Table 2 Genes and variants enriched in the PEG cohort ranked by disease severity x pesticide exposure score
From: Lysosomal genes contribute to Parkinson’s disease near agriculture with high intensity pesticide use
Gene Symbol | Gene Name | Gene Function | Variants Enriched in PEG Cohort | Variant Population P value | Average Disease x Pesticide Score |
|---|---|---|---|---|---|
EP300 | E1A Binding Protein P300 | Regulates transcription via chromatin remodeling and cell proliferation and differentiation | NP_001420.2:p.Asp2412Glu NP_001420.2:p.Asn251Ser | 8.40E-21 2.98E-02 | 0.497 |
HDAC6 | Histone Deacetylase 6 | Alters chromosome structure and affects transcription factor access to DNA | NP_006035.2:p.Gly844Arg NP_006035.2:p.Leu508Ser | 7.30E-22 5.34E-05 | 0.259 |
HTT | Huntingtin | Regulate transcription and is required for normal development | NP_002102.4:p.Asp758Asn NP_002102.4:p.Arg3109His | 2.30E-40 1.38E-17 | 0.235 |
CTSD | Cathepsin D | Protein turnover and in the proteolytic activation of hormones and growth factors | NP_001900.1:p.Ile198Val | 5.40E-13a | 0.230 |
ACP2 | Acid Phosphatase 2, Lysosomal | Hydrolyze orthophosphoric monoesters to alcohol and phosphate | NP_001601.1:p.Thr358Ile | 1.26E-06 | 0.229 |
PRKN (PARK2) | Parkin RBR E3 Ubiquitin Protein Ligase | Multiprotein E3 ubiquitin ligase complex mediate substrate proteins for proteasomal degradation | NP_004553.2:p.Pro37Leu | 4.59E-02 | 0.229 |
FBXO7 | F-Box Protein 7 | SCFs (SKP1-cullin-F-box) ubiquitin protein ligase complex for phosphorylation-dependent ubiquitination | NP_036311.3:p.Asp516His NP_036311.3:p.Val485Ile | 1.76E-04a 1.71E-02 | 0.207 |
APP | Amyloid Beta Precursor Protein | Promote transcriptional activation | NP_000475.1:p.Glu665Lys | 7.18E-21 | 0.166 |
MAPT | Microtubule Associated Protein Tau | Maintain stability of microtubules in axons | NP_001116538.2:p.Thr30Ile NP_001116538.2:p.Lys293Arg | 9.77E-04 2.29E-03 | 0.160 |
ATG4C | Autophagy Related 4C Cysteine Peptidase | Autophagy | NP_116241.2:p.Thr452Met | 7.90E-10 | 0.130 |
HIP1R | Huntingtin Interacting Protein 1 Related | Phosphatidylinositol phosphate binding activity | NP_003950.1:p.Arg613Gln NP_003950.1:p.Arg586Trp | 4.44E-23 2.32E-07 | 0.124 |
GNPTAB | N-Acetylglucosamine-1-Phosphate Transferase Subunits Alpha And Beta | Catalyzes synthesis of mannose 6-phosphate recognition markers for trafficking of lysosomal enzymes | NP_077288.2:p.Met1175Ile | 2.78E-14 | 0.111 |
GBA1 | Glucosylceramidase Beta 1 | Glycolipid metabolism | NP_001005742.1:p.Arg78Cys | 8.43E-31a | 0.110 |
LAMP1 | Lysosomal Associated Membrane Protein 1 | Provides selectins with carbohydrate ligands | NP_005552.3:p.Thr189Ser NP_005552.3:p.Ile309Thr | 8.29E-06, 4.12E-02a 7.91E-03 | 0.105 |
SMPD1 | Sphingomyelin Phosphodiesterase 1 | Converts sphingomyelin to ceramide | NP_001007594.2:p.Arg497Leu | 1.96E-07 | 0.088 |
PINK1 | PTEN Induced Kinase 1 | Protect cells from stress-induced mitochondrial dysfunction | NP_115785.1:p.Ala383Thr | 1.10E-04a | 0.076 |
BLOC1S1 | Biogenesis Of Lysosomal Organelles Complex 1 Subunit 1 | Biogenesis of specialized organelles of the endosomal-lysosomal system | NP_001478.2:p.Asp68Asn | 4.36E-02 | 0.074 |
MCCC1 | Methylcrotonyl-CoA Carboxylase Subunit 1 | Catalyzes the carboxylation of 3-methylcrotonyl-CoA to form 3-methylglutaconyl-CoA | NP_064551.3:p.Glu717Lys | 1.89E-05 | 0.073 |
BAG6 | BAG Cochaperone 6 | Control of apoptosis and acetylation of p53 in response to DNA damage | NP_542434.1:p.Pro429Leu NP_542434.1:p.Glu293Lys | 7.72E-88 8.78E-04 | 0.063 |
GAK | Cyclin G Associated Kinase | Cyclin-dependent protein kinase | NP_005246.2:p.Ile413Val NP_005246.2:p.Arg654Gln | 4.40E-03a 3.44E-02 | 0.062 |
GALC | Galactosylceramidase | Hydrolyzes galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride | NP_000144.2:p.Ile144Leufs*27 NP_000144.2:p.Thr112Ala | 6.21E-09 6.04E-03 | 0.056 |
NPC1 | NPC Intracellular Cholesterol Transporter 1 | Mediates intracellular cholesterol trafficking | NP_000262.2:p.Ile787Val | 2.63E-02 | 0.055 |
ACMSD | Aminocarboxymuconate Semialdehyde Decarboxylase | NAD synthesis | NP_612199.2:p.Lys134Glu | 3.36E-02 | 0.049 |
MCOLN1 | Mucolipin TRP Cation Channel 1 | Regulation of lysosomal exocytosis | NP_065394.1:p.Ala164Thr | 2.17E-03 | 0.047 |
TSC1 | TSC Complex Subunit 1 | Rapamycin complex 1 (mTORC1) signaling | NP_001155899.1:p.Gly984Ser | 7.49E-04 | 0.046 |
LAMP3 | Lysosomal Associated Membrane Protein 3 | Differentiate dendritic cells | NP_055213.2:p.Ala267Thr | 5.36E-10 | 0.036 |
