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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LIMK1
LIM domain kinase 1
Chromosome 7 · 7q11.23
NCBI Gene: 3984Ensembl: ENSG00000106683.16HGNC: HGNC:6613UniProt: P53667
169PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedKinase
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmubiquitin ligase inhibitor activityprotein phosphorylationprotein serine/threonine kinase activityalcohol drinkingHernia of the abdominal wallneurodegenerative diseaseundetermined early-onset epileptic encephalopathy
✦AI Summary

LIMK1 is a serine/threonine protein kinase containing LIM and PDZ domains that acts as a key regulator of actin cytoskeletal dynamics 1. Its primary function involves phosphorylating cofilin, an actin-depolymerization factor, thereby promoting F-actin accumulation and stabilization 1. LIMK1 integrates extracellular signals through Rac-GTP to modulate cytoskeletal reorganization, controlling cell morphology and mobility 1. In development, LIMK1 regulates trophoblast invasion and placental differentiation through HIF-2α-dependent mechanisms that modify cytoskeletal integrity and matrix metalloproteinase processing 2. Notably, LIMK1 is downregulated in preeclampsia, suggesting its importance in normal placentation 2. LIMK1 deletion contributes to neurological and behavioral phenotypes in Williams Syndrome, a 7q11.23 microdeletion disorder, with particular effects on visuospatial abilities 34. In Alzheimer's disease, the LIMK1-cofilin-actin axis shows dysregulation within dendritic spines, contributing to synaptic dysfunction and cognitive decline 5. Additionally, high LIMK1 expression promotes chemoresistance in colorectal cancer through m6A-regulated mechanisms affecting protein translation and stress responses 6. LIMK1 expression declines with oocyte aging, potentially impacting reproductive function 7.

Sources cited
1
LIMK1 phosphorylates cofilin to promote F-actin accumulation and acts as a key component linking extracellular stimuli to cytoskeletal changes
PMID: 10224665
2
LIMK1 regulates trophoblast invasion and differentiation through cytoskeletal modulation and is downregulated in preeclampsia
PMID: 25307528
3
LIMK1 deletion in Williams Syndrome contributes to neurological and behavioral phenotypes through cytoskeletal defects
PMID: 14745832
4
LIMK1 deletion has particular effects on visuospatial abilities in Williams Syndrome patients with atypical deletions
PMID: 36520254
5
LIMK1-cofilin-actin axis regulates dendritic spine dynamics and is dysregulated in Alzheimer's disease, contributing to synaptic dysfunction
PMID: 40461464
6
High LIMK1 expression promotes chemoresistance to 5-fluorouracil in colorectal cancer through m6A-regulated mechanisms and eIF2α phosphorylation
PMID: 37778684
7
LIMK1 expression is significantly downregulated in oocytes with advanced maternal age
PMID: 40731018
Disease Associationsⓘ20
alcohol drinkingOpen Targets
0.35Weak
Hernia of the abdominal wallOpen Targets
0.35Weak
neurodegenerative diseaseOpen Targets
0.34Weak
undetermined early-onset epileptic encephalopathyOpen Targets
0.33Weak
diverticular diseaseOpen Targets
0.32Weak
hemorrhoidOpen Targets
0.31Weak
Venous thrombosisOpen Targets
0.31Weak
lupus erythematosusOpen Targets
0.16Weak
Inguinal herniaOpen Targets
0.13Weak
neoplasmOpen Targets
0.11Weak
myopiaOpen Targets
0.11Weak
pathological myopiaOpen Targets
0.11Weak
HerniaOpen Targets
0.11Weak
gastric cancerOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.10Weak
lung adenocarcinomaOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.10Suggestive
osteosarcomaOpen Targets
0.09Suggestive
posterior cortical atrophyOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
Pathogenic Variants2
NM_002314.4(LIMK1):c.1532G>C (p.Gly511Ala)Pathogenic
Undetermined early-onset epileptic encephalopathy
☆☆☆☆2023→ Residue 511
NM_002314.4(LIMK1):c.127G>A (p.Ala43Thr)Likely pathogenic
See cases
☆☆☆☆→ Residue 43
View on ClinVar ↗
Related Genes
CDC42Protein interaction100%HSP90AB1Protein interaction100%SSH1Protein interaction100%SSH3Protein interaction99%BMPR2Protein interaction99%SSH2Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Lung
41%
Ovary
40%
Heart
26%
Bone Marrow
24%
Liver
12%
Gene Interaction Network
Click a node to explore
LIMK1CDC42HSP90AB1SSH1SSH3BMPR2SSH2
PROTEIN STRUCTURE
Preparing viewer…
PDB3S95 · 1.65 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.34Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.22 [0.15–0.34]
RankingsWhere LIMK1 stands among ~20K protein-coding genes
  • #2,625of 20,598
    Most Researched169 · top quartile
  • #4,260of 5,498
    Most Pathogenic Variants2
  • #1,443of 17,882
    Most Constrained (LOEUF)0.34 · top 10%
Genes detectedLIMK1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Williams syndrome.
PMID: 34140529
Nat Rev Dis Primers · 2021
1.00
2
LIMK1 m
PMID: 37778684
Cancer Lett · 2023
0.90
3
Discovery of MDI-114215: A Potent and Selective LIMK Inhibitor To Treat Fragile X Syndrome.
PMID: 39711116
J Med Chem · 2025
0.80
4
LIM-kinase1.
PMID: 10224665
Int J Biochem Cell Biol · 1999
0.80
5
Visuospatial construction.
PMID: 10521286
Am J Hum Genet · 1999
0.70