LRRK1 leucine rich repeat kinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LRRK1provided by HGNC
Official Full Name: leucine rich repeat kinase 1provided by HGNC
Primary source: HGNC:HGNC:18608
See related: Ensembl:ENSG00000154237 MIM:610986; AllianceGenome:HGNC:18608
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: OSMD; RIPK6; Roco1
Summary: This gene encodes a multi-domain protein that is a leucine-rich repeat kinase and a GDP/GTP binding protein. The encoded protein is thought to play a role in the regulation of bone mass. Mice lacking a similar gene showed severe osteopetrosis, increased bone mineralization and decreased bone resorption. [provided by RefSeq, Jan 2017]
Expression: Ubiquitous expression in lymph node (RPKM 6.0), spleen (RPKM 4.4) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q26.3

Exon count:: 34

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (100919357..101078257)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (98673894..98832884)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (101459562..101618462)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structure and regulation of full-length human leucine-rich repeat kinase 1.
Title: Structure and regulation of full-length human leucine-rich repeat kinase 1.
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain.
Title: PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain.
Broadening the phenotype of LRRK1 mutations - Features of malignant osteopetrosis and optic nerve atrophy with intrafamilial variable expressivity.
Title: Broadening the phenotype of LRRK1 mutations - Features of malignant osteopetrosis and optic nerve atrophy with intrafamilial variable expressivity.
Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms.
Title: Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms.
data suggest that LRRK1 variant (rs2924835) and LRRK2 variants (rs34594498, rs34410987, and rs33949390) are not associated with essential tremor in this Han Chinese population
Title: Genetic Analysis of LRRK1 and LRRK2 Variants in Essential Tremor Patients.
LRRK1 plays a critical role in the regulation of bone mass in humans.
Title: Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity.
A novel LRRK1 mutation has been identified in two siblings in an Indian family with osteosclerotic metaphyseal dysplasia.
Title: Identification of a novel LRRK1 mutation in a family with osteosclerotic metaphyseal dysplasia.
We find that LRRK1-mediated phosphorylation of CLIP-170 causes the accumulation of p150(Glued) (also known as DCTN1) a subunit of dynactin, at microtubule plus ends, thereby facilitating the migration of EGFR-containing endosomes.
Title: LRRK1-phosphorylated CLIP-170 regulates EGFR trafficking by recruiting p150Glued to microtubule plus ends.
LRRK1 regulates mitotic spindle orientation downstream of PLK1 through CDK5RAP2-dependent centrosome maturation.
Title: PLK1-dependent activation of LRRK1 regulates spindle orientation by phosphorylating CDK5RAP2.
LRRK1 carries out distinct functions from LRRK2 by interacting with different cellular proteins.
Title: Differential protein-protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Osteosclerotic metaphyseal dysplasia MedGen: C3554665 OMIM: 615198 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-N32240 (e-PCR)
- UniSTS:13355

SHGC-64945 (e-PCR)
- UniSTS:66661

RH44810 (e-PCR)
- UniSTS:624

RH93536 (e-PCR)
- UniSTS:83639

D15S1136 (e-PCR)
- UniSTS:154556

D10S1702 (e-PCR)
- UniSTS:52940

STS-Z40893 (e-PCR)
- UniSTS:24566

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables GTP binding	IEA Inferred from Electronic Annotation more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in bone resorption	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in osteoclast development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: leucine-rich repeat serine/threonine-protein kinase 1

NP_078928.3

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_052791.1 RefSeqGene

Range

5199..158874

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_024652.6 → NP_078928.3 leucine-rich repeat serine/threonine-protein kinase 1

See identical proteins and their annotated locations for NP_078928.3

Status: REVIEWED

Source sequence(s)

AC019254, AC090907, AK058028, AK131075, AW592808, BC171802, BQ187037, DQ013130

Consensus CDS

CCDS42086.1

UniProtKB/Swiss-Prot

Q38SD2, Q6NVH5, Q6NYC0, Q6ZNL9, Q6ZNM9, Q96JN5, Q9H5S3

Related

ENSP00000373600.3, ENST00000388948.8

Conserved Domains (11) summary

smart00220
Location:1245 → 1511

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG1100
Location:635 → 781

Gem1; GTPase SAR1 family domain [General function prediction only]

COG4886
Location:302 → 614

LRR; Leucine-rich repeat (LRR) protein [Transcription]

cd00116
Location:214 → 488

LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...

cd00204
Location:95 → 214

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd14067
Location:1248 → 1523

STKc_LRRK1; Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1

sd00033
Location:304 → 330

LRR_RI; leucine-rich repeat [structural motif]

pfam12796
Location:126 → 221

Ank_2; Ankyrin repeats (3 copies)

pfam16095
Location:844 → 1036

COR; C-terminal of Roc, COR, domain

sd00045
Location:156 → 186

ANK; ANK repeat [structural motif]

cl21455
Location:639 → 821

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

100919357..101078257

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

98673894..98832884

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001039843.1: Suppressed sequence

Description

NM_001039843.1: This RefSeq record was removed by NCBI staff. Contact [email protected] for further information.