MYLK

Summary

MYLK (myosin light chain kinase, HGNC:7590) is a protein-coding gene on chromosome 3q21.1, encoding Myosin light chain kinase, smooth muscle (Q15746). Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). It is haploinsufficient (ClinGen: sufficient evidence).

This gene, a muscle member of the immunoglobulin gene superfamily, encodes myosin light chain kinase which is a calcium/calmodulin dependent enzyme. This kinase phosphorylates myosin regulatory light chains to facilitate myosin interaction with actin filaments to produce contractile activity. This gene encodes both smooth muscle and nonmuscle isoforms. In addition, using a separate promoter in an intron in the 3’ region, it encodes telokin, a small protein identical in sequence to the C-terminus of myosin light chain kinase, that is independently expressed in smooth muscle and functions to stabilize unphosphorylated myosin filaments. A pseudogene is located on the p arm of chromosome 3. Four transcript variants that produce four isoforms of the calcium/calmodulin dependent enzyme have been identified as well as two transcripts that produce two isoforms of telokin. Additional variants have been identified but lack full length transcripts.

Source: NCBI Gene 4638 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial thoracic aortic aneurysm and aortic dissection (Strong, ClinGen) — +4 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 2,557 total — 49 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 67
• Druggable target: yes — 28 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_053025

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7590
Approved symbol	MYLK
Name	myosin light chain kinase
Location	3q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MLCK, smMLCK, MYLK1, MLCK1, KRP, Telokin, MLCK108, MLCK210, MYLK-L
Ensembl gene	ENSG00000065534
Ensembl biotype	protein_coding
OMIM	600922
Entrez	4638

Gene structure

Transcript identifiers

Ensembl transcripts: 61 — 30 protein_coding, 14 protein_coding_CDS_not_defined, 11 retained_intron, 6 nonsense_mediated_decay

ENST00000346322, ENST00000360304, ENST00000360772, ENST00000418370, ENST00000464489, ENST00000504946, ENST00000506361, ENST00000508240, ENST00000510571, ENST00000510775, ENST00000511058, ENST00000513111, ENST00000514623, ENST00000515434, ENST00000578202, ENST00000583087, ENST00000684879, ENST00000684882, ENST00000685021, ENST00000685170, ENST00000685259, ENST00000685665, ENST00000685744, ENST00000685907, ENST00000685953, ENST00000686039, ENST00000686245, ENST00000686281, ENST00000686388, ENST00000686406, ENST00000686458, ENST00000686761, ENST00000686822, ENST00000687375, ENST00000687434, ENST00000687709, ENST00000687848, ENST00000688024, ENST00000688223, ENST00000689227, ENST00000689446, ENST00000689868, ENST00000689918, ENST00000689957, ENST00000690086, ENST00000690167, ENST00000690176, ENST00000690457, ENST00000690534, ENST00000690656, ENST00000691367, ENST00000691933, ENST00000692352, ENST00000692356, ENST00000692507, ENST00000692811, ENST00000693689, ENST00000971487, ENST00000971488, ENST00000971489, ENST00000971490

RefSeq mRNA: 7 — MANE Select: NM_053025 NM_001321309, NM_053025, NM_053026, NM_053027, NM_053028, NM_053031, NM_053032

CCDS: CCDS3023, CCDS43141, CCDS46896, CCDS46897, CCDS58849, CCDS93356

Canonical transcript exons

ENST00000360304 — 34 exons

Exon	Start	End
ENSE00001392945	123831548	123831670
ENSE00001400013	123876559	123876617
ENSE00001515671	123610049	123614349
ENSE00003465644	123626818	123626941
ENSE00003473221	123682224	123682310
ENSE00003485108	123620207	123620336
ENSE00003507438	123700020	123701005
ENSE00003510616	123629474	123629626
ENSE00003512695	123739953	123740001
ENSE00003524767	123725944	123726078
ENSE00003525910	123752331	123752538
ENSE00003526501	123664105	123664258
ENSE00003532236	123618639	123618770
ENSE00003533777	123737378	123737543
ENSE00003543138	123707754	123708003
ENSE00003544345	123793677	123793844
ENSE00003547551	123640287	123640504
ENSE00003550188	123709756	123709893
ENSE00003560107	123738897	123739062
ENSE00003599845	123722128	123722280
ENSE00003603809	123692735	123692851
ENSE00003606081	123733687	123734222
ENSE00003618433	123735398	123735416
ENSE00003642776	123708698	123708895
ENSE00003643066	123701438	123701509
ENSE00003644449	123649162	123649194
ENSE00003644732	123666219	123666346
ENSE00003651647	123648971	123649064
ENSE00003652135	123647224	123647427
ENSE00003671757	123638071	123638194
ENSE00003672633	123667137	123667187
ENSE00003684559	123732896	123733102
ENSE00003785691	123657126	123657428
ENSE00003899919	123884206	123884332

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.2439 / max 1610.9502, expressed in 1394 samples.

FANTOM5 promoters (32 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44223	23.1179	1133
44181	13.8807	563
44194	3.2704	297
44188	2.0424	510
44224	1.9789	581
44198	1.7259	258
44182	1.2830	275
44175	0.7240	260
44197	0.3576	161
44216	0.3232	134

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	99.97	gold quality
saphenous vein	UBERON:0007318	99.93	gold quality
seminal vesicle	UBERON:0000998	99.92	gold quality
nipple	UBERON:0002030	99.78	gold quality
urethra	UBERON:0000057	99.76	gold quality
vena cava	UBERON:0004087	99.73	gold quality
myometrium	UBERON:0001296	99.66	gold quality
superficial temporal artery	UBERON:0001614	99.66	gold quality
caput epididymis	UBERON:0004358	99.61	gold quality
corpus epididymis	UBERON:0004359	99.53	gold quality
visceral pleura	UBERON:0002401	99.51	gold quality
left uterine tube	UBERON:0001303	99.50	gold quality
adult organism	UBERON:0007023	99.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.47	gold quality
lower esophagus	UBERON:0013473	99.43	gold quality
body of uterus	UBERON:0009853	99.41	gold quality
mucosa of stomach	UBERON:0001199	99.39	gold quality
blood vessel layer	UBERON:0004797	99.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.36	gold quality
popliteal artery	UBERON:0002250	99.33	gold quality
tibial artery	UBERON:0007610	99.33	gold quality
right coronary artery	UBERON:0001625	99.31	gold quality
gall bladder	UBERON:0002110	99.30	gold quality
urinary bladder	UBERON:0001255	99.28	gold quality
penis	UBERON:0000989	99.27	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.25	gold quality
mammary duct	UBERON:0001765	99.24	gold quality
aorta	UBERON:0000947	99.18	gold quality
descending thoracic aorta	UBERON:0002345	99.13	gold quality
colonic epithelium	UBERON:0000397	99.06	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	3869.53
E-MTAB-10287	yes	2957.11
E-MTAB-8221	yes	2791.73
E-MTAB-10885	yes	2402.22
E-MTAB-10662	yes	2315.98
E-MTAB-8410	yes	2175.75
E-MTAB-9841	yes	1824.76
E-HCAD-11	yes	1386.55
E-ENAD-21	yes	1249.76
E-CURD-7	yes	1249.21
E-HCAD-38	yes	1100.87
E-MTAB-8530	yes	494.74
E-MTAB-8142	yes	125.99
E-HCAD-1	yes	39.64
E-GEOD-134144	yes	32.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, ELK1, FOXA1, FOXF1, FOXN1, FOXO4, FOXQ1, GATA6, HOXA10, HOXB8, MYOCD, NFKB1, NFKB, NR3C1, PITX2, RELA, SRF, TBXT, TEF

miRNA regulators (miRDB)

127 targeting MYLK, 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-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-613	99.91	71.50	1710

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• a novel function in regulating the activation of volume-sensitive organic osmolyte/anion channels by mediating Ca2+ entry in response to hypotonicity (PMID:11976941)
• activation by Pro33 polymorphism of integrin beta3 (PMID:12460991)
• Increasing Ca(2+) increases MLCK activation. (PMID:14741352)
• cortactin and EC myosin light chain kinase have roles in mediating lung vascular barrier augmentation evoked by S1P (PMID:15056655)
• myosin light chain kinase has a role in ATP- augmented von Willebrand factor-dependent shear-induced platelet aggregation (PMID:15087444)
• MLCK1 is the isoform responsible for tight junction regulation in absorptive enterocytes (PMID:15507455)
• IFN-gamma can prime intestinal epithelial monolayers to respond to TNF-alpha by disrupting tight junction morphology and barrier function via MLCK up-regulation and MLC phosphorylation (PMID:15681825)
• Complementary roles for these kinases in purse-string closure of experimental and in vivo oligocellular epithelial wounds; rho and ROCK are critical for actin ring assembly, while the activity of MLCK drives contraction. (PMID:15825080)
• findings suggest intracellular Ca(2+)-calmodulin activates MLCK thereby maintaining TRPC5 activity by the promotion of plasma membrane TRPC5 distribution under control of phosphorylation/dephosphorylation equilibrium of myosin light chain (PMID:16284075)
• Results suggest that calmodulin and myosin light chain kinase modulate the activation process of transient receptor potential channel 5. (PMID:16306123)
• MYLK genetic variants are implicated to confer increased risk of sepsis and sepsis-associated ALI. (PMID:16399953)
• These studies demonstrate a newly discovered role for MLCK in the generation of pro-survival signals in both untransformed and transformed epithelial cells (PMID:16723733)
• Data show that either AP-1 or NFkappaB can up-regulate long MLCK transcription, but the mechanisms by which TNF up-regulates intestinal epithelial long MLCK transcription from exon 1A are differentiation-dependent. (PMID:16835238)
• MLC2 phosphorylation is regulated by both ROCK and MLC kinase and plays an important role in platelet biogenesis by controlling proplatelet formation and fragmentation. (PMID:17244674)
• MYLK genetic variants studied in European and African Americans with asthma and severe asthma and identified a single polymorphism (Pro147Ser) restricted to African populations and which was associated with severe asthma in African Americans. (PMID:17266121)
• Protein kinase A activity prevents activation of beta2 integrins and cell adhesion by inhibiting myosin light chain kinase in neutrophils. (PMID:18218860)
• These studies provide novel insight into the cellular and molecular mechanisms that regulate basal and TNF-alpha-induced modulation of MLCK gene activity. (PMID:18363837)
• Myosin light-chain kinase contributes to the proliferation and migration of breast cancer cells through cross-talk with activated ERK1/2. (PMID:18710790)
• Selective overexpression of airway smooth muscle genes in asthmatic airways leads to increased Vmax, thus contributing to the airway hyperresponsiveness observed in asthma. (PMID:19011151)
• MYLK polymorphism is associated with high blood eosinophil level among asthmatic patients. (PMID:19277499)
• LNCaP cells express both long (non-muscle) and short (smooth muscle) isoforms, and that both isoforms are down-regulated by androgens. (PMID:19429448)
• MLCK inhibits the restoration of GPIbalpha in PAR1 pathway during the course of thrombin receptor activation in platelets. (PMID:19549383)
• hARD1 is a bona fide regulator of MLCK, and hARD1 plays a crucial role in the balance between tumor cell migration and stasis (PMID:19826488)
• Data provide insights into the molecular basis for vascular barrier-regulatory cytoskeletal responses and quantified the critical interactions between non-muscle MLCK isoenzymes and cortactin during vascular barrier regulation. (PMID:20053363)
• No association between snps in the myosin light chain kinase gene and either the need for positive-pressure ventilation or the development of acute lung injury/acute respiratory distress syndrome was observed in children with community-acquired pneumonia. (PMID:20081554)
• membrane blebbing in response to AT(1)R signaling is dependent on beta-arrestin2 and is mediated by a RhoA/ROCK/MLCK-dependent pathway (PMID:20181817)
• study concludes MLCK is responsible for high proliferative ability of breast cancer cells through anti-apoptosis, in which p38 pathway was involved (PMID:20453870)
• Studies indicate an essential role for Abl kinase in vascular barrier regulation via posttranslational modification of nmMLCK. (PMID:20861316)
• genetic and functional studies support the conclusion that heterozygous loss-of-function mutations in MYLK are associated with aortic dissections. (PMID:21055718)
• Data identify a novel interaction between cardiac-specific Ig-like domain C0 and the regulatory light chain of myosin, thus placing the N terminus of the protein in proximity to the motor domain of myosin. (PMID:21297165)
• Results provide evidence that neutrophil transmigration is regulated by myosin light chain kinase-mediated endothelial cell contraction and that this event depends on subendothelial cell matrix stiffness. (PMID:21652678)
• MYLK SNPs downregulate smooth muscle MLCK promoter activity due to interruption of a FOXN1 binding site. These data provide new insights into the contribution of MYLK SNPs to inflammatory disease susceptibility. (PMID:22015949)
• IL-18 may potentiate inflammation in the context of inflammatory bowel disease by facilitating neutrophil transepithelial migration via MLCK-dependent disruption of tight junctional occludin. (PMID:22135309)
• MLCK is essential for the translocation and association of cortactin and p47phox. (PMID:22219181)
• Hypermethylated FAM5C and MYLK in serum are strongly associated with the development of gastric cancer and can be used as potential biomarkers for diagnosis and pre-warning. (PMID:22377736)
• The approximate time period of changes in the ratios of MLCK-108 and MLCK-210 was revealed (between 8-9 and 13 weeks), that can be associated with functional changes in the developing myocardium. (PMID:22808459)
• Claudin-2 assumes an important role in colorectal inflammation, and furthermore implicates the involvement of MLCK in colon inflammation. (PMID:23306855)
• Increased human lung endothelial cell expression of MYLK by bioactive agonists (excessive mechanical stress, TNF-alpha) is regulated in part by specific miRNAs (miR-374a, miR-374b, miR-520c-3p, and miR-1290). (PMID:23492194)
• these studies show that the IL-1beta-induced increase in intestinal tight junction permeability was regulated by p38 kinase activation of ATF-2 and by ATF-2 regulation of MLCK gene activity (PMID:23656735)
• Results suggest that Aurora B, but not Rho/MLCK (myosin-light-chain kinase) signaling, is essential for the localization of 2P-MRLC (myosin regulatory light chains) to the midzone in dividing HeLa cells. (PMID:23951055)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mylkb	ENSDARG00000004753
danio_rerio	mylka	ENSDARG00000034801
mus_musculus	Mylk	ENSMUSG00000022836
rattus_norvegicus	Mylk	ENSRNOG00000002215

Paralogs (4): DAPK2 (ENSG00000035664), NEXN (ENSG00000162614), DAPK3 (ENSG00000167657), DAPK1 (ENSG00000196730)

Protein

Protein identifiers

Myosin light chain kinase, smooth muscle — Q15746 (reviewed: Q15746)

Alternative names: Kinase-related protein, Telokin

All UniProt accessions (21): Q15746, A0A8I5KQY6, A0A8I5KS78, A0A8I5KTQ1, A0A8I5KU53, A0A8I5KUB2, A0A8I5KUH4, A0A8I5KUP2, A0A8I5KVV3, A0A8I5KXG8, A0A8I5KYA1, A0A8I5KYB9, A0A8I5KYZ0, A0A8I5KZ33, A0A8I5QJT9, A0A8I5QJW9, A0A8I5QKL9, A0A8I5QKW8, A0A8J9G5A3, D6R9C2, F8WBL7

UniProt curated annotations — full annotation on UniProt →

Function. Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis.

Subunit / interactions. All isoforms including Telokin bind calmodulin. Interacts with SVIL. Interacts with CTTN; this interaction is reduced during thrombin-induced endothelial cell (EC) contraction but is promoted by the barrier-protective agonist sphingosine 1-phosphate (S1P) within lamellipodia. A complex made of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Binds to NAA10/ARD1 and PTK2B/PYK2.

Subcellular location. Cytoplasm. Cell projection. Lamellipodium. Cleavage furrow. Cytoskeleton. Stress fiber.

Tissue specificity. Smooth muscle and non-muscle isozymes are expressed in a wide variety of adult and fetal tissues and in cultured endothelium with qualitative expression appearing to be neither tissue- nor development-specific. Non-muscle isoform 2 is the dominant splice variant expressed in various tissues. Telokin has been found in a wide variety of adult and fetal tissues. Accumulates in well differentiated enterocytes of the intestinal epithelium in response to tumor necrosis factor (TNF).

Post-translational modifications. Can probably be down-regulated by phosphorylation. Tyrosine phosphorylation by ABL1 increases kinase activity, reverses MLCK-mediated inhibition of Arp2/3-mediated actin polymerization, and enhances CTTN-binding. Phosphorylation by SRC at Tyr-464 and Tyr-471 promotes CTTN binding. The C-terminus is deglutamylated by AGTPBP1/CCP1, AGBL1/CCP4 and AGBL4/CCP6, leading to the formation of Myosin light chain kinase, smooth muscle, deglutamylated form. The consequences of C-terminal deglutamylation are unknown. Acetylated at Lys-608 by NAA10/ARD1 via a calcium-dependent signaling; this acetylation represses kinase activity and reduces tumor cell migration.

Disease relevance. Aortic aneurysm, familial thoracic 7 (AAT7) [MIM:613780] A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as ‘medial necrosis’ or ‘Erdheim cystic medial necrosis’ in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. The disease is caused by variants affecting the gene represented in this entry. Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) [MIM:249210] A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Isoform 1 is activated by phosphorylation on Tyr-464 and Tyr-471. Isoforms which lack these tyrosine residues are not regulated in this way. All catalytically active isoforms require binding to calcium and calmodulin for activation. Repressed by organometallic pyridylnaphthalimide complexes, wortmannin, ML-7 (a synthetic naphthalenesulphonyl derivative that inhibits the binding of ATP to MLCK) and ML-9.

Induction. Accumulates in individuals with asthma (at protein levels). Induced by tumor necrosis factor (TNF). Repressed by androgens (e.g. R1881).

Miscellaneous. In asthmatic patients, overexpression promotes actin filament propulsion, thus contributing to airway hyperresponsiveness. Some MYLK variants may contribute to acute lung injury (ALI) susceptibility. Potential therapeutic target in the treatment of burn edema. Transcribed from an alternative promoter resulting in the usage of Met-923 as initiator codon. Transcribed from an alternative promoter resulting in the usage of Met-1761 as initiator codon. Has no catalytic activity. Initiator Met is removed. Transcribed from an alternative promoter resulting in the usage of Met-1761 as initiator codon. Initiator Met is removed. Transcribed from an alternative promoter resulting in the usage of Met-923 as initiator codon.

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

Isoforms (11)

UniProt ID	Names	Canonical?
Q15746-1	1, Non-muscle isozyme	yes
Q15746-2	2
Q15746-3	3A
Q15746-4	3B
Q15746-5	4
Q15746-6	Del-1790
Q15746-7	5, Smooth-muscle isozyme
Q15746-8	6, Telokin
Q15746-9	7
Q15746-10	8
Q15746-11	9

RefSeq proteins (7): NP_001308238, NP_444253, NP_444254, NP_444255, NP_444256, NP_444259, NP_444260 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015725	MLCK1_kinase_dom	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF00041, PF00069, PF07679, PF16620

Enzyme classification (BRENDA):

• EC 2.7.11.18 — myosin-light-chain kinase (BRENDA: 19 organisms, 213 substrates, 192 inhibitors, 48 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.05–0.224	9
MYOSIN LIGHT CHAIN	0.0043–0.019	6
MYOSIN REGULATORY LIGHT CHAIN	0.0067–0.014	3
CALMODULIN	—	2
BPAKKRAARATSNVFA	0.0075	1
DICTYOSTELIUM MYOSIN	0.004	1
KEMPTAMIDE	0.11	1
KKRAARATSNVFA	0.0084	1
LIMULUS MYOSIN LIGHT CHAIN	0.0156	1
MYOSIN	0.004	1
TURKEY GIZZARD MYOSIN LIGHT CHAIN	0.04	1
UNPHOSPHORYLATED MYOSIN II REGULATORY LIGHT CHAI	0.0066	1
[NON-MUSCLE HEAVY MEROMYOSIN IIB]	0.0025	1
[NON-MUSCLE REGULATORY LIGHT CHAIN]	0.0051	1
[SMOOTH MUSCLE HEAVY MEROMYOSIN]	0.0026	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[myosin light chain] + ATP = O-phospho-L-seryl-[myosin light chain] + ADP + H(+) (RHEA:22004)
• L-threonyl-[myosin light chain] + ATP = O-phospho-L-threonyl-[myosin light chain] + ADP + H(+) (RHEA:53900)

UniProt features (173 total): sequence variant 30, sequence conflict 28, strand 27, modified residue 25, repeat 11, domain 11, region of interest 11, splice variant 7, compositionally biased region 6, disulfide bond 6, chain 2, helix 2, initiator methionine 2, binding site 2, mutagenesis site 1, turn 1, active site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9MXD	X-RAY DIFFRACTION	1.17
9MVW	X-RAY DIFFRACTION	1.58
5JQA	X-RAY DIFFRACTION	1.8
5JTH	X-RAY DIFFRACTION	1.84
6C6M	X-RAY DIFFRACTION	2.5
2CQV	SOLUTION NMR
2YR3	SOLUTION NMR
2K0F	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15746-F1	66.54	0.19

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): 1585 (proton acceptor)

Ligand- & substrate-binding residues (2): 1470–1478; 1493

Post-translational modifications (25): 2, 2, 231, 305, 343, 365, 464, 471, 556, 608, 611, 792, 846, 947, 1438, 1449, 1575, 1635, 1759, 1760 …

Disulfide bonds (6): 182–233, 435–487, 535–583, 742–805, 1119–1170, 1830–1882

Mutagenesis-validated functional residues (1):

Position	Phenotype
608	loss of acetylation and no kinase activity repression by naa10/ard1.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-445355	Smooth Muscle Contraction
R-HSA-5627123	RHO GTPases activate PAKs
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-397014	Muscle contraction
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 584 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, WWTAAGGC_UNKNOWN, GOBP_REGULATION_OF_WOUND_HEALING, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, RORA1_01, MODULE_64, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, MODULE_128, AP4_Q6, GOBP_ARTERY_DEVELOPMENT, TGACCTY_ERR1_Q2, CHEOK_RESPONSE_TO_HD_MTX_UP

GO Biological Process (11): protein phosphorylation (GO:0006468), smooth muscle contraction (GO:0006939), tonic smooth muscle contraction (GO:0014820), positive regulation of cell migration (GO:0030335), bleb assembly (GO:0032060), positive regulation of calcium ion transport (GO:0051928), aorta smooth muscle tissue morphogenesis (GO:0060414), cellular hypotonic response (GO:0071476), positive regulation of wound healing (GO:0090303), regulation of synaptic vesicle endocytosis (GO:1900242), muscle organ development (GO:0007517)

GO Molecular Function (12): actin binding (GO:0003779), myosin light chain kinase activity (GO:0004687), calmodulin binding (GO:0005516), ATP binding (GO:0005524), metal ion binding (GO:0046872), scaffold protein binding (GO:0097110), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (10): stress fiber (GO:0001725), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), cleavage furrow (GO:0032154), synapse (GO:0045202), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Muscle contraction	1
RHO GTPase Effectors	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein binding	2
phosphorylation	1
protein modification process	1
muscle contraction	1
smooth muscle contraction	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
plasma membrane bounded cell projection assembly	1
calcium ion transport	1
positive regulation of monoatomic ion transport	1
regulation of calcium ion transport	1
aorta morphogenesis	1
smooth muscle tissue development	1
muscle tissue morphogenesis	1
hypotonic response	1
cellular response to osmotic stress	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
regulation of endocytosis	1
synaptic vesicle endocytosis	1
regulation of synaptic vesicle recycling	1
animal organ development	1
muscle structure development	1
cytoskeletal protein binding	1
protein serine/threonine kinase activity	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
protein kinase activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Protein interactions and networks

STRING

2612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYLK	CALM1	P02593	993
MYLK	CALML6	Q8TD86	993
MYLK	CALML3	P27482	993
MYLK	CALML4	Q96GE6	993
MYLK	CALML5	Q9NZT1	993
MYLK	MYH11	P35749	826
MYLK	KALRN	O60229	814
MYLK	ARHGAP31	Q2M1Z3	813
MYLK	MYL9	P24844	785
MYLK	ACTA2	P03996	710
MYLK	FBN1	P35555	620
MYLK	SLC2A10	O95528	611
MYLK	TPM1	P09493	610
MYLK	TPM2	P06468	602
MYLK	ACTG2	P12718	599

IntAct

36 interactions, top by confidence:

A	B	Type	Score
MYLK	GOPC	psi-mi:“MI:0915”(physical association)	0.560
GOPC	MYLK	psi-mi:“MI:0915”(physical association)	0.560
MYLK	MYL12A	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MYLK	GRB2	psi-mi:“MI:0915”(physical association)	0.400
MYLK	NCK1	psi-mi:“MI:0915”(physical association)	0.400
MYLK	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
MYLK	SDR42E2	psi-mi:“MI:0915”(physical association)	0.400
MYLK	HNRNPAB	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	MYLK	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
MYLK2		psi-mi:“MI:0914”(association)	0.350
MYLK2	PSMD3	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
ZBTB18	DNASE1L1	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
MYLK	ACOT7	psi-mi:“MI:0914”(association)	0.350
	PIK3R2	psi-mi:“MI:0914”(association)	0.350
MYLK	FKBP8	psi-mi:“MI:2364”(proximity)	0.270
CTTN	MYLK	psi-mi:“MI:2364”(proximity)	0.270
MYLK		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (115): MYLK (Affinity Capture-MS), GOPC (Two-hybrid), MYLK (Two-hybrid), MYLK (Affinity Capture-MS), MYLK (Affinity Capture-MS), MYLK (Affinity Capture-MS), MYLK (Affinity Capture-MS), MYLK (Affinity Capture-MS), MYLK (Affinity Capture-MS), CTTN (Co-localization), MYLK (Affinity Capture-RNA), MYLK (Affinity Capture-MS), MYLK (Two-hybrid), MYLK (Two-hybrid), MYLK (Affinity Capture-MS)

ESM2 similar proteins: A2AAJ9, A2ABU4, A2RUH7, B4GBH0, D3ZGQ5, O09127, O70468, O75038, O88599, O95382, P16419, P21709, P22455, P22607, P29322, P54760, P54761, P55144, P55146, P56741, P70218, P70402, Q00653, Q06418, Q13203, Q13308, Q13425, Q14896, Q15746, Q290N5, Q32P44, Q4LDD4, Q5FW53, Q5PQM4, Q5VST9, Q5VTT5, Q60750, Q61851, Q68LP1, Q80UW5

Diamond homologs: A0A140LHF2, P0DP72, P11464, P16573, P31809, P31997, P35329, Q00887, Q15223, Q15746, Q16557, Q58EX2, Q6V4S5, Q96FE5, Q9D1T0, Q9GL76, Q9N008, A0QQK3, A8WUG4, A8X5H5, A8X6H1, A8XJQ6, A8XW88, F1M7Y5, F4HYG2, F4J6F6, G4NH08, O02827, O76360, O88664, P00517, P0DPS8, P10421, P10830, P11799, P16054, P16912, P17612, P18431, P18654

SIGNOR signaling

24 interactions.

A	Effect	B	Mechanism
ROCK1	up-regulates	MYLK	binding
MYLK	down-regulates	CALD1	phosphorylation
ABL1	up-regulates	MYLK	phosphorylation
MYLK	up-regulates	MYL9	phosphorylation
wortmannin	down-regulates	MYLK	“chemical inhibition”
PAK1	“down-regulates activity”	MYLK	phosphorylation
MAPK1	“up-regulates activity”	MYLK	phosphorylation
MYLK	“up-regulates activity”	MYL2	phosphorylation
MYLK	up-regulates	MYL6B	phosphorylation
SRC	up-regulates	MYLK	phosphorylation
FOXQ1	“down-regulates quantity by repression”	MYLK	“transcriptional regulation”
HOXB8	“down-regulates quantity by repression”	MYLK	“transcriptional regulation”
HOXA10	“up-regulates quantity by expression”	MYLK	“transcriptional regulation”
PAK2	“down-regulates activity”	MYLK	phosphorylation
CAMK2G	“down-regulates activity”	MYLK	phosphorylation
PAK	“down-regulates activity”	MYLK	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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
Signaling by ALK fusions and activated point mutants	5	34.1×	5e-05
PIP3 activates AKT signaling	5	15.2×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

2557 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	49
Likely pathogenic	24
Uncertain significance	1372
Likely benign	798
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069085	NM_053025.4(MYLK):c.4114del (p.Asp1372fs)	Pathogenic
1356169	NM_053025.4(MYLK):c.4470G>A (p.Trp1490Ter)	Pathogenic
1391929	NM_053025.4(MYLK):c.4422del (p.Lys1474fs)	Pathogenic
1415008	NM_053025.4(MYLK):c.3751_3752del (p.Ala1251fs)	Pathogenic
1451428	NM_053025.4(MYLK):c.3231C>A (p.Cys1077Ter)	Pathogenic
1454045	NM_053025.4(MYLK):c.4093_4094del (p.Ser1365fs)	Pathogenic
1457767	NC_000003.11:g.(?123332952)(123386054_?)del	Pathogenic
2015715	NM_053025.4(MYLK):c.2965A>T (p.Lys989Ter)	Pathogenic
2024190	NM_053025.4(MYLK):c.3876_3937del (p.Ser1293fs)	Pathogenic
2199590	NM_053025.4(MYLK):c.2814_2815del (p.Val938_Ser939insTer)	Pathogenic
264987	NM_053025.4(MYLK):c.3838_3844dup (p.Glu1282fs)	Pathogenic
268202	NM_053025.4(MYLK):c.4372C>T (p.Gln1458Ter)	Pathogenic
268203	NM_053025.4(MYLK):c.4459C>T (p.Arg1487Ter)	Pathogenic
2709626	NM_053025.4(MYLK):c.2824G>T (p.Glu942Ter)	Pathogenic
2801842	NM_053025.4(MYLK):c.3967dup (p.Val1323fs)	Pathogenic
2844838	NM_053025.4(MYLK):c.3072dup (p.Pro1025fs)	Pathogenic
2851655	NM_053025.4(MYLK):c.4404_4407del (p.Glu1468fs)	Pathogenic
3246910	NC_000003.11:g.(?123345645)(123345808_?)del	Pathogenic
3246911	NC_000003.11:g.(?123471158)(123471405_?)del	Pathogenic
3401141	NM_053025.4(MYLK):c.4091_4092del (p.Gln1364fs)	Pathogenic
3642990	NM_053025.4(MYLK):c.2943del (p.Arg982fs)	Pathogenic
3649921	NM_053025.4(MYLK):c.4522C>T (p.Gln1508Ter)	Pathogenic
3660967	NM_053025.4(MYLK):c.4056G>A (p.Trp1352Ter)	Pathogenic
3663775	NM_053025.4(MYLK):c.3059C>G (p.Ser1020Ter)	Pathogenic
3664949	NM_053025.4(MYLK):c.4874del (p.Pro1625fs)	Pathogenic
3693824	NM_053025.4(MYLK):c.3377dup (p.Ala1127fs)	Pathogenic
3700084	NM_053025.4(MYLK):c.3636del (p.Val1213fs)	Pathogenic
3725509	NM_053025.4(MYLK):c.4414dup (p.Ser1472fs)	Pathogenic
4084588	NM_053025.4(MYLK):c.1641G>A (p.Trp547Ter)	Pathogenic
409685	NM_053025.4(MYLK):c.4489_4493del (p.Ala1497fs)	Pathogenic

SpliceAI

6276 predictions. Top by Δscore:

Variant	Effect	Δscore
3:123614356:C:CT	acceptor_gain	1.0000
3:123614358:C:CT	acceptor_gain	1.0000
3:123618634:CTTA:C	donor_loss	1.0000
3:123618635:TTA:T	donor_loss	1.0000
3:123618636:TA:T	donor_loss	1.0000
3:123618637:A:AC	donor_gain	1.0000
3:123618638:C:CC	donor_gain	1.0000
3:123618638:CCTT:C	donor_gain	1.0000
3:123618766:ATCTT:A	acceptor_gain	1.0000
3:123618768:CTT:C	acceptor_gain	1.0000
3:123618769:TT:T	acceptor_gain	1.0000
3:123618771:C:CC	acceptor_gain	1.0000
3:123629465:A:C	donor_gain	1.0000
3:123629470:T:C	donor_gain	1.0000
3:123629472:A:AC	donor_gain	1.0000
3:123629473:C:CC	donor_gain	1.0000
3:123629473:CTT:C	donor_gain	1.0000
3:123629475:T:TA	donor_gain	1.0000
3:123629484:T:A	donor_gain	1.0000
3:123629507:T:TA	donor_gain	1.0000
3:123629625:CT:C	acceptor_gain	1.0000
3:123638069:A:AC	donor_gain	1.0000
3:123638070:C:CC	donor_gain	1.0000
3:123640284:TACCC:T	donor_loss	1.0000
3:123640285:A:AC	donor_gain	1.0000
3:123640285:AC:A	donor_gain	1.0000
3:123640286:C:CC	donor_gain	1.0000
3:123640286:CC:C	donor_gain	1.0000
3:123640286:CCCAG:C	donor_gain	1.0000
3:123640289:AG:A	donor_gain	1.0000

AlphaMissense

12566 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:123657206:C:G	R1403P	0.999
3:123657209:A:G	F1402S	0.999
3:123722191:A:C	Y581D	0.999
3:123725956:A:G	W547R	0.999
3:123725956:A:T	W547R	0.999
3:123614326:A:G	W1842R	0.998
3:123614326:A:T	W1842R	0.998
3:123666237:C:A	W1271C	0.998
3:123666237:C:G	W1271C	0.998
3:123666239:A:G	W1271R	0.998
3:123666239:A:T	W1271R	0.998
3:123692798:A:C	Y1168D	0.998
3:123700077:A:G	W1131R	0.998
3:123700077:A:T	W1131R	0.998
3:123722229:A:G	L568P	0.998
3:123732959:A:C	Y485D	0.998
3:123733073:A:G	W447R	0.998
3:123733073:A:T	W447R	0.998
3:123737441:A:C	Y231D	0.998
3:123738946:A:G	F180S	0.998
3:123752393:T:G	Y104S	0.998
3:123752394:A:C	Y104D	0.998
3:123752508:A:G	W66R	0.998
3:123752508:A:T	W66R	0.998
3:123614160:A:G	L1897P	0.997
3:123614250:A:G	L1867S	0.997
3:123618656:A:G	F1828S	0.997
3:123638099:A:G	W1645R	0.997
3:123638099:A:T	W1645R	0.997
3:123647401:A:G	L1481P	0.997

dbSNP variants (sampled 300 via entrez): RS1000000764 (3:123675698 T>A,G), RS1000001994 (3:123883085 C>A,G), RS1000038045 (3:123883338 T>A,G), RS1000041589 (3:123785378 C>G), RS1000047355 (3:123620960 C>T), RS1000047621 (3:123631770 C>T), RS1000060506 (3:123753224 A>T), RS1000077174 (3:123828841 T>C), RS1000116095 (3:123834514 G>A), RS1000142040 (3:123819165 T>C), RS1000151177 (3:123624410 C>G), RS1000152145 (3:123735483 C>G,T), RS1000152964 (3:123668792 T>C), RS1000164877 (3:123659243 T>C), RS1000177729 (3:123789950 C>G)

Disease associations

OMIM: gene MIM:600922 | disease phenotypes: MIM:613780, MIM:607086, MIM:249210, MIM:609192, MIM:100070, MIM:611788, MIM:154700, MIM:155310, MIM:108800, MIM:617168

GenCC curated gene-disease

Disease	Classification	Inheritance
aortic aneurysm, familial thoracic 7	Strong	Autosomal dominant
familial thoracic aortic aneurysm and aortic dissection	Strong	Unknown
megacystis-microcolon-intestinal hypoperistalsis syndrome 1	Strong	Autosomal recessive
connective tissue disorder	Moderate	Autosomal dominant
megacystis-microcolon-intestinal hypoperistalsis syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
familial thoracic aortic aneurysm and aortic dissection	Strong	AD

Mondo (15): aortic aneurysm, familial thoracic 7 (MONDO:0013418), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), megacystis-microcolon-intestinal hypoperistalsis syndrome 1 (MONDO:0100354), prostate cancer (MONDO:0008315), Loeys-Dietz syndrome (MONDO:0018954), aortic aneurysm, familial abdominal, 1 (MONDO:0024521), connective tissue disorder (MONDO:0003900), megacystis-microcolon-intestinal hypoperistalsis syndrome (MONDO:0025986), aortic aneurysm, familial thoracic 6 (MONDO:0012730), aortic aneurysm, familial thoracic 1 (MONDO:0024559), Marfan syndrome (MONDO:0007947), visceral myopathy 1 (MONDO:0020754), atrial septal defect (MONDO:0006664), aortic aneurysm, familial thoracic 10 (MONDO:0014950), (MONDO:0007960)

Orphanet (9): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Familial prostate cancer (Orphanet:1331), Loeys-Dietz syndrome (Orphanet:60030), Megacystis-microcolon-intestinal hypoperistalsis syndrome (Orphanet:2241), Familial aortic dissection (Orphanet:229), Marfan syndrome type 1 (Orphanet:284963), Marfan syndrome (Orphanet:558), Familial visceral myopathy (Orphanet:2604), Interatrial communication (Orphanet:1478)

HPO phenotypes

67 total (30 of 67 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000021	Megacystis
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000072	Hydroureter
HP:0000098	Tall stature
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000525	Abnormality iris morphology
HP:0000766	Abnormal sternum morphology
HP:0000822	Hypertension
HP:0000965	Cutis marmorata
HP:0000978	Bruising susceptibility
HP:0001166	Arachnodactyly
HP:0001297	Stroke
HP:0001522	Death in infancy
HP:0001537	Umbilical hernia
HP:0001539	Omphalocele
HP:0001561	Polyhydramnios
HP:0001562	Oligohydramnios
HP:0001640	Cardiomegaly
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001659	Aortic regurgitation
HP:0001677	Coronary artery atherosclerosis
HP:0001699	Sudden death
HP:0001763	Pes planus
HP:0002017	Nausea and vomiting

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006269_915	General cognitive ability	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D006344	Heart Septal Defects, Atrial	C14.240.400.560.375; C14.280.400.560.375; C16.131.240.400.560.375
D055947	Loeys-Dietz Syndrome	C05.660.207.532; C14.907.055.239.587; C14.907.109.139.587; C16.131.077.537; C16.320.510
D008382	Marfan Syndrome	C05.116.099.674; C14.240.400.725; C14.280.400.725; C16.131.077.550; C16.131.240.400.720; C16.320.540; C17.300.500
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C562834	Aortic Aneurysm, Familial Thoracic 1 (supp.)
C567085	Aortic Aneurysm, Familial Thoracic 6 (supp.)
C536138	Megacystis microcolon intestinal hypoperistalsis syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2428 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

28 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 248,808 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL38380	FASUDIL	3	11,953
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1090090	VX-702	2	1,045
CHEMBL1721885	SU-014813	2	363
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL1950289	TANZISERTIB	2
CHEMBL2029988	CEP-32496	2
CHEMBL206834	BAFETINIB	2
CHEMBL3991932	PEXMETINIB	2
CHEMBL475251	R-406	2
CHEMBL513909	BI-2536	2
CHEMBL1908397	KW-2449	1
CHEMBL536151	IMD-0354	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Myosin Light Chain Kinase (MLCK) family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
RKI-1447	Inhibition	7.81	pIC50
MLCK inhibitor peptide 18	Inhibition	7.3	pIC50

Binding affinities (BindingDB)

11 measured of 28 human assays (28 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
HS38	IC50	200 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
N-[2-[6-(4-cyclopropyl-1,2,4-triazol-3-yl)-2-pyridinyl]-1-oxo-3H-isoindol-5-yl]acetamide	IC50	600 nM	US-10150755: ASK1 inhibitor compounds and uses thereof
2-[6-(4-cyclopropyl-1,2,4-triazol-3-yl)-2-pyridinyl]-N,N-dimethyl-3-oxo-1H-isoindole-5-carboxamide	IC50	600 nM	US-10150755: ASK1 inhibitor compounds and uses thereof
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol	KD	2400 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

144 potent at pChembl≥5 of 170 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.50	Kd	0.317	nM	CHEMBL5653589
9.42	ED50	0.38	nM	CHEMBL5653589
8.52	Kd	3	nM	VX-702
8.00	IC50	10	nM	STAUROSPORINE
7.96	Kd	11	nM	CHEMBL464552
7.92	Kd	12	nM	LESTAURTINIB
7.89	Kd	13	nM	LESTAURTINIB
7.82	Kd	15	nM	STAUROSPORINE
7.81	IC50	15.63	nM	CHEMBL3218297
7.77	Ki	17	nM	CHEMBL416056
7.75	IC50	18	nM	CHEMBL155929
7.70	Ki	20	nM	K-252A
7.66	IC50	22	nM	K-252A
7.64	Kd	23	nM	SUNITINIB
7.60	IC50	25	nM	CHEMBL94678
7.52	IC50	30	nM	CHEMBL348563
7.50	IC50	32	nM	CHEMBL156433
7.40	IC50	40	nM	STAUROSPORINE
7.37	IC50	43.2	nM	STAUROSPORINE
7.31	IC50	49	nM	CHEMBL347154
7.29	IC50	51.3	nM	STAUROSPORINE
7.26	IC50	55	nM	CHEMBL348177
7.14	Kd	72	nM	DASATINIB
7.13	IC50	73.2	nM	STAUROSPORINE
7.09	Kd	81	nM	PEXMETINIB
7.01	Kd	97	nM	BI-2536
7.00	Kd	99	nM	PONATINIB
6.92	IC50	120	nM	CHEMBL157822
6.92	IC50	120	nM	CHEMBL156172
6.82	Kd	150	nM	CHEMBL408019
6.77	IC50	170	nM	WORTMANNIN
6.75	IC50	180	nM	CHEMBL348902
6.73	Kd	188	nM	GILTERITINIB
6.70	IC50	200	nM	CHEMBL345593
6.69	Kd	205.7	nM	CHEMBL3752910
6.66	IC50	220	nM	CHEMBL157967
6.66	Kd	220	nM	MIDOSTAURIN
6.66	Kd	220	nM	TAE-684
6.61	ED50	246.8	nM	CHEMBL3752910
6.60	IC50	250	nM	CHEMBL157892
6.58	IC50	265	nM	CHEMBL5174830
6.55	Kd	280	nM	SUNITINIB
6.54	Kd	290	nM	RUBOXISTAURIN
6.54	Kd	290	nM	NINTEDANIB
6.53	Kd	298	nM	CHEMBL4576489
6.52	Ki	300	nM	CHEMBL249089
6.51	IC50	310	nM	CHEMBL157528
6.48	IC50	334	nM	CHEMBL5093741
6.48	Kd	330	nM	CHEMBL1241674
6.44	Kd	360	nM	SU-014813

PubChem BioAssay actives

101 with measured affinity, of 1199 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148810: Binding affinity to human MYLK incubated for 45 mins by Kinobead based pull down assay	kd	0.0003	uM
6-(N-carbamoyl-2,6-difluoroanilino)-2-(2,4-difluorophenyl)pyridine-3-carboxamide	1425081: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0030	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	624709: Binding constant for MYLK kinase domain	kd	0.0110	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507625: Binding affinity to MLCK	kd	0.0120	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	435664: Binding constant for MYLK kinase domain	kd	0.0150	uM
1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea;methanesulfonic acid	1119789: Inhibition of MLCK1 (unknown origin)	ic50	0.0156	uM
methyl (15R,16S,18S)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate	325647: Inhibition of human myosin light chain kinase	ki	0.0170	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate	550538: Inhibition of MLCK by HTRF assay	ki	0.0200	uM
Sunitinib	507625: Binding affinity to MLCK	kd	0.0230	uM
methyl (15S,16S,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate	106875: Inhibition of Myosin light chain kinase 1 (MLCK1)	ic50	0.0250	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	1425081: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0720	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[[5-fluoro-2-[1-(2-hydroxyethyl)indazol-5-yl]oxyphenyl]methyl]urea	1425081: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0810	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	624709: Binding constant for MYLK kinase domain	kd	0.0970	uM
Ponatinib	1425081: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0990	uM
N-[6-(3-hydroxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]cyclopropanecarboxamide	389083: Binding affinity to human SKMLCK	kd	0.1500	uM
[(1R,3R,5S,9R,18S)-18-(methoxymethyl)-1,5-dimethyl-6,11,16-trioxo-13,17-dioxapentacyclo[10.6.1.02,10.05,9.015,19]nonadeca-2(10),12(19),14-trien-3-yl] acetate	550538: Inhibition of MLCK by HTRF assay	ic50	0.1700	uM
Gilteritinib	1425081: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1880	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148810: Binding affinity to human MYLK incubated for 45 mins by Kinobead based pull down assay	kd	0.2057	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624709: Binding constant for MYLK kinase domain	kd	0.2200	uM
Midostaurin	507637: Binding affinity to MYLK	kd	0.2200	uM
16-[3-(dimethylamino)prop-1-ynyl]-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-4-amine	1856583: Inhibition of MYLK in HEK293 cells by NanoBRET assay	ic50	0.2650	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624709: Binding constant for MYLK kinase domain	kd	0.2900	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	435664: Binding constant for MYLK kinase domain	kd	0.2900	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526265: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MYLK (unknown origin) (1428 to 1771 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.2980	uM
1-(5-iodonaphthalen-1-yl)sulfonyl-1,4-diazepane	550538: Inhibition of MLCK by HTRF assay	ki	0.3000	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624709: Binding constant for MYLK kinase domain	kd	0.3300	uM
10,14-dimethyl-9-oxo-3-(trifluoromethyl)-4,5,10,13,14,19,21-heptazapentacyclo[15.5.2.12,5.012,16.020,23]pentacosa-1(22),2(25),3,12,15,17(24),18,20(23)-octaene-15-carbonitrile	1823460: Inhibition of MYLK (unknown origin) at 1 uM by kinome scan method	ic50	0.3340	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435664: Binding constant for MYLK kinase domain	kd	0.3600	uM
Ruxolitinib	624709: Binding constant for MYLK kinase domain	kd	0.3600	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526265: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MYLK (unknown origin) (1428 to 1771 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.3690	uM
Quizartinib	507625: Binding affinity to MLCK	kd	0.4100	uM
Bosutinib	624709: Binding constant for MYLK kinase domain	kd	0.4900	uM
Fedratinib	624709: Binding constant for MYLK kinase domain	kd	0.5200	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624709: Binding constant for MYLK kinase domain	kd	0.5900	uM
3,7-dihydroxy-9-methoxy-4a-methylbenzo[c]chromene-2,6-dione	452814: Inhibition of MLCK	ic50	0.6900	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624709: Binding constant for MYLK kinase domain	kd	0.7400	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624709: Binding constant for MYLK kinase domain	kd	0.8700	uM
N-[6-benzyl-2-(2-phenylethylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]naphthalene-2-sulfonamide	526407: Inhibition of MLCK	ic50	0.9000	uM
4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-N-[4-methyl-3-[(4-pyrimidin-5-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide	1425081: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.2090	uM
3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenol	435664: Binding constant for MYLK kinase domain	kd	1.5000	uM
3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one	378678: Inhibition of MLCK	ki	1.7000	uM
Nifedipine	1248192: Inhibition of MLCK (unknown origin) incubated for 15 mins using [gamma-32P]-ATP by scintillation counting method	ic50	2.0200	uM
1-[2-methyl-4-(3-nitrophenyl)-4H-pyrimido[2,1-b][1,3]benzothiazol-3-yl]ethanone	1248192: Inhibition of MLCK (unknown origin) incubated for 15 mins using [gamma-32P]-ATP by scintillation counting method	ic50	2.0400	uM
1-[2-methyl-4-(4-nitrophenyl)-4H-pyrimido[2,1-b][1,3]benzothiazol-3-yl]ethanone	1248192: Inhibition of MLCK (unknown origin) incubated for 15 mins using [gamma-32P]-ATP by scintillation counting method	ic50	2.0400	uM
1-[2-methyl-4-(3-nitrophenyl)-4H-pyrimido[2,1-b][1,3]benzothiazol-3-yl]propan-1-one	1248192: Inhibition of MLCK (unknown origin) incubated for 15 mins using [gamma-32P]-ATP by scintillation counting method	ic50	2.1000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435664: Binding constant for MYLK kinase domain	kd	2.1000	uM
1-[4-(4-methoxyphenyl)-2-methyl-4H-pyrimido[2,1-b][1,3]benzothiazol-3-yl]ethanone	1248192: Inhibition of MLCK (unknown origin) incubated for 15 mins using [gamma-32P]-ATP by scintillation counting method	ic50	2.1400	uM
1-[4-(4-methoxyphenyl)-2-methyl-4H-pyrimido[2,1-b][1,3]benzothiazol-3-yl]propan-1-one	1248192: Inhibition of MLCK (unknown origin) incubated for 15 mins using [gamma-32P]-ATP by scintillation counting method	ic50	2.1700	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	1425081: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.1800	uM
4-[[9-[(3S)-oxolan-3-yl]-8-(2,4,6-trifluoroanilino)purin-2-yl]amino]cyclohexan-1-ol	1425081: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.6250	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression	9
ML 7	affects reaction, decreases activity, increases activity, decreases reaction, decreases phosphorylation	7
Aflatoxin B1	decreases expression, increases methylation, affects expression	6
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	5
trichostatin A	affects cotreatment, decreases expression, increases expression	4
Estradiol	affects cotreatment, decreases expression, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases activity, decreases expression, decreases reaction, increases expression	3
Acetaminophen	decreases expression	3
Cyclosporine	decreases expression, affects expression	3
Particulate Matter	decreases expression, decreases reaction, increases abundance	3
mercuric bromide	affects cotreatment, decreases expression	2
ML 9	affects reaction, decreases activity, increases activity	2
entinostat	decreases expression, affects cotreatment	2
monomethylarsonous acid	decreases expression	2
Arsenic Trioxide	decreases reaction, increases expression, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Ethanol	increases activity, increases expression, decreases reaction	2
Vehicle Emissions	decreases reaction, decreases methylation, decreases expression	2
Calcium	increases activity, decreases reaction	2
Cisplatin	affects cotreatment, increases expression, decreases response to substance	2
Copper	affects binding, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, decreases expression	2
tert-Butylhydroperoxide	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1

ChEMBL screening assays

303 unique, capped per target: 303 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000633	Binding	Inhibition of smooth muscle MLCK at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7VF	Ubigene A-549 MYLK KO	Cancer cell line	Male
CVCL_D8QY	Ubigene HCT 116 MYLK KO	Cancer cell line	Male
CVCL_D9KV	Ubigene HEK293 MYLK KO	Transformed cell line	Female
CVCL_E0IM	Ubigene HeLa MYLK KO	Cancer cell line	Female
CVCL_SZ60	HAP1 MYLK (-) 1	Cancer cell line	Male
CVCL_SZ61	HAP1 MYLK (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy