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): 128 total
• GTEx eGene: eQTL in 29 tissues, sQTL in 36 (q < 0.05)
• ChEMBL bioactivity: 23 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.13 (intermediate), LOEUF 0.58 (moderately constrained)
• MANE Select transcript: NM_005569
• Notable: 128 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 38 — 21 protein_coding, 13 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000331728

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 2, TSL 3: 2, TSL 5: 1

ENST00000331728, ENST00000333611, ENST00000340552, ENST00000406516, ENST00000425203, ENST00000462625, ENST00000465937, ENST00000467301, ENST00000482270, ENST00000887560, ENST00000887561, ENST00000887562, ENST00000887563, ENST00000887564, ENST00000887565, ENST00000937842, ENST00000937843, ENST00000961695, ENST00000961696, ENST00000979494, ENST00000979495, ENST00000979496, ENST00001035770, ENST00001035771, ENST00001035772, ENST00001035773, ENST00001082488, ENST00001082489, ENST00001082490, ENST00001082491, ENST00001082492, ENST00001082493, ENST00001082495, ENST00001082496, ENST00001082497, ENST00001107027, ENST00001131229, ENST00001131770

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.

Highest expression (Bgee): cervix squamous epithelium, gingival epithelium, esophagus squamous epithelium, squamous epithelium, blood.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LIMK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 36 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 65 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	sqtl	3.0e-84	-0.92	22:31182893:A:G
Skin Sun Exposed Lower leg	sqtl	1.3e-54	+0.80	22:31321813:T:G
Skin Not Sun Exposed Suprapubic	sqtl	3.7e-44	-0.71	22:31203997:T:C
Thyroid	sqtl	1.1e-42	-0.68	22:31276766:A:C
Nerve Tibial	sqtl	6.9e-34	+0.73	22:31162563:C:T
Lung	sqtl	1.7e-29	-0.61	22:31203997:T:C
Adipose Visceral Omentum	sqtl	1.5e-27	+0.59	22:31453036:G:GA
Esophagus Mucosa	sqtl	1.1e-20	-0.46	22:31215563:A:G
Breast Mammary Tissue	sqtl	2.7e-17	-0.59	22:31162563:C:T
Artery Tibial	sqtl	1.4e-16	+0.61	22:31203997:T:C
Muscle Skeletal	sqtl	2.3e-14	+0.46	22:31384528:G:A
Artery Aorta	sqtl	3.6e-14	-0.60	22:31390975:T:A
Colon Sigmoid	eqtl	4.7e-14	+0.33	22:31156716:A:G
Thyroid	eqtl	9.6e-14	+0.28	22:31249773:C:T
Spleen	sqtl	1.1e-13	-0.66	22:31182893:A:G
Heart Atrial Appendage	sqtl	2.3e-13	+0.58	22:31199094:T:C
Adipose Subcutaneous	sqtl	1.0e-12	-0.51	22:31328986:CA:C
Testis	sqtl	3.1e-12	+0.68	22:31276766:A:C
Artery Tibial	eqtl	7.2e-12	+0.24	22:31174450:G:A
Esophagus Muscularis	sqtl	9.9e-12	+0.49	22:31199094:T:C

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

showing 100 of 292 tissues 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
epithelium of bronchus	UBERON:0002031	93.14	gold quality
upper lobe of left lung	UBERON:0008952	93.11	gold quality
visceral pleura	UBERON:0002401	93.00	gold quality
bronchus	UBERON:0002185	92.86	gold quality
transverse colon	UBERON:0001157	92.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.82	gold quality
vermiform appendix	UBERON:0001154	92.78	gold quality
amniotic fluid	UBERON:0000173	92.58	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.27	gold quality
upper lobe of lung	UBERON:0008948	92.11	gold quality
granulocyte	CL:0000094	92.08	gold quality
vagina	UBERON:0000996	92.03	gold quality
right lung	UBERON:0002167	91.98	gold quality
body of stomach	UBERON:0001161	91.92	gold quality
spinal cord	UBERON:0002240	91.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.46	gold quality
colonic epithelium	UBERON:0000397	91.43	gold quality
sural nerve	UBERON:0015488	91.33	gold quality
gall bladder	UBERON:0002110	91.23	gold quality
spleen	UBERON:0002106	91.03	gold quality
esophagus	UBERON:0001043	90.99	gold quality
tonsil	UBERON:0002372	90.88	gold quality
stomach	UBERON:0000945	90.60	gold quality
caecum	UBERON:0001153	90.58	gold quality
renal glomerulus	UBERON:0000074	90.40	gold quality
metanephros cortex	UBERON:0010533	90.20	gold quality
small intestine	UBERON:0002108	90.13	gold quality
prostate gland	UBERON:0002367	90.12	gold quality
pleura	UBERON:0000977	89.98	gold quality
metanephric glomerulus	UBERON:0004736	89.89	gold quality
tibial nerve	UBERON:0001323	89.83	gold quality
intestine	UBERON:0000160	89.69	gold quality
colon	UBERON:0001155	89.69	gold quality
large intestine	UBERON:0000059	89.67	gold quality
adenohypophysis	UBERON:0002196	89.59	gold quality
body of pancreas	UBERON:0001150	89.56	gold quality
upper arm skin	UBERON:0004263	89.48	gold quality
medial globus pallidus	UBERON:0002477	89.38	gold quality
choroid plexus epithelium	UBERON:0003911	89.22	gold quality
omental fat pad	UBERON:0010414	89.20	gold quality
peritoneum	UBERON:0002358	89.18	gold quality
colonic mucosa	UBERON:0000317	89.10	gold quality
upper leg skin	UBERON:0004262	89.05	gold quality
left ovary	UBERON:0002119	89.00	gold quality
tibia	UBERON:0000979	88.91	gold quality
oral cavity	UBERON:0000167	88.82	gold quality
parietal pleura	UBERON:0002400	88.80	gold quality
lung	UBERON:0002048	88.79	gold quality
ectocervix	UBERON:0012249	88.77	gold quality
germinal epithelium of ovary	UBERON:0001304	88.75	gold quality
epithelial cell of pancreas	CL:0000083	88.74	gold quality
descending thoracic aorta	UBERON:0002345	88.71	gold quality
pancreas	UBERON:0001264	88.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.58	gold quality
right coronary artery	UBERON:0001625	88.57	gold quality
right ovary	UBERON:0002118	88.55	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.54	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.53	gold quality
left uterine tube	UBERON:0001303	88.49	gold quality
cerebellar hemisphere	UBERON:0002245	88.43	gold quality
female reproductive system	UBERON:0000474	88.38	gold quality
metanephros	UBERON:0000081	88.32	gold quality
epithelium of mammary gland	UBERON:0003244	88.21	gold quality
cerebellar cortex	UBERON:0002129	88.20	gold quality
mammary gland	UBERON:0001911	88.19	gold quality
ascending aorta	UBERON:0001496	88.17	gold quality
fallopian tube	UBERON:0003889	88.17	gold quality
thoracic mammary gland	UBERON:0005200	88.12	gold quality
thoracic aorta	UBERON:0001515	88.09	gold quality
endometrium	UBERON:0001295	88.08	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	58.7
Skin 1	tissue	56.4	low
Bone marrow	tissue	50.8	medium
Locus coeruleus	tissue	45.3
Placenta	tissue	45.1	high
Vagina	tissue	42.4	low
Thyroid gland	tissue	38.1	high
Appendix	tissue	37.6	low
Frontal cortex	tissue	35.7
Esophagus	tissue	34.3	low
Caudate putamen	tissue	33.9
Rectum	tissue	32.6	medium
Fallopian tube	tissue	32.2	medium
Colon	tissue	31.9	medium
Hippocampus	tissue	30.5	low
Nucleus accumbens	tissue	29.3
Stomach 1	tissue	28.3	medium
Salivary gland	tissue	25.7	not detected
Parathyroid gland	tissue	25.4	low
Breast	tissue	24.9	medium
Urinary bladder	tissue	24.0	medium
Retina	tissue	23.6
Lung	tissue	23.2	low
Prostate	tissue	22.5	medium
Lymph node	tissue	21.7	low
Pituitary gland	tissue	21.0
Substantia nigra	tissue	20.8
Postcentral gyrus	tissue	20.8
Corpus callosum	tissue	20.7
Small intestine	tissue	20.4	medium
Hippocampal formation	tissue	20.4
Gallbladder	tissue	19.9	high
Duodenum	tissue	19.9	medium
Thymus	tissue	19.9
Spinal cord	tissue	19.6
Thalamus	tissue	19.3
Midbrain	tissue	18.5
Medulla oblongata	tissue	18.4
Superior colliculi	tissue	18.4
Amygdala	tissue	18.2
Cerebellum	tissue	18.2	medium
Seminal vesicle	tissue	18.0	medium
Pancreas	tissue	17.8	high
Ovary	tissue	17.6	high
Periaqueductal gray	tissue	17.2
Tonsil	tissue	16.6	medium
Pons	tissue	16.5
Cerebral cortex	tissue	16.1	low
Insular cortex	tissue	16.1
Somatosensory cortex	tissue	15.9
Hypothalamus	tissue	15.8
Motor cortex	tissue	15.4
Spleen	tissue	15.4	medium
Retrosplenial cortex	tissue	15.0
Smooth muscle	tissue	14.8	high
Entorhinal cortex	tissue	14.7
Temporal cortex	tissue	14.6
Prefrontal cortex	tissue	14.4
Endometrium 1	tissue	14.2	high
Adipose tissue	tissue	13.7	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Area postrema (70.6), Periaquaductal grey, lateral (62.8), Posterior thalamic nucleus (62.5), Cervical spinal cord, ventral horn (59.8), Medial olivary nucleus (58.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

Targeting LIMK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 100 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.134, LOEUF 0.582, missense Z 2.57 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000331728 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
22:31,212,409–31,272,658	514 / 661.3	0.78	no
22:31,272,659–31,278,323	63 / 122.8	0.51	no
22:31,278,324–31,278,438	46 / 46.9	0.98	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1197517) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 25 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased incidence of corneal inflammation	2
short mandible	1
small seminiferous tubules	1
abnormal spermatogenesis	1
increased body weight	1
eyelids open at birth	1
abnormal cornea morphology	1
cornea opacity	1
abnormal kidney morphology	1
dilated renal tubule	1
early eyelid opening	1
abnormal locomotor activation	1
long tibia	1
decreased renal glomerulus number	1
decreased testis weight	1
cornea vascularization	1
abnormal cornea epithelium morphology	1
abnormal spermatocyte morphology	1
retina neovascularization	1
failure of eyelid fusion	1
abnormal eyelid development	1
anterior iris synechia	1
increased male germ cell apoptosis	1
increased inner canthal distance	1
decreased eye anterior chamber depth	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Muntiacus reevesi	Q07DX3	100.0%	Diamond
Muntiacus muntjak	Q09YK3	100.0%	Diamond
Felis catus	A0M8S5	99.8%	Diamond
Neofelis nebulosa	Q07E40	99.8%	Diamond
Ovis aries	Q09YJ2	99.5%	Diamond
Bos taurus	Q2YDE9	99.5%	Diamond
Canis lupus familiaris	A0M8U6	98.3%	Diamond
Xenopus tropicalis	Q6DIR5	96.9%	Diamond
Equus caballus	Q2QLB2	96.7%	Diamond
Loxodonta africana	Q108U9	96.0%	Diamond
Rhinolophus ferrumequinum	Q2IBC3	95.5%	Diamond
Atelerix albiventris	Q00PK1	95.2%	Diamond
Dasypus novemcinctus	Q07E51	95.0%	Diamond
Oryctolagus cuniculus	Q09YN8	93.6%	Diamond
Monodelphis domestica	Q2QLA1	87.4%	Diamond
Gallus gallus	P53666	86.5%	Diamond
Xenopus laevis	O42565	72.1%	Diamond
Caenorhabditis elegans	Q21192	49.1%	Diamond
Dictyostelium discoideum	Q8MML5	48.7%	Diamond
Arabidopsis thaliana	Q9SF12	48.4%	Diamond
Drosophila melanogaster	Q8IR79	44.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PLA2G3	protein-coding	50487
RNF185	protein-coding	91445
PIK3IP1-DT	ncRNA	101929760
PIK3IP1	protein-coding	113791
PATZ1	protein-coding	23598
MIR3928	ncRNA	100500901

Protein

Protein identifiers

LIM domain kinase 2 — P53671 (reviewed: P53671)

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

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)

• 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 (69 total): helix 22, strand 19, 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 by resolution:

PDB	Title	Method	Resolution (Å)
7QHG	LIM domain kinase 2 (LIMK2) in complex with TH-470	X-RAY DIFFRACTION	1.45
5NXD	LIM Domain Kinase 2 (LIMK2) In Complex With TH-300	X-RAY DIFFRACTION	1.9
8GI4	Crystal structure of human LIMK2 PDZ domain	X-RAY DIFFRACTION	2.06
8WSW	The Crystal Structure of LIMK2a from Biortus	X-RAY DIFFRACTION	2.5
8S3X	LIM Domain Kinase 2 (LIMK2) bound to compound 52	X-RAY DIFFRACTION	2.59
4TPT	Crystal Structure of the Human LIMK2 Kinase Domain In Complex With a Non-ATP Competitive …	X-RAY DIFFRACTION	2.6
1X6A	Solution structures of the second LIM domain of human LIM-kinase 2 (LIMK2)	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, TKL Ser/Thr protein kinases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
451

Ligand- & substrate-binding residues (2)

Position	Role
337–345	ATP
360	ATP

Post-translational modifications (4)

Type	Positions
Phosphothreonine	210, 505
Phosphoserine	293, 298

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

0 curated (TAS) of 13; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-422475	Axon guidance	—
R-HSA-1266738	Developmental Biology	—
R-HSA-2682334	EPH-Ephrin signaling	—
R-HSA-3928662	EPHB-mediated forward signaling	electronic
R-HSA-9675108	Nervous system development	—
R-HSA-195258	RHO GTPase Effectors	—
R-HSA-5627117	RHO GTPases Activate ROCKs	electronic
R-HSA-400685	Sema4D in semaphorin signaling	—
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse	electronic
R-HSA-373755	Semaphorin interactions	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
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 (7): protein phosphorylation (GO:0006468), actin cytoskeleton organization (GO:0030036), astral microtubule organization (GO:0030953), establishment of vesicle localization (GO:0051650), 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 (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cis-Golgi network (GO:0005801), centrosome (GO:0005813), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), mitotic spindle (GO:0072686), spindle (GO:0005819), membrane (GO:0016020)

Reactome top-level categories

10 top-level categories:

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

48 GO namespaces:

Category	Terms
cellular anatomical structure	5
phosphorylation	2
protein kinase activity	2
phosphoprotein phosphatase activity	2
phosphatase regulator activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
protein modification process	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
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
anion 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
enzyme inhibitor activity	1
phosphatase activity	1
protein phosphatase binding	1
nuclear lumen	1
intracellular anatomical structure	1
Golgi apparatus	1
centriole	1
microtubule organizing center	1
spindle	1
microtubule cytoskeleton	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 29 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
astral microtubule organization	BP	direct assay
establishment of vesicle localization	BP	mutant phenotype
negative regulation of cilium assembly	BP	mutant phenotype
positive regulation of protein localization to nucleus	BP	mutant phenotype
protein phosphorylation	BP	direct assay
centrosome	CC	direct assay
cytosol	CC	direct assay
mitotic spindle	CC	direct assay
nucleoplasm	CC	direct assay
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 769 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIMK2	COLEC12	Q5KU26	915
LIMK2	CFL1	P23528	877
LIMK2	CFL2	Q9Y281	876
LIMK2	SSH1	Q8WYL5	538
LIMK2	PDXP	Q96GD0	523
LIMK2	RHOA	P06749	509
LIMK2	SSH3	Q8TE77	465
LIMK2	CDC42	P21181	462
LIMK2	DSTN	P18282	404
LIMK2	SSH2	Q76I76	384
LIMK2	CCDC154	A6NI56	370
LIMK2	FZD4	Q9ULV1	362
LIMK2	STAT3	P40763	361
LIMK2	OXR1	Q8N573	357
LIMK2	PPP1R12A	O14974	350

IntAct

Human interaction partners of LIMK2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 424 partners by confidence:

Partner	Interaction type	MIscore	Records
CDC37	physical association	0.690	2
HSP90AB1	physical association	0.640	2
APPL1	direct interaction	0.590	1
FKBP4	direct interaction	0.590	1
RCN1	direct interaction	0.590	1
RCN2	direct interaction	0.590	1
PPP1R14B	physical association	0.560	1
LIMK1	association	0.530	2
E6	direct interaction	0.440	5
E	direct interaction	0.440	2
PDLIM4	direct interaction	0.440	2
PTEN	direct interaction	0.440	2
RPS6KA1	direct interaction	0.440	2
ABCA1	direct interaction	0.440	1
ABCA2	direct interaction	0.440	1
ABCA7	direct interaction	0.440	1
ABCC4	direct interaction	0.440	1
ABCC6	direct interaction	0.440	1
ABRAXAS2	direct interaction	0.440	1
ACE2	direct interaction	0.440	1
ACOT6	direct interaction	0.440	1
ACTN2	direct interaction	0.440	1
ACVR2A	direct interaction	0.440	1
ADAM22	direct interaction	0.440	1
ADGRA1	direct interaction	0.440	1
ADGRA2	direct interaction	0.440	1
ADGRA3	direct interaction	0.440	1
ADGRE5	direct interaction	0.440	1
ADGRG1	direct interaction	0.440	1
ADRA1D	direct interaction	0.440	1

BioGRID (142 interactions; top human partners by supporting records): LIMK1 (Biochemical Activity; 4 records), HSP90AA1 (Affinity Capture-MS; 3 records), NF1 (Two-hybrid; 3 records), ROCK1 (Affinity Capture-Western; 3 records), TTC1 (Affinity Capture-MS; 3 records), UNC119 (Affinity Capture-MS; 3 records), CDC37 (Affinity Capture-MS; 2 records), CFL1 (Biochemical Activity; 2 records), FKBP4 (Affinity Capture-MS; 2 records), FKBP5 (Affinity Capture-MS; 2 records), HNRNPLL (Affinity Capture-MS; 2 records), PPP1R14B (Affinity Capture-MS; 2 records), SLC18A1 (Affinity Capture-MS; 2 records), TRIM35 (Affinity Capture-MS; 2 records), UBB (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 10 of 13 signaling 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 424 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
Tight junction interactions	14	17.3×	1e-11
Long-term potentiation	8	12.8×	3e-05
Unblocking of NMDA receptors, glutamate binding and activation	7	12.8×	8e-05
Ephrin signaling	6	11.5×	5e-04
MECP2 regulates neuronal receptors and channels	5	10.1×	4e-03
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	6	10.0×	1e-03
Signaling by Hippo	5	9.1×	6e-03
Trafficking of AMPA receptors	5	9.1×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
calcium-independent cell-cell adhesion	12	24.3×	1e-11
glutamate receptor signaling pathway	9	21.2×	5e-08
positive regulation of synaptic transmission, glutamatergic	10	15.7×	1e-07
sodium-independent organic anion transport	5	14.2×	1e-03
prepulse inhibition	5	14.2×	1e-03
regulation of cardiac conduction	6	12.7×	6e-04
bicellular tight junction assembly	14	11.7×	8e-09
maintenance of blood-brain barrier	9	10.9×	2e-05

Disease & clinical

Genetic variants

Variant evidence for LIMK2: 128 ClinVar records (0 pathogenic / likely pathogenic); 16 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	3
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 1,468):

Position(s)	Effect	Δscore	Sites
22:31258289–31258290	acceptor_loss	1.0000	6
22:31258372	donor_gain	1.0000
22:31258427–31258428	donor_loss	1.0000	5
22:31259119–31259120	acceptor_loss	1.0000	6
22:31259231–31259232	donor_loss	1.0000	6
22:31259887–31259888	acceptor_loss	1.0000	6
22:31260078	donor_loss	1.0000
22:31262240–31262241	donor_loss	1.0000	4
22:31267769	acceptor_gain	1.0000
22:31267774–31267775	acceptor_loss	1.0000	5

AlphaMissense

1,709 missense substitutions predicted likely pathogenic (of 4,209 scored), across 376 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M513	9	0.992	1.000
M517	9	0.969	0.999
M439	9	0.907	0.998
M357	9	0.878	0.993
D469	8	1.000	1.000
D451	8	0.999	1.000
D528	8	0.999	1.000
H449	8	0.998	1.000
H443	8	0.997	0.999
N456	8	0.997	1.000
F470	8	0.997	1.000
F373	8	0.990	0.999
F530	8	0.985	1.000
H92	8	0.975	0.995
F96	8	0.971	0.997
F342	8	0.971	1.000
D202	8	0.969	0.989
F594	8	0.968	0.996
H385	8	0.967	0.996
D546	8	0.967	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:601988 | disease phenotypes:

GWAS associations

16 associations:

Study	Trait	p-value
GCST004617_119	Eosinophil percentage of granulocytes	2e-17
GCST004600_120	Eosinophil percentage of white cells	9e-17
GCST90002404_593	Red cell distribution width	7e-16
GCST010135_30	Oily fish consumption	1e-15
GCST010140_6	Pork consumption	1e-15
GCST004623_8	Neutrophil percentage of granulocytes	6e-15
GCST90002396_411	Mean reticulocyte volume	2e-12
GCST004606_6	Eosinophil count	1e-11
GCST010142_11	Fish- and plant-related diet	1e-11
GCST010135_45	Oily fish consumption	3e-10
GCST010140_21	Pork consumption	3e-10
GCST004624_55	Sum eosinophil basophil counts	8e-9
GCST009597_10	Multiple sclerosis	1e-8
GCST010142_89	Fish- and plant-related diet	3e-8
GCST002074_2	Paclitaxel-induced neuropathy	3e-6
GCST000909_5	Type 2 diabetes nephropathy	4e-6

EFO canonical traits (from GWAS)

8 canonical traits:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 168,374 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

23 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL2325741	CAPIVASERTIB	4	2,281
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL5416410	DASATINIB	4	674
CHEMBL3301612	ENCORAFENIB	4	4,898
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL2035187	PACRITINIB	4	3,544
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL1336	SORAFENIB	4	87,476
CHEMBL223360	LINIFANIB	3	4,094
CHEMBL587723	AEE-788	2	2,800
CHEMBL495727	AT-9283	2	1,442
CHEMBL402548	DANUSERTIB	2	2,036
CHEMBL1230609	FORETINIB	2	3,230
CHEMBL2107823	GANDOTINIB	2	1,069
CHEMBL475251	R-406	2	787
CHEMBL1738757	REBASTINIB	2	1,567
CHEMBL1950289	TANZISERTIB	2	433
CHEMBL572878	TOZASERTIB	2	3,128
CHEMBL3545360	ASP-3026	1	711
CHEMBL574738	AST-487	1
CHEMBL482967	CYC-116	1
CHEMBL3356433	LX-7101	1

PharmGKB: 1 entry (CPIC guideline: no)

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

Binding affinities (BindingDB)

314 measured of 414 human assays (416 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL3797519	IC50	0.1 nM
CHEMBL3623439	IC50	0.3 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
(S)-N-(3-bromophenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	0.5 nM
(S)-3-(N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamido)-N-(2-hydroxyethyl)benzamide	IC50	0.8 nM
CHEMBL3356431	IC50	1 nM
CHEMBL3623442	IC50	1 nM
(S)-N-(3-tert-butylphenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	1.1 nM
CHEMBL3356064	IC50	1.2 nM
(S)-N-(3-bromophenyl)-4-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N’-cyano-2-methylpiperazine-1-carboximidamide	IC50	1.2 nM
(S)-N’-cyano-N-(3-cyanophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	1.2 nM
CHEMBL5169387	IC50	1.4 nM
(S)-N-(3-chlorophenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	1.6 nM
(S)-N’-cyano-N-(3-(N-isopropylsulfamoyl)phenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	1.7 nM
(S)-N’-cyano-N-(3-fluorophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	1.8 nM
CHEMBL3356424	IC50	1.9 nM
(S)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(trifluoromethyl)phenyl)piperazine-1-carboximidamide	IC50	1.9 nM
(S)-3-(2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamido)phenyl dimethylcarbamate	IC50	2 nM
CHEMBL3356426	IC50	2.2 nM
(S)-N-(3-chlorophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	IC50	2.3 nM
CHEMBL3356430	IC50	2.7 nM
CHEMBL3356063	IC50	2.7 nM
N-[3-(4-methoxyphenyl)phenyl]-4-(7,9,11-triazatricyclo[6.4.0.02,6]dodeca-1(12),2(6),8,10-tetraen-12-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	KI	2.75 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
(S)-N’-cyano-N-(3-(N-(2-hydroxyethyl)sulfamoyl)phenyl)-2-methyl-4-(5-methyl-7Hpyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	2.9 nM
(S)-N-(3-(2-hydroxyethylcarbamoyl)phenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	IC50	3 nM
(S)-N-(3-(1,3-dihydroxypropan-2-ylcarbamoyl)phenyl)-2-methyl-4-(5-methyl-7Hpyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	IC50	3 nM
N-methyl-4-[3-[[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,6-dihydro-2H-pyridine-1-carbonyl]amino]phenoxy]pyridine-2-carboxamide	KI	3.08 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
CHEMBL3356425	IC50	3.2 nM
(S)-3-(N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamido)-N-(2-(dimethylamino)ethyl)benzamide	IC50	3.4 nM
CEP-701	KD	3.4 nM
(S)-3-(N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamido)-N-isopropylbenzamide	IC50	3.5 nM
(S)-N-(3-bromo-4-fluorophenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	3.7 nM
4-(5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-[3-(4-methoxyphenyl)phenyl]-3,6-dihydro-2H-pyridine-1-carboxamide	KI	3.71 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
(S)-N-(3-bromophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	IC50	3.9 nM
Trans-N-(3-bromophenyl)-N’-cyano-2,5-dimethyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	3.9 nM
N1-(4-(2-chlorophenyl)-6-(2-(isopropylamino)thiazol-5-yl)pyrimidin-2-yl)-N2,N2-dimethylethane-1,2-diamine	IC50	4.01 nM
(S)-N-(3-bromophenyl)-N’-cyano-2-isopropyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	4.2 nM
(S)-N-(3-bromophenyl)-N’-cyano-2-methyl-4-(6-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide	IC50	4.2 nM
N-[3-[3-(methylcarbamoyl)phenoxy]phenyl]-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	KI	4.59 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
CHEMBL3356427	IC50	4.8 nM
[3-[3-[[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,6-dihydro-2H-pyridine-1-carbonyl]amino]phenoxy]phenyl] N,N-dimethylcarbamate	KI	4.88 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
N-[3-(3-acetamidophenoxy)phenyl]-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	KI	4.93 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
N-[3-(3-methoxyphenyl)phenyl]-4-(7,9,11-triazatricyclo[6.4.0.02,6]dodeca-1(12),2(6),8,10-tetraen-12-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	KI	4.97 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
N-(3-fluorophenyl)-4-(7,9,11-triazatricyclo[6.4.0.02,6]dodeca-1(12),2(6),8,10-tetraen-12-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	KI	5 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
CHEMBL3356429	IC50	5.1 nM
N-(3-bromophenyl)-4-(6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]indol-4-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	KI	5.37 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
(S)-N-(3-(isopropylcarbamoyl)phenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxamide	IC50	5.5 nM
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	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
N-(3-chlorophenyl)-4-(7,9,11-triazatricyclo[6.4.0.02,6]dodeca-1(12),2(6),8,10-tetraen-12-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	KI	5.78 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
N-(3-methoxyphenyl)-4-(7,9,11-triazatricyclo[6.4.0.02,6]dodeca-1(12),2(6),8,10-tetraen-12-yl)-3,6-dihydro-2H-pyridine-1-carboxamide	KI	6.1 nM	US-20230312576: 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER

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

382 with measured affinity, of 914 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

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

Chemical	Actions (top 5)	PubMed papers
Ethinyl Estradiol	affects expression, decreases 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	increases abundance, affects expression	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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F6DW	EDITGENE LIMK2 Knockout HAP1 Cell Line	Cancer cell line	Male
CVCL_SV60	HAP1 LIMK2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

1 trials:

NCT	Phase	Status	Title
NCT03356314	Not specified	COMPLETED	Prenatal Ultrasound Screening of Intestinal Malrotation With a Higher Risk of Volvulus

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LIMK2 across ~30M SureChEMBL compounds — explore on Sugi Predict.