LIMK1

Summary

LIMK1 (LIM domain kinase 1, HGNC:6613) is a protein-coding gene on chromosome 7q11.23, encoding LIM domain kinase 1 (P53667). Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics.

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. LIMK1 is a serine/threonine kinase that regulates actin polymerization via phosphorylation and inactivation of the actin binding factor cofilin. This protein is ubiquitously expressed during development and plays a role in many cellular processes associated with cytoskeletal structure. This protein also stimulates axon growth and may play a role in brain development. LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 3984 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 156 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 186
• Druggable target: yes — 38 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002314

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6613
Approved symbol	LIMK1
Name	LIM domain kinase 1
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	LIMK
Ensembl gene	ENSG00000106683
Ensembl biotype	protein_coding
OMIM	601329
Entrez	3984

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000336180, ENST00000418310, ENST00000435201, ENST00000476792, ENST00000483414, ENST00000486361, ENST00000491052, ENST00000538333, ENST00000911292, ENST00000911293

RefSeq mRNA: 2 — MANE Select: NM_002314 NM_001204426, NM_002314

CCDS: CCDS5563, CCDS56491

Canonical transcript exons

ENST00000336180 — 16 exons

Exon	Start	End
ENSE00000843220	74085748	74085844
ENSE00001632126	74121139	74122525
ENSE00001952680	74083804	74084045
ENSE00003695320	74111648	74111707
ENSE00003696398	74105875	74105980
ENSE00003696542	74107010	74107193
ENSE00003697116	74096622	74096760
ENSE00003697254	74106077	74106243
ENSE00003697591	74120583	74120638
ENSE00003697592	74111933	74111998
ENSE00003698568	74107871	74107957
ENSE00003698966	74097080	74097189
ENSE00003699178	74108905	74109036
ENSE00003700618	74120892	74121049
ENSE00003700810	74099032	74099238
ENSE00003700929	74115802	74115958

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 95.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.9432 / max 369.4710, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79069	33.8214	1815
79071	5.3293	534
79068	1.7072	1110
79070	0.0853	48

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	95.70	gold quality
right frontal lobe	UBERON:0002810	95.39	gold quality
cingulate cortex	UBERON:0003027	93.79	gold quality
anterior cingulate cortex	UBERON:0009835	93.59	gold quality
prefrontal cortex	UBERON:0000451	93.11	gold quality
amygdala	UBERON:0001876	91.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.09	gold quality
granulocyte	CL:0000094	90.56	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.49	gold quality
ganglionic eminence	UBERON:0004023	89.61	gold quality
cortical plate	UBERON:0005343	88.91	gold quality
neocortex	UBERON:0001950	88.87	gold quality
monocyte	CL:0000576	88.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.43	gold quality
leukocyte	CL:0000738	88.32	gold quality
mononuclear cell	CL:0000842	88.25	gold quality
frontal cortex	UBERON:0001870	88.23	gold quality
hypothalamus	UBERON:0001898	87.66	gold quality
cerebellar hemisphere	UBERON:0002245	87.66	gold quality
cerebellar cortex	UBERON:0002129	87.55	gold quality
buccal mucosa cell	CL:0002336	87.40	gold quality
cerebral cortex	UBERON:0000956	86.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.41	gold quality
ectocervix	UBERON:0012249	85.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.72	gold quality
telencephalon	UBERON:0001893	85.62	gold quality
cerebellum	UBERON:0002037	85.38	gold quality
nucleus accumbens	UBERON:0001882	85.34	gold quality
endocervix	UBERON:0000458	85.21	gold quality
forebrain	UBERON:0001890	85.17	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	328.34
E-ENAD-17	no	128.09
E-MTAB-6379	no	64.08
E-ANND-3	no	4.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting LIMK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mitosis-specific activation of LIM motif-containing protein kinase and roles of cofilin phosphorylation and dephosphorylation in mitosis. (PMID:11925442)
• identification as interaction partner of 14-3-3 zeta (PMID:12323073)
• LIM kinase 1 (LIMK1), a critical regulator of actin dynamics, plays a regulatory role in tumor cell invasion. (PMID:12777619)
• LIMK1 has a role in regulating cell division and invasive property of prostate cancer cells; the effect is not mediated by phosphorylation of cofilin (PMID:12821664)
• LIM-kinase 1 is translocated to the nucleus after being bound by p57kip2 (PMID:14530263)
• LIMK1 is enriched in both axonal and dendritic growth cones of E18 hippocampal pyramidal neurons where it is found in punctae that extend far out into filopodia, as well as in a perinuclear region identified as Golgi. (PMID:15023529)
• LIMK1 is cleaved and activated during antiFas antibody-induced apoptosis. Expression of an N-terminally truncated LMK1 fragment induced membrane blebbing. (PMID:15189451)
• LATS1 is a novel cytoskeleton regulator that affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. (PMID:15220930)
• a multi-protein complex consisting of SSH-1L, LIMK1, actin, and the scaffolding protein, 14-3-3zeta, is involved, along with the kinase, PAK4, in the regulation of ADF/cofilin activity (PMID:15660133)
• LIMK1 activity is required for thrombin-induced modulation of microtubule destabilization and actin polymerization (PMID:15897190)
• Rnf6 controls cellular LIMK1 concentrations and indicate a new function for the ubiquitin/proteasome system in regulating local growth cone actin dynamics (PMID:16204183)
• results suggested an important role for LIMK1 signaling in breast cancer tumor growth, angiogenesis and invasion and a regulatory connection between LIMK1 and the uPA system (PMID:16381000)
• LIMK1 may play a role different from that of LIMK2 in regulating mitotic spindle organization, chromosome segregation, and cytokinesis during the cell division cycle. (PMID:16455074)
• Elastin and LIMK1 SNPs effect in the at-risk haplotype possibly by weakening the vascular wall and promoting the development of IA (PMID:16611674)
• Taken together, our novel findings presented in this paper implicate that LIMK1 signaling indeed plays a pivotal role in the regulation of EGFR trafficking through the endocytic pathway in invasive tumor cells. (PMID:16763828)
• the structure, regulation and function; possible contributions to human disease (Review) (PMID:17294230)
• These findings demonstrate a cell-type dependent functional interaction between parkin and LIMK1 and provide new evidence that links parkin and LIMK1 in the pathogenesis of familial PD. (PMID:17512523)
• gamma-tubulin associates with phosphorylated LIMK1 and LIMK2 but not with dephosphorylated LIMK1 or LIMK2. (PMID:18000399)
• LIMK1 phosphorylation of p25 blocks p25 activity, thus promoting microtubule disassembly. (PMID:18028908)
• LIMK1-mediated cofilin phosphorylation is required for accurate spindle orientation by stabilizing cortical actin networks during mitosis. (PMID:18079118)
• PDGF participates in actin dynamics by dual regulation of cofilin activity via LIMK and SSH1L in aortic smooth muscle cells (PMID:18096821)
• These results support a model whereby hepatocyte growth factor-stimulated cell migration also requires a cofilin phosphorylation step that is mediated by PAK4. (PMID:18424072)
• LIMK1 may mediate TGF-beta-dependent signaling during ocular inflammation. (PMID:18978953)
• findings indicate that spatial deficits associated with Williams Syndrome also affect large-scale spatial processing and suggest that hemizygous deletion of LIMK1 is not sufficient to account for any of the spatial deficits associated with this syndrome. (PMID:19662944)
• the p57(Kip2) control of LIMK-1 ultimately affects cell mobility negatively. (PMID:19734939)
• DGCR6L, a novel PAK4 interacting protein, regulated PAK4-mediated migration of human gastric cancer cells via LIMK1. (PMID:19778628)
• Both LIMK1 and LIMK2 single knock down led to a reduction of invasion and metastatic behavior in the zebrafish xenograft metastasis assay. (PMID:20047470)
• phosphorylation of annexin 1 regulates the angiogenic effect that is associated with the activation of the p38/LIM kinase 1 axis by VEGF (PMID:20061392)
• LIMK1 mediates both the mesenchymal and amoeboid modes of invasion of HT1080 cells. (PMID:20100465)
• FXa induced myosin light chain phosphorylation and LIMK1 activation resulting in cofilin inactivation (PMID:20347121)
• High LIMK1 is associated with cervical cancer dysplasia. (PMID:20622363)
• Changes in the expression of cytoskeletal regulatory proteins such as LIMK and cofilin may play a role in weakening thoracic aortic medial tissue, as a precondition to thoracic aortic dissection. (PMID:20873970)
• LIM kinase1 modulates function of membrane type matrix metalloproteinase 1 in prostate cancer cells (PMID:21219645)
• evealed a SNP, rs6460071 located on LIMK1 gene (P = 0.00069) to be significantly associated with increased risk of intracranial aneurysm (PMID:21228795)
• LIM kinase 1 modulates cortical actin and CXCR4 cycling and is activated by HIV-1 to initiate viral infection. (PMID:21321123)
• LIMK1 activity in both the cytoplasmic and nuclear compartments promotes breast cancer progression. (PMID:21682918)
• LIMK1 has a dual role in regulating lamellipodium extension by decelerating actin retrograde flow and polymerization. (PMID:21868383)
• Data describe the role of LIMK1-mediated CFL1 pathway and actin dynamics in retinoid receptor mediated function and show that LIMK1-mediated phosphocycling of CFL1 plays a role in maintaining actin homeostasis and receptor activity. (PMID:21923909)
• Aur-A physically associates with LIMK1 and activates it through phosphorylation, which is important for its centrosomal and spindle pole localization. (PMID:22214762)
• demonstrated that LIMK1, a key regulator of actin cytoskeleton, was overexpressed at both mRNA and protein levels in MG63/VCR cells and the higher LIMK1 protein level was correlated with higher level of phosphorylated cofilin (PMID:22715593)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	limk1b	ENSDARG00000003022
danio_rerio	limk1a	ENSDARG00000103467
mus_musculus	Limk1	ENSMUSG00000029674
rattus_norvegicus	Limk1	ENSRNOG00000001470

Paralogs (23): MAP3K9 (ENSG00000006432), TESK2 (ENSG00000070759), MAP3K13 (ENSG00000073803), ARAF (ENSG00000078061), MAP3K20 (ENSG00000091436), RIPK2 (ENSG00000104312), TESK1 (ENSG00000107140), TNNI3K (ENSG00000116783), RIPK3 (ENSG00000129465), MAP3K10 (ENSG00000130758), RAF1 (ENSG00000132155), RIPK1 (ENSG00000137275), MAP3K12 (ENSG00000139625), KSR1 (ENSG00000141068), MAP3K21 (ENSG00000143674), BRAF (ENSG00000157764), ILK (ENSG00000166333), MLKL (ENSG00000168404), KSR2 (ENSG00000171435), MOS (ENSG00000172680), MAP3K11 (ENSG00000173327), LIMK2 (ENSG00000182541), LRRK2 (ENSG00000188906)

Protein

Protein identifiers

LIM domain kinase 1 — P53667 (reviewed: P53667)

All UniProt accessions (2): P53667, E9PC47

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton. In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation. Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly. Stimulates axonal outgrowth and may be involved in brain development. Has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1).

Subunit / interactions. Interacts (via LIM domain) with the cytoplasmic domain of NRG1. Interacts with NISCH. Interacts with RLIM and RNF6. Self-associates to form homodimers. Interacts with HSP90AA1; this interaction promotes LIMK1 dimerization and subsequent transphosphorylation. Interacts with CDKN1C. Interacts with SSH1. Interacts with ROCK1. Interacts (via LIM zinc-binding domains) with FAM89B/LRAP25 (via LRR repeat). Forms a tripartite complex with CDC42BPA, CDC42BPB and FAM89B/LRAP25.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Cell projection. Lamellipodium.

Tissue specificity. Highest expression in both adult and fetal nervous system. Detected ubiquitously throughout the different regions of adult brain, with highest levels in the cerebral cortex. Expressed to a lesser extent in heart and skeletal muscle.

Post-translational modifications. Autophosphorylated. Phosphorylated on Thr-508 by ROCK1 and PAK1, resulting in activation. Phosphorylated by PAK4 which increases the ability of LIMK1 to phosphorylate cofilin. Phosphorylated at Ser-323 by MAPKAPK2 during activation of VEGFA-induced signaling, which results in activation of LIMK1 and promotion of actin reorganization, cell migration, and tubule formation of endothelial cells. Dephosphorylated and inactivated by SSH1. Phosphorylated by CDC42BP. Ubiquitinated. ‘Lys-48’-linked polyubiquitination by RNF6 leads to proteasomal degradation through the 26S proteasome, modulating LIMK1 levels in the growth cone and its effect on axonal outgrowth. Also polyubiquitinated by RLIM.

Disease relevance. LIMK1 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Isoforms (4)

UniProt ID	Names	Canonical?
P53667-1	1	yes
P53667-2	2
P53667-3	3
P53667-4	4

RefSeq proteins (2): NP_001191355, NP_002305* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001478	PDZ	Domain
IPR001781	Znf_LIM	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR036034	PDZ_sf	Homologous_superfamily
IPR050940	Actin_reg-Ser/Thr_kinase	Family

Pfam: PF00412, PF00595, PF07714

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (62 total): strand 12, helix 12, modified residue 9, mutagenesis site 9, domain 4, splice variant 4, sequence variant 4, turn 2, binding site 2, chain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
3S95	X-RAY DIFFRACTION	1.65
8AAU	X-RAY DIFFRACTION	1.74
6WLY	X-RAY DIFFRACTION	1.9
5HVJ	X-RAY DIFFRACTION	2.2
5NXC	X-RAY DIFFRACTION	2.25
5L6W	X-RAY DIFFRACTION	2.53
7ATS	X-RAY DIFFRACTION	2.8
7ATU	X-RAY DIFFRACTION	2.8
7B8W	X-RAY DIFFRACTION	2.8
5HVK	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53667-F1	76.07	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 460

Ligand- & substrate-binding residues (2): 345–353; 368

Post-translational modifications (9): 210, 229, 298, 302, 307, 310, 323, 337, 508

Mutagenesis-validated functional residues (9):

Position	Phenotype
84	enhances actin aggregation.
177–178	enhances actin aggregation.
460	abrogates kinase activity.
496–506	reduces actin aggregation.
503–505	abolishes kinase activity.
508	abolishes activation by rock1.
508	phosphomimetic mutant; enhances kinase activity.
508	enhances kinase activity.
508	reduces kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-399954	Sema3A PAK dependent Axon repulsion
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse
R-HSA-5627117	RHO GTPases Activate ROCKs
R-HSA-5627123	RHO GTPases activate PAKs
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-373755	Semaphorin interactions
R-HSA-400685	Sema4D in semaphorin signaling
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 715 (showing top): BIOCARTA_RHO_PATHWAY, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEURON_PROJECTION_EXTENSION, BIOCARTA_MAL_PATHWAY, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, CACCAGC_MIR138, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (11): protein phosphorylation (GO:0006468), signal transduction (GO:0007165), Rho protein signal transduction (GO:0007266), nervous system development (GO:0007399), actin cytoskeleton organization (GO:0030036), positive regulation of actin filament bundle assembly (GO:0032233), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), stress fiber assembly (GO:0043149), positive regulation of axon extension (GO:0045773), axon extension (GO:0048675), positive regulation of stress fiber assembly (GO:0051496)

GO Molecular Function (12): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), heat shock protein binding (GO:0031072), ubiquitin protein ligase binding (GO:0031625), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), ubiquitin ligase inhibitor activity (GO:1990948), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (14): male germ cell nucleus (GO:0001673), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), focal adhesion (GO:0005925), membrane (GO:0016020), nuclear speck (GO:0016607), lamellipodium (GO:0030027), neuron projection (GO:0043005), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cell junction (GO:0030054), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Semaphorin interactions	2
RHO GTPase Effectors	2
Axon guidance	2
Fcgamma receptor (FCGR) dependent phagocytosis	1
EPH-Ephrin signaling	1
Sema4D in semaphorin signaling	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Innate Immune System	1
Nervous system development	1
Developmental Biology	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein kinase activity	2
plasma membrane bounded cell projection	2
synapse	2
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
small GTPase-mediated signal transduction	1
system development	1
cytoskeleton organization	1
actin filament-based process	1
regulation of actin filament bundle assembly	1
positive regulation of cellular component biogenesis	1
actin filament bundle assembly	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
Fc receptor mediated stimulatory signaling pathway	1
phagocytosis	1
Fc-gamma receptor signaling pathway	1
contractile actin filament bundle assembly	1
actomyosin structure organization	1
positive regulation of cell growth	1
regulation of axon extension	1
positive regulation of developmental growth	1
axon extension	1
positive regulation of axonogenesis	1
axonogenesis	1
neuron projection extension	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1

Protein interactions and networks

STRING

2907 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIMK1	CFL2	Q9Y281	983
LIMK1	CFL1	P23528	983
LIMK1	SSH1	Q8WYL5	937
LIMK1	SSH3	Q8TE77	891
LIMK1	SSH2	Q76I76	865
LIMK1	CLIP2	Q9UDT6	863
LIMK1	BMPR2	Q13873	855
LIMK1	RHOA	P06749	828
LIMK1	EIF4H	Q15056	792
LIMK1	PDXP	Q96GD0	786
LIMK1	GTF2IRD1	Q9UHL9	747
LIMK1	CDC42	P21181	716
LIMK1	ELN	P15502	691
LIMK1	TBL2	Q9Y4P3	677
LIMK1	NISCH	Q9Y2I1	676

IntAct

91 interactions, top by confidence:

A	B	Type	Score
CFL1	LIMK1	psi-mi:“MI:0915”(physical association)	0.720
LIMK1	CFL1	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
SSH1	LIMK1	psi-mi:“MI:0403”(colocalization)	0.680
SSH1	LIMK1	psi-mi:“MI:0915”(physical association)	0.680
SSH1	LIMK1	psi-mi:“MI:0407”(direct interaction)	0.680
LIMK1	SSH1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.680
PAK1	LIMK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
LIMK1	PAK1	psi-mi:“MI:0915”(physical association)	0.620
LIMK1	PAK1	psi-mi:“MI:0403”(colocalization)	0.620
HUNK	LIMK1	psi-mi:“MI:0915”(physical association)	0.570
LIMK1	PAK2	psi-mi:“MI:0407”(direct interaction)	0.560
PAK2	LIMK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
LIMK1	C22orf15	psi-mi:“MI:0915”(physical association)	0.560
	LIMK1	psi-mi:“MI:0915”(physical association)	0.560
LIMK1	LATS1	psi-mi:“MI:0915”(physical association)	0.560
LATS1	LIMK1	psi-mi:“MI:0915”(physical association)	0.560
LIMK1	LATS1	psi-mi:“MI:0403”(colocalization)	0.560
LIMK1	LIMK2	psi-mi:“MI:0914”(association)	0.530
LIMK2	LIMK1	psi-mi:“MI:0914”(association)	0.530
Prkcg	LIMK1	psi-mi:“MI:0915”(physical association)	0.520
LIMK1	Prkcg	psi-mi:“MI:0915”(physical association)	0.520
Arrb1	LIMK1	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (114): BAD (Affinity Capture-MS), BLMH (Affinity Capture-MS), FYN (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), POLR2D (Affinity Capture-MS), RRAS (Affinity Capture-MS), UXT (Affinity Capture-MS), RAD54L (Affinity Capture-MS), TADA3 (Affinity Capture-MS), RTEL1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), MIIP (Affinity Capture-MS), SARNP (Affinity Capture-MS), OSBPL5 (Affinity Capture-MS)

ESM2 similar proteins: A1DZY4, A6QP66, O35626, O35929, O88910, O88954, P0C0E4, P35295, P51157, P51158, P53667, P53668, P53669, P55040, P55041, P55043, P63032, P63033, Q06AU5, Q12829, Q13368, Q13637, Q3SWY9, Q5E9J3, Q5FVY2, Q5R541, Q5RFI2, Q6DGN0, Q6IMA3, Q6IMA7, Q6IMB1, Q6P0U3, Q6T310, Q8AVS6, Q8IYK8, Q8QFP8, Q8VEL9, Q8VHP8, Q8VHQ4, Q8WXH6

Diamond homologs: A0JNI8, A2I8Z7, A2PZF9, G5EC36, G5EE86, O14639, O35652, O60663, O88609, O94929, O97581, P20154, P25791, P25800, P25801, P29673, P29674, P34764, P34765, P36198, P36200, P37137, P48742, P50211, P50212, P50458, P50480, P50481, P52889, P53405, P53406, P53407, P53408, P53409, P53410, P53411, P53412, P53413, P53667, P53668

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
MAPKAPK2	up-regulates	LIMK1	phosphorylation
LIMK1	down-regulates	CFL1	phosphorylation
RNF6	“down-regulates quantity by destabilization”	LIMK1	polyubiquitination
SSH1	“down-regulates activity”	LIMK1	dephosphorylation
PAK6	“up-regulates activity”	LIMK1	phosphorylation
AURKA	“up-regulates activity”	LIMK1	phosphorylation
CAMK4	“up-regulates activity”	LIMK1	phosphorylation
LIMK1	“down-regulates activity”	CFL2	phosphorylation
PAK1	“up-regulates activity”	LIMK1	phosphorylation
ROCK1	“up-regulates activity”	LIMK1	phosphorylation
CDC42BPA	“up-regulates activity”	LIMK1	phosphorylation
PTPRG	“down-regulates activity”	LIMK1	dephosphorylation
dabrafenib	“down-regulates activity”	LIMK1	“chemical inhibition”
LIMK1	“up-regulates activity”	AURKA	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPase Effectors	5	11.0×	2e-03
Signaling by Receptor Tyrosine Kinases	5	8.3×	4e-03
Signaling by Rho GTPases	6	6.6×	4e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	6	6.5×	4e-03
Infectious disease	7	5.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
MAPK cascade	5	17.0×	2e-03
intracellular protein localization	5	11.6×	6e-03
protein phosphorylation	7	10.6×	1e-03
intracellular signal transduction	9	7.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

156 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	78
Likely benign	37
Benign	10

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2674589	NM_002314.4(LIMK1):c.1532G>C (p.Gly511Ala)	Pathogenic
563396	GRCh37/hg19 7q11.23(chr7:72718123-74141784)x1	Pathogenic
3251243	NM_002314.4(LIMK1):c.127G>A (p.Ala43Thr)	Likely pathogenic

SpliceAI

2410 predictions. Top by Δscore:

Variant	Effect	Δscore
7:74084042:G:GT	donor_gain	1.0000
7:74084043:A:T	donor_gain	1.0000
7:74085740:C:G	acceptor_gain	1.0000
7:74085743:TGCA:T	acceptor_loss	1.0000
7:74085744:GCA:G	acceptor_loss	1.0000
7:74085746:A:AG	acceptor_gain	1.0000
7:74085746:A:T	acceptor_loss	1.0000
7:74085746:AG:A	acceptor_gain	1.0000
7:74085747:G:GC	acceptor_gain	1.0000
7:74085747:G:T	acceptor_loss	1.0000
7:74085747:GG:G	acceptor_gain	1.0000
7:74085747:GGAA:G	acceptor_gain	1.0000
7:74085840:TTCAG:T	donor_loss	1.0000
7:74085842:CAGG:C	donor_loss	1.0000
7:74085843:AGG:A	donor_loss	1.0000
7:74085844:GGTAG:G	donor_loss	1.0000
7:74085845:GTAGG:G	donor_loss	1.0000
7:74085846:T:G	donor_loss	1.0000
7:74096750:G:T	donor_gain	1.0000
7:74096759:TGG:T	donor_loss	1.0000
7:74096761:GTGA:G	donor_loss	1.0000
7:74096762:T:A	donor_loss	1.0000
7:74097067:A:AG	acceptor_gain	1.0000
7:74097076:C:G	acceptor_gain	1.0000
7:74097187:CTGG:C	donor_loss	1.0000
7:74097190:G:GC	donor_loss	1.0000
7:74097190:G:GG	donor_gain	1.0000
7:74097191:T:G	donor_loss	1.0000
7:74099013:A:AG	acceptor_gain	1.0000
7:74099013:ACCCC:A	acceptor_gain	1.0000

AlphaMissense

4251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:74096719:T:C	C84R	1.000
7:74096721:C:G	C84W	1.000
7:74097110:T:C	C108R	1.000
7:74097112:T:G	C108W	1.000
7:74097119:T:C	C111R	1.000
7:74097120:G:A	C111Y	1.000
7:74097121:C:G	C111W	1.000
7:74107129:T:C	F334S	1.000
7:74107144:T:A	L339H	1.000
7:74107144:T:C	L339P	1.000
7:74107170:G:C	G348R	1.000
7:74107176:T:C	F350L	1.000
7:74107178:C:A	F350L	1.000
7:74107178:C:G	F350L	1.000
7:74107180:G:A	G351D	1.000
7:74107907:A:C	K368Q	1.000
7:74107909:G:C	K368N	1.000
7:74107909:G:T	K368N	1.000
7:74107946:T:C	F381L	1.000
7:74107947:T:C	F381S	1.000
7:74107948:C:A	F381L	1.000
7:74107948:C:G	F381L	1.000
7:74108942:T:A	L397H	1.000
7:74108942:T:C	L397P	1.000
7:74108947:T:C	F399L	1.000
7:74108948:T:C	F399S	1.000
7:74108949:C:A	F399L	1.000
7:74108949:C:G	F399L	1.000
7:74108953:G:A	G401R	1.000
7:74108953:G:C	G401R	1.000

dbSNP variants (sampled 300 via entrez): RS1000025042 (7:74095361 C>T), RS1000075077 (7:74100684 C>A,T), RS1000285575 (7:74090232 G>A), RS1000369539 (7:74101853 C>A), RS1000385131 (7:74083351 C>T), RS1000414401 (7:74084127 C>G,T), RS1000614766 (7:74090009 C>G), RS1000864923 (7:74119781 G>A), RS1001021773 (7:74091415 G>A), RS1001121981 (7:74107720 C>T), RS1001640453 (7:74103250 T>C), RS1001723389 (7:74115235 C>G), RS1001862582 (7:74110669 T>C), RS1002033634 (7:74098420 T>C), RS1002056543 (7:74098798 C>T)

Disease associations

OMIM: gene MIM:601329 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (1): Non-specific early-onset epileptic encephalopathy (Orphanet:442835)

HPO phenotypes

186 total (30 of 186 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006626_43	Pulse pressure	2.000000e-10
GCST007278_17	Systemic seropositive rheumatic diseases (Systemic sclerosis or systemic lupus erythematosus or rheumatoid arthritis or idiopathic inflammatory myopathies)	3.000000e-09
GCST011011_33	Youthful appearance (self-reported)	3.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3836 (SINGLE PROTEIN), CHEMBL3885599 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

38 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 299,331 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL939	GEFITINIB	4	117,814
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL1950289	TANZISERTIB	2	419
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980297	ILORASERTIB	2
CHEMBL1980715	LAUROGUADINE	2
CHEMBL2107823	GANDOTINIB	2
CHEMBL3039525	GOLVATINIB	2
CHEMBL402548	DANUSERTIB	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL572878	TOZASERTIB	2
CHEMBL587723	AEE-788	2
CHEMBL1980391	RG-1530	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — LIMK subfamily

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
compound 14 [PMID: 19831390]	Inhibition	9.3	pIC50
RKI-1447	Inhibition	8.76	pIC50
LIMKi3	Inhibition	8.15	pIC50
voruciclib	Inhibition	7.66	pIC50
ZAK inhibitor 6p	Inhibition	7.64	pKd
compound 30 [PMID: 22902653]	Inhibition	7.64	pIC50
compound 35 [PMID: 22902653]	Inhibition	7.52	pIC50
SR7826	Inhibition	7.37	pIC50
compound 31 [PMID: 22902653]	Inhibition	7.24	pIC50

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	IC50	10 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
BMS-354825	KD	27 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM

ChEMBL bioactivities

865 potent at pChembl≥5 of 930 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL3623439
9.52	IC50	0.3	nM	CHEMBL5278261
9.30	IC50	0.5	nM	CHEMBL570126
9.00	IC50	1	nM	CHEMBL2070615
9.00	IC50	1	nM	CHEMBL3623442
9.00	IC50	1	nM	CHEMBL5275331
8.84	IC50	1.445	nM	CHEMBL5169387
8.76	IC50	1.74	nM	CHEMBL3218297
8.70	IC50	1.995	nM	CHEMBL570116
8.61	IC50	2.44	nM	STAUROSPORINE
8.57	IC50	2.71	nM	STAUROSPORINE
8.54	IC50	2.9	nM	STAUROSPORINE
8.52	IC50	3	nM	CHEMBL3623438
8.52	IC50	3	nM	CHEMBL3623441
8.52	IC50	3.02	nM	CHEMBL570116
8.49	IC50	3.2	nM	CHEMBL570116
8.43	IC50	3.7	nM	CHEMBL565452
8.40	IC50	4	nM	CHEMBL3623437
8.40	Ki	4	nM	CHEMBL5549785
8.40	IC50	4.01	nM	CHEMBL1258976
8.30	IC50	5	nM	CHEMBL3623435
8.30	IC50	5	nM	CHEMBL3182065
8.28	IC50	5.248	nM	CHEMBL570116
8.22	Kd	6	nM	CHEMBL4465866
8.19	IC50	6.457	nM	CHEMBL2141887
8.19	IC50	6.457	nM	CHEMBL5169387
8.18	IC50	6.6	nM	CHEMBL570820
8.15	IC50	7	nM	CHEMBL5169387
8.15	IC50	7	nM	CHEMBL2141887
8.15	Ki	7	nM	CHEMBL5505895
8.13	IC50	7.413	nM	CHEMBL3609326
8.12	IC50	7.6	nM	CHEMBL3613609
8.10	IC50	8	nM	CHEMBL3410056
8.10	IC50	8	nM	CHEMBL3623443
8.10	IC50	8	nM	CHEMBL5275515
8.10	IC50	8	nM	CHEMBL5289711
8.05	Ki	9	nM	CHEMBL5517889
8.01	IC50	9.8	nM	CHEMBL5169387
8.00	IC50	10	nM	CHEMBL2141887
8.00	IC50	10	nM	CHEMBL3629276
8.00	Ki	10	nM	CHEMBL1983715
7.96	IC50	11	nM	CHEMBL3629277
7.92	IC50	12	nM	CHEMBL3586447
7.92	Ki	12	nM	CHEMBL5532060
7.91	IC50	12.3	nM	LX-7101
7.91	IC50	12.3	nM	CHEMBL5436237
7.89	IC50	13	nM	CHEMBL3622874
7.89	Ki	13	nM	CHEMBL5557696
7.89	Ki	13	nM	CHEMBL5555533
7.82	IC50	15	nM	CHEMBL3622867

PubChem BioAssay actives

422 with measured affinity, of 2223 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[[5-[3-(2-chloro-4-methylphenyl)-4-pyridinyl]-1,3-thiazol-2-yl]amino]phenol	1941048: Inhibition of human LIMK1 (321 to 647 residues) expressed in Sf9 cells using dextrin as substrate incubated for 30 mins by micro-scintillation fluid method	ic50	0.0003	uM
4-[[5-[3-(2-chlorophenyl)-4-pyridinyl]-1,3-thiazol-2-yl]amino]phenol	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0003	uM
(2S)-N’-(3-bromophenyl)-N-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	441216: Inhibition of LIMK1	ic50	0.0005	uM
N-[5-[3-(2-chloro-4-methylphenyl)-4-pyridinyl]-1,3-thiazol-2-yl]-2-methylpropanamide	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0010	uM
1-[5-[3-(2-chloro-4-methylphenyl)-4-pyridinyl]-1,3-thiazol-2-yl]-2-methylpropan-1-one	1941048: Inhibition of human LIMK1 (321 to 647 residues) expressed in Sf9 cells using dextrin as substrate incubated for 30 mins by micro-scintillation fluid method	ic50	0.0010	uM
N-[2-[benzyl-[4-(phenylsulfamoyl)benzoyl]amino]ethyl]-2-(2-methylpropanoylamino)-1,3-thiazole-5-carboxamide	1857472: Inhibition of PAK mediated recombinant LIMK1 phosphorylation (330 to 637 residues) (unknown origin) incubated for 45 mins followed by ATP addition measured after 105 mins by RapidFire Mass Spectrometry kinase assay	ic50	0.0014	uM
1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea;methanesulfonic acid	1119788: Inhibition of LIMK1 (unknown origin)	ic50	0.0017	uM
[3-[[(2S)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1857470: Inhibition of recombinant LIMK1 (330 to 637 residues) (unknown origin) incubated for 45 mins followed by ATP addition measured after 105 mins by RapidFire Mass Spectrometry kinase assay	ic50	0.0020	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1531747: Inhibition of human LIMK1 using cofilin as substrate by [gamma-33P]-ATP assay	ic50	0.0024	uM
N-[5-[3-(2-chlorophenyl)-4-pyridinyl]-1,3-thiazol-2-yl]-2-methylpropanamide	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0030	uM
5-[3-(2-chlorophenyl)-4-pyridinyl]-N-phenyl-1,3-thiazol-2-amine	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0030	uM
(2S)-N’-(3-bromo-4-fluorophenyl)-N-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	441216: Inhibition of LIMK1	ic50	0.0037	uM
4-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-[3-(4-methoxyphenyl)phenyl]-3,6-dihydro-2H-pyridine-1-carboxamide	2063282: Inhibition of LIMK1 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0040	uM
N-[4-(2-chlorophenyl)-6-[2-(propan-2-ylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]-N’,N’-dimethylethane-1,2-diamine	516603: Inhibition of LIMK1	ic50	0.0040	uM
5-[3-(2-chlorophenyl)-4-pyridinyl]-N-[(1R)-1-phenylethyl]-1,3-thiazol-2-amine	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0040	uM
5-[3-(2-chlorophenyl)-4-pyridinyl]-N-(2-methylpropyl)-1,3-thiazol-2-amine	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0050	uM
N-[5-[1-(2,6-dichlorophenyl)-3-(difluoromethyl)pyrazol-5-yl]-1,3-thiazol-2-yl]cyclopropanecarboxamide	1941048: Inhibition of human LIMK1 (321 to 647 residues) expressed in Sf9 cells using dextrin as substrate incubated for 30 mins by micro-scintillation fluid method	ic50	0.0050	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526150: Binding affinity to truncated human N-terminal GST-tagged LIMK1 (285 to 638 residues) expressed in baculovirus expression system using cofilin2 as substrate incubated for 1 hr by TR-FRET assay	kd	0.0060	uM
N-[5-[1-(2,6-dichlorophenyl)-3-(difluoromethyl)pyrazol-5-yl]-1,3-thiazol-2-yl]-2-methylpropanamide	1857470: Inhibition of recombinant LIMK1 (330 to 637 residues) (unknown origin) incubated for 45 mins followed by ATP addition measured after 105 mins by RapidFire Mass Spectrometry kinase assay	ic50	0.0065	uM
(2S)-N-(3-bromo-4-fluorophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	441216: Inhibition of LIMK1	ic50	0.0066	uM
N-(3-bromophenyl)-4-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	2063282: Inhibition of LIMK1 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0070	uM
6-(2,4-dichlorophenyl)-8-ethyl-2-(3-fluoro-4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidin-7-one	1857470: Inhibition of recombinant LIMK1 (330 to 637 residues) (unknown origin) incubated for 45 mins followed by ATP addition measured after 105 mins by RapidFire Mass Spectrometry kinase assay	ic50	0.0074	uM
prop-2-ynyl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244617: Inhibition of LIMK1 (unknown origin) by radiometric assay	ic50	0.0076	uM
N-[5-[3-[4-methoxy-2-(trifluoromethyl)phenyl]-4-pyridinyl]-1,3-thiazol-2-yl]-2-methylpropanamide	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0080	uM
1-(4-chlorophenyl)-3-[4-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluorophenyl]-1-(2-methoxyethyl)urea	1197751: Inhibition of human Limk1 using cofilin substrate, ATP and [gamma33P]ATP	ic50	0.0080	uM
1-(4-chlorophenyl)-3-[4-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3-fluorophenyl]-1-(2-methoxyethyl)urea	1941061: Inhibition of LIMK1 (unknown origin) phosphorylation of cofilin	ic50	0.0080	uM
1-[5-[3-[4-methoxy-2-(trifluoromethyl)phenyl]-4-pyridinyl]-1,3-thiazol-2-yl]-2-methylpropan-1-one	1941048: Inhibition of human LIMK1 (321 to 647 residues) expressed in Sf9 cells using dextrin as substrate incubated for 30 mins by micro-scintillation fluid method	ic50	0.0080	uM
4-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-phenylphenyl)-3,6-dihydro-2H-pyridine-1-carboxamide	2063282: Inhibition of LIMK1 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0090	uM
1-[2-fluoro-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]-3-(4-methoxyphenyl)urea	1254430: Inhibition of LIMK1 (unknown origin) using 1 uM cofilin as substrate	ic50	0.0100	uM
2-[5-(2-anilinopyrimidin-4-yl)-4-[3-[(2,6-difluorophenyl)sulfonylamino]-2-fluorophenyl]-1,3-thiazol-2-yl]-N-methylacetamide	2063309: Inhibition of LIMK1 (unknown origin)	ic50	0.0100	uM
1-[2-fluoro-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]-3-(6-methyl-3-pyridinyl)urea	1254430: Inhibition of LIMK1 (unknown origin) using 1 uM cofilin as substrate	ic50	0.0110	uM
N-[3-(4-methoxyphenyl)phenyl]-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	2063282: Inhibition of LIMK1 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0120	uM
4-amino-8-(5-methyl-1H-indazol-6-yl)cinnoline-3-carboxamide	1230653: Inhibition of human recombinant LIMK1 by LanthaScreen Binding assay	ic50	0.0120	uM
N-[2,4-difluoro-3-[4-[3-(1-prop-2-enoylpyrrolidin-3-yl)oxy-1H-pyrazolo[5,4-b]pyridin-5-yl]triazol-1-yl]phenyl]-3-phenylbenzenesulfonamide	1990329: Inhibition of full length human LIMK1 by KINOMEscan assay	ic50	0.0123	uM
[3-[[4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1857470: Inhibition of recombinant LIMK1 (330 to 637 residues) (unknown origin) incubated for 45 mins followed by ATP addition measured after 105 mins by RapidFire Mass Spectrometry kinase assay	ic50	0.0123	uM
5-[3-[4-methoxy-2-(trifluoromethyl)phenyl]-4-pyridinyl]-N-propyl-1,3-thiazol-2-amine	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0130	uM
4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-phenylphenyl)-3,6-dihydro-2H-pyridine-1-carboxamide	2063282: Inhibition of LIMK1 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0130	uM
4-(5-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-pyrrol-1-ylphenyl)-3,6-dihydro-2H-pyridine-1-carboxamide	2063282: Inhibition of LIMK1 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0130	uM
5-[3-(2-chlorophenyl)-4-pyridinyl]-N-propyl-1,3-thiazol-2-amine	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0150	uM
N-[3-(3-methoxyphenyl)phenyl]-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	2063282: Inhibition of LIMK1 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0150	uM
4-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-methoxyphenyl)-3,6-dihydro-2H-pyridine-1-carboxamide	2063282: Inhibition of LIMK1 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0150	uM
methyl 3-[[4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244617: Inhibition of LIMK1 (unknown origin) by radiometric assay	ic50	0.0160	uM
4-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-phenyl-3,6-dihydro-2H-pyridine-1-carboxamide	2063282: Inhibition of LIMK1 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0170	uM
methyl 3-[[4-amino-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244617: Inhibition of LIMK1 (unknown origin) by radiometric assay	ic50	0.0180	uM
3-[[2-fluoro-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]carbamoylamino]-N-propan-2-ylbenzamide	1197751: Inhibition of human Limk1 using cofilin substrate, ATP and [gamma33P]ATP	ic50	0.0180	uM
4-fluoro-N-[4-[(6-oxo-5H-benzo[c][1,8]naphthyridin-1-yl)amino]phenyl]-2-(trifluoromethyl)benzamide	746819: Inhibition of LIMK1 (unknown origin)	ic50	0.0180	uM
1-(4-chlorophenyl)-1-[2-(dimethylamino)ethyl]-3-[4-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-fluorophenyl]urea	1197751: Inhibition of human Limk1 using cofilin substrate, ATP and [gamma33P]ATP	ic50	0.0190	uM
1-[2-fluoro-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]-3-(2-methyl-4-pyridinyl)urea	1254430: Inhibition of LIMK1 (unknown origin) using 1 uM cofilin as substrate	ic50	0.0190	uM
[3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1244617: Inhibition of LIMK1 (unknown origin) by radiometric assay	ic50	0.0190	uM
N-[5-[3-(2-chlorophenyl)-4-pyridinyl]-1,3-thiazol-2-yl]acetamide	1251124: Inhibition of recombinant N-terminal 6His-tagged LIMK1 (unknown origin) expressed in Sf21 cells by HTRF assay using cofilin as a substrate	ic50	0.0200	uM

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression	3
sodium arsenite	affects expression, increases expression	3
bisphenol F	affects cotreatment, increases methylation, increases expression	2
Estradiol	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
lead acetate	increases expression	1
zinc chromate	decreases expression, increases abundance	1
diallyl disulfide	decreases reaction, decreases expression	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
cupric chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
Y 27632	decreases expression	1
U 0126	affects expression, affects reaction	1
abrine	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Amphotericin B	increases expression	1
Benzene	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

307 unique, capped per target: 306 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1025745	Binding	Binding affinity to human LIMK1 at 10 uM relative to control	Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. — J Med Chem
CHEMBL1963749	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LIMK1	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1XB	Abcam A-549 LIMK1 KO	Cancer cell line	Male
CVCL_D2BL	Abcam HCT 116 LIMK1 KO	Cancer cell line	Male
CVCL_SV58	HAP1 LIMK1 (-) 1	Cancer cell line	Male
CVCL_SV59	HAP1 LIMK1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.