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LRRK2 Gene

protein-coding GIFtS: 66
GCID: GC12P040590

Leucine-Rich Repeat Kinase 2

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

See LRRK2-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Leucine-Rich Repeat Kinase 2¹ ²		ROCO2²
PARK8¹ ² ³ ⁵		Augmented In Rheumatoid Arthritis 17²
Parkinson Disease (Autosomal Dominant) 8¹		Leucine-Rich Repeat Serine/Threonine-Protein Kinase 2²
AURA17²		Dardarin³
DARDARIN²		EC 2.7.11.1³
RIPK7²

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, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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. GO annotations related to this gene include GTP binding and protein homodimerization activity. An important paralog of this gene is LRRK1.

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 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

(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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000012.11 NT_029419.13 NC_018923.2

Regulatory elements:

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 Chromatin IP Primers for LRRK2

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing 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, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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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

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

Explore proteomics data for LRRK2 at MOPED

Post-translational modifications:

Autophosphorylated¹

Modification sites at neXtProt

Modification sites at PhosphoSitePlus

See LRRK2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_940980.3

ENSEMBL proteins:

ENSP00000398726 ENSP00000341930 ENSP00000298910 ENSP00000410821

LRRK2 Human Recombinant Protein Products:

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

PARK: Parkinson disease

IUPHAR Guide to PHARMACOLOGY protein family classification: leucine-rich repeat kinase 2

Leucine-rich repeat kinase (LRRK) family

Selected InterPro protein domains (see all 18):

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 domains:

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

Find genes that share domains with LRRK2 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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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): Selected molecular function terms (see all 18): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003924	GTPase activity	IDA	--
GO:0004672	protein kinase activity	IDA	16269541
GO:0004674	protein serine/threonine kinase activity	IDA	17200152
GO:0004708	MAP kinase kinase activity	IDA	19302196
GO:0004713	protein tyrosine kinase activity	--	--

Find genes that share ontologies with LRRK2 About GenesLikeMe

Phenotypes:
2 GenomeRNAi human phenotypes for LRRK2:

Decreased viability with pacli

Upregulation of Wnt/beta-caten

15 MGI mutant phenotypes (inferred from 14 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	normal	pigmentation	renal/urinary system	respiratory system

Find genes that share phenotypes with LRRK2           About GenesLikeMe

Animal Models:
     MGI mouse knock-outs for LRRK2: Lrrk2^tm1Mjfa Lrrk2^tm1.2Npa Lrrk2^tm1.1Mjff Lrrk2^tm1.1Npa Lrrk2^tm1.1Cai Lrrk2^tm1Tmd
                                                     Lrrk2^tm2.1Shn Lrrk2^tm3.1Shn Lrrk2^tm1Arte

genOway: Develop your customized and physiologically relevant rodent model for LRRK2

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

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Gene Editing
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for LRRK2

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

LRRK2_HUMAN, Q5S007: Cytoplasm. Membrane; Peripheral membrane protein. Mitochondrion. Note=Localized in the

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

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
mitochondrion	5
nucleus	3
cytoskeleton	2
lysosome	2
plasma membrane	2
vacuole	2
cytosol	1
endosome	1
golgi apparatus	1

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Gene Ontology (GO): Selected cellular component terms (see all 21): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005615	extracellular space	IDA	--
GO:0005622	intracellular	--	--
GO:0005737	cytoplasm	IDA	16321986
GO:0005739	mitochondrion	IDA	--
GO:0005802	trans-Golgi network	IEA	--

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(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, 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 Apr 2014 via Entrez Gene).
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SuperPaths for LRRK2 About

See pathways by source

Powered
by

SuperPath

Contained pathways About

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

Parkinson's disease

0.57

Wnt Signaling Pathway (WikiPathways)

Wnt Signaling Pathway and Pluripotency

0.55

MAPK signaling pathway

MAPK signaling pathway

0.50

Parkinsons Disease Pathway

Parkinsons Disease Pathway

Neuroscience

Neuroscience

Find genes that share SuperPaths with LRRK2 About GenesLikeMe

Pathways by source See SuperPaths
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

Pathway & Disease-focused RT² Profiler PCR Array including LRRK2:

Parkinson's Disease in human mouse rat

Interactions:

GeneGlobe Interaction Network for LRRK2

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

Selected Interacting proteins for LRRK2 (Q5S007^{1, 2, 3} ENSP00000298910⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 111)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PARK2	O60260¹^,³, ENSP00000355865⁴	EBI-5323863,EBI-716346 I2D: score=1 STRING: ENSP00000355865
AKT1	P31749¹^,²^,³, ENSP00000270202⁴	EBI-5323863,EBI-296087 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

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Gene Ontology (GO): Selected biological process terms (see all 40): 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	--

Find genes that share ontologies with LRRK2 About GenesLikeMe

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Compounds for LRRK2 available from Tocris Bioscience About this table

Compound	Action	CAS #
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 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 inferred 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)

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 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,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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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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		Selected qRT-PCR 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

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		QuantiFast Probe-based Assays in human, mouse, rat LRRK2

Additional mRNA 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

Selected AceView cDNA sequences (see all 53):

AK122640 BU634341 BM280361 AL834529 AW772282 AA906444 BF331667 BF942699

AA827621 BX119871 AK127729 AK131537 AA741317 AW237822 AL832453 AW118991

BX640975 AV705213 BQ437477 BM998398 AI952066 AA384842 BX499147 AI831901

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™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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LRRK2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: --

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LRRK2 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 4) fully expand


Brain (Nervous System) fully expand to see all 15 entries
Oligodendrocyte Precursor Cells Forebrain White Matter
Thalamus
Septum

Ovary (Reproductive System)
Cumulus Cells Antral Follicle

Blood (Hematopoietic System)
Granulocytes Peripheral Blood

Spinal Cord (Nervous System)

LRRK2 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

LRRK2 Protein Expression

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

Pathway & Disease-focused RT² Profiler PCR Array including LRRK2:

Parkinson's Disease in human mouse rat

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for LRRK2

(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)
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This gene was present in the common ancestor of animals.

Orthologs for LRRK2 gene from Selected species (see all 14) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Lrrk2^{1 , 5}	leucine-rich repeat kinase 2^{1, 5}	83.27(n)¹ 86.69(a)¹		15 (46.07 cM)⁵ 66725¹ NM_025730.3¹ NP_080006.3¹ 91673175⁵
chicken (Gallus gallus)	Aves	LRRK2¹	leucine-rich repeat kinase 2	73.11(n) 72.73(a)		427844 XM_003640340.2 XP_003640388.2
lizard (Anolis carolinensis)	Reptilia	LRRK2⁶	leucine-rich repeat kinase 2	72(a)	1 ↔ 1	5(98165490-98290914)
tropical clawed frog (Xenopus tropicalis)	Amphibia	lrrk2¹	leucine-rich repeat kinase 2	65.86(n) 63.5(a)		100145062 XM_002932204.2 XP_002932250.2
zebrafish (Danio rerio)	Actinopterygii	lrrk2¹	leucine-rich repeat kinase 2	55.71(n) 49.76(a)		559366 NM_001201456.1 NP_001188385.1
fruit fly (Drosophila melanogaster)	Insecta	Lrrk⁶	Leucine-rich repeat kinase	18(a)	1 → many	3R(16461910-16469856)
worm (Caenorhabditis elegans)	Secernentea	lrk-1⁶	Protein LRK-1 (lrk-1) mRNA, complete cds	16(a)	1 → many	I(10879766-10894237) WBGene00003068

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)
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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

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(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, 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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 12 pos	Sequence	#	AA Chg	Type	More	#	Pop	Total sample
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs34805604^1,2,,4	C	Parkinson disease 8 (PARK8)⁴ pathogenic¹	40537151(+)	`CAGGGA/GTATGC`	2	I V	mis¹		2	NA	4
rs33939927^1,2,,4	C	Parkinson disease 8 (PARK8)⁴ pathogenic¹	40548463(+)	`AGGCTC/G/TGCGCT`	3	R G C	mis¹		2	NA	4
rs34995376^1,2,,4	C	Parkinson disease 8 (PARK8)⁴ pathogenic¹	40548464(+)	`GGCTCG/ACGCTT`	2	/H /R	mis¹		2	NA	4
rs35507033^1,2,,4	C,F	Parkinson disease 8 (PARK8)⁴ unknown¹	40552005(+)	`GATCCG/AAGATC`	2	/Q /R	mis¹		5	NA EU	5723
rs33958906^1,2,,4	C,F	Parkinson disease 8 (PARK8)⁴ unknown¹	40552088(+)	`ATGTGC/TCAATT`	2	P S	mis¹		5	NA EU	5954
rs721710^1,2,,4	C,H	Parkinson disease 8 (PARK8)⁴ unknown¹	40553295(+)	`CTTTGT/AGGAAC`	2	/E /V	mis¹ ese³		7	NA NS EA	504
rs35801418^1,2,,4	C	Parkinson disease 8 (PARK8)⁴ pathogenic¹	40559141(+)	`GCCTTA/GTTTTC`	2	Y C	mis¹		1	NA	2
rs35602796^1,2,,4	C	Parkinson disease 8 (PARK8)⁴ unknown¹	40561284(+)	`TATTAT/CGTTGA`	2	/T /M	mis¹		3	NA	124
rs34015634^1,2,,4	C	Parkinson disease 8 (PARK8)⁴ unknown¹	40578409(+)	`CATCAT/CTGCAA`	2	/T /I	mis¹		1	NA	2
rs34637584^1,2,,4	C,F	Parkinson disease 8 (PARK8)⁴ pathogenic¹	40578429(+)	`ACTACG/AGCATT`	2	/S /G	mis¹		4	NA EU	5875

HapMap Linkage Disequilibrium report for LRRK2 (40590546 - 40763087 bp)

Structural Variations
Database of Genomic Variants (DGV) Selected variations for LRRK2 (see all 14): About this table

Variant ID	Type	Subtype	PubMed ID
esv2745783	CNV	Deletion	23290073
esv2432211	CNV	Deletion	19546169
esv2745786	CNV	Deletion	23290073
esv2745787	CNV	Deletion	23290073
dgv205e201	CNV	Deletion	23290073
esv1215291	CNV	Deletion	17803354
esv2454181	CNV	Insertion	19546169
esv273841	CNV	Insertion	20981092
esv274613	CNV	Insertion	20981092
esv268820	CNV	Insertion	20981092

Human Gene Mutation Database (HGMD): LRRK2
Locus Specific Mutation Databases (LSDB): LRRK2

Site Specific Mutation Identification with 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.)
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OMIM gene information: 609007
OMIM disorders: 607060
UniProtKB/Swiss-Prot: LRRK2_HUMAN, Q5S007

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. Note=The disease is caused by

mutations affecting the gene represented in this entry

9 diseases for LRRK2:
About MalaCards

parkinson disease 8 lrrk2-related parkinson disease parkinson's disease tremor

essential tremor primary progressive aphasia parkinson disease 1 rheumatoid arthritis

movement disease

4 inferred disease relationships from the University of Copenhagen DISEASES database for LRRK2:

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

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Selected Novoseek inferred 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
GeneReviews: LRRK2
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)
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PubMed articles for LRRK2 gene, integrated from 10 sources (see all 634):
(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. (Neurology 2005)
LRRK2 mutations are not common in Alzheimer's disease. (PubMed id 16087219)^{1, 2, 4, 9} Toft M....Farrer M.J. (Mech. Ageing Dev. 2005)
LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance. (PubMed id 16533964)^{1, 2, 4, 9} Gaig C....Tolosa E. (Arch. Neurol. 2006)
Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls. (PubMed id 18213618)^{1, 2, 4, 9} Paisan-Ruiz C.... Singleton A.B. (Hum. Mutat. 2008)
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. (Neurology 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. (Mov. Disord. 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. (J. Med. Genet. 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. (Ann. Neurol. 2005)
A common LRRK2 mutation in idiopathic Parkinson's disease. (PubMed id 15680457)^{1, 2, 4, 9} Gilks W.P.... Wood N.W. (Lancet 2005)
The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence. (PubMed id 17019612)^{1, 2, 4} Tan E.K.... Liu J.J. (Hum. Genet. 2007)

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

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for LRRK2	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=LRRK2[genesymbol]

Intellectual Property for LRRK2 gene
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Patent Information for LRRK2 gene:
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LRRK2 Gene

Leucine-Rich Repeat Kinase 2

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