LIMK2
protein-codingLIM domain kinase 2, the group of LIM domain containing|PDZ domain containing|LIMK/TESK kinase family
Gene summary
There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. The protein encoded by this gene is phosphorylated and activated by ROCK, a downstream effector of Rho, and the encoded protein, in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. It is thought that this pathway contributes to Rho-induced reorganization of the actin cytoskeleton. At least three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~67.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LIMK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005569.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 3 | |||
| missense | 72 | 3 | 75 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 78 | 3 | 2 | 83 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005560.1 | 16 | MANE Select | |
| Ensembl | ENSP00000332687.4 | 16 | MANE Select | |
| RefSeq | NP_001026971.1 | 15 | Standard | |
| RefSeq | NP_057952.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fc gamma R-mediated phagocytosis - Homo sapiens (human)
- Regulation of actin cytoskeleton - Homo sapiens (human)
- Axon guidance - Homo sapiens (human)
- Androgen receptor signaling pathway
- TGF-beta Signaling Pathway
Biological Process
- protein phosphorylation
- spermatogenesis
- phosphorylation
- actin cytoskeleton organization
- head development
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- metal ion binding
- protein heterodimerization activity
Cellular Component
- nucleus
- cytoplasm
- cis-Golgi network
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000340552
- Coding exons
- 15
- Length
- 67842
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125748
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 342 | 423 | 0.809 | 0.0000259 | 4503 |
| Missense (PolyPhen) | 68 | 124.49 | 0.54621 | 1397 | ||
| Synonymous | -0.114 | 170 | 168 | 1.01 | 0.0000103 | 1341 |
| Loss of Function | 3.57 | 9 | 30.2 | 0.298 | 0.00000156 | 355 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.000046 | 0.000044 | rare |
| South Asian | 0.00027 | 0.00026 | rare |
| Other | 0.00035 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro. {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11018042}.;
Recessive Scores
- pRec
- 0.206
Intolerance Scores
- LoFtool
- 0.117
- RVIS EVS
- 0.11
- RVIS percentile EVS
- 62.14
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |