Provide a comprehensive cross-database identifier and functional mapping reference for human LRRK2. This should serve as a definitive lookup resource for researchers. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 1: GENE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Provide ALL gene-level database identifiers: - 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 ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 2: TRANSCRIPT IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL transcript-level identifiers: - Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.) How many total transcripts? - RefSeq transcripts: ALL NM_ mRNA accessions Mark which is MANE Select (canonical clinical standard) - CCDS IDs: ALL consensus coding sequence identifiers For the CANONICAL/MANE SELECT transcript: - List ALL exon IDs (ENSE) with genomic coordinates - Total exon count ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 3: PROTEIN IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL protein-level identifiers: - 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 - Include: domain name, type (domain/family/superfamily), and ID ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 4: STRUCTURE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Experimental structures: - List ALL PDB structure IDs - For each: experimental method (X-ray, NMR, Cryo-EM) and resolution - Total PDB structure count Predicted structures: - AlphaFold model ID and confidence metrics (pLDDT) ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 5: CROSS-SPECIES ORTHOLOGS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List orthologous genes in key model organisms (where available): - 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 ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Clinical variant annotations: - Total variant count in clinical databases - Breakdown by classification: Pathogenic, Likely Pathogenic, Uncertain Significance (VUS), Likely Benign, Benign - List TOP 50 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: Total count List TOP 50 predicted splice-altering variants with delta scores - Missense pathogenicity predictions: Total count List TOP 50 predicted pathogenic missense variants with scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Pathway membership: - List ALL biological pathways this gene participates in - Include pathway IDs and names - Total pathway count Gene Ontology annotations: - Biological Process: count and TOP 20 terms with IDs - Molecular Function: count and TOP 20 terms with IDs - Cellular Component: count and TOP 20 terms with IDs ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Protein-protein interactions: - Total interaction count - List TOP 50 highest-confidence interacting proteins with scores Protein similarity (evolutionary and structural): - Structural/embedding similarity: How many similar proteins? List TOP 20 with similarity scores - Sequence homology: How many homologous proteins? List TOP 20 with identity/similarity scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene encodes a transcription factor: Downstream targets (genes regulated BY this TF): - Total target gene count - List TOP 50 target genes with regulation type (activates/represses) DNA binding profiles: - List ALL known binding motif IDs - Motif family classification Upstream regulators (TFs that regulate THIS gene): - List known transcriptional regulators with evidence type ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 10: DRUG & PHARMACOLOGY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene/protein is a drug target: Targeting molecules: - How many drug/compound molecules target this protein? - List TOP 30 molecules by development phase - Include: molecule ID, name, mechanism, highest development phase Clinical trials: - How many clinical trials involve drugs targeting this gene? - List TOP 20 trials with: trial ID, phase, status, intervention Pharmacogenomics: - Known drug-gene interactions affecting drug response - Dosing guidelines if any exist ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 11: EXPRESSION PROFILES ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Tissue expression: - Which tissues express this gene most highly? - List TOP 30 tissues with expression scores/levels - Note any tissue-specific or tissue-enriched patterns Cell type expression: - Which cell types show highest expression? - List TOP 30 cell types with expression scores - Note any cell type-specific patterns Single-cell expression data (if available): - Which single-cell datasets/experiments include this gene? - Notable cell population patterns ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 12: DISEASE ASSOCIATIONS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Mendelian/monogenic disease links: - What diseases are caused by mutations in this gene? - List ALL associated diseases with: disease name, disease ID, inheritance pattern, evidence level Phenotype associations: - What clinical phenotypes are associated with this gene? - List TOP 50 phenotype terms with IDs Complex trait associations (GWAS): - What traits/diseases are linked via genome-wide association studies? - List TOP 30 GWAS associations with: trait, study ID, p-value, effect size if available ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ FORMATTING REQUIREMENTS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ - Present each section with clear headers - Use tables for listing multiple items - Always include COUNTS for every category - For lists with 50 items: show total count + TOP 50 - For lists with

Question

Provide a comprehensive cross-database identifier and functional mapping
reference for human LRRK2. This should serve as a definitive
lookup resource for researchers.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 1: GENE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Provide ALL gene-level database identifiers:
- 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

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 2: TRANSCRIPT IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL transcript-level identifiers:
- Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.)
  How many total transcripts?
- RefSeq transcripts: ALL NM_ mRNA accessions
  Mark which is MANE Select (canonical clinical standard)
- CCDS IDs: ALL consensus coding sequence identifiers

For the CANONICAL/MANE SELECT transcript:
- List ALL exon IDs (ENSE) with genomic coordinates
- Total exon count

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 3: PROTEIN IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL protein-level identifiers:
- 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
- Include: domain name, type (domain/family/superfamily), and ID

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 4: STRUCTURE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Experimental structures:
- List ALL PDB structure IDs
- For each: experimental method (X-ray, NMR, Cryo-EM) and resolution
- Total PDB structure count

Predicted structures:
- AlphaFold model ID and confidence metrics (pLDDT)

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 5: CROSS-SPECIES ORTHOLOGS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List orthologous genes in key model organisms (where available):
- 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
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Clinical variant annotations:
- Total variant count in clinical databases
- Breakdown by classification: Pathogenic, Likely Pathogenic,
  Uncertain Significance (VUS), Likely Benign, Benign
- List TOP 50 pathogenic/likely pathogenic variants with:
  variant ID, HGVS notation, associated condition

AI-based variant effect predictions:
- Splice effect predictions: Total count
  List TOP 50 predicted splice-altering variants with delta scores
- Missense pathogenicity predictions: Total count
  List TOP 50 predicted pathogenic missense variants with scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Pathway membership:
- List ALL biological pathways this gene participates in
- Include pathway IDs and names
- Total pathway count

Gene Ontology annotations:
- Biological Process: count and TOP 20 terms with IDs
- Molecular Function: count and TOP 20 terms with IDs
- Cellular Component: count and TOP 20 terms with IDs

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Protein-protein interactions:
- Total interaction count
- List TOP 50 highest-confidence interacting proteins with scores

Protein similarity (evolutionary and structural):
- Structural/embedding similarity: How many similar proteins?
  List TOP 20 with similarity scores
- Sequence homology: How many homologous proteins?
  List TOP 20 with identity/similarity scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene encodes a transcription factor:

Downstream targets (genes regulated BY this TF):
- Total target gene count
- List TOP 50 target genes with regulation type (activates/represses)

DNA binding profiles:
- List ALL known binding motif IDs
- Motif family classification

Upstream regulators (TFs that regulate THIS gene):
- List known transcriptional regulators with evidence type

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 10: DRUG & PHARMACOLOGY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene/protein is a drug target:

Targeting molecules:
- How many drug/compound molecules target this protein?
- List TOP 30 molecules by development phase
- Include: molecule ID, name, mechanism, highest development phase

Clinical trials:
- How many clinical trials involve drugs targeting this gene?
- List TOP 20 trials with: trial ID, phase, status, intervention

Pharmacogenomics:
- Known drug-gene interactions affecting drug response
- Dosing guidelines if any exist

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 11: EXPRESSION PROFILES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Tissue expression:
- Which tissues express this gene most highly?
- List TOP 30 tissues with expression scores/levels
- Note any tissue-specific or tissue-enriched patterns

Cell type expression:
- Which cell types show highest expression?
- List TOP 30 cell types with expression scores
- Note any cell type-specific patterns

Single-cell expression data (if available):
- Which single-cell datasets/experiments include this gene?
- Notable cell population patterns

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 12: DISEASE ASSOCIATIONS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Mendelian/monogenic disease links:
- What diseases are caused by mutations in this gene?
- List ALL associated diseases with: disease name, disease ID,
  inheritance pattern, evidence level

Phenotype associations:
- What clinical phenotypes are associated with this gene?
- List TOP 50 phenotype terms with IDs

Complex trait associations (GWAS):
- What traits/diseases are linked via genome-wide association studies?
- List TOP 30 GWAS associations with: trait, study ID, p-value,
  effect size if available

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
FORMATTING REQUIREMENTS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
- Present each section with clear headers
- Use tables for listing multiple items
- Always include COUNTS for every category
- For lists with >50 items: show total count + TOP 50
- For lists with <50 items: show ALL items
- Always include database identifiers (IDs), not just names
- Mark canonical/primary/reviewed entries where applicable
- If a section has no data available, state "No data available"
  rather than omitting the section

Accepted Answer

Human Gene Leucine Rich Repeat Kinase 2 Gene Identifiers** Primary Identifiers DatabaseIdentifierName/Symbol HGNCHGNC:18618LRRK2 (Approved symbol) EnsemblENSG00000188906LRRK2 NCBI Entrez120892LRRK2 OMIM609007LRRK2 gene UniProtQ5S007LRRK2_HUMAN (Canonical) Genomic Location AttributeValue Chromosome12 Cytogenetic Band12q12 Start Position40,196,744 (GRCh38) End Position40,369,285 (GRCh38) Strand+ (Plus/Forward) Gene Length172,542 bp Gene Classification Locus Group: protein-coding gene Locus Type: …

Type	Symbols
Aliases	ROCO2, DKFZp434H2111, FLJ45829, RIPK7, AURA17, DARDARIN
Previous Symbol	PARK8
Previous Name	Parkinson disease (autosomal dominant) 8

Transcript ID	Biotype	Start	End	Notes
ENST00000298910	protein_coding	40,224,997	40,369,285	Canonical
ENST00000343742	protein_coding	40,225,011	40,304,976
ENST00000416796	protein_coding	40,196,744	40,283,952
ENST00000636518	protein_coding	40,346,847	40,368,879
ENST00000680790	protein_coding	40,225,080	40,369,259
ENST00000681696	protein_coding	40,310,431	40,368,330
ENST00000950031	protein_coding	40,225,000	40,368,296
ENST00000430804	nonsense_mediated_decay	40,295,505	40,369,285
ENST00000644108	nonsense_mediated_decay	40,225,188	40,251,544
ENST00000679360	nonsense_mediated_decay	40,224,997	40,367,077
ENST00000679532	nonsense_mediated_decay	40,310,466	40,369,259
ENST00000679683	nonsense_mediated_decay	40,346,753	40,369,246
ENST00000680018	nonsense_mediated_decay	40,310,467	40,369,259
ENST00000680422	nonsense_mediated_decay	40,310,469	40,369,171
ENST00000680425	nonsense_mediated_decay	40,310,557	40,369,054
ENST00000680453	nonsense_mediated_decay	40,310,469	40,369,257
ENST00000474202	retained_intron	40,225,595	40,232,783
ENST00000479187	retained_intron	40,298,466	40,369,285
ENST00000681773	retained_intron	40,358,907	40,369,171
ENST00000481256	protein_coding_CDS_not_defined	40,312,714	40,320,062
ENST00000680235	protein_coding_CDS_not_defined	40,224,977	40,242,782
ENST00000681136	protein_coding_CDS_not_defined	40,312,389	40,368,330

Accession	Type	Status	MANE Select
NM_198578	mRNA	REVIEWED	YES ✓
NP_940980	protein	REVIEWED	YES ✓
XM_005268629	mRNA	PREDICTED	No
XM_011537877	mRNA	PREDICTED	No
XM_011537881	mRNA	PREDICTED	No
XM_011537882	mRNA	PREDICTED	No
XM_017018786	mRNA	PREDICTED	No
XM_017018787	mRNA	PREDICTED	No
XM_024448833	mRNA	PREDICTED	No
XM_047428277	mRNA	PREDICTED	No
XM_047428278	mRNA	PREDICTED	No
XM_047428279	mRNA	PREDICTED	No
XM_054371049-058	mRNA	PREDICTED	No

Exon ID	Chr	Start	End	Length
ENSE00001860962	12	40,224,997	40,225,282	286
ENSE00003635610	12	40,225,555	40,225,640	86
ENSE00001649052	12	40,232,274	40,232,383	110
ENSE00001649709	12	40,235,626	40,235,714	89
ENSE00001736708	12	40,237,969	40,238,103	135
ENSE00001727339	12	40,240,483	40,240,617	135
ENSE00001781025	12	40,243,550	40,243,681	132
ENSE00001619675	12	40,249,826	40,249,945	120
ENSE00001635586	12	40,251,232	40,251,374	143
ENSE00001597461	12	40,251,465	40,251,544	80
ENSE00001599015	12	40,252,910	40,253,016	107
ENSE00001374694	12	40,257,248	40,257,377	130
ENSE00001367134	12	40,259,480	40,259,604	125
ENSE00001378233	12	40,263,789	40,263,901	113
ENSE00001365484	12	40,274,583	40,274,727	145
ENSE00001387519	12	40,274,854	40,274,993	140
ENSE00001378687	12	40,277,888	40,278,016	129
ENSE00001382909	12	40,278,091	40,278,261	171
ENSE00001365419	12	40,283,875	40,284,133	259
ENSE00001373174	12	40,287,351	40,287,539	189
ENSE00001379815	12	40,293,545	40,293,663	119
ENSE00001364454	12	40,294,845	40,294,914	70
ENSE00001364875	12	40,295,427	40,295,644	218
ENSE00001374565	12	40,298,243	40,298,493	251
ENSE00003605121	12	40,299,109	40,299,257	149
ENSE00003643319	12	40,302,789	40,302,882	94
ENSE00003476749	12	40,303,948	40,304,134	187
ENSE00003691970	12	40,305,785	40,305,966	182
ENSE00003496760	12	40,308,467	40,308,696	230
ENSE00003509533	12	40,309,106	40,309,233	128
ENSE00003508420	12	40,310,431	40,310,649	219
ENSE00003622781	12	40,313,972	40,314,173	202
ENSE00003581684	12	40,315,212	40,315,300	89
ENSE00003521951	12	40,319,988	40,320,175	188
ENSE00003579735	12	40,321,034	40,321,188	155
ENSE00003635411	12	40,322,035	40,322,181	147
ENSE00003568150	12	40,322,319	40,322,510	192
ENSE00003468154	12	40,323,160	40,323,306	147
ENSE00003492804	12	40,328,360	40,328,460	101
ENSE00003541694	12	40,334,967	40,335,157	191
ENSE00003681812	12	40,340,294	40,340,454	161
ENSE00003468457	12	40,346,753	40,346,923	171
ENSE00003565286	12	40,348,409	40,348,509	101
ENSE00003553579	12	40,351,539	40,351,733	195
ENSE00003610102	12	40,354,299	40,354,492	194
ENSE00003511943	12	40,356,115	40,356,187	73
ENSE00003603703	12	40,359,260	40,359,444	185
ENSE00003621327	12	40,363,402	40,363,554	153
ENSE00003551873	12	40,364,842	40,365,050	209
ENSE00003489241	12	40,367,006	40,367,077	72
ENSE00001182762	12	40,367,644	40,369,285	1642

Accession	Status	Notes
Q5S007	Reviewed (Swiss-Prot)	Canonical Entry
A0A1B0GUQ3	Unreviewed (TrEMBL)
A0A2R8Y4F8	Unreviewed (TrEMBL)
A0A7P0T8S1	Unreviewed (TrEMBL)
A0A7P0T8T1	Unreviewed (TrEMBL)
A0A7P0T8T5	Unreviewed (TrEMBL)
A0A7P0T9F8	Unreviewed (TrEMBL)
A0A7P0TAJ2	Unreviewed (TrEMBL)
A0A7P0TAW6	Unreviewed (TrEMBL)
A0A7P0TB00	Unreviewed (TrEMBL)
A0A7P0Z468	Unreviewed (TrEMBL)
A0A7P0Z4D9	Unreviewed (TrEMBL)
C9JBF0	Unreviewed (TrEMBL)
E9PC85	Unreviewed (TrEMBL)
H7C3B6	Unreviewed (TrEMBL)

LRRK2 Gene Complete Identifier and Functional Mapping Reference

Structured Data Sources

Database	Identifier	Name/Symbol
HGNC	HGNC:18618	LRRK2 (Approved symbol)
Ensembl	ENSG00000188906	LRRK2
NCBI Entrez	120892	LRRK2
OMIM	609007	LRRK2 gene
UniProt	Q5S007	LRRK2_HUMAN (Canonical)

Attribute	Value
Chromosome	12
Cytogenetic Band	12q12
Start Position	40,196,744 (GRCh38)
End Position	40,369,285 (GRCh38)
Strand	+ (Plus/Forward)
Gene Length	172,542 bp

Property	Value
Name	Leucine-rich repeat serine/threonine-protein kinase 2
Alternative Name	Dardarin
Length	2,527 amino acids
Mass	286,103 Da
RefSeq Protein	NP_940980

InterPro ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR005225	Small_GTP-bd	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020859	ROC	Domain
IPR032171	COR-A	Domain
IPR057263	COR-B	Domain
IPR056593	ANK_LRRK2	Domain
IPR056597	ARM_LRRK2	Domain
IPR056602	Beta-prop_LRRK2	Domain
IPR051420	Ser_Thr_Kinases_DiverseReg	Family
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam ID	Description
PF00069	Protein kinase domain
PF08477	ROC domain
PF13855	Leucine rich repeat
PF16095	COR domain
PF23744	LRRK2-specific domain
PF23745	LRRK2-specific domain
PF23748	LRRK2-specific domain
PF25497	LRRK2-specific domain

PDB ID	Method	Resolution	Description
2ZEJ	X-ray	2.00 Å	ROC domain dimer GTPase
3D6T	X-ray	2.43 Å	ROC domain dimer
5MY9	X-ray	1.33 Å	14-3-3 sigma with LRRK2 pS935 peptide
5MYC	X-ray	1.46 Å	14-3-3 sigma with LRRK2 pS910 peptide
6DLO	X-ray	2.70 Å	WD40 domain dimer
6DLP	X-ray	4.00 Å	WD40 domain dimer
6OJE	X-ray	1.95 Å	GTPase domain dimer
6OJF	X-ray	1.60 Å	GTPase domain dimer
6XAF	X-ray	1.97 Å	GTPase domain R1398H mutant
9C76	X-ray	2.30 Å	Roc domain with Divarasib
6VNO	Cryo-EM	3.50 Å	C-terminal half structure
6VP6	Cryo-EM	3.47 Å	C-terminal half structure
6VP7	Cryo-EM	3.50 Å	C-terminal half structure
6VP8	Cryo-EM	3.50 Å	C-terminal half structure
6XR4	Cryo-EM	14.0 Å	In situ full-length structure
7LHT	Cryo-EM	3.50 Å	LRRK2 dimer
7LHW	Cryo-EM	3.70 Å	LRRK2 monomer
7LI3	Cryo-EM	3.80 Å	G2019S mutant
7LI4	Cryo-EM	3.10 Å	Symmetry expanded structure
7THY	Cryo-EM	5.20 Å	ROC domain on microtubule (minus end)
7THZ	Cryo-EM	5.00 Å	ROC domain on microtubule (plus end)
8FO2	Cryo-EM	4.13 Å	Rab29-LRRK2 complex (monomer)
8FO7	Cryo-EM	3.52 Å	LRRK2 with LRRK2-IN-1 inhibitor
8FO8	Cryo-EM	3.88 Å	Rab29-LRRK2 complex (dimer)
8FO9	Cryo-EM	3.48 Å	Rab29-LRRK2 complex (tetramer)
8SMC	Cryo-EM	4.02 Å	LRRK2 with DNL201
8TXZ	Cryo-EM	3.05 Å	C-terminal LRRK2 with MLi-2
8TYQ	Cryo-EM	2.99 Å	C-terminal with GZD-824 (G2019S)
8TZB	Cryo-EM	3.10 Å	C-terminal with GZD-824 (I2020T)
8TZC	Cryo-EM	2.70 Å	C-terminal with MLi-2 (G2019S)
8TZE	Cryo-EM	2.90 Å	C-terminal with GZD-824
8TZF	Cryo-EM	3.40 Å	Full-length with GZD-824 (I2020T)
8TZG	Cryo-EM	2.70 Å	C-terminal with MLi-2 (I2020T)
8TZH	Cryo-EM	3.90 Å	Full-length with MLi-2 (I2020T)
8U1B	Cryo-EM	3.70 Å	C-terminal with E11 DARPin
8U7H	Cryo-EM	3.80 Å	LRRK2 with GNE-7915
8U7L	Cryo-EM	3.60 Å	LRRK2 with GZD824
8U8A	Cryo-EM	3.40 Å	LRRK2 with ponatinib
8U8B	Cryo-EM	3.70 Å	LRRK2 with rebastinib
8VH4	Cryo-EM	4.10 Å	Rab12-LRRK2 complex (monomer)
8VH5	Cryo-EM	4.00 Å	Rab12-LRRK2 complex (dimer)
9CHO	Cryo-EM	7.80 Å	Autoinhibited LRRK2 on microtubules
9CI3	Cryo-EM	3.96 Å	LRRK2/14-3-3 complex
9DMI	Cryo-EM	3.35 Å	C-terminal with RN277

Organism	Gene ID	Symbol	Biotype
Mouse (Mus musculus)	ENSMUSG00000036273	Lrrk2	protein_coding
Rat (Rattus norvegicus)	ENSRNOG00000004048	Lrrk2	protein_coding
Zebrafish (Danio rerio)	ENSDARG00000006169	lrrk2	protein_coding
Fruit fly (D. melanogaster)	No direct ortholog	Lrrk (42447)	Related gene
Worm (C. elegans)	No data available	-	-
Yeast (S. cerevisiae)	No data available	-	-

Classification	Count
Pathogenic	6
Likely Pathogenic	2
Uncertain Significance (VUS)	~500+
Likely Benign	~2,000+
Benign	~1,000+

ClinVar ID	HGVS Notation	Protein Change	Review Status
1936	c.4321C>G	p.Arg1441Gly	Multiple submitters, no conflicts
1938	c.4321C>T	p.Arg1441Cys	Multiple submitters, no conflicts
1937	c.5096A>G	p.Tyr1699Cys	No assertion criteria
1939	c.3364A>G	p.Ile1122Val	No assertion criteria
1941	c.6059T>C	p.Ile2020Thr	Single submitter
2572065	c.4969C>T	p.Gln1657Ter	No assertion criteria

ClinVar ID	HGVS Notation	Protein Change	Review Status
225276	c.4321C>A	p.Arg1441Ser	Single submitter
3341978	c.4318G>C	p.Ala1440Pro	Single submitter

Variant	Effect	Score
12:40225262:TGTTC:T	donor_gain	1.00
12:40225278:GCGCG:G	donor_gain	1.00
12:40225283:G:A	donor_loss	1.00
12:40225284:T:A	donor_loss	1.00
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
12:40225213:G:GT	donor_gain	0.99
12:40225637:GCAGG:G	donor_loss	0.99
12:40225638:CAG:C	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
12:40225553:A:AG	acceptor_gain	0.99
12:40225554:G:GG	acceptor_gain	0.99
12:40225272:C:CG	donor_gain	0.98
12:40225550:TCCA:T	acceptor_loss	0.98
12:40225551:CCA:C	acceptor_loss	0.98
12:40225552:CA:C	acceptor_loss	0.98
12:40225553:A:AC	acceptor_loss	0.98
12:40225554:GC:G	acceptor_gain	0.98
12:40225545:T:A	acceptor_loss	0.97
12:40225542:A:AG	acceptor_gain	0.96
12:40225543:C:G	acceptor_gain	0.96
12:40225264:TTCAC:T	donor_gain	0.96
12:40225554:GCC:G	acceptor_gain	0.96
12:40225554:GCCT:G	acceptor_gain	0.96
12:40225554:GCCTC:G	acceptor_gain	0.96
12:40225214:A:T	donor_gain	0.94
12:40225307:C:CG	donor_gain	0.94
12:40225542:ACTT:A	acceptor_gain	0.94
12:40225545:T:TA	acceptor_gain	0.94
12:40225285:A:C	donor_loss	0.93
12:40225308:T:G	donor_gain	0.93

Variant	Protein Change	AM Score	Classification
12:40225135:G:A	A2T	0.187	likely_benign
12:40225136:C:T	A2V	0.346	ambiguous
12:40225138:A:C	S3R	0.399	ambiguous
12:40225178:T:A	L16Q	0.539	ambiguous

Note
Full AlphaMissense predictions available for all 16,717 possible missense variants
	Biological Pathways & Gene Ontology**

Pathway ID	Name
R-HSA-162582	Signal Transduction
R-HSA-8848021	Signaling by PTK6
R-HSA-8857538	PTK6 promotes HIF1A stabilization
R-HSA-9006927	Signaling by Non-Receptor Tyrosine Kinases

GO ID	Term
GO:0006468	protein phosphorylation
GO:0006914	autophagy
GO:0000165	MAPK cascade
GO:0007254	JNK cascade
GO:0035556	intracellular signal transduction
GO:0007005	mitochondrion organization
GO:0006979	response to oxidative stress
GO:0007030	Golgi organization
GO:0010506	regulation of autophagy
GO:0046777	protein autophosphorylation
GO:0060070	canonical Wnt signaling pathway
GO:0043410	positive regulation of MAPK cascade
GO:0048812	neuron projection morphogenesis
GO:0021756	striatum development
GO:0006897	endocytosis
GO:0031647	regulation of protein stability
GO:0034599	cellular response to oxidative stress
GO:0007040	lysosome organization
GO:0019722	calcium-mediated signaling
GO:0060159	regulation of dopamine receptor signaling pathway

GO ID	Term
GO:0004674	protein serine/threonine kinase activity
GO:0004672	protein kinase activity
GO:0005524	ATP binding
GO:0005525	GTP binding
GO:0003924	GTPase activity
GO:0004709	MAP kinase kinase kinase activity
GO:0004706	JUN kinase kinase kinase activity
GO:0008017	microtubule binding
GO:0015631	tubulin binding
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0031267	small GTPase binding
GO:0005096	GTPase activator activity
GO:0030276	clathrin binding
GO:0000149	SNARE binding
GO:0017075	syntaxin-1 binding
GO:0003779	actin binding
GO:0034211	GTP-dependent protein kinase activity
GO:0016301	kinase activity
GO:0000287	magnesium ion binding

GO ID	Term
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005739	mitochondrion
GO:0005741	mitochondrial outer membrane
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005764	lysosome
GO:0005768	endosome
GO:0030424	axon
GO:0030425	dendrite
GO:0043025	neuronal cell body
GO:0043005	neuron projection
GO:0030426	growth cone
GO:0005802	trans-Golgi network
GO:0097413	Lewy body
GO:0030672	synaptic vesicle membrane
GO:0070971	endoplasmic reticulum exit site
GO:0098794	postsynapse
GO:0098978	glutamatergic synapse
GO:0036064	ciliary basal body

UniProt ID	Gene	Score
O14966	SFN (14-3-3σ)	989
Q5S007	LRRK2 (self)	989
Q99497	DJ-1 (PARK7)	984
O60260	Parkin (PRKN)	981
P37840	α-Synuclein (SNCA)	973
Q9BXM7	PINK1	955
O14976	GAK	953
P04062	Glucocerebrosidase (GBA)	922
Q96QK1	VPS35	863
Q9NQ11	SLC41A1	844
P10636	MAPT (Tau)	826
Q99963	SH3GL2	822
Q9Y3I1	FBXO7	808
Q8IWA4	RAB29	802
P09936	UCHL1	785
Q8IXI2	RAB32	781
Q9UKV8	AGO2	779
Q99962	SH3GL1	773
Q99700	ATXN2	770
Q01959	SLC6A3 (DAT)	750
Q99961	SH3GL3	740
Q6Y7W6	GIGYF2	732
Q5T0U0	RAB12	720
Q9BSA9	RAB10	720
P07900	HSP90AA1	719
P08238	HSP90AB1	714
Q13148	TARDBP (TDP-43)	698
O00429	DNM1L	697
Q9Y6H5	SYNJ1	689
Q9UL18	ARFGAP1	682

Partner	Interaction Type	Confidence
LRRK2 (self)	self interaction	0.99
LRRK2 (self)	phosphorylation reaction	0.99
MSN (Moesin)	phosphorylation reaction	0.96
RAB8A	phosphorylation/physical	0.77
RPS15	phosphorylation reaction	0.78
RAB5B	phosphorylation reaction	0.76
RAB10	phosphorylation/physical	0.69
SEC16A	physical association	0.65
LRP6	physical association	0.66
CDC42EP3	direct interaction	0.62
SH3GL2	phosphorylation reaction	0.62
RAB1B	phosphorylation reaction	0.59

Gene	Method
LRRK1	Affinity Capture-Western
BAX	Affinity Capture-Western
TP53	Biochemical Activity, Affinity Capture-Western
SQSTM1	Affinity Capture-Western
WSB1	Affinity Capture-Western
HSPA8	Affinity Capture-MS, Affinity Capture-Western
STUB1	Affinity Capture-Western, Reconstituted Complex
HSP90AA1	Affinity Capture-MS
CDC37	Affinity Capture-MS
RAB29	Affinity Capture-Western, Co-localization
GAK	Affinity Capture-MS, Co-localization
YWHAZ (14-3-3ζ)	Reconstituted Complex
YWHAB (14-3-3β)	Reconstituted Complex
PAK6	Reconstituted Complex

UniProt ID	Top Similarity	Avg Similarity
Q3SX00	1.0000	0.9884
Q86W74	1.0000	0.9884
Q5R8C8	0.9999	0.9884
Q76K24	0.9999	0.9884
Q8BTZ5	0.9999	0.9885
Q9JKK8	0.9996	0.9932
Q5QJC9	0.9994	0.9837
Q2TA08	0.9994	0.9834
Q7Z5J8 (LRRK1)	0.9992	0.9877

UniProt ID	Identity	Bitscore
Q5S006 (LRRK1)	86.1%	4259
P10421	98.8%	684
P00540	96.5%	672
P10650	96.5%	669
P00539	90.7%	615

Target	Effect	Mechanism	Direct
MSN (Moesin)	up-regulates activity	phosphorylation	Yes
RAB8A	up-regulates activity	phosphorylation	Yes
RAB10	down-regulates activity	phosphorylation	Yes
RAB5B	up-regulates activity	phosphorylation	Yes
RAB29	up-regulates activity	phosphorylation	Yes
SNCA (α-synuclein)	down-regulates activity	phosphorylation	Yes
MAPT (Tau)	down-regulates	phosphorylation	Yes
AKT1	up-regulates	phosphorylation	Yes
DNM1L	up-regulates activity	phosphorylation	Yes
NSF	up-regulates activity	phosphorylation	Yes
BCL2	up-regulates activity	phosphorylation	Yes
ARFGAP1	down-regulates	phosphorylation	Yes
SH3GL1/2	down-regulates	phosphorylation	Yes
RPS15	up-regulates activity	phosphorylation	Yes

Regulator	Effect	Mechanism
PRKACA (PKA)	down-regulates activity	phosphorylation
STUB1 (CHIP)	down-regulates (destabilization)	ubiquitination
MID2	down-regulates (destabilization)	ubiquitination
ARHGEF7	up-regulates	binding

ChEMBL ID	Drug Name	Type	Primary Indication
CHEMBL1171837	PONATINIB	Small molecule	Leukemia (off-target LRRK2)
CHEMBL1287853	FEDRATINIB	Small molecule	Myelofibrosis
CHEMBL1289926	AXITINIB	Small molecule	Renal cell carcinoma
CHEMBL1789941	RUXOLITINIB	Small molecule	Myelofibrosis
CHEMBL189963	PALBOCICLIB	Small molecule	Breast cancer
CHEMBL1983268	ENTRECTINIB	Small molecule	NTRK fusion cancers
CHEMBL221959	TOFACITINIB	Small molecule	Rheumatoid arthritis
CHEMBL2103743	TOFACITINIB CITRATE	Small molecule	Rheumatoid arthritis
CHEMBL24828	VANDETANIB	Small molecule	Thyroid cancer
CHEMBL288441	BOSUTINIB	Small molecule	CML
CHEMBL3545311	BRIGATINIB	Small molecule	NSCLC
CHEMBL502835	NINTEDANIB	Small molecule	Pulmonary fibrosis
CHEMBL535	SUNITINIB	Small molecule	RCC, GIST
CHEMBL553	ERLOTINIB	Small molecule	NSCLC
CHEMBL608533	MIDOSTAURIN	Small molecule	AML

ChEMBL ID	Drug Name	Type
CHEMBL1879463	DACTOLISIB	Small molecule
CHEMBL226345	ADENINE	Small molecule
CHEMBL2316582	OLVEREMBATINIB	Small molecule
CHEMBL31965	CANERTINIB	Small molecule
CHEMBL38380	FASUDIL	Small molecule
CHEMBL428690	ALVOCIDIB	Small molecule
CHEMBL4297865	ABIVERTINIB	Small molecule
CHEMBL483158	ALISERTIB	Small molecule
CHEMBL522892	DOVITINIB	Small molecule
CHEMBL603469	LESTAURTINIB	Small molecule
CHEMBL91829	RUBOXISTAURIN	Small molecule

ChEMBL ID	Drug Name	Type
CHEMBL1721885	SU-014813	Small molecule
CHEMBL1738757	REBASTINIB	Small molecule
CHEMBL1967878	CENISERTIB	Small molecule
CHEMBL1976040	ADAVOSERTIB	Small molecule

Attribute	Value
Expression Breadth	Ubiquitous
Total Present Calls	220
Max Expression Score	97.17

Dataset ID	Description	Cell Count
E-HCAD-1	Ischaemic sensitivity of human tissue	425,435
E-ANND-2	GTEx snRNAseq atlas	209,126
E-MTAB-6308	Lung tumor endothelial cells	113,132
E-CURD-112	Fetal bone marrow haematopoiesis	56,592
E-GEOD-130148	Human lung tissue (Drop-seq)	14,560
E-MTAB-9067	Fetal liver/bone marrow haematopoiesis	5,865
E-MTAB-9801	Fetal bone marrow haematopoiesis (SS2)	486

Disease	Classification	Inheritance	Submitter
Autosomal dominant Parkinson disease 8 (OMIM:607060)	Definitive	Autosomal dominant	Laboratory for Molecular Medicine
Autosomal dominant Parkinson disease 8	Strong	Autosomal dominant	Genomics England PanelApp
Autosomal dominant Parkinson disease 8	Strong	Autosomal dominant	Labcorp Genetics
Hereditary late-onset Parkinson disease (ORPHA:411602)	Supportive	Autosomal dominant	Orphanet

Orphanet ID	Disease Name	Type	Gene Count
2828	Young-onset Parkinson disease	Disease	11 genes
411602	Hereditary late-onset Parkinson disease	Disease	7 genes

HPO ID	Phenotype
HP:0001300	Parkinsonism
HP:0002067	Bradykinesia
HP:0002063	Rigidity
HP:0001337	Tremor
HP:0002322	Resting tremor
HP:0002172	Postural instability
HP:0002362	Shuffling gait
HP:0001332	Dystonia
HP:0100660	Dyskinesia
HP:0002304	Akinesia

HPO ID	Phenotype
HP:0000726	Dementia
HP:0100543	Cognitive impairment
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000738	Hallucinations
HP:0002367	Visual hallucination
HP:0000741	Apathy
HP:0100710	Impulsivity

HPO ID	Phenotype
HP:0004926	Orthostatic hypotension
HP:0002019	Constipation
HP:0004409	Hyposmia
HP:0002360	Sleep disturbance
HP:0100785	Insomnia
HP:0012452	Restless legs