LIMK2

Summary

LIMK2 (LIM domain kinase 2, HGNC:6614) is a protein-coding gene on chromosome 22q12.2, encoding LIM domain kinase 2 (P53671). 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. 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.

Source: NCBI Gene 3985 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 127 total
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005569

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6614
Approved symbol	LIMK2
Name	LIM domain kinase 2
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182541
Ensembl biotype	protein_coding
OMIM	601988
Entrez	3985

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000331728, ENST00000333611, ENST00000340552, ENST00000406516, ENST00000425203, ENST00000462625, ENST00000465937, ENST00000467301, ENST00000482270, ENST00000887560, ENST00000887561, ENST00000887562, ENST00000887563, ENST00000887564, ENST00000887565, ENST00000937842, ENST00000937843, ENST00000961695, ENST00000961696

RefSeq mRNA: 3 — MANE Select: NM_005569 NM_001031801, NM_005569, NM_016733

CCDS: CCDS13891, CCDS13892, CCDS33637

Canonical transcript exons

ENST00000331728 — 16 exons

Exon	Start	End
ENSE00001304549	31268144	31268200
ENSE00001308533	31259121	31259230
ENSE00001316612	31266984	31267070
ENSE00001317796	31272530	31272704
ENSE00001321366	31271136	31271201
ENSE00001328141	31267776	31267907
ENSE00001342351	31278297	31280080
ENSE00001951544	31212298	31212424
ENSE00003525460	31262134	31262239
ENSE00003538682	31273452	31273507
ENSE00003559126	31258291	31258426
ENSE00003563401	31265946	31266132
ENSE00003637120	31275151	31275308
ENSE00003654572	31259889	31260077
ENSE00003677127	31225720	31225819
ENSE00003691953	31262595	31262791

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 97.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.3332 / max 1555.1345, expressed in 1810 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191771	18.1476	1734
191791	6.9899	1069
191790	3.3806	1139
191792	0.5069	312
191772	0.2219	68
191789	0.0864	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	97.04	gold quality
gingival epithelium	UBERON:0001949	96.72	gold quality
esophagus squamous epithelium	UBERON:0006920	96.67	gold quality
squamous epithelium	UBERON:0006914	96.33	gold quality
blood	UBERON:0000178	96.32	gold quality
skin of abdomen	UBERON:0001416	95.98	gold quality
skin of leg	UBERON:0001511	95.85	gold quality
esophagus mucosa	UBERON:0002469	95.72	gold quality
epithelium of esophagus	UBERON:0001976	95.54	gold quality
hair follicle	UBERON:0002073	95.50	gold quality
right uterine tube	UBERON:0001302	95.34	gold quality
palpebral conjunctiva	UBERON:0001812	95.22	gold quality
minor salivary gland	UBERON:0001830	95.19	gold quality
zone of skin	UBERON:0000014	95.16	gold quality
gingiva	UBERON:0001828	94.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.84	gold quality
mouth mucosa	UBERON:0003729	94.73	gold quality
mucosa of transverse colon	UBERON:0004991	94.72	gold quality
epithelium of nasopharynx	UBERON:0001951	94.57	gold quality
left lobe of thyroid gland	UBERON:0001120	94.56	gold quality
rectum	UBERON:0001052	94.11	gold quality
thyroid gland	UBERON:0002046	94.10	gold quality
right lobe of thyroid gland	UBERON:0001119	93.93	gold quality
nasal cavity epithelium	UBERON:0005384	93.69	gold quality
lower esophagus mucosa	UBERON:0035834	93.67	gold quality
saliva-secreting gland	UBERON:0001044	93.52	gold quality
nasal cavity mucosa	UBERON:0001826	93.32	gold quality
placenta	UBERON:0001987	93.21	gold quality
bronchial epithelial cell	CL:0002328	93.20	gold quality
penis	UBERON:0000989	93.15	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	24.00
E-ANND-3	yes	8.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

100 targeting LIMK2, 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-3925-3P	100.00	69.95	1237
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4775	99.98	75.00	6394
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-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4804-3P	99.65	67.78	866

Literature-anchored findings (GeneRIF, showing 36)

• a novel pathway emanating from the TGF-beta type I receptor and leading to regulation of actin assembly, via the kinase LIMK2. (PMID:15647284)
• PKC-mediated exclusion of LIMK2 from the nucleus might be a mechanism to relieve suppression of cyclin D1 expression by LIMK2 (PMID:15923181)
• LIMK2 may play a role different from that of LIMK1 in regulating mitotic spindle organization, chromosome segregation, and cytokinesis during the cell division cycle. (PMID:16455074)
• analysis of phosphorylation-dependent regulation of unique nuclear and nucleolar localization signals of LIM kinase 2 in endothelial cells (PMID:16820362)
• the structure, regulation and function; possible contributions to human disease (Review) (PMID:17294230)
• gamma-tubulin associates with phosphorylated LIMK1 and LIMK2 but not with dephosphorylated LIMK1 or LIMK2. (PMID:18000399)
• direct interaction between ROCK1 and LIMK2 in polarised but not blebbing cells; results point to a specific role for the ROCK1:LIMK2 pathway in mesenchymal-mode migration (PMID:18852895)
• Both LIMK1 and LIMK2 single knock down led to a reduction of invasion and metastatic behavior in the zebrafish xenograft metastasis assay. (PMID:20047470)
• a novel pathway whereby LIMK2b, acting downstream of p53, ensures proper execution of checkpoint arrest by modulating the dynamics of actin polymerization (PMID:20190821)
• LIMK2 variant isoforms were found to be regulated by p53 through direct interaction with regulatory elements within the LIMK2 gene. (PMID:21079653)
• LIMK2 is a key regulator that acts through different substrates to provide functional links between the actin cytoskeleton and spindle dynamics. (PMID:22328514)
• LIMK2 positively regulates the level of Aurora A, thereby engaging in a positive-feedback loop, promoting Aurora-A-mediated oncogenic pathways. (PMID:22492986)
• A novel activity of Rho in promoting a complex between fascin-1 and LIMK1/2 that modulates the interaction of fascin-1 with actin, was identified. (PMID:22883572)
• Nf1/LIMK2 interaction and inhibition allows to directly connect neurofibromatosis type I to actin cytoskeleton remodeling. (PMID:23082153)
• Overexpression of LIMK2 is associated with breast cancer growth and invasiveness. (PMID:23239465)
• LIMK2 expression was reduced in intestinal tumours of cancer-prone mice and in human colorectal cancer cell lines and tumours. LIMK2 expression progressively decreased with advancing stage of colorectal cancer. (PMID:23585469)
• results highlight the exciting possibility of combining specific LIMK2 inhibitors with anticancer drugs in the treatment of multi-drug resistant cancers (PMID:23991158)
• Results show that in addition to a potential role in promoting metastasis, changes in LIMK1 and LIMK2 expression and/or activity might contribute to AR function in prostate cancer via regulation of microtubule cytoskeletal dynamics. (PMID:25344584)
• Actin remodelling factor LIMK2 is a key player in the ciliogenesis control network in which YAP/TAZ and directional vesicle trafficking are integral components. (PMID:25849865)
• This study showed that LIMK2 messenger RNA levels was significantly upregulated in subjects with schizophrenia in laminar and cellular samples. (PMID:25981171)
• LIMK2 (rs149034313) is associated with Behcet’s disease. The LIMK2 association is a missense variant with predicted protein damage that may influence functional interactions with proteins involved in cytoskeletal regulation by Rho GTPase, inflammation mediated by chemokine and cytokine signaling pathways, T cell activation, and angiogenesis. (PMID:26662719)
• We observed marked increases in LIM kinase 2 (LIMK2) and cofilin 1 (CFL1) gene expressions in metabolic syndrome patients. (PMID:26956845)
• In turn, LIMK1 and LIMK2 are required for MT1-MMP-dependent matrix degradation and cell invasion in a three-dimensional type I collagen environment. (PMID:27116935)
• these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2. (PMID:28069000)
• High LIMK2 expression is associated with alcoholic hepatitis. (PMID:28818508)
• rs4141404:A>C(LIMK2) may be a marker of risk of grade 2/3 paclitaxel-induced peripheral sensory neuropathy. (PMID:29125099)
• Analysis localized LIMK2 SNP rs2073859 (G-to-A allele) within the microRNA-135a binding region and revealed lower LIMK2 G allele expression. The frequency of A genotypes was higher in the bladder cancer (BC) group than normal controls and correlated with risks of higher grade and stage BC. LIMK2 may function as an oncogene in human BC, while allele-specific regulation by microRNA-135a may influence disease risk. (PMID:30006972)
• LIM domain kinase 2 isoform LIMK2-1 (LIMK2-1) has a protein phosphatase 1 (PP1) inhibitory domain at its C-terminus which its two isoenzymes LIMK2a and LIMK2b do not. (PMID:30373762)
• Compared to the other LIMK2 isoforms, LIMK2-1 contains a supplementary C-terminal phosphatase 1 inhibitory domain (PP1i). This isoform was hominidae-specific and showed that it was expressed in human fetal brain and faintly in adult brain. An association of a rare missense variant in the PP1i domain was found in patients with sporadic non-syndromic intellectual disability. (PMID:30594563)
• It has been found that LIMK1/LIMK2 is critical for GPER activation-induced breast cancer cell migration. (PMID:31277940)
• LIMK1and LIMK2 expression status is associated with glioblastoma (GBM) grade and poor prognosis. Simultaneous knockdown of both isoforms strongly reduced the invasive motility of continuous culture models and human GBM tumor-initiating cells. LIMK1/2 functionally regulated cell invasiveness, in part, by disrupting polarized cell motility under confinement and cell chemotaxis. (PMID:31641031)
• NUDT21 inhibits bladder cancer progression through ANXA2 and LIMK2 by alternative polyadenylation. (PMID:31695759)
• Negative cross talk between LIMK2 and PTEN promotes castration resistant prostate cancer pathogenesis in cells and in vivo. (PMID:32931887)
• Involvement of LIMK2 in actin cytoskeleton remodeling during the definitive endoderm differentiation. (PMID:33977398)
• The Diagnostic and Prognostic Value of LIMK1/2: A Pan-Cancer Analysis. (PMID:34686503)
• LIMK2 Is a Novel Prognostic Biomarker and Correlates With Tumor Immune Cell Infiltration in Lung Squamous Cell Carcinoma. (PMID:35273591)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	limk2	ENSDARG00000005104
mus_musculus	Limk2	ENSMUSG00000020451
rattus_norvegicus	Limk2	ENSRNOG00000019000

Paralogs (23): MAP3K9 (ENSG00000006432), TESK2 (ENSG00000070759), MAP3K13 (ENSG00000073803), ARAF (ENSG00000078061), MAP3K20 (ENSG00000091436), RIPK2 (ENSG00000104312), LIMK1 (ENSG00000106683), 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), LRRK2 (ENSG00000188906)

Protein

Protein identifiers

LIM domain kinase 2 — P53671 (reviewed: P53671)

All UniProt accessions (3): P53671, B5MC51, C9JK61

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. Involved in astral microtubule organization and mitotic spindle orientation during early stages of mitosis by mediating phosphorylation of TPPP. Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro. Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of directional trafficking of ciliary vesicles to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1.

Subunit / interactions. Interacts with LIMK2b. Interacts with LIMK2a. Binds ROCK1 and MARF1 (PubMed:10436159, PubMed:11018042, Ref.9). Interacts with NISCH.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Microtubule organizing center. Centrosome Cytoplasm. Nucleus Cytoplasm. Perinuclear region. Nucleus.

Post-translational modifications. Phosphorylated on serine and/or threonine residues by ROCK1.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P53671-1	LIMK2a	yes
P53671-2	LIMK2b
P53671-3	3

RefSeq proteins (3): NP_001026971, NP_005560, NP_057952 (=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 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

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 (65 total): helix 19, strand 18, sequence variant 6, domain 4, modified residue 4, mutagenesis site 3, turn 3, splice variant 2, binding site 2, chain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7QHG	X-RAY DIFFRACTION	1.45
5NXD	X-RAY DIFFRACTION	1.9
8GI4	X-RAY DIFFRACTION	2.06
8WSW	X-RAY DIFFRACTION	2.5
8S3X	X-RAY DIFFRACTION	2.59
4TPT	X-RAY DIFFRACTION	2.6
1X6A	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53671-F1	76.28	0.34

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): 451

Ligand- & substrate-binding residues (2): 337–345; 360

Post-translational modifications (4): 210, 293, 298, 505

Mutagenesis-validated functional residues (3):

Position	Phenotype
451	abrogates kinase activity.
505	phosphomimetic mutant; enhances kinase activity.
505	abolishes cofilin phosphorylation and enhancement of stress fiber formation.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse
R-HSA-5627117	RHO GTPases Activate ROCKs
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
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: 344 (showing top): FXR_IR1_Q6, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, MODULE_522, MODULE_45, AREB6_03, AAGCCAT_MIR135A_MIR135B, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, FOXO4_01, AP2_Q3, GOBP_MALE_GAMETE_GENERATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER

GO Biological Process (10): protein phosphorylation (GO:0006468), spermatogenesis (GO:0007283), actin cytoskeleton organization (GO:0030036), astral microtubule organization (GO:0030953), establishment of vesicle localization (GO:0051650), head development (GO:0060322), cornea development in camera-type eye (GO:0061303), positive regulation of protein localization to nucleus (GO:1900182), negative regulation of cilium assembly (GO:1902018), regulation of phosphorylation (GO:0042325)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein phosphatase inhibitor activity (GO:0004864), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphatase inhibitor activity (GO:0019212), protein phosphatase regulator activity (GO:0019888)

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), cis-Golgi network (GO:0005801), centrosome (GO:0005813), perinuclear region of cytoplasm (GO:0048471), mitotic spindle (GO:0072686), spindle (GO:0005819), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Axon guidance	2
EPH-Ephrin signaling	1
Sema4D in semaphorin signaling	1
RHO GTPase Effectors	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Semaphorin interactions	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	3
phosphorylation	2
anatomical structure development	2
protein kinase activity	2
phosphoprotein phosphatase activity	2
phosphatase regulator activity	2
intracellular membrane-bounded organelle	2
intracellular membraneless organelle	2
protein modification process	1
developmental process involved in reproduction	1
male gamete generation	1
cytoskeleton organization	1
actin filament-based process	1
spindle organization	1
cytoplasmic microtubule organization	1
vesicle localization	1
establishment of localization in cell	1
establishment of organelle localization	1
camera-type eye development	1
protein localization to nucleus	1
regulation of protein localization to nucleus	1
positive regulation of protein localization	1
cilium assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
negative regulation of organelle assembly	1
regulation of metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Protein interactions and networks

STRING

2049 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIMK2	COLEC12	Q5KU26	922
LIMK2	CFL2	Q9Y281	901
LIMK2	CFL1	P23528	900
LIMK2	SSH1	Q8WYL5	574
LIMK2	PDXP	Q96GD0	532
LIMK2	RHOA	P06749	528
LIMK2	DSTN	P18282	521
LIMK2	CDC42BPA	Q5VT25	515
LIMK2	SSH3	Q8TE77	507
LIMK2	BMPR2	Q13873	481
LIMK2	CDC42	P21181	475
LIMK2	HSP90AA1	P07900	447
LIMK2	CCDC154	A6NI56	445
LIMK2	SSH2	Q76I76	439
LIMK2	HSP90AB1	P08238	438

IntAct

462 interactions, top by confidence:

A	B	Type	Score
LIMK2	CDC37	psi-mi:“MI:0915”(physical association)	0.690
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
TSC22D4	TSC22D2	psi-mi:“MI:0914”(association)	0.640
HSP90AB1	LIMK2	psi-mi:“MI:0915”(physical association)	0.640
PPP1R14B	LIMK2	psi-mi:“MI:0915”(physical association)	0.560
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
TRIM35	MTA2	psi-mi:“MI:0914”(association)	0.530
LIMK1	LIMK2	psi-mi:“MI:0914”(association)	0.530
UNC119	PDE8A	psi-mi:“MI:0914”(association)	0.530
LIMK2	LIMK1	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
CREBBP	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
E6	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
Tax	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
E	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
NET1	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
PTEN	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
RPS6KA1	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
GP1	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCA1	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC4	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
ABRAXAS2	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
ACE2	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2A	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
ADRB2	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (138): ATP1A1 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), CALU (Affinity Capture-MS), CDK4 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS), EMD (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), HSP90B1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), LMNA (Affinity Capture-MS), RCN1 (Affinity Capture-MS), RCN2 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS)

ESM2 similar proteins: A0FGR8, A4IJ05, A7MBL8, F1QGZ6, O08625, O08874, O54785, P15056, P24507, P28028, P34908, P53666, P53670, P53671, Q00944, Q04982, Q07139, Q16513, Q32L23, Q4VX76, Q5FWL4, Q5R8Q5, Q5RCK6, Q5SPC5, Q62136, Q62728, Q62807, Q6XYQ8, Q7TN84, Q80T23, Q812E4, Q86SS6, Q8BWW9, Q8N9U0, Q8NB59, Q8TDW5, Q8VHQ7, Q920M7, Q925C0, Q96C24

Diamond homologs: A0A1L8F1M4, A0M8R4, A0M8S5, A0M8U6, A1Z6W3, A8WH69, O42565, O43900, O54785, O70209, P47226, P49023, P49024, P50464, P53666, P53667, P53668, P53669, P53670, P53671, Q00PK1, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q108U9, Q14192, Q174I2, Q17QE2, Q28FG2, Q292U2, Q292U5

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
LIMK2	“down-regulates activity”	CFL1	phosphorylation
PRKCD	down-regulates	LIMK2	phosphorylation
LIMK2	“down-regulates activity”	SPOP	phosphorylation
LIMK2	“down-regulates activity”	PTEN	phosphorylation
LIMK2	“down-regulates activity”	NKX3-1	phosphorylation
LIMK2	“up-regulates quantity”	TWIST1	phosphorylation
LIMK2	“up-regulates activity”	SRPK1	phosphorylation
ROCK1	up-regulates	LIMK2	phosphorylation
CDC42BPA	“up-regulates activity”	LIMK2	phosphorylation
ROCK1	“up-regulates activity”	LIMK2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 201 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
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	5	18.9×	6e-04
EPHB-mediated forward signaling	7	14.2×	9e-05
RHOQ GTPase cycle	8	11.1×	9e-05
Cell death signalling via NRAGE, NRIF and NADE	6	10.1×	2e-03
RHOJ GTPase cycle	6	9.2×	3e-03
Constitutive Signaling by NOTCH1 PEST Domain Mutants	6	9.0×	3e-03
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	6	9.0×	3e-03
Neurexins and neuroligins	6	9.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of synaptic transmission, glutamatergic	5	16.9×	3e-03
positive regulation of excitatory postsynaptic potential	5	14.2×	6e-03
ephrin receptor signaling pathway	6	11.2×	4e-03
transport across blood-brain barrier	8	7.8×	3e-03
protein-containing complex assembly	9	5.5×	7e-03
chemical synaptic transmission	11	4.6×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2724 predictions. Top by Δscore:

Variant	Effect	Δscore
22:31258286:TTCA:T	acceptor_loss	1.0000
22:31258287:TCA:T	acceptor_loss	1.0000
22:31258289:A:AG	acceptor_gain	1.0000
22:31258289:AG:A	acceptor_gain	1.0000
22:31258290:G:GA	acceptor_gain	1.0000
22:31258290:GG:G	acceptor_gain	1.0000
22:31258290:GGT:G	acceptor_gain	1.0000
22:31258372:G:GT	donor_gain	1.0000
22:31258372:G:T	donor_gain	1.0000
22:31258424:ATGG:A	donor_loss	1.0000
22:31258425:TG:T	donor_gain	1.0000
22:31258426:GG:G	donor_gain	1.0000
22:31258426:GGT:G	donor_loss	1.0000
22:31258427:G:GA	donor_loss	1.0000
22:31258427:G:GG	donor_gain	1.0000
22:31258428:T:A	donor_loss	1.0000
22:31258429:GAGT:G	donor_loss	1.0000
22:31259115:TCACA:T	acceptor_loss	1.0000
22:31259116:CACA:C	acceptor_loss	1.0000
22:31259118:CAGG:C	acceptor_loss	1.0000
22:31259119:A:AC	acceptor_loss	1.0000
22:31259120:G:GT	acceptor_loss	1.0000
22:31259226:TACTG:T	donor_loss	1.0000
22:31259227:ACTG:A	donor_loss	1.0000
22:31259228:CTGGT:C	donor_loss	1.0000
22:31259231:G:A	donor_loss	1.0000
22:31259232:T:A	donor_loss	1.0000
22:31259875:T:TA	acceptor_gain	1.0000
22:31259884:CCCA:C	acceptor_loss	1.0000
22:31259886:CAG:C	acceptor_loss	1.0000

AlphaMissense

4209 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:31266083:T:C	L331P	1.000
22:31266109:G:C	G340R	1.000
22:31266115:T:C	F342L	1.000
22:31266117:T:A	F342L	1.000
22:31266117:T:G	F342L	1.000
22:31266119:G:A	G343E	1.000
22:31267020:A:C	K360Q	1.000
22:31267021:A:T	K360I	1.000
22:31267022:A:C	K360N	1.000
22:31267022:A:T	K360N	1.000
22:31271143:T:G	L442W	1.000
22:31271163:C:G	H449D	1.000
22:31271167:G:C	R450P	1.000
22:31271170:A:C	D451A	1.000
22:31271170:A:G	D451G	1.000
22:31271170:A:T	D451V	1.000
22:31271171:T:A	D451E	1.000
22:31271171:T:G	D451E	1.000
22:31271173:T:C	L452P	1.000
22:31271184:A:G	N456D	1.000
22:31271189:C:G	C457W	1.000
22:31272551:G:C	D469H	1.000
22:31272552:A:C	D469A	1.000
22:31272552:A:G	D469G	1.000
22:31272552:A:T	D469V	1.000
22:31272553:C:A	D469E	1.000
22:31272553:C:G	D469E	1.000
22:31272554:T:C	F470L	1.000
22:31272556:T:A	F470L	1.000
22:31272556:T:G	F470L	1.000

dbSNP variants (sampled 300 via entrez): RS1000015860 (22:31212744 C>T), RS1000068151 (22:31212454 C>G), RS1000084059 (22:31271243 C>G,T), RS1000139953 (22:31264502 G>A), RS1000151162 (22:31218941 G>A), RS1000188049 (22:31228697 C>T), RS1000189408 (22:31250130 CTTG>C), RS1000197992 (22:31270819 G>C,T), RS1000202544 (22:31277958 C>G,T), RS1000250557 (22:31268738 C>T), RS1000281656 (22:31268425 C>G,T), RS1000324007 (22:31232996 C>T), RS1000399217 (22:31226024 G>A,T), RS1000433039 (22:31275340 A>C,G), RS1000463105 (22:31261695 G>C)

Disease associations

OMIM: gene MIM:601988 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000909_5	Type 2 diabetes nephropathy	4.000000e-06
GCST002074_2	Paclitaxel-induced neuropathy	3.000000e-06
GCST004600_120	Eosinophil percentage of white cells	9.000000e-17
GCST004606_98	Eosinophil count	1.000000e-11
GCST004617_44	Eosinophil percentage of granulocytes	2.000000e-17
GCST004623_43	Neutrophil percentage of granulocytes	6.000000e-15
GCST004624_30	Sum eosinophil basophil counts	8.000000e-09
GCST009597_160	Multiple sclerosis	1.000000e-08
GCST010135_20	Oily fish consumption	3.000000e-10
GCST010135_5	Oily fish consumption	1.000000e-15
GCST010140_12	Pork consumption	3.000000e-10
GCST010140_49	Pork consumption	1.000000e-15
GCST010142_11	Fish- and plant-related diet	1.000000e-11
GCST010142_79	Fish- and plant-related diet	3.000000e-08
GCST90002396_87	Mean reticulocyte volume	2.000000e-12
GCST90002404_593	Red cell distribution width	7.000000e-16

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0008111	diet measurement
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885599 (PROTEIN FAMILY), CHEMBL5932 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 162,596 (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
CHEMBL5416410	DASATINIB	4	655
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL1950289	TANZISERTIB	2	419
CHEMBL2107823	GANDOTINIB	2	1,013
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL475251	R-406	2	762
CHEMBL495727	AT-9283	2	1,376
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL587723	AEE-788	2	2,697
CHEMBL3356433	LX-7101	1	136
CHEMBL3545360	ASP-3026	1
CHEMBL482967	CYC-116	1
CHEMBL574738	AST-487	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 (7 total), top 7:

Ligand	Action	Affinity	Parameter
compound 22m [PMID: 19831390]	Inhibition	9.1	pIC50
compound 14 [PMID: 19831390]	Inhibition	9.05	pIC50
compound 35 [PMID: 22902653]	Inhibition	8.1	pIC50
LIMKi3	Inhibition	8.1	pIC50
compound 30 [PMID: 22902653]	Inhibition	7.8	pIC50
compound 31 [PMID: 22902653]	Inhibition	7.42	pIC50
ZAK inhibitor 6p	Inhibition	7.2	pKd

ChEMBL bioactivities

427 potent at pChembl≥5 of 435 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL3800458
10.00	IC50	0.1	nM	CHEMBL3799318
10.00	IC50	0.1	nM	CHEMBL3797519
9.70	IC50	0.2	nM	CHEMBL3798142
9.70	IC50	0.2	nM	CHEMBL3800259
9.70	IC50	0.2	nM	CHEMBL3798662
9.70	IC50	0.2	nM	CHEMBL3799270
9.52	IC50	0.3	nM	CHEMBL3799925
9.52	IC50	0.3	nM	CHEMBL3800357
9.40	IC50	0.4	nM	CHEMBL3799236
9.40	IC50	0.4	nM	CHEMBL3800330
9.40	IC50	0.4	nM	CHEMBL3797658
9.15	IC50	0.7	nM	CHEMBL3797874
9.15	IC50	0.7	nM	CHEMBL3797519
9.10	IC50	0.8	nM	CHEMBL3800144
9.10	IC50	0.8	nM	CHEMBL571057
9.05	IC50	0.9	nM	CHEMBL3799695
9.05	IC50	0.9	nM	CHEMBL3797634
9.05	IC50	0.9	nM	CHEMBL570126
9.00	IC50	1	nM	CHEMBL3356431
9.00	IC50	1	nM	CHEMBL3623439
9.00	IC50	1	nM	CHEMBL3797469
8.96	IC50	1.1	nM	CHEMBL570115
8.92	IC50	1.2	nM	CHEMBL3356064
8.92	IC50	1.2	nM	CHEMBL570116
8.92	IC50	1.2	nM	CHEMBL577194
8.92	IC50	1.2	nM	CHEMBL569861
8.85	IC50	1.4	nM	CHEMBL3613624
8.85	IC50	1.4	nM	CHEMBL3799326
8.85	IC50	1.4	nM	CHEMBL3800261
8.82	IC50	1.5	nM	CHEMBL3613600
8.82	IC50	1.5	nM	CHEMBL565452
8.80	IC50	1.6	nM	LX-7101
8.80	IC50	1.6	nM	CHEMBL3613623
8.80	IC50	1.6	nM	CHEMBL570832
8.77	IC50	1.7	nM	CHEMBL566746
8.74	IC50	1.82	nM	CHEMBL570116
8.74	IC50	1.8	nM	CHEMBL584090
8.72	IC50	1.9	nM	CHEMBL3356424
8.72	IC50	1.9	nM	CHEMBL571947
8.70	IC50	2	nM	CHEMBL3800273
8.68	IC50	2.1	nM	CHEMBL3613606
8.66	IC50	2.2	nM	CHEMBL3356426
8.66	IC50	2.2	nM	CHEMBL3613607
8.64	IC50	2.3	nM	CHEMBL583464
8.61	IC50	2.455	nM	CHEMBL570116
8.57	IC50	2.7	nM	CHEMBL3356430
8.57	IC50	2.7	nM	CHEMBL3356063
8.55	IC50	2.8	nM	CHEMBL3613621
8.54	IC50	2.9	nM	CHEMBL565453

PubChem BioAssay actives

355 with measured affinity, of 883 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
methyl 2-[3-[[4-(aminomethyl)-1-(6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]indol-4-yl)piperidine-4-carbonyl]amino]phenyl]acetate	1941054: Inhibition of LIMK2 (unknown origin) in presence of ATP at 200 uM	ic50	0.0001	uM
methyl 2-[3-[[4-(aminomethyl)-1-(7,9,11-triazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),9,11-tetraen-12-yl)piperidine-4-carbonyl]amino]phenyl]acetate	1941054: Inhibition of LIMK2 (unknown origin) in presence of ATP at 200 uM	ic50	0.0001	uM
4-(dimethylamino)-N-(3-phenylphenyl)-1-(6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]indol-4-yl)piperidine-4-carboxamide	1941060: Inhibition of LIMK2 (unknown origin)	ic50	0.0001	uM
methyl 2-[3-[[4-(aminomethyl)-1-(6-fluoro-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]indol-4-yl)piperidine-4-carbonyl]amino]phenyl]acetate	1941054: Inhibition of LIMK2 (unknown origin) in presence of ATP at 200 uM	ic50	0.0001	uM
[3-[[4-(aminomethyl)-1-(6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]indol-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1941054: Inhibition of LIMK2 (unknown origin) in presence of ATP at 200 uM	ic50	0.0007	uM
3-[[(cyanoamino)-[(2S)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]methylidene]amino]-N-(2-hydroxyethyl)benzamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0008	uM
(2S)-N’-(3-bromophenyl)-N-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0009	uM
methyl 3-[[4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0010	uM
methyl 2-[3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenoxy]acetate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0010	uM
methyl 2-[3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl]acetate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0010	uM
prop-2-ynyl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0010	uM
4-[[5-[3-(2-chlorophenyl)-4-pyridinyl]-1,3-thiazol-2-yl]amino]phenol	1251126: Inhibition of human N-terminal GST-tagged LIMK2	ic50	0.0010	uM
[3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0010	uM
[3-[[4-(1H-imidazol-5-ylmethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1177352: Inhibition of human full-length LIMK2 assessed as incorporation of P33 from ATP into biotinylated-cofilin substrate by scintillation counting analysis in presence of 2 uM ATP	ic50	0.0010	uM
(2S)-N’-(3-tert-butylphenyl)-N-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0011	uM
(2S)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-phenylpiperazine-1-carboxamide	1177352: Inhibition of human full-length LIMK2 assessed as incorporation of P33 from ATP into biotinylated-cofilin substrate by scintillation counting analysis in presence of 2 uM ATP	ic50	0.0012	uM
(2S)-N-cyano-N’-(3-cyanophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0012	uM
(2S)-N’-(3-bromophenyl)-4-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-cyano-2-methylpiperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0012	uM
[3-[[(2S)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1177352: Inhibition of human full-length LIMK2 assessed as incorporation of P33 from ATP into biotinylated-cofilin substrate by scintillation counting analysis in presence of 2 uM ATP	ic50	0.0012	uM
[3-[[4-[(dimethylamino)methyl]-1-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0014	uM
[3-[[4-(aminomethyl)-1-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1941054: Inhibition of LIMK2 (unknown origin) in presence of ATP at 200 uM	ic50	0.0014	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0015	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	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0015	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0016	uM
(2S)-N’-(3-chlorophenyl)-N-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0016	uM
[3-[[4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0016	uM
(2S)-N-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N’-[3-(propan-2-ylsulfamoyl)phenyl]piperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0017	uM
(2S)-N-cyano-N’-(3-fluorophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0018	uM
(2S)-N-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N’-[3-(trifluoromethyl)phenyl]piperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0019	uM
N-(3-chlorophenyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-prop-2-enylpiperidine-4-carboxamide	1177352: Inhibition of human full-length LIMK2 assessed as incorporation of P33 from ATP into biotinylated-cofilin substrate by scintillation counting analysis in presence of 2 uM ATP	ic50	0.0019	uM
propyl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0021	uM
[3-[[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-prop-2-enylpiperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1177352: Inhibition of human full-length LIMK2 assessed as incorporation of P33 from ATP into biotinylated-cofilin substrate by scintillation counting analysis in presence of 2 uM ATP	ic50	0.0022	uM
propan-2-yl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0022	uM
(2S)-N-(3-chlorophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0023	uM
(2S)-N-(3-methoxyphenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	1177352: Inhibition of human full-length LIMK2 assessed as incorporation of P33 from ATP into biotinylated-cofilin substrate by scintillation counting analysis in presence of 2 uM ATP	ic50	0.0027	uM
[3-[[4-(2-methoxyethoxymethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1177352: Inhibition of human full-length LIMK2 assessed as incorporation of P33 from ATP into biotinylated-cofilin substrate by scintillation counting analysis in presence of 2 uM ATP	ic50	0.0027	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244618: Inhibition of LIMK2 (unknown origin) by radiometric assay	ic50	0.0028	uM
(2S)-N-cyano-N’-[3-(2-hydroxyethylsulfamoyl)phenyl]-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0029	uM
N-[5-[3-(2-chloro-4-methylphenyl)-4-pyridinyl]-1,3-thiazol-2-yl]-2-methylpropanamide	1251126: Inhibition of human N-terminal GST-tagged LIMK2	ic50	0.0030	uM
[3-[[4-(5-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,6-dihydro-2H-pyridine-1-carbonyl]amino]phenyl] N,N-dimethylcarbamate	2063283: Inhibition of LIMK2 (unknown origin) assessed as inhibition constant by LanthScreen Eu kinase binding assay	ki	0.0030	uM
(2S)-N-[3-(2-hydroxyethylcarbamoyl)phenyl]-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0030	uM
N-benzyl-N-ethyl-4-(phenylsulfamoyl)benzamide	1177224: Inhibition of human full-length LIMK2 expressed in Sf9 cells assessed as incorporation of [33P] from ATP into biotinylated-cofilin substrate in presence of 300 uM ATP	ic50	0.0030	uM
(2S)-N-[3-(1,3-dihydroxypropan-2-ylcarbamoyl)phenyl]-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0030	uM
N-[4-(2-chlorophenyl)-6-[2-(propan-2-ylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]-N’,N’-dimethylethane-1,2-diamine	516604: Inhibition of LIMK2	ic50	0.0031	uM
(2S)-N-(3-bromo-4-fluorophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0032	uM
N-(3-tert-butylphenyl)-4-methyl-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide	1177352: Inhibition of human full-length LIMK2 assessed as incorporation of P33 from ATP into biotinylated-cofilin substrate by scintillation counting analysis in presence of 2 uM ATP	ic50	0.0032	uM
3-[[(cyanoamino)-[(2S)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]methylidene]amino]-N-[2-(dimethylamino)ethyl]benzamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0034	uM
3-[[(cyanoamino)-[(2S)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]methylidene]amino]-N-propan-2-ylbenzamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0035	uM
(2S)-N-(3-bromophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0039	uM
(2S,5R)-N’-(3-bromophenyl)-N-cyano-2,5-dimethyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	441214: Inhibition of human recombinant LIMK2 expressed in baculovirus-Sf9 system by scintillation counting	ic50	0.0039	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ethinyl Estradiol	decreases expression, affects expression	3
bisphenol A	affects expression, affects methylation	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	affects expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
TL8-506	affects cotreatment, increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
cupric oxide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
eprenetapopt	increases expression, affects reaction	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Doxorubicin	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Fluorouracil	affects response to substance	1
Formaldehyde	increases expression	1

ChEMBL screening assays

191 unique, capped per target: 191 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1109058	Binding	Inhibition of LIMK1/2 phosphorylation in human U937 cells at 0.1 to 100 nM after 24 hrs by Western blotting	Cucurbitacin E as a new inhibitor of cofilin phosphorylation in human leukemia U937 cells. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SV60	HAP1 LIMK2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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