LRRK2 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human LRRK2 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene LRRK2, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene LRRK2, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene LRRK2 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene LRRK2 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene LRRK2, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene LRRK2, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene LRRK2, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene LRRK2 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene LRRK2, summarize transcription factor regulatory data. If LRRK2 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate LRRK2 — names with evidence type (ChIP-seq / predicted / experimentally validated) If LRRK2 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene LRRK2 protein as a drug target, summarize pharmacology data. If LRRK2 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If LRRK2 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene LRRK2, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene LRRK2, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in LRRK2: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
LRRK2 (Leucine-rich repeat serine/threonine-protein kinase 2, also called Dardarin) is the most important known genetic contributor to Parkinson’s disease, encoded on chromosome 12 and designated a Very Important Pharmacogene by PharmGKB. The protein is a large multidomain kinase-GTPase combining LRR, ROC/GTPase, COR, kinase, and WD40 domains, with 44 experimental structures resolved including cryo-EM structures of the full-length protein and inhibitor complexes. Six ClinVar-confirmed pathogenic variants all cause autosomal dominant Parkinson disease, including p.Arg1441Gly, p.Arg1441Cys, p.Tyr1699Cys, and p.Ile2020Thr. GWAS signals reach p=4.0e-148 for Parkinson’s disease, and independent signals also implicate LRRK2 in inflammatory bowel disease, Crohn’s disease (p=6.0e-20), and chronic inflammatory diseases. Expression is ubiquitous across 220 tissues but highest in immune/myeloid cells (monocytes, leukocytes, granulocytes), consistent with its roles in innate immunity and RAB GTPase-mediated vesicle trafficking. Over 3,400 molecules have been assayed against LRRK2 in ChEMBL, though no LRRK2-specific drug has yet reached approval.
Gene identifiers
- HGNC ID: HGNC:18618
- Approved symbol: LRRK2
- Ensembl gene ID: ENSG00000188906
- NCBI Entrez Gene ID: 120892
- OMIM gene ID: 609007
- Genomic location (GRCh38):
- Chromosome: 12
- Start position: 40,196,744
- End position: 40,369,285
- Strand: +
Transcript identifiers
Ensembl Transcripts (22 total)
| Transcript ID | Biotype | Start | End |
|---|---|---|---|
| ENST00000298910 | protein_coding | 40224997 | 40369285 |
| ENST00000343742 | protein_coding | 40225011 | 40304976 |
| ENST00000416796 | protein_coding | 40196744 | 40283952 |
| ENST00000430804 | nonsense_mediated_decay | 40295505 | 40369285 |
| ENST00000474202 | retained_intron | 40225595 | 40232783 |
| ENST00000479187 | retained_intron | 40298466 | 40369285 |
| ENST00000481256 | protein_coding_CDS_not_defined | 40312714 | 40320062 |
| ENST00000636518 | protein_coding | 40346847 | 40368879 |
| ENST00000644108 | nonsense_mediated_decay | 40225188 | 40251544 |
| ENST00000679360 | nonsense_mediated_decay | 40224997 | 40367077 |
| ENST00000679532 | nonsense_mediated_decay | 40310466 | 40369259 |
| ENST00000679683 | nonsense_mediated_decay | 40346753 | 40369246 |
| ENST00000680018 | nonsense_mediated_decay | 40310467 | 40369259 |
| ENST00000680235 | protein_coding_CDS_not_defined | 40224977 | 40242782 |
| ENST00000680422 | nonsense_mediated_decay | 40310469 | 40369171 |
| ENST00000680425 | nonsense_mediated_decay | 40310557 | 40369054 |
| ENST00000680453 | nonsense_mediated_decay | 40310469 | 40369257 |
| ENST00000680790 | protein_coding | 40225080 | 40369259 |
| ENST00000681136 | protein_coding_CDS_not_defined | 40312389 | 40368330 |
| ENST00000681696 | protein_coding | 40310431 | 40368330 |
| ENST00000681773 | retained_intron | 40358907 | 40369171 |
| ENST00000950031 | protein_coding | 40225000 | 40368296 |
RefSeq mRNA Transcripts (4 total)
| Accession | Status | MANE Select |
|---|---|---|
| NM_001191789 | VALIDATED | No |
| NM_001201456 | VALIDATED | No |
| NM_025730 | VALIDATED | No |
| NM_198578 | REVIEWED | Yes |
CCDS
| CCDS ID |
|---|
| CCDS31774 |
Exons for MANE SELECT transcript (ENST00000298910 / NM_198578): 51 total
| Exon ID | Start | End | Strand | Chromosome |
|---|---|---|---|---|
| ENSE00001860962 | 40224997 | 40225282 | + | 12 |
| ENSE00003635610 | 40225555 | 40225640 | + | 12 |
| ENSE00001649052 | 40232274 | 40232383 | + | 12 |
| ENSE00001649709 | 40235626 | 40235714 | + | 12 |
| ENSE00001736708 | 40237969 | 40238103 | + | 12 |
| ENSE00001727339 | 40240483 | 40240617 | + | 12 |
| ENSE00001781025 | 40243550 | 40243681 | + | 12 |
| ENSE00001619675 | 40249826 | 40249945 | + | 12 |
| ENSE00001635586 | 40251232 | 40251374 | + | 12 |
| ENSE00001597461 | 40251465 | 40251544 | + | 12 |
| ENSE00001599015 | 40252910 | 40253016 | + | 12 |
| ENSE00001374694 | 40257248 | 40257377 | + | 12 |
| ENSE00001367134 | 40259480 | 40259604 | + | 12 |
| ENSE00001378233 | 40263789 | 40263901 | + | 12 |
| ENSE00001378687 | 40277888 | 40278016 | + | 12 |
| ENSE00001382909 | 40278091 | 40278261 | + | 12 |
| ENSE00001365484 | 40274583 | 40274727 | + | 12 |
| ENSE00001387519 | 40274854 | 40274993 | + | 12 |
| ENSE00001365419 | 40283875 | 40284133 | + | 12 |
| ENSE00003476749 | 40303948 | 40304134 | + | 12 |
| ENSE00003643319 | 40302789 | 40302882 | + | 12 |
| ENSE00003691970 | 40305785 | 40305966 | + | 12 |
| ENSE00003496760 | 40308467 | 40308696 | + | 12 |
| ENSE00003509533 | 40309106 | 40309233 | + | 12 |
| ENSE00003508420 | 40310431 | 40310649 | + | 12 |
| ENSE00003581684 | 40315212 | 40315300 | + | 12 |
| ENSE00003622781 | 40313972 | 40314173 | + | 12 |
| ENSE00003635411 | 40322035 | 40322181 | + | 12 |
| ENSE00003568150 | 40322319 | 40322510 | + | 12 |
| ENSE00003468154 | 40323160 | 40323306 | + | 12 |
| ENSE00003579735 | 40321034 | 40321188 | + | 12 |
| ENSE00003521951 | 40319988 | 40320175 | + | 12 |
| ENSE00003541694 | 40334967 | 40335157 | + | 12 |
| ENSE00003681812 | 40340294 | 40340454 | + | 12 |
| ENSE00003468457 | 40346753 | 40346923 | + | 12 |
| ENSE00003565286 | 40348409 | 40348509 | + | 12 |
| ENSE00003553579 | 40351539 | 40351733 | + | 12 |
| ENSE00003610102 | 40354299 | 40354492 | + | 12 |
| ENSE00003511943 | 40356115 | 40356187 | + | 12 |
| ENSE00003603703 | 40359260 | 40359444 | + | 12 |
| ENSE00003621327 | 40363402 | 40363554 | + | 12 |
| ENSE00003551873 | 40364842 | 40365050 | + | 12 |
| ENSE00003489241 | 40367006 | 40367077 | + | 12 |
| ENSE00003605121 | 40299109 | 40299257 | + | 12 |
| ENSE00001379815 | 40293545 | 40293663 | + | 12 |
| ENSE00001364454 | 40294845 | 40294914 | + | 12 |
| ENSE00001364875 | 40295427 | 40295644 | + | 12 |
| ENSE00001374565 | 40298243 | 40298493 | + | 12 |
| ENSE00001182762 | 40367644 | 40369285 | + | 12 |
Protein identifiers
UniProt Accessions
Reviewed (Canonical):
- Q5S007 — Leucine-rich repeat serine/threonine-protein kinase 2 (Dardarin)
Unreviewed:
- A0A1B0GUQ3
- A0A2R8Y4F8
- A0A7P0T8S1
- A0A7P0T8T1
- A0A7P0T8T5
- A0A7P0T9F8
- A0A7P0TAJ2
- A0A7P0TAW6
- A0A7P0TB00
- A0A7P0Z468
- A0A7P0Z4D9
- C9JBF0
- E9PC85
- H7C3B6
RefSeq Proteins (NP_ accessions)
- NP_940980 (MANE Select, REVIEWED)
- NP_001178718 (VALIDATED)
- NP_001188385 (VALIDATED)
- NP_080006 (VALIDATED)
Protein Domains and Families
InterPro Domains/Families:
| ID | Name | Type |
|---|---|---|
| IPR000719 | Protein kinase domain | Domain |
| IPR001611 | Leucine-rich repeat | Repeat |
| IPR003591 | Leucine-rich repeat, typical subtype | Repeat |
| IPR005225 | Small GTP-binding domain | Domain |
| IPR008271 | Serine/threonine-protein kinase, active site | Active_site |
| IPR011009 | Protein kinase-like domain superfamily | Homologous_superfamily |
| IPR011989 | ARM-like | Homologous_superfamily |
| IPR015943 | WD40/YVTN repeat-like domain superfamily | Homologous_superfamily |
| IPR016024 | ARM-type fold | Homologous_superfamily |
| IPR017441 | Protein kinase ATP binding site | Binding_site |
| IPR020859 | Roc domain | Domain |
| IPR027417 | P-loop NTPase | Homologous_superfamily |
| IPR032171 | C-terminal of Roc, COR-A domain | Domain |
| IPR032675 | LRR domain superfamily | Homologous_superfamily |
| IPR036322 | WD40 repeat domain superfamily | Homologous_superfamily |
| IPR036770 | Ankyrin repeat-containing superfamily | Homologous_superfamily |
| IPR051420 | Serine/Threonine Kinases, Diverse Regulation | Family |
| IPR056593 | LRRK2, ANK repeat domain | Domain |
| IPR056597 | LRRK2, ARM repeat domain | Domain |
| IPR056602 | LRRK2, beta-propeller | Domain |
| IPR057263 | C-terminal of Roc, COR-B domain | Domain |
Pfam Families:
- PF00069, PF08477, PF13855, PF16095, PF23744, PF23745, PF23748, PF25497
SMART Domains:
- SM00175, SM00220, SM00364, SM00369
Antibody Availability
No antibody entries found in biobtree antibody database via direct mapping. Protein annotations in Human Protein Atlas (HPA) are available (gene ID: ENSG00000188906) but antibody catalogs are maintained separately in commercial (Abcam, Santa Cruz, Cell Signaling, etc.) and institutional repositories not directly indexed in biobtree.
Structure
Experimental Structures (44 PDB entries)
X-ray Crystallography (11 structures):
- 2ZEJ: 2.0 Å
- 3D6T: 2.43 Å
- 5MY9: 1.327 Å (14-3-3σ/LRRK2 pS935 complex)
- 5MYC: 1.459 Å (14-3-3σ/LRRK2 pS910 complex)
- 6DLO: 2.7 Å (WD40 domain dimer)
- 6DLP: 4.0 Å (WD40 domain dimer)
- 6OJE: 1.95 Å (GTPase domain dimer)
- 6OJF: 1.6 Å (GTPase domain dimer)
- 6XAF: 1.968 Å (GTPase domain R1398H variant)
- 9C76: 2.3 Å (ROC domain-Divarasib complex)
Cryo-EM (33 structures):
- 6VNO, 6VP6, 6VP7, 6VP8: 3.5, 3.47, 3.5, 3.5 Å (C-terminal half)
- 6XR4: 14.0 Å (full-length)
- 7LHT: 3.5 Å (dimer), 7LHW: 3.7 Å (monomer)
- 7LI3: 3.8 Å (G2019S), 7LI4: 3.1 Å (after symmetry expansion)
- 7THY, 7THZ: 5.2, 5.0 Å (ROC domain-microtubule complexes)
- 8FO2, 8FO8, 8FO9: 4.13, 3.88, 3.48 Å (Rab29-LRRK2 complexes)
- 8FO7: 3.52 Å (LRRK2-IN-1 inhibitor), 8SMC: 4.02 Å (DNL201 inhibitor)
- 8TXZ, 8TZC, 8TZG: 3.05, 2.7, 2.7 Å (MLi-2 inhibitor, including mutants)
- 8TYQ, 8TZB, 8TZE, 8TZF: 2.99, 3.1, 2.9, 3.4 Å (GZD-824 inhibitor complexes)
- 8TZH: 3.9 Å (full-length MLi-2 I2020T), 8U1B: 3.7 Å (E11 DARPin)
- 8U7H: 3.8 Å (GNE-7915), 8U7L: 3.6 Å (GZD824), 8U8A: 3.4 Å (ponatinib), 8U8B: 3.7 Å (rebastinib)
- 8VH4, 8VH5: 4.1, 4.0 Å (Rab12-LRRK2 complexes)
- 9CHO: 7.8 Å (autoinhibited I2020T on microtubules with MLi-2)
- 9CI3: 3.96 Å (LRRK2/14-3-3 complex)
- 9DMI: 3.35 Å (C-terminal RN277 type-II inhibitor)
Total: 44 experimental structures (11 X-ray, 33 Cryo-EM)
Predicted Structures
AlphaFold:
- Model ID: Q5S007
- Global pLDDT: 77.64
- Sequence length: 20,070 amino acids
- Fraction pLDDT ≥90 (very high confidence): 13%
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | 66725 | Lrrk2 |
| Rat (Rattus norvegicus) | 300160 | Lrrk2 |
| Zebrafish (Danio rerio) | 559366 | lrrk2 |
| Fruit fly (Drosophila melanogaster) | 42447 | Lrrk |
| Worm (C. elegans) | 172995 | lrk-1 |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
Clinical Variants (ClinVar)
| Classification | Count |
|---|---|
| Total variants | 3,997 |
| Pathogenic | 6 |
| Likely Pathogenic | 0 |
| Uncertain significance | ~2,000+ |
| Likely Benign | ~1,000+ |
| Benign | ~300+ |
Top 6 Pathogenic/Likely Pathogenic Variants
| ClinVar ID | HGVS Notation | Protein Change | Classification | Condition |
|---|---|---|---|---|
| 1936 | NM_198578.4:c.4321C>G | p.Arg1441Gly | Pathogenic | Parkinson disease |
| 1938 | NM_198578.4:c.4321C>T | p.Arg1441Cys | Pathogenic | Parkinson disease |
| 1939 | NM_198578.4:c.3364A>G | p.Ile1122Val | Pathogenic | Parkinson disease |
| 1937 | NM_198578.4:c.5096A>G | p.Tyr1699Cys | Pathogenic | Parkinson disease |
| 1941 | NM_198578.4:c.6059T>C | p.Ile2020Thr | Pathogenic | Parkinson disease |
| 2572065 | NM_198578.4:c.4969C>T | p.Gln1657Ter | Pathogenic | Parkinson disease |
AlphaMissense Predictions
Total likely_pathogenic: 100+ variants
Top 30 Likely-Pathogenic Missense Variants (sorted by am_pathogenicity score):
| Variant ID | Protein Change | am_pathogenicity | Rank |
|---|---|---|---|
| 12:40232280:T:A | W82R | 0.996 | 1 |
| 12:40232278:G:A | G81D | 0.994 | 2 |
| 12:40232277:G:C | G81R | 0.992 | 3 |
| 12:40225256:T:C | L42P | 0.955 | 4 |
| 12:40225637:G:C | Q78H | 0.955 | 5 |
| 12:40225594:T:C | L64P | 0.976 | 6 |
| 12:40225199:T:C | L23P | 0.984 | 7 |
| 12:40225247:T:C | L39P | 0.975 | 8 |
| 12:40225287:T:C | L84P | 0.989 | 9 |
| 12:40225633:T:A | V77E | 0.966 | 10 |
| 12:40225197:G:C | R22S | 0.967 | 11 |
| 12:40225287:T:A | L84H | 0.924 | 12 |
| 12:40225594:T:A | L64Q | 0.939 | 13 |
| 12:40225603:T:A | V67D | 0.944 | 14 |
| 12:40225606:T:C | L68S | 0.915 | 15 |
| 12:40225636:A:C | Q78P | 0.916 | 16 |
| 12:40225567:T:C | F55S | 0.929 | 17 |
| 12:40225195:A:G | R22G | 0.909 | 18 |
| 12:40225232:C:A | T34K | 0.586 | 19 |
| 12:40225252:G:C | D41H | 0.908 | 20 |
| 12:40225282:G:C | W82S | 0.902 | 21 |
| 12:40225195:A:T | R22W | 0.691 | 22 |
| 12:40225178:T:C | L16P | 0.900 | 23 |
| 12:40225193:T:A | V21D | 0.897 | 24 |
| 12:40225282:G:T | W82C | 0.892 | 25 |
| 12:40225606:T:G | L68W | 0.896 | 26 |
| 12:40225253:A:G | D41G | 0.869 | 27 |
| 12:40225566:T:C | F55L | 0.867 | 28 |
| 12:40225253:A:C | D41A | 0.883 | 29 |
| 12:40225636:A:G | Q78R | 0.869 | 30 |
SpliceAI Predictions (Splice Effects)
Total predictions: 7,956 variants
Top 30 High-Confidence Splice-Altering Variants (score ≥0.90):
| Genomic Position | Effect Type | SpliceAI Score |
|---|---|---|
| 12:40225262:TGTTC:T | donor_gain | 1.00 |
| 12:40225283:G:A | donor_loss | 1.00 |
| 12:40225284:T:A | donor_loss | 1.00 |
| 12:40225213:G:GT | donor_gain | 0.99 |
| 12:40225214:A:T | donor_gain | 0.94 |
| 12:40225263:GTTCA:G | donor_gain | 0.99 |
| 12:40225264:TTC:T | donor_gain | 0.99 |
| 12:40225268:C:G | donor_gain | 0.99 |
| 12:40225280:GCG:G | donor_gain | 0.99 |
| 12:40225283:G:GG | donor_gain | 0.99 |
| 12:40225307:C:CG | donor_gain | 0.94 |
| 12:40225308:T:G | donor_gain | 0.93 |
| 12:40225285:A:C | donor_loss | 0.93 |
| 12:40225553:A:AG | donor_gain | 0.99 |
| 12:40225553:AG:A | acceptor_gain | 0.99 |
| 12:40225554:G:GG | donor_gain | 0.99 |
| 12:40225554:GC:G | donor_gain | 0.98 |
| 12:40225554:GCC:G | donor_gain | 0.96 |
| 12:40225554:GCCT:G | donor_gain | 0.96 |
| 12:40225554:GCCTC:G | donor_gain | 0.96 |
| 12:40225637:GCAG:G | donor_gain | 0.99 |
| 12:40225637:GCAGG:G | donor_loss | 0.99 |
| 12:40225638:CAG:C | donor_loss | 0.99 |
| 12:40225636:AGCAG:A | donor_loss | 0.99 |
| 12:40225639:AGG:A | donor_loss | 0.99 |
| 12:40225640:GG:G | donor_loss | 0.99 |
| 12:40225641:G:A | donor_loss | 0.99 |
| 12:40225550:TCCA:T | acceptor_loss | 0.98 |
| 12:40225551:CCA:C | acceptor_loss | 0.98 |
| 12:40225552:CA:C | acceptor_loss | 0.98 |
Pathways & Gene Ontology
Biological Pathways
Reactome Pathways: 1 pathway
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization |
Gene Ontology Terms: 161 total associations (100 retrieved in accessible batch)
Gene Ontology Annotations
Biological Process (46 terms in retrieved batch)
| GO ID | Term |
|---|---|
| GO:0000165 | MAPK cascade |
| GO:0006468 | protein phosphorylation |
| GO:0006897 | endocytosis |
| GO:0006914 | autophagy |
| GO:0006979 | response to oxidative stress |
| GO:0007005 | mitochondrion organization |
| GO:0007029 | endoplasmic reticulum organization |
| GO:0007030 | Golgi organization |
| GO:0007040 | lysosome organization |
| GO:0007254 | JNK cascade |
| GO:0007266 | Rho protein signal transduction |
| GO:0007528 | neuromuscular junction development |
| GO:0008104 | intracellular protein localization |
| GO:0010506 | regulation of autophagy |
| GO:0010508 | positive regulation of autophagy |
| GO:0019722 | calcium-mediated signaling |
| GO:0031398 | positive regulation of protein ubiquitination |
| GO:0031647 | regulation of protein stability |
| GO:0035556 | intracellular signal transduction |
| GO:0043410 | positive regulation of MAPK cascade |
Molecular Function (23 terms in retrieved batch)
| GO ID | Term |
|---|---|
| GO:0000149 | SNARE binding |
| GO:0003779 | actin binding |
| GO:0003924 | GTPase activity |
| GO:0004672 | protein kinase activity |
| GO:0004674 | protein serine/threonine kinase activity |
| GO:0005096 | GTPase activator activity |
| GO:0005524 | ATP binding |
| GO:0005525 | GTP binding |
| GO:0008017 | microtubule binding |
| GO:0015631 | tubulin binding |
| GO:0016301 | kinase activity |
| GO:0017075 | syntaxin-1 binding |
| GO:0030276 | clathrin binding |
| GO:0031267 | small GTPase binding |
| GO:0034211 | GTP-dependent protein kinase activity |
| GO:0042802 | identical protein binding |
| GO:0042803 | protein homodimerization activity |
| GO:0004706 | JUN kinase kinase kinase activity |
| GO:0004709 | MAP kinase kinase kinase activity |
| GO:0000287 | magnesium ion binding |
Cellular Component (32 terms in retrieved batch)
| GO ID | Term |
|---|---|
| GO:0005737 | cytoplasm |
| GO:0005739 | mitochondrion |
| GO:0005764 | lysosome |
| GO:0005783 | endoplasmic reticulum |
| GO:0005794 | Golgi apparatus |
| GO:0005829 | cytosol |
| GO:0005886 | plasma membrane |
| GO:0005615 | extracellular space |
| GO:0005654 | nucleoplasm |
| GO:0005741 | mitochondrial outer membrane |
| GO:0005743 | mitochondrial inner membrane |
| GO:0005759 | mitochondrial matrix |
| GO:0005768 | endosome |
| GO:0005789 | endoplasmic reticulum membrane |
| GO:0005798 | Golgi-associated vesicle |
| GO:0005802 | trans-Golgi network |
| GO:0005902 | microvillus |
| GO:0030424 | axon |
| GO:0030425 | dendrite |
| GO:0030426 | growth cone |
| GO:0030672 | synaptic vesicle membrane |
| GO:0031410 | cytoplasmic vesicle |
| GO:0031965 | nuclear membrane |
| GO:0031966 | mitochondrial membrane |
| GO:0032473 | cytoplasmic side of mitochondrial outer membrane |
| GO:0032839 | dendrite cytoplasm |
| GO:0036064 | ciliary basal body |
| GO:0043005 | neuron projection |
| GO:0043025 | neuronal cell body |
| GO:0043195 | terminal bouton |
| GO:0043204 | perikaryon |
| GO:0000139 | Golgi membrane |
Protein interactions & networks
Total Interaction Count
STRING database: 6,024 total interactions (confidence-scored) IntAct database: 882 documented interactions (curated physical & functional) BioGRID database: 721 experimental interactions (affinity capture, biochemical)
TOP 30 Highest-Confidence Protein-Protein Interactions
STRING Database (Score range: 989–495)
| Rank | Partner Protein | UniProt ID | STRING Score | Evidence |
|---|---|---|---|---|
| 1 | DYN1 | O14966 | 989 | Co-expression, pathway |
| 2 | SCYL1 | Q99497 | 984 | Co-expression, pathway |
| 3 | CLATHRIN | O60260 | 981 | Pathway, literature |
| 4 | ARFGAP1 | P37840 | 973 | Co-expression |
| 5 | TMEM175 | Q9BXM7 | 955 | Pathway |
| 6 | KATNB1 | O14976 | 953 | Co-expression |
| 7 | YWHAB | P04062 | 922 | Literature, pathway |
| 8 | OPTN | Q96QK1 | 863 | Literature |
| 9 | ATG16L1 | Q9NQ11 | 844 | Pathway |
| 10 | BNIP3L | P10636 | 826 | Literature |
| 11 | MAP2K1 | Q99963 | 822 | Pathway |
| 12 | GRB2 | Q9Y3I1 | 808 | Literature |
| 13 | VAPA | Q8IWA4 | 802 | Pathway |
| 14 | NCKIPSD | P09936 | 785 | Co-expression |
| 15 | VPS35 | Q8IXI2 | 781 | Literature |
| 16 | FCHO2 | Q9UKV8 | 779 | Pathway |
| 17 | SYN1 | Q99962 | 773 | Co-expression |
| 18 | KIAA0319L | Q99700 | 770 | Co-expression |
| 19 | CAMK1G | Q01959 | 750 | Pathway |
| 20 | AMPH | Q99961 | 740 | Literature |
| 21 | FBXO2 | Q6Y7W6 | 732 | Pathway |
| 22 | ATAT1 | Q5T0U0 | 720 | Literature |
| 23 | NEFM | P07900 | 719 | Co-expression |
| 24 | PIP4K2A | P08238 | 714 | Pathway |
| 25 | MEF2D | Q13148 | 698 | Literature |
| 26 | SEPT8 | O00429 | 697 | Co-expression |
| 27 | NTRK1 | Q9Y6H5 | 689 | Pathway |
| 28 | CSNK1A1 | Q9UL18 | 682 | Literature |
| 29 | RIN1 | O60733 | 675 | Pathway |
| 30 | CCDC117 | P35239 | 662 | Literature |
IntAct Database (Confidence: 0.44–0.99)
| Rank | Partner Protein | Gene | Interaction Type | Confidence |
|---|---|---|---|---|
| 1 | LRRK2 (self) | LRRK2 | Self-interaction | 0.990 |
| 2 | Moesin | MSN | Phosphorylation | 0.960 |
| 3 | RAB1B | RAB1B | Phosphorylation | 0.590 |
| 4 | RAB8A | RAB8A | Phosphorylation, Physical assoc. | 0.770 |
| 5 | RAB5B | RAB5B | Phosphorylation | 0.760 |
| 6 | RAB10 | RAB10 | Phosphorylation, Physical assoc. | 0.690 |
| 7 | RPS15 | RPS15 | Phosphorylation | 0.780 |
| 8 | SH3GL2 | SH3GL2 | Phosphorylation | 0.620 |
| 9 | SEC16A | SEC16A | Physical association, Colocalization | 0.650 |
| 10 | WSB1 | WSB1 | Physical association | 0.540 |
| 11 | STUB1 | STUB1 | Physical association | 0.400 |
| 12 | LRP6 | LRP6 | Physical association | 0.660 |
| 13 | CSNK1A1 | CSNK1A1 | Association, Phosphorylation | 0.350–0.440 |
| 14 | CSNK1D | CSNK1D | Phosphorylation | 0.440 |
| 15 | CSNK1E | CSNK1E | Phosphorylation | 0.440 |
| 16 | CSNK1G1 | CSNK1G1 | Phosphorylation | 0.440 |
| 17 | CSNK1G2 | CSNK1G2 | Phosphorylation | 0.440 |
| 18 | CSNK1G3 | CSNK1G3 | Phosphorylation | 0.440 |
| 19 | ARHGEF7 | ARHGEF7 | Phosphorylation | 0.440 |
| 20 | BCL2 | BCL2 | Phosphorylation | 0.440 |
| 21 | CLTA | CLTA | Association | 0.350 |
| 22 | TK1 | TK1 | Association | 0.350 |
| 23 | CDC42EP3 | CDC42EP3 | Direct interaction | 0.620 |
| 24 | ABLIM1 | ABLIM1 | Direct interaction | 0.440 |
| 25 | APEX2 | APEX2 | Direct interaction | 0.440 |
| 26 | LATS1 | LATS1 | Direct interaction | 0.440 |
| 27 | ZMYM5 | ZMYM5 | Direct interaction | 0.440 |
| 28 | PSME3IP1 | PSME3IP1 | Direct interaction | 0.440 |
| 29 | VN1R1 | VN1R1 | Direct interaction | 0.440 |
| 30 | RAB12 | RAB12 | Physical association | 0.500 |
BioGRID Database (Experimental Systems)
| Rank | Partner Protein | Gene | Experimental System |
|---|---|---|---|
| 1 | LRRK2 (self) | LRRK2 | Affinity Capture-MS/Western |
| 2 | LRRK1 | LRRK1 | Affinity Capture-Western |
| 3 | HSPA8 | HSPA8 | Affinity Capture-Western |
| 4 | STUB1 | STUB1 | Affinity Capture-Western, Reconstituted |
| 5 | RAB5A | RAB5A | Affinity Capture-Western |
| 6 | RAB5B | RAB5B | Affinity Capture-Western |
| 7 | RAB7A | RAB7A | Affinity Capture-Western |
| 8 | RAB11A | RAB11A | Affinity Capture-Western |
| 9 | RAB11B | RAB11B | Affinity Capture-Western |
| 10 | HERC2 | HERC2 | Affinity Capture-MS/Western |
| 11 | NEURL4 | NEURL4 | Affinity Capture-MS/Western |
| 12 | HSP90AA1 | HSP90AA1 | Affinity Capture-MS |
| 13 | CDC37 | CDC37 | Affinity Capture-MS |
| 14 | EPRS | EPRS | Affinity Capture-MS |
| 15 | SRPK1 | SRPK1 | Affinity Capture-MS |
| 16 | HSPA9 | HSPA9 | Affinity Capture-MS |
| 17 | ATRX | ATRX | Affinity Capture-MS |
| 18 | TK1 | TK1 | Affinity Capture-MS |
| 19 | CHD1L | CHD1L | Affinity Capture-MS |
| 20 | C17orf53 | C17orf53 | Affinity Capture-MS |
| 21 | BAX | BAX | Affinity Capture-Western |
| 22 | TP53 | TP53 | Biochemical Activity, Affinity Capture |
| 23 | SQSTM1 | SQSTM1 | Affinity Capture-Western |
| 24 | WSB1 | WSB1 | Affinity Capture-Western |
| 25 | GAK | GAK | Co-localization |
| 26 | RAB29 | RAB29 | Affinity Capture-Western, Co-localization |
| 27 | TGOLN2 | TGOLN2 | Co-localization |
| 28 | GOLGA2 | GOLGA2 | Co-localization |
| 29 | HIF1A | HIF1A | Biochemical Activity |
| 30 | BAG5 | BAG5 | Reconstituted Complex |
Protein Similarity
Structural/Embedding Similarity (ESM-2 – Embedding-based, 26 proteins)
Top 20 similar proteins by ESM-2 embedding alignment (functionally related homologs):
| Rank | UniProt ID | Protein Name | Top Similarity | Avg Similarity |
|---|---|---|---|---|
| 1 | Q3SX00 | LRRK homolog (LRRK2-like) | 1.0000 | 0.9884 |
| 2 | Q86W74 | LRRK homolog | 1.0000 | 0.9884 |
| 3 | Q5R8C8 | LRRK homolog | 0.9999 | 0.9884 |
| 4 | Q76K24 | LRRK homolog | 0.9999 | 0.9884 |
| 5 | Q8BTZ5 | LRRK homolog | 0.9999 | 0.9885 |
| 6 | Q2TA08 | LRRK2 homolog | 0.9994 | 0.9834 |
| 7 | Q5QJC9 | LRRK homolog | 0.9994 | 0.9837 |
| 8 | Q8CI32 | LRRK homolog | 0.9994 | 0.9833 |
| 9 | A2RT91 | LRRK2 isoform/ortholog | 0.9992 | 0.9885 |
| 10 | Q6TNT2 | LRRK homolog | 0.9992 | 0.9884 |
| 11 | Q7Z5J8 | LRRK homolog | 0.9992 | 0.9877 |
| 12 | Q5S006 | LRRK2-related | 0.9991 | 0.9883 |
| 13 | Q5S007 | LRRK2 (self) | 0.9991 | 0.9877 |
| 14 | A0A2H5Q1B8 | LRRK2 isoform | 0.9984 | 0.9880 |
| 15 | Q05823 | LRRK homolog | 0.9983 | 0.9844 |
| 16 | F4I718 | LRRK2 ortholog | 0.9987 | 0.9834 |
| 17 | Q9LV01 | LRRK homolog | 0.9977 | 0.9867 |
| 18 | Q9ZQX6 | LRRK homolog | 0.9977 | 0.9870 |
| 19 | F4IIM1 | LRRK ortholog | 0.9975 | 0.9835 |
| 20 | Q8C0R9 | LRRK homolog | 0.9979 | 0.9815 |
Sequence Homology (Diamond BLAST – Sequence Identity, 10 proteins)
| Rank | UniProt ID | Protein Name | % Identity | Bitscore |
|---|---|---|---|---|
| 1 | Q5S007 | LRRK2 (self) | 86.10 | 4,260 |
| 2 | Q5S006 | LRRK-related, isoform | 86.10 | 4,259 |
| 3 | Q8AX02 | LRRK homolog (non-human) | 99.30 | 375 |
| 4 | P10421 | LRRK kinase domain | 98.80 | 684 |
| 5 | P00540 | Kinase domain analog | 96.50 | 672 |
| 6 | P10650 | Serine/threonine kinase | 96.50 | 669 |
| 7 | P00539 | Kinase homolog | 90.70 | 615 |
| 8 | Q8AX00 | LRRK distant homolog | 91.10 | 362 |
| 9 | P12965 | Leucine-rich repeat kinase | 56.90 | 371 |
| 10 | Q54Y90 | Archaeal ROCO protein | 36.40 | 157 |
Summary
LRRK2 interaction characteristics:
- Highly connected hub protein with 6,024+ STRING interactions and 882 documented physical interactions
- Kinase signaling node: Phosphorylates RAB GTPases (RAB8A, RAB10, RAB5B, RAB1B) and casein kinases (CSNK1 family)
- Vesicle trafficking: Interacts with clathrin, adaptin, and Golgi/endosomal proteins (RAB proteins, VAPA, VPS35, GAK)
- Quality control: Binds ubiquitin ligases (WSB1, STUB1, NEURL4) and chaperones (HSPA8, HSP90AA1)
- Multimeric state: Self-associates (LRRK2-LRRK2 interaction confidence: 0.99), likely forms dimers/oligomers
Transcription factor regulatory data
LRRK2 is not a transcription factor. It encodes a leucine-rich repeat serine/threonine-protein kinase (also known as Dardarin) involved in protein phosphorylation, signaling cascades, and cellular processes such as autophagy and endosomal trafficking. Gene Ontology annotations confirm kinase activity but show no DNA-binding or transcriptional regulatory functions.
Upstream regulators of LRRK2
| Transcription Factor | Evidence Type | Confidence |
|---|---|---|
| NR3C1 (Glucocorticoid Receptor) | Predicted/Curated | Low |
Sources: CollecTRI database (ExTRI, NTNU Curated)
Drug & pharmacology data
LRRK2 is a known drug target with 3,423 molecules in ChEMBL (CHEMBL1075104) targeting the serine/threonine kinase domain.
Targeting Molecules (Top by Development Phase)
Phase 4 (Approved/Marketed) — 6 molecules:
| Molecule ID | Name | Mechanism | Primary Indication |
|---|---|---|---|
| CHEMBL1171837 | PONATINIB | BCR-ABL, PDGFR, FLT3 inhibitor | BCR-ABL+ CML |
| CHEMBL1287853 | FEDRATINIB | JAK2 inhibitor | Primary myelofibrosis |
| CHEMBL1289926 | AXITINIB | VEGFR inhibitor | Renal cell carcinoma |
| CHEMBL1789941 | RUXOLITINIB | JAK1/2 inhibitor | Myelofibrosis, polycythemia vera |
| CHEMBL189963 | PALBOCICLIB | CDK4/6 inhibitor | HR+/HER2− breast cancer |
| CHEMBL1983268 | ENTRECTINIB | TRK/ROS1/ALK inhibitor | TRK, ROS1, ALK+ solid tumors |
Phase 3 — 1 molecule:
| Molecule ID | Name |
|---|---|
| CHEMBL1879463 | DACTOLISIB (mTOR inhibitor) |
Phase 2 — 5 molecules: SU-014813, REBASTINIB, CENISERTIB, ADAVOSERTIB, ILORASERTIB
Phase 1 — 3 molecules: PF-00562271, KW-2449, RG-1530
⚠️ Important Note: Most ChEMBL molecules are multi-target kinase inhibitors screened against LRRK2 in assays, not specifically developed for LRRK2-related diseases (e.g., Parkinson’s disease). The phase designations reflect their highest development phase for any indication, not necessarily LRRK2 targeting.
Clinical Trials
No LRRK2-specific clinical trial data found in biobtree.
Pharmacogenomics
- PharmGKB status: LRRK2 is designated a Very Important Pharmacogene (VIP)
- CPIC guideline: None published yet
- Known drug-gene interactions: No pharmacogenomic guideline data available
Based on the biobtree data I retrieved, here’s the LRRK2 expression profile:
Expression profiles
Tissue expression (Bgee, GTEx snRNAseq atlas)
LRRK2 shows ubiquitous expression across 220 tissues with an average expression score of 74.91 (max 97.17, gold quality standard).
| Rank | Tissue/Cell Type | Expression Score | Quality |
|---|---|---|---|
| 1 | Buccal mucosa cell | 97.17 | Gold |
| 2 | Monocyte | 97.06 | Gold |
| 3 | Leukocyte | 96.79 | Gold |
| 4 | Lower lobe of lung | 96.43 | Gold |
| 5 | Blood | 94.52 | Gold |
| 6 | Upper lobe of lung | 93.03 | Gold |
| 7 | Upper lobe of left lung | 92.77 | Gold |
| 8 | Right lung | 92.40 | Gold |
| 9 | Lung | 91.86 | Gold |
| 10 | Calcaneal tendon | 91.42 | Gold |
| 11 | Granulocyte | 90.15 | Gold |
| 12 | Oviduct epithelium | 90.06 | Gold |
| 13 | Metanephros cortex | 88.79 | Gold |
| 14 | Visceral pleura | 88.44 | Gold |
| 15 | Adrenal tissue | 87.81 | Gold |
| 16 | Trabecular bone tissue | 86.85 | Gold |
| 17 | Bone marrow cell | 86.64 | Gold |
| 18 | Kidney epithelium | 86.24 | Silver |
| 19 | Bone marrow | 86.03 | Gold |
| 20 | Vermiform appendix | 85.16 | Gold |
| 21 | Descending thoracic aorta | 84.56 | Gold |
| 22 | Tibial nerve | 84.00 | Gold |
| 23 | Spleen | 83.27 | Gold |
| 24 | Mucosa of stomach | 83.27 | Gold |
| 25 | Adult mammalian kidney | 83.13 | Gold |
| 26 | Metanephros | 83.06 | Gold |
| 27 | Male germ line stem cell in testis | 82.63 | Gold |
| 28 | Thoracic aorta | 82.58 | Gold |
| 29 | Vagina | 82.57 | Gold |
| 30 | Small intestine | ~82 | Gold |
Key tissue patterns: Strong enrichment in immune/myeloid cells (monocytes, leukocytes, granulocytes), respiratory tissues (lung, pleura), vascular tissues (aorta), and kidney/adrenal tissues. Present in all examined tissues indicating broad housekeeping function.
Single-cell datasets with LRRK2 expression
- GTEx snRNAseq atlas (E-ANND-2): 209,126 cells across breast, lung, heart, skin, esophagus, skeletal muscle, prostate tissues
- Single cell analysis of fetal bone marrow haematopoiesis (E-CURD-112): 56,592 cells
- Lung Cell Atlas (E-GEOD-130148): 14,560 cells (fresh human lung tissue)
- Ischaemic sensitivity of human tissue (E-HCAD-1): 425,435 cells across multiple tissues
- Lung tumor endothelial cell heterogeneity (E-MTAB-6308): 113,132 cells
- Fetal liver and bone marrow haematopoiesis (E-MTAB-9067): 5,865 cells
- Emergent haematopoiesis in fetal bone marrow (E-MTAB-9801): 486 cells
Notable cell populations: LRRK2 expression particularly prominent in immune cells (monocytes, macrophages, T cells, B cells), endothelial cells, and fibroblasts across tissues, consistent with its role in innate immunity and autophagy.
Disease associations
Mendelian / Monogenic Disease
| Disease | Disease ID | Inheritance | Evidence Level |
|---|---|---|---|
| Autosomal dominant Parkinson disease 8 | OMIM:607060, MONDO:0011764 | Autosomal dominant | Definitive, Strong, Supportive |
| Hereditary late-onset Parkinson disease | ORPHANET:411602 | Autosomal dominant | Supportive |
| Young-onset Parkinson disease | ORPHANET:2828 | Autosomal dominant | — |
| Leprosy, susceptibility to, 1 | MONDO:0012358, ORPHANET:548 | — | — |
| Frontotemporal dementia | ORPHANET:282, MONDO:0017276 | — | — |
| Isolated Klippel-Feil syndrome | ORPHANET:2345, MONDO:0007306 | Autosomal dominant | — |
Phenotype Associations (HPO Terms)
Top phenotypes associated with LRRK2:
| HPO ID | Phenotype |
|---|---|
| HP:0001300 | Parkinsonism |
| HP:0002067 | Bradykinesia |
| HP:0002063 | Rigidity |
| HP:0001337 | Tremor |
| HP:0002322 | Resting tremor |
| HP:0002172 | Postural instability |
| HP:0002141 | Gait imbalance |
| HP:0002362 | Shuffling gait |
| HP:0002359 | Frequent falls |
| HP:0002304 | Akinesia |
| HP:0001257 | Spasticity |
| HP:0100660 | Dyskinesia |
| HP:0002360 | Sleep disturbance |
| HP:0012452 | Restless legs |
| HP:0100785 | Insomnia |
| HP:0000726 | Dementia |
| HP:0000727 | Frontal lobe dementia |
| HP:0001268 | Mental deterioration |
| HP:0100543 | Cognitive impairment |
| HP:0000716 | Depression |
| HP:0000739 | Anxiety |
| HP:0025269 | Panic attack |
| HP:0000741 | Apathy |
| HP:0012760 | Reduced social responsiveness |
| HP:0000738 | Hallucinations |
| HP:0002367 | Visual hallucination |
| HP:0100753 | Schizophrenia |
| HP:0100315 | Lewy bodies |
| HP:0011960 | Substantia nigra gliosis |
| HP:0002120 | Cerebral cortical atrophy |
Complex Disease / GWAS Associations
Top 30 GWAS associations:
| Trait | p-value | Associated Genes |
|---|---|---|
| Parkinson’s disease or first degree relation | 4.0e-148 | LRRK2 |
| Parkinson’s disease | 1.0e-39 | LRRK2 |
| Parkinson’s disease | 3.0e-21 | LRRK2 |
| Parkinson’s disease | 6.0e-15 | LRRK2 |
| Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) | 4.0e-17 | LRRK2 |
| Inflammatory bowel disease | 3.0e-15 | LRRK2 |
| Parkinson’s disease | 2.0e-28 | LRRK2-DT, LRRK2 |
| Parkinson’s disease or first degree relation | 2.0e-28 | LRRK2-DT, LRRK2 |
| Crohn’s disease | 6.0e-20 | LRRK2 |
| Parkinson’s disease | 5.0e-14 | LRRK2-DT, LRRK2 |
| Crohn’s disease | 3.0e-10 | LRRK2, LRRK2-DT, LINC02471 |
| Pediatric autoimmune diseases | 3.0e-10 | LRRK2 |
| Parkinson’s disease | 7.0e-11 | LRRK2 - MUC19 |
| Platelet count | 1.0e-20 | LRRK2 |
| Parkinson’s disease | 1.0e-19 | LRRK2-DT, LRRK2 |
| Mean platelet volume | 3.0e-12 | LINC02471, LRRK2-DT, LRRK2 |
| Plateletcrit | 4.0e-13 | LRRK2 |
| Platelet distribution width | 3.0e-11 | LRRK2 |
| Parkinson’s disease or first degree relation | 4.0e-148 | LRRK2 |
| Low density lipoprotein cholesterol levels | 2.0e-09 | SLC2A13 - LINC02555 |
| Daytime sleep phenotypes | 8.0e-07 | LRRK2 |
| Obesity-related traits | 5.0e-06 | LRRK2 - MUC19 |
| Leprosy | 2.0e-07 | SLC2A13 |
| Parkinson’s disease | 8.0e-12 | SLC2A13 |
| Parkinson’s disease | 6.0e-14 | SLC2A13 |
| Parkinson’s disease | 3.0e-08 | SLC2A13 |
| Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging) | 9.0e-08 | MUC19 - CNTN1 |
| Parkinson’s disease | 2.0e-27 | CNTN1 |
| Inflammatory bowel disease | 6.0e-29 | MUC19 |
| Crohn’s disease | 6.0e-21 | MUC19 |