSP00000261207⁴	I2D: score=1 STRING: ENSP00000261207
RAI14	Q9P0K7³, ENSP00000265109⁴	I2D: score=1 STRING: ENSP00000265109
HSP90AA1	P07900³, ENSP00000335153⁴	I2D: score=1 STRING: ENSP00000335153
SNCA	P37840³, ENSP00000338345⁴	I2D: score=1 STRING: ENSP00000338345
UBC	P0CG48³, ENSP00000344818⁴	I2D: score=1 STRING: ENSP00000344818
NFATC2	Q13469¹, ENSP00000379330⁴	EBI-5323863,EBI-716258 STRING: ENSP00000379330
ARPC2	O15144³, ENSP00000295685⁴	I2D: score=1 STRING: ENSP00000295685
ARPC4	P59998³, ENSP00000380431⁴	I2D: score=1 STRING: ENSP00000380431
MPC2	O95563³, ENSP00000271373⁴	I2D: score=1 STRING: ENSP00000271373
PLEC	Q15149³, ENSP00000323856⁴	I2D: score=1 STRING: ENSP00000323856
MPRIP	Q6WCQ1³, ENSP00000379156⁴	I2D: score=1 STRING: ENSP00000379156
ACTB	P60709³	I2D: score=1
ACTBL2	Q562R1³	I2D: score=1
ACTG1	P63261³	I2D: score=1
ACTR2	P61160³	I2D: score=1
ACTR3	P61158³	I2D: score=1
ARPC1B	O15143³	I2D: score=1
ARPC5	O15511³	I2D: score=1
ATP5L	O75964³	I2D: score=1
CAPZB	P47756³	I2D: score=1
EFHD2	Q96C19³	I2D: score=1
GNAI2	P04899³	I2D: score=1
MYL12B	O14950³	I2D: score=1
MYL6	P60660³	I2D: score=1
MYO1B	O43795³	I2D: score=1
MYO1C	O00159³	I2D: score=1
MYO1D	O94832³	I2D: score=1
MYO1F	O00160³	I2D: score=1
TMOD3	Q9NYL9³	I2D: score=1
TPM1	P09493³	I2D: score=1
TPM2	P07951³	I2D: score=1
TPM3	P06753³	I2D: score=1
DAPK1	P53355¹	EBI-5323863,EBI-358616
DNM1L	O00429¹	EBI-5323863,EBI-724571
LRP6	O75581¹	EBI-5323863,EBI-910915
LRRK1	Q38SD2¹	EBI-5323863,EBI-1050422
LRRK2	Q5S007¹	EBI-5323863,EBI-5323863

About this table

Gene Ontology (GO): 5/33 biological process terms (GO ID links to tree view) (see all 33): About this table

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	IDA	19302196
GO:0001934	positive regulation of protein phosphorylation	IMP	--
GO:0006184	GTP catabolic process	IDA	--

LRRK2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

LRRK2 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Compounds for LRRK2 available from Tocris Bioscience About this table

Compound	Action	CAS #
LRRK2-IN-1	Potent and selective LRRK2 inhibitor	[1234480-84-2]

3 HMDB Compounds for LRRK2 About this table

Compound	Synonyms	CAS #	PubMed Ids
ADP	adenosindiphosphorsaeure (see all 8)	58-64-0	--
Adenosine triphosphate	5'-(tetrahydrogen triphosphate) Adenosine (see all 24)	56-65-5	--
Guanosine triphosphate	5'-GTP (see all 10)	86-01-1	--

4 Novoseek chemical compound relationships for LRRK2 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
levodopa	35.6	2	17614947 (1), 17427941 (1)
gtp	35.3	13	17260967 (4), 17706965 (2), 16980962 (1), 19712061 (1) (see all 5)
dopamine	26.1	6	19625511 (2), 17625107 (1), 19726410 (1), 18272292 (1) (see all 5)
lipid	1.83	7	17341485 (4)

Search CenterWatch for drugs/clinical trials and news about LRRK2

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for LRRK2 gene:

NM_198578.3

Unigene Cluster for LRRK2:

Leucine-rich repeat kinase 2

Hs.187636 [show with all ESTs]

Unigene Representative Sequence: NM_198578

7 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000416796 ENST00000343742(uc001rmh.1) ENST00000298910(uc001rmg.4)

ENST00000474202 ENST00000430804(uc009zjw.3) ENST00000479187(uc001rmi.3)

ENST00000481256

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		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat LRRK2
		8/17 QIAGEN miScript miRNA Assays for microRNAs that regulate LRRK2 (see all 17):
		hsa-miR-607 hsa-miR-181c hsa-miR-301a hsa-miR-130b hsa-miR-181b hsa-miR-301b hsa-miR-205 hsa-miR-181a

		SwitchGear 3'UTR luciferase reporter plasmid: LRRK2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for LRRK2 (see all 4) OriGene shRNA RFP: LRRK2 OriGene siRNA: LRRK2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat LRRK2
		Sirion Biotech Custom design and validation of potent shRNA sequences against LRRK2

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for LRRK2 (see all 2) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for LRRK2 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: LRRK2 (NM_198578)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for LRRK2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat LRRK2

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for LRRK2 Browse OriGene validated miRNA SYBR primer pairs
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		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat LRRK2
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat LRRK2

Additional cDNA sequence:

AK026776.1 AK122640.1 AK127729.1 AK131537.1 AL832453.2 AL834529.1 AY792511.1 BC117180.1

BX640975.1 EF212257.1

8 DOTS entries:

DT.92042415 DT.301521 DT.91844472 DT.95116671 DT.91980049 DT.408537 DT.95338047 DT.65285196

24/53 AceView cDNA sequences (see all 53):

AL834529 AA827621 AK122640 BF942699 AA906444 BX119871 AW772282 AK131537

AA741317 AW237822 AK127729 BU634341 BF331667 BM280361 BX640975 AK026776

AV705213 CA406939 AW118991 AA278300 BQ437477 BX499147 BG546973 AL832453

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

LRRK2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

LRRK2 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

Human kidney epithelial cell spheroids (Kidney spheroids for...)

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See LRRK2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for LRRK2

SOURCE GeneReport for Unigene cluster: Hs.187636

UniProtKB/Swiss-Prot: LRRK2_HUMAN, Q5S007

Tissue specificity: 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

SABiosciences Expression via Pathway-Focused PCR Array including LRRK2:

Parkinson's Disease in human mouse rat

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for LRRK2 gene from 5/18 species (see all 18) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	LOC427844¹	leucine-rich repeat serine/threonine-protein kinase more	73.19(n) 72.81(a)		427844 XM_003640340.1 XP_003640388.1
lizard (Anolis carolinensis)	Reptilia	LRRK2⁶	--	72(a)	1 ↔ 1	5(98166841-98263943)
zebrafish (Danio rerio)	Actinopterygii	lrrk2¹	leucine-rich repeat kinase 2	55.38(n) 49.4(a)		559366 NM_001201456.1 NP_001188385.1
fruit fly (Drosophila melanogaster)	Insecta	Lrrk⁶	Leucine-rich repeat kinase	17(a)	possible ortholog	3R(16461910-16469856)
worm (Caenorhabditis elegans)	Secernentea	lrk-1⁶	Leucine-rich repeat serine/threonine-protein kinas...	15(a)	possible ortholog	I(10879759-10894230)

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

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for LRRK2 gene

LRRK1²

3 SIMAP similar genes for LRRK2 using alignment to 5 protein entries: LRRK2_HUMAN (see all proteins):

DKFZp686E15222 AURA17 STK11

LRRK2 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 12 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs34594498^1,2	C,F	pathogenic	37674515(+)	`ATCTGC/TGAATG`	2	A V	mis¹		4		EA NA	5242
rs34410987^1,2	C,F	pathogenic	37705347(+)	`CAGTCC/TCAAAT`	2	P L	mis¹		3		EA NA	188
rs35808389^1,2	C	pathogenic	37719923(+)	`ATTTTA/GGAAGG`	2	L	syn¹		2		NA	4550
rs34805604^1,2	C	pathogenic	37720560(+)	`CAGGGA/GTATGC`	2	I V	mis¹		2		NA	4
rs74163686^1,2	C	pathogenic	37730660(+)	`TCTTCA/CATATA`	2	N H	mis¹		0	--	--	--	--
rs33939927^1,2	C	pathogenic	37731869(+)	`AGGCTC/G/TGCGCT`	3	R G C	mis¹		2		NA	4
rs34995376^1,2	C	pathogenic	37731870(+)	`GGCTCG/ACGCTT`	2	/H /R	mis¹		2		NA	4
rs33949390^1,2	C,F	pathogenic	37741479(+)	`TTCGCA/C/GTAGAG`	3	H P R	mis¹		3		NA	4156
rs35801418^1,2	C	pathogenic	37742550(+)	`GCCTTA/GTTTTC`	2	Y C	mis¹		1		NA	2
rs34637584^1,2	C,F	pathogenic	37761838(+)	`ACTACG/AGCATT`	2	/S /G	mis¹		4		NA EU	5875

HapMap Linkage Disequilibrium report for LRRK2 (40590546 - 40763087 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 3 variations for LRRK2
2 CNVs: 101488 101487
1 Indel: 58569
Human Gene Mutation Database (HGMD): LRRK2

Locus Specific Mutation Databases (LSDB): LRRK2

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

LRRK2 for disorders           About GeneDecksing

OMIM gene information: 609007
OMIM disorders: 607060
UniProtKB/Swiss-Prot: LRRK2_HUMAN, Q5S007

Defects in LRRK2 are the cause of Parkinson disease type 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

20/31 diseases for LRRK2 (see all 31): About MalaCards

parkinson's disease rheumatoid arthritis supranuclear palsy lewy body dementia

progressive supranuclear palsy arthritis primary progressive aphasia essential tremor

frontotemporal dementia multiple system atrophy parkinson disease 10 amyotrophic lateral sclerosis

aphasia tremor ankylosing spondylitis lateral sclerosis

tauopathy dementia inflammatory bowel disease neurodegenerative disease

4 diseases from the University of Copenhagen DISEASES database for LRRK2:

Parkinson's disease Movement disease Lewy body dementia Multiple system atrophy

10/18 Novoseek disease relationships for LRRK2 gene (see all 18) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
parkinson disease, autosomal dominant	95	56	17222106 (2), 15680455 (1), 19357115 (1), 15732108 (1) (see all 26)
parkinson disease	91.5	414	18322396 (5), 17419834 (4), 19804413 (4), 16272164 (4) (see all 99)
autosomal dominant parkinsonism	88.3	11	15726496 (2), 17116211 (1), 16172858 (1), 15680456 (1) (see all 7)
parkinsonism	87.1	86	16406842 (3), 15541309 (2), 16966501 (2), 16781064 (2) (see all 52)
lewy body disease	74.9	7	17611037 (2), 17713120 (1), 19680143 (1), 19878656 (1)
movement disorders	72.8	3	16250030 (1), 19205068 (1), 18704525 (1)
neurodegenerative diseases	66.7	15	19680143 (2), 15541309 (1), 19879924 (1), 18214993 (1) (see all 10)
neurodegeneration	63.1	24	17200152 (2), 17400507 (2), 19176810 (2), 17611037 (2) (see all 14)
multiple system atrophy	57.3	5	18936941 (2), 19513331 (1), 16602113 (1), 17230458 (1) (see all 5)
frontotemporal dementia	47.4	8	17151837 (2), 19142648 (1), 18759352 (1)

GeneTests: LRRK2

LRRK2-Related Parkinson Disease

Parkinson Disease

Genetic Association Database (GAD): LRRK2
Human Genome Epidemiology (HuGE) Navigator: LRRK2 (182 documents)

Export disorders for LRRK2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for LRRK2 gene, integrated from 9 sources (see all 562):
(articles sorted by number of sources associating them with LRRK2)

Utopia: connect your pdf to the dynamic
world of online information

LRRK2 gene in Parkinson disease: mutation analysis and case control association study. (PubMed id 16157901)^{1, 2, 4, 9} Paisan-Ruiz C....Rogaeva E. (2005)
LRRK2 mutations are not common in Alzheimer's disease. (PubMed id 16087219)^{1, 2, 4, 9} Toft M....Farrer M.J. (2005)
A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations. (PubMed id 16157909)^{1, 2, 4, 9} Zabetian C.P.... Griffith A. (2005)
Parkinson's disease and LRRK2: frequency of a common mutation in U.S. movement disorder clinics. (PubMed id 16250030)^{1, 2, 4, 9} Kay D.M.... Payami H. (2006)
The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor. (PubMed id 16272257)^{1, 2, 4, 9} Goldwurm S.... Bonifati V. (2005)
Clinical features of LRRK2-associated Parkinson's disease in central Norway. (PubMed id 15852371)^{1, 2, 4, 9} Aasly J.O.... Farrer M.J. (2005)
A common LRRK2 mutation in idiopathic Parkinson's disease. (PubMed id 15680457)^{1, 2, 4, 9} Gilks W.P.... Wood N.W. (2005)
LRRK2 G2019S is a common mutation in Spanish patients with late-onset Parkinson's disease. (PubMed id 16298482)^{1, 2, 4} Infante J.... Berciano J. (2006)
G2019S LRRK2 mutation in French and North African families with Parkinson's disease. (PubMed id 16240353)^{1, 2, 4} Lesage S....Brice A. (2005)
Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease. (PubMed id 16251215)^{1, 2, 4} Berg D.... Naegele T. (2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 120892	HGNC: 18618	AceView: DKFZp434H2111	Ensembl:ENSG00000188906	euGenes: HUgn120892
ECgene: LRRK2	Kegg: 120892	H-InvDB: LRRK2

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for LRRK2	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LRRK2

Intellectual Property for LRRK2 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for LRRK2 gene:
Search GeneIP for patents involving LRRK2

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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leucine-rich repeat kinase 2

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LRRK2 Gene

leucine-rich repeat kinase 2

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