LRRK1
Chr 15ARleucine rich repeat kinase 1
The protein is a serine/threonine kinase that phosphorylates RAB proteins involved in intracellular trafficking and negatively regulates bone mass through osteoclast maturation. Autosomal recessive mutations cause osteosclerotic metaphyseal dysplasia, a bone disorder characterized by increased bone density and abnormal bone development. The gene is highly constrained against loss-of-function variants (LOEUF 0.493), indicating that complete loss of protein function is likely pathogenic.
Some data sources returned errors (1)
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is gain-of-function.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
LRRK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools