PhenoModifier-Gene Detail

Gene "LRRK2"

Found 2 records

Gene information

Gene symbol:

LRRK2

See related:

Ensembl: ENSG00000188906, Gene ID: 120892

Additive variants :

Detected

Genetic interaction partners

Confidence	Stringent (ε>0.16 or ε<-0.12)	Intermediate (-0.16≤ε≤-0.08 or 0.08≤ε≤0.16)	Lenient (\|ε\|<0.08)
Positive interactions	PRPSAP2 NRAS USP35 RPL23 FOXJ3 XPC EP400 PPME1 HDAC7 UBE3C CCNA2 EIF2D GPX7 DNPEP SLC25A26 YPEL2 HAGHL H3F3C MCCC1 MTO1 KIAA1109 ACTR6 CWF19L1 PTPRN2 UBL5 XRN1 CHCHD2 RACK1 PGLS SBF1 GORASP1 BRD1 XPA STRIP2 LENG8 RPS28 RBMX2 CORO2B PSAT1 DPH6 ATXN2 SLC25A3 GOLT1A DPYSL2 EXO1 SLC25A35 MRE11 PEX12 ABHD5 PXMP2 PPAT SERINC2 TXNL1 NOLC1 PUM1 NAP1L1 TBC1D30 MUS81 CDC73 C2orf76 TRMT10B LSM1 NMNAT1 HIBCH RAB5B GLIPR2 SDHAF2 RPL26 CCNA2 PPP2R5C SLC25A4 SRXN1 show allhide
Negative interactions	MIOS ATAD2 CFDP1 THNSL1 MRM2 CLIP1 RPS29 PUM3 NF1 GATA2 NAA30 SIN3A SC5D DNAJA4 LEO1 ALG10B SLC27A3 PPP6R3 ABCF3 MAF1 TRMT11 RPS24 PGM2L1 FKBP7 CTPS1 ANKRD11 WDR76 PPP3CC VRK1 ASH1L ZDHHC6 EGR3 EEF2 VAMP2 AP1G1 CYB5R1 RPL7 PHGDH TAT KYNU PFKFB2 LSM14B SDHB RPS29 UCK2 RAD52 EDEM2 HSP90B1 RPS6KA1 SLC32A1 CLUH show allhide

Modifier statisitcs

Record:

Disorder:

Vriant:

Reference:

Effect type:

Expressivity(1) ,Penetrance(1)

Modifier effect:

Altered incidence(1) ,Altered onset time(1)

Details：

Variant 1:

LRRK2:rs34637584

Gene:

LRRK2

Genomic location:

dbSNP ID:

rs34637584

Target disease:

Parkinson's disease(DOID_14330)

Effect type:

Penetrance

Modifier effect:

Altered incidence

Evidence:

From review article

Effect:

Age-related penetrance for the most common LRRK2 Gly2019Ser mutation can range from ~30% to 70%

Reference:

PMID29977663

Title:

Genetic Modifiers in Neurodegeneration.

Species studied:

Human

Abstract:

To review the evidence for genetic modifier effects in the neurodegenerative diseases Huntington's Disease (HD), Frontotemporal Lobar Degeneration (FTLD), Alzheimer's Disease (AD), and Parkinson's Disease (PD).
Variant 2:

LRRK2:c.7153G>A(p.Gly2385Arg)

Gene:

LRRK2

Genomic location:

chr12:40757328

dbSNP ID:

rs34778348

Target disease:

Parkinsonism(HP:0001300)

Effect type:

Expressivity

Modifier effect:

Altered onset time

Evidence:

OR=3.760, 95% CI: (2.113–6.689), p <0.0001

Effect:

LRRK2 p.G2385R variant and BDNF p.V66M significantly increased the risk of PD.

Reference:

PMID21924942

Title:

Brain-derived neurotrophic factor (BDNF) genetic polymorphism greatly increases risk of leucine-rich repeat kinase 2 (LRRK2) for Parkinson's disease.

Species studied:

Human

Abstract:

Parkinson's disease (PD) is a complex neurodegenerative disorder. Although the p.G2385R allele of leucine-rich repeat kinase 2 (LRRK2) has been recently reported as a common genetic variant that increases the risk for typical PD exclusively among Asian population, its genetic modifiers is yet to be studied. Brain-derived neurotrophic factor (BDNF) has been shown to play an important role in the survival of dopaminergic neurons and its genetic polymorphism was associated with an increased risk for PD at an older age onset. The current case-control study was performed to investigate the interaction between LRRK2 p.G2385R and BDNF p.V66M in a Chinese PD cohort. A total of 464 PD patients and 549 controls were involved in this study.LRRK2 p.G2385R variant (odds ratio [OR]=3.2; 95% confidence interval [CI]=1.96-5.15, p<0.0001), not BDNF p.V66M alone significantly increased the risk of PD. However, the simultaneous presence of bothLRRK2 and BDNF variants significantly enhanced the risk for PD (OR=4.033; 95% CI=2.188-7.435, p<0.0001), particularly in patients with an onset age of older than 60 (OR=6.439; 95% CI=3.096-13.389, p<0.0001). Our results further support that LRRK2 variants are an independent genetic risk factor for typical PD, but BDNF variants can greatly increase LRRK2-induced risk for patients with an onset age of older than 60 indicating an additive effect between the 2 genes, which might aid in studying the mechanism underlying LRRK2 parkinsonism and developing potential therapeutic strategies.