LRRK1

leucine rich repeat kinase 1, the group of ROCO family

Basic information

Region (hg38): 15:100919327-101078257

Links

ENSG00000154237 ∙ NCBI:79705 ∙ OMIM:610986 ∙ HGNC:18608 ∙ Uniprot:Q38SD2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteosclerotic metaphyseal dysplasia	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	23610867; 27055475; 27829680; 31571209; 32119750

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LRRK1 gene.

• not_provided (771 variants)
• Inborn_genetic_diseases (283 variants)
• LRRK1-related_disorder (76 variants)
• Osteosclerotic_metaphyseal_dysplasia (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRRK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024652.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		1	286	29	317
missense			406	38	17	461
nonsense	8		2			10
start loss						0
frameshift	7	1				8
splice donor/acceptor (+/-2bp)		4	2		1	7
Total	16	5	411	324	47

Highest pathogenic variant AF is 0.0000047915

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRRK1	protein_coding	protein_coding	ENST00000388948	33	150898

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.52e-10	1.00	125548	0	70	125618	0.000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.72	931	1.20e+3	0.779	0.0000748	13108
Missense in Polyphen		271	470.79	0.57562		5210
Synonymous	-1.04	554	524	1.06	0.0000371	4032
Loss of Function	5.54	33	89.5	0.369	0.00000435	1043

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000390	0.000385
Ashkenazi Jewish	0.000300	0.000298
East Asian	0.000277	0.000273
Finnish	0.000164	0.000139
European (Non-Finnish)	0.000280	0.000273
Middle Eastern	0.000277	0.000273
South Asian	0.000426	0.000425
Other	0.000664	0.000652

dbNSFP

Source: dbNSFP

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.478
• rvis_EVS: -1.61
• rvis_percentile_EVS: 2.97

Haploinsufficiency Scores

• pHI: 0.137
• hipred: Y
• hipred_score: 0.693
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.723

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Lrrk1
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; limbs/digits/tail phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype

Gene ontology

• Biological process: protein phosphorylation;osteoclast development;bone resorption;positive regulation of peptidyl-tyrosine phosphorylation;negative regulation of peptidyl-tyrosine phosphorylation;positive regulation of canonical Wnt signaling pathway;positive regulation of intracellular signal transduction
• Cellular component: mitochondrion;cytosol
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;GTP binding;identical protein binding;metal ion binding