MYLK2

Summary

MYLK2 (myosin light chain kinase 2, HGNC:16243) is a protein-coding gene on chromosome 20q11.21, encoding Myosin light chain kinase 2, skeletal/cardiac muscle (Q9H1R3). Implicated in the level of global muscle contraction and cardiac function.

This gene encodes a myosin light chain kinase, a calcium/calmodulin dependent enzyme, that is exclusively expressed in adult skeletal muscle.

Source: NCBI Gene 85366 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypertrophic cardiomyopathy 1 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 779 total — 1 likely-pathogenic
• Phenotypes (HPO): 6
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_033118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16243
Approved symbol	MYLK2
Name	myosin light chain kinase 2
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	skMLCK, KMLC, MLCK2
Ensembl gene	ENSG00000101306
Ensembl biotype	protein_coding
OMIM	606566
Entrez	85366

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375985, ENST00000375994, ENST00000468730, ENST00000965978, ENST00000965979, ENST00000965980

RefSeq mRNA: 1 — MANE Select: NM_033118 NM_033118

CCDS: CCDS13191

Canonical transcript exons

ENST00000375985 — 13 exons

Exon	Start	End
ENSE00000661108	31823477	31823582
ENSE00000661109	31824259	31824352
ENSE00000661110	31826605	31826714
ENSE00000661111	31826797	31826938
ENSE00000859869	31820126	31820546
ENSE00000859870	31821439	31821737
ENSE00001420701	31819356	31819428
ENSE00001469052	31819533	31819632
ENSE00003499428	31831703	31831855
ENSE00003543129	31832004	31832136
ENSE00003555240	31831013	31831141
ENSE00003582775	31830819	31830889
ENSE00003897776	31833717	31834684

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 99.16.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.1208 / max 1042.1144, expressed in 54 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183989	1.8260	50
183987	0.1968	17
183990	0.0504	11
183988	0.0476	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.16	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.06	gold quality
gastrocnemius	UBERON:0001388	97.73	gold quality
skeletal muscle tissue	UBERON:0001134	96.38	gold quality
vastus lateralis	UBERON:0001379	96.30	gold quality
biceps brachii	UBERON:0001507	96.27	gold quality
quadriceps femoris	UBERON:0001377	96.18	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.68	gold quality
muscle of leg	UBERON:0001383	95.62	gold quality
tibialis anterior	UBERON:0001385	95.17	silver quality
deltoid	UBERON:0001476	93.52	gold quality
muscle tissue	UBERON:0002385	90.58	gold quality
myocardium	UBERON:0002349	83.46	gold quality
left ventricle myocardium	UBERON:0006566	81.47	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.24	gold quality
nasal cavity epithelium	UBERON:0005384	77.17	gold quality
tendon of biceps brachii	UBERON:0008188	75.67	gold quality
body of pancreas	UBERON:0001150	75.44	gold quality
buccal mucosa cell	CL:0002336	75.37	gold quality
gingival epithelium	UBERON:0001949	75.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.12	gold quality
trabecular bone tissue	UBERON:0002483	73.10	gold quality
gingiva	UBERON:0001828	72.88	gold quality
cerebellar vermis	UBERON:0004720	71.48	gold quality
cartilage tissue	UBERON:0002418	70.03	gold quality
parotid gland	UBERON:0001831	69.92	gold quality
mucosa of sigmoid colon	UBERON:0004993	69.92	gold quality
body of tongue	UBERON:0011876	69.83	silver quality
heart right ventricle	UBERON:0002080	69.49	gold quality
pancreatic ductal cell	CL:0002079	68.91	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting MYLK2, 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-4673	100.00	66.64	1490
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-4686	98.77	66.87	964

Literature-anchored findings (GeneRIF, showing 7)

• the P2X1-ERK2-Myosin Light Chain Kinase axis contributes to collagen-induced platelet activation by enhancing platelet degranulation (PMID:14500714)
• These data suggest that the kinase domain of MYLK2 is rarely mutated in common human carcinomas and that it does not play a dominant role in cancer pathogenesis. (PMID:16448786)
• MYLK gene is a risk factor for the development of acute lung injuries. (PMID:18828194)
• Data show that that the prototypical CaM target sequence skMLCK, a fragment from skeletal muscle myosin light chain kinase, binds to CaM in a highly cooperative way, while only a lower degree of interdomain binding cooperativity emerges for CaMKK. (PMID:19667195)
• Chinese family with dual LQT1 and HCM phenotypes associated with tetrad heterozygous mutations in KCNQ1, MYH7, MYLK2, and TMEM70 mutations. (PMID:25825456)
• FLNC and MYLK2 Gene Mutations in a Chinese Family with Different Phenotypes of Cardiomyopathy. (PMID:33455984)
• A novel tumor suppressor role of myosin light chain kinase splice variants through downregulation of the TEAD4/CD44 axis. (PMID:34000008)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mylk2	ENSMUSG00000027470
rattus_norvegicus	Mylk2	ENSRNOG00000008235

Paralogs (22): CAMKK1 (ENSG00000004660), CAMK1G (ENSG00000008118), CAMK2B (ENSG00000058404), CAMK2A (ENSG00000070808), CAMKK2 (ENSG00000110931), STK11 (ENSG00000118046), STK33 (ENSG00000130413), PNCK (ENSG00000130822), DCLK1 (ENSG00000133083), CAMK1 (ENSG00000134072), MYLK3 (ENSG00000140795), CAMK2D (ENSG00000145349), MYLK4 (ENSG00000145949), PSKH2 (ENSG00000147613), CAMK2G (ENSG00000148660), PHKG2 (ENSG00000156873), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), PHKG1 (ENSG00000164776), DCLK2 (ENSG00000170390), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Myosin light chain kinase 2, skeletal/cardiac muscle — Q9H1R3 (reviewed: Q9H1R3)

All UniProt accessions (1): Q9H1R3

UniProt curated annotations — full annotation on UniProt →

Function. Implicated in the level of global muscle contraction and cardiac function. Phosphorylates a specific serine in the N-terminus of a myosin light chain.

Subunit / interactions. May interact with centrin.

Subcellular location. Cytoplasm.

Tissue specificity. Heart and skeletal muscles. Increased expression in the apical tissue compared to the interventricular septal tissue.

Disease relevance. Cardiomyopathy, familial hypertrophic (CMH) [MIM:192600] A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_149109* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR042717	MLCK2_STKc	Domain

Pfam: PF00069

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 (24 total): sequence variant 6, modified residue 5, compositionally biased region 3, binding site 2, region of interest 2, initiator methionine 1, chain 1, domain 1, sequence conflict 1, helix 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3KF9	X-RAY DIFFRACTION	2.6
2LV6	SOLUTION SCATTERING, SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1R3-F1	68.90	0.43

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): 406 (proton acceptor)

Ligand- & substrate-binding residues (2): 314; 291–299

Post-translational modifications (5): 2, 143, 149, 151, 445

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 141 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, MODULE_503, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GTGCCTT_MIR506, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, MODULE_195, GOBP_MUSCLE_CONTRACTION, ROZANOV_MMP14_TARGETS_UP, NF1_Q6_01, GOBP_HEART_MORPHOGENESIS, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION

GO Biological Process (12): striated muscle contraction (GO:0006941), signal transduction (GO:0007165), neuromuscular synaptic transmission (GO:0007274), positive regulation of gene expression (GO:0010628), skeletal muscle satellite cell differentiation (GO:0014816), peptidyl-threonine phosphorylation (GO:0018107), regulation of muscle filament sliding (GO:0032971), skeletal muscle cell differentiation (GO:0035914), protein autophosphorylation (GO:0046777), cardiac muscle tissue morphogenesis (GO:0055008), cardiac muscle contraction (GO:0060048), protein phosphorylation (GO:0006468)

GO Molecular Function (11): calcium/calmodulin-dependent protein kinase activity (GO:0004683), myosin light chain kinase activity (GO:0004687), calmodulin binding (GO:0005516), ATP binding (GO:0005524), myosin light chain binding (GO:0032027), 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 (4): nucleus (GO:0005634), cytoplasm (GO:0005737), sarcomere (GO:0030017), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein phosphorylation	2
protein serine/threonine kinase activity	2
cellular anatomical structure	2
muscle contraction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
chemical synaptic transmission	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
skeletal muscle cell differentiation	1
peptidyl-threonine modification	1
regulation of muscle contraction	1
muscle filament sliding	1
regulation of intracellular transport	1
regulation of actin filament-based movement	1
skeletal muscle tissue development	1
cell differentiation	1
heart morphogenesis	1
cardiac muscle tissue development	1
muscle tissue morphogenesis	1
striated muscle contraction	1
heart contraction	1
phosphorylation	1
protein modification process	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
myosin 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

Protein interactions and networks

STRING

1857 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYLK2	CALM1	P02593	994
MYLK2	CALML3	P27482	994
MYLK2	CALML5	Q9NZT1	994
MYLK2	CALML6	Q8TD86	993
MYLK2	CALML4	Q96GE6	993
MYLK2	MYL12A	P19105	910
MYLK2	MYL9	P24844	873
MYLK2	MYL3	P08590	794
MYLK2	MYL2	P10916	748
MYLK2	CSRP3	P50461	705
MYLK2	PTPRK	Q15262	690
MYLK2	PRKAG2	Q9UGJ0	681
MYLK2	MYBPC3	Q14896	672
MYLK2	GUCY2F	P51841	664
MYLK2	MYH7	P12883	653

IntAct

60 interactions, top by confidence:

A	B	Type	Score
ESR1	ESR1	psi-mi:“MI:0914”(association)	0.870
HSP90AA1	HSP90AB1	psi-mi:“MI:0914”(association)	0.840
TRIM49	CKS1B	psi-mi:“MI:0914”(association)	0.740
YWHAZ	HSPB1	psi-mi:“MI:0914”(association)	0.680
HSP90AA1	CHUK	psi-mi:“MI:0914”(association)	0.670
ESR1	TRIM24	psi-mi:“MI:0914”(association)	0.640
MTRFR	MYLK2	psi-mi:“MI:0915”(physical association)	0.590
SMDT1	MYLK2	psi-mi:“MI:0915”(physical association)	0.590
MYLK2	WFS1	psi-mi:“MI:0915”(physical association)	0.560
MYLK2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
MEF2C	MYLK2	psi-mi:“MI:0915”(physical association)	0.540
MYLK2	MEF2C	psi-mi:“MI:0217”(phosphorylation reaction)	0.540
GSTT1	MID1	psi-mi:“MI:0914”(association)	0.530
HSP90AA1	USP19	psi-mi:“MI:0914”(association)	0.530
MYLK2	RPS6KA4	psi-mi:“MI:0914”(association)	0.530
TRIM54	MYLK2	psi-mi:“MI:0915”(physical association)	0.510
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
	MYLK2	psi-mi:“MI:0407”(direct interaction)	0.440
TRIM63	MYLK2	psi-mi:“MI:0915”(physical association)	0.400
TRIM55	MYLK2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (123): FBXO11 (Affinity Capture-MS), RPS6KA4 (Affinity Capture-MS), MYLK2 (Affinity Capture-MS), MYLK2 (Affinity Capture-MS), MYLK2 (Affinity Capture-MS), RPS6KA4 (Affinity Capture-MS), MYLK2 (Affinity Capture-MS), MYLK2 (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), MYLK2 (Affinity Capture-MS), MYLK2 (Affinity Capture-MS), MYLK2 (FRET), MYLK2 (Affinity Capture-RNA), MYLK2 (Affinity Capture-MS), SLC25A5 (Affinity Capture-MS)

ESM2 similar proteins: A4IFM7, A8C984, B6D5P1, B6D5P6, E9PT87, O08815, O54988, O55092, O70551, O88831, P00519, P00520, P00521, P07313, P0C865, P13234, P20689, P42684, P46087, Q13164, Q14028, Q16566, Q2KI23, Q32MK0, Q3SYS4, Q3UH66, Q3UIZ8, Q3ULB5, Q4JIM5, Q4KMM3, Q4V8B0, Q5R8Z4, Q5RDG7, Q5TGJ6, Q63553, Q6AYH9, Q6PDI6, Q80XI3, Q8BHL3, Q8BWQ5

Diamond homologs: A0A509AFG4, A0A5K1K8H0, A2AAJ9, A2ZVI7, A4IFM7, A8C984, A8WXF6, B9FKW9, C0HKC8, C0HKC9, E9PT87, O02827, O43293, O44997, O54784, O62305, O70150, O75147, O80673, O88764, O94768, P07313, P08414, P11801, P13234, P15735, P18653, P20689, P29294, P31325, P34101, P43292, P53355, P53681, Q00168, Q00771, Q0KHT7, Q0V7M1, Q10KY3, Q14012

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MYLK2	“up-regulates activity”	MEF2C	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
HSF1 activation	5	46.4×	3e-05
The role of GTSE1 in G2/M progression after G2 checkpoint	6	23.5×	4e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	18.8×	5e-04
G2/M Checkpoints	5	16.4×	5e-04
RHO GTPase Effectors	6	9.9×	7e-04
Viral Infection Pathways	7	5.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	403
Likely benign	287
Benign	26

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1526688	GRCh37/hg19 20p11.21-q11.21(chr20:24162775-31820857)	Likely pathogenic

SpliceAI

2228 predictions. Top by Δscore:

Variant	Effect	Δscore
20:31821553:A:T	donor_gain	1.0000
20:31821581:G:GT	donor_gain	1.0000
20:31821581:G:T	donor_gain	1.0000
20:31821582:A:T	donor_gain	1.0000
20:31821617:GC:G	donor_gain	1.0000
20:31821618:C:G	donor_gain	1.0000
20:31821644:GGGAT:G	donor_gain	1.0000
20:31821645:GGAT:G	donor_gain	1.0000
20:31821646:GAT:G	donor_gain	1.0000
20:31824255:CCA:C	acceptor_loss	1.0000
20:31824256:CAGT:C	acceptor_loss	1.0000
20:31824257:A:AG	acceptor_gain	1.0000
20:31824257:AGT:A	acceptor_gain	1.0000
20:31824258:G:C	acceptor_loss	1.0000
20:31824258:G:GG	acceptor_gain	1.0000
20:31824258:GT:G	acceptor_gain	1.0000
20:31824258:GTG:G	acceptor_gain	1.0000
20:31824258:GTGGC:G	acceptor_gain	1.0000
20:31826595:T:A	acceptor_gain	1.0000
20:31826712:GTA:G	donor_gain	1.0000
20:31826715:G:GG	donor_gain	1.0000
20:31830887:G:GT	donor_gain	1.0000
20:31831008:CCCA:C	acceptor_loss	1.0000
20:31831011:AGG:A	acceptor_loss	1.0000
20:31831099:A:G	donor_gain	1.0000
20:31831114:G:GT	donor_gain	1.0000
20:31831117:G:GG	donor_gain	1.0000
20:31831139:GCT:G	donor_gain	1.0000
20:31831698:TCTAG:T	acceptor_loss	1.0000
20:31831700:TA:T	acceptor_loss	1.0000

AlphaMissense

3938 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:31824266:T:C	F296L	1.000
20:31824268:T:A	F296L	1.000
20:31824268:T:G	F296L	1.000
20:31824270:G:A	G297E	1.000
20:31824318:C:A	A313D	1.000
20:31824320:A:C	K314Q	1.000
20:31824320:A:G	K314E	1.000
20:31824322:G:C	K314N	1.000
20:31824322:G:T	K314N	1.000
20:31826891:G:T	G393W	1.000
20:31826892:G:A	G393E	1.000
20:31826928:T:C	L405P	1.000
20:31826930:G:C	D406H	1.000
20:31826931:A:C	D406A	1.000
20:31826931:A:G	D406G	1.000
20:31826931:A:T	D406V	1.000
20:31826932:C:A	D406E	1.000
20:31826932:C:G	D406E	1.000
20:31826934:T:C	L407P	1.000
20:31826936:A:G	K408E	1.000
20:31826938:G:C	K408N	1.000
20:31826938:G:T	K408N	1.000
20:31830820:C:A	P409Q	1.000
20:31830825:A:C	N411H	1.000
20:31830825:A:G	N411D	1.000
20:31830825:A:T	N411Y	1.000
20:31830826:A:C	N411T	1.000
20:31830826:A:G	N411S	1.000
20:31830826:A:T	N411I	1.000
20:31830827:C:A	N411K	1.000

dbSNP variants (sampled 300 via entrez): RS1000396287 (20:31820805 C>T), RS1000780970 (20:31818139 T>A,C), RS1000785542 (20:31819249 C>A,T), RS1000791171 (20:31825927 A>C), RS1000843471 (20:31825617 G>A), RS1001140463 (20:31819459 G>A), RS1001400082 (20:31822620 G>A), RS1001452588 (20:31822379 G>A), RS1001555277 (20:31825149 G>A), RS1001650127 (20:31825409 C>A,T), RS1001843474 (20:31827114 G>A), RS1001887107 (20:31826520 G>A,T), RS1001906404 (20:31828430 G>A,C), RS1001982237 (20:31826758 C>T), RS1002178262 (20:31831583 TG>T)

Disease associations

OMIM: gene MIM:606566 | disease phenotypes: MIM:192600, MIM:301500, MIM:615248

GenCC curated gene-disease

Disease	Classification	Inheritance
hypertrophic cardiomyopathy 1	Limited	Autosomal dominant
hypertrophic cardiomyopathy	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Disputed	AD

Mondo (8): hypertrophic cardiomyopathy 1 (MONDO:0008647), cardiomyopathy (MONDO:0004994), Fabry disease (MONDO:0010526), hypertrophic cardiomyopathy (MONDO:0005045), familial hypertrophic cardiomyopathy (MONDO:0024573), long QT syndrome (MONDO:0002442), ventricular tachycardia (MONDO:0005477), dilated cardiomyopathy 1KK (MONDO:0014100)

Orphanet (7): Rare cardiomyopathy (Orphanet:167848), Fabry disease (Orphanet:324), Rare hypertrophic cardiomyopathy (Orphanet:217569), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Familial isolated dilated cardiomyopathy (Orphanet:154), Familial isolated restrictive cardiomyopathy (Orphanet:75249), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

6 total (7 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001635	Congestive heart failure
HP:0001670	Asymmetric septal hypertrophy
HP:0001682	Subvalvular aortic stenosis
HP:0001699	Sudden death
HP:0011675	Arrhythmia
HP:0001639	Hypertrophic cardiomyopathy

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003030_10	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	3.000000e-06
GCST003030_9	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	4.000000e-06
GCST004602_229	Mean corpuscular volume	1.000000e-18
GCST004603_282	Platelet count	6.000000e-17
GCST004607_33	Plateletcrit	5.000000e-22
GCST010703_295	Brain morphology (MOSTest)	1.000000e-14
GCST010991_47	Parkinson’s disease	6.000000e-07
GCST90002400_295	Plateletcrit	7.000000e-51
GCST90002402_587	Platelet count	1.000000e-39

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007679	oppositional defiant disorder measurement
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D000795	Fabry Disease	C10.228.140.163.100.435.825.200; C10.228.140.300.275.374; C14.907.253.329.374; C16.320.322.124; C16.320.565.189.435.825.200; C16.320.565.398.641.803.300; C16.320.565.595.554.825.200; C18.452.132.100.435.825.200; C18.452.584.563.641.803.300; C18.452.648.189.435.825.200; C18.452.648.398.641.803.300; C18.452.648.595.554.825.200
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2777 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 460,034 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL939	GEFITINIB	4	117,814
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908397	KW-2449	1	622
CHEMBL296468	BMS-387032	1	2,075
CHEMBL574738	AST-487	1	451

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
GSK2606414	Inhibition	6.15	pIC50

Binding affinities (BindingDB)

134 measured of 134 human assays (134 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
ERLOTINIB HYDROCHLORIDE	KD	1200 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
3a-hydroxy-6-methyl-1-phenyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	1500 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(9S)-9-hydroxy-12-(4-methoxyphenyl)-5,6-dimethyl-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one	KI	1600 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
BMS-387072	KD	1800 nM
GEFITINIB	IC50	2300 nM	US-9416123: Kinase modulators for the treatment of cancer
(3aS)-1-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	2400 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
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
(3aS)-3a-hydroxy-6,7-dimethyl-1-(4-methylphenyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	2800 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(9S)-12-(4-chlorophenyl)-9-hydroxy-5,6-dimethyl-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one	KI	2800 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 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
(3aS)-3a-hydroxy-6,7-dimethyl-1-(2-methyl-1,3-thiazol-5-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	3500 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-(4-methoxyphenyl)-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	4200 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-(6-methoxy-3-pyridinyl)-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	4400 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-[2-(hydroxymethyl)-1-benzofuran-5-yl]-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	4600 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-fluoro-3a-hydroxy-7-methyl-1-(4-methylphenyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	5000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6,7-dimethyl-1-(1-methylpyrazol-4-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	5200 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6,7-dimethyl-1-thiophen-2-yl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	5300 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-chloro-3a-hydroxy-1-(4-methylphenyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	5500 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6,7-dimethyl-1-(2-methyl-1,3-benzoxazol-5-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	5500 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
4-[(3aS)-3a-hydroxy-6,7-dimethyl-4-oxo-2,3-dihydropyrrolo[2,3-b]quinolin-1-yl]benzonitrile	KI	5700 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6,7-dimethyl-1-(1,2,3,4-tetrahydroquinolin-7-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	5800 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(4-chlorophenyl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	6000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-fluoro-3a-hydroxy-1-(2-methyl-1,3-thiazol-5-yl)-7-(trifluoromethyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	6200 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-chloro-1-(4-chlorophenyl)-3a-hydroxy-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	8000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	8400 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(9S)-5-ethyl-9-hydroxy-12-(4-methylphenyl)-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one	KI	8900 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-chloro-3a-hydroxy-7-methyl-1-phenyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	9000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(9S)-9-hydroxy-12-(4-iodophenyl)-5,6-dimethyl-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one	KI	9000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(1-benzofuran-6-yl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	9100 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-6-methyl-1-pyrazolo[1,5-a]pyridin-5-yl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	9500 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(3,4-dihydro-2H-1,4-benzothiazin-6-yl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	9700 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-fluoro-3a-hydroxy-7-methyl-1-(2-methyl-1,3-benzoxazol-5-yl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	10500 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-(4-methoxyphenyl)-6-(trifluoromethyl)-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	11000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(9S)-5-ethyl-9-hydroxy-12-(4-methoxyphenyl)-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one	KI	11000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-3a-hydroxy-1-(4-iodophenyl)-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	11000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(2-ethyl-1,3-benzothiazol-5-yl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	11000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
4-[(3aS)-6-fluoro-3a-hydroxy-7-methyl-4-oxo-2,3-dihydropyrrolo[2,3-b]quinolin-1-yl]benzonitrile	KI	12000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	12000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-fluoro-3a-hydroxy-7-methyl-1-phenyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	13000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(9S)-12-(1-benzofuran-6-yl)-9-hydroxy-5-methyl-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one	KI	14000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-fluoro-3a-hydroxy-7-methyl-1-thiophen-2-yl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	14000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(2,1,3-benzothiadiazol-5-yl)-3a-hydroxy-6-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	14000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-6-fluoro-3a-hydroxy-1-(4-methoxyphenyl)-7-methyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	15000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS
(3aS)-1-(2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-3a-hydroxy-6,7-dimethyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-one	KI	15000 nM	US-20250163056: NONMUSCLE MYOSIN II INHIBITORS

ChEMBL bioactivities

58 potent at pChembl≥5 of 59 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.86	IC50	13.9	nM	STAUROSPORINE
7.81	IC50	15.5	nM	STAUROSPORINE
7.72	IC50	19	nM	STAUROSPORINE
7.37	Kd	43	nM	TOZASERTIB
7.31	Kd	49	nM	SUNITINIB
7.28	Kd	52	nM	KW-2449
7.25	Kd	56	nM	LESTAURTINIB
7.24	Kd	57	nM	SUNITINIB
7.21	Kd	61	nM	STAUROSPORINE
7.04	Kd	92	nM	DOVITINIB
6.96	Kd	110	nM	STAUROSPORINE
6.80	IC50	157	nM	CHEMBL3774448
6.72	Kd	190	nM	SU-014813
6.72	Kd	190	nM	CHEMBL386051
6.48	Kd	330	nM	AST-487
6.46	IC50	350	nM	CHEMBL4092824
6.35	IC50	450	nM	CHEMBL5199698
6.32	IC50	479	nM	CHEMBL5091582
6.22	IC50	600	nM	CHEMBL5195653
6.19	IC50	650	nM	CHEMBL5205578
6.15	IC50	701	nM	CHEMBL2171124
6.02	Kd	960	nM	CHEMBL4452939
6.02	Kd	960	nM	PHA-665752
6.01	Kd	980	nM	BMS-387032
6.01	Kd	970	nM	ERLOTINIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.95	IC50	1119	nM	CHEMBL5086901
5.89	Kd	1300	nM	SORAFENIB
5.89	Kd	1300	nM	AXITINIB
5.75	Kd	1800	nM	PELITINIB
5.75	IC50	1800	nM	CHEMBL5170576
5.72	Kd	1900	nM	GEFITINIB
5.70	Kd	2000	nM	PAZOPANIB
5.64	Kd	2300	nM	FORETINIB
5.55	Kd	2800	nM	LINIFANIB
5.52	Kd	3000	nM	FEDRATINIB
5.46	Kd	3500	nM	DASATINIB
5.43	IC50	3670	nM	CHEMBL5091582
5.41	Kd	3900	nM	PELITINIB
5.40	Kd	4000	nM	NINTEDANIB
5.31	IC50	4860	nM	CHEMBL2312654
5.27	Kd	5400	nM	SORAFENIB
5.08	IC50	8270	nM	CHEMBL2312649

PubChem BioAssay actives

55 with measured affinity, of 344 total; 34 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
(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	1531776: Inhibition of human MLCK2 using KKLNRTLSFAEPG as substrate by [gamma-33P]-ATP assay	ic50	0.0139	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435415: Binding constant for MYLK2 kinase domain	kd	0.0430	uM
Sunitinib	435415: Binding constant for MYLK2 kinase domain	kd	0.0490	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624705: Binding constant for MYLK2 kinase domain	kd	0.0520	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	507638: Binding affinity to MYLK2	kd	0.0560	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435415: Binding constant for MYLK2 kinase domain	kd	0.0920	uM
(5Z)-5-(quinolin-6-ylmethylidene)-2-sulfanylidene-1,3-thiazolidin-4-one	1284922: Inhibition of full length recombinant human N-terminal GST-tagged MLCK expressed in baculovirus expression system by lantha screen kinase binding assay	ic50	0.1570	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	435415: Binding constant for MYLK2 kinase domain	kd	0.1900	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624705: Binding constant for MYLK2 kinase domain	kd	0.1900	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435415: Binding constant for MYLK2 kinase domain	kd	0.3300	uM
(2S)-1-[[4-(difluoromethyl)-6-(2-methyl-4-pyridinyl)-3-pyridinyl]oxy]-2,4-dimethylpentan-2-amine	1904670: Inhibition of MYLK2 (unknown origin)	ic50	0.3500	uM
(2S)-1-[[4-(difluoromethyl)-6-[2-(difluoromethyl)-4-pyridinyl]-3-pyridinyl]oxy]-2,4-dimethylpentan-2-amine	1904670: Inhibition of MYLK2 (unknown origin)	ic50	0.4500	uM
4-N-[2-(1H-imidazol-5-yl)ethyl]-2-N-[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrimidine-2,4-diamine	1823797: Inhibition of full length recombinant human MYLK2 using KKLNRTLSFAEPG as substrate incubated for 40 mins in presence of [gamma-33P-ATP] by radiometric scintillation assay	ic50	0.4790	uM
methyl N-[4-[5-[(2S)-2-amino-2,4-dimethylpentoxy]-4-methyl-2-pyridinyl]-2-pyridinyl]carbamate	1904670: Inhibition of MYLK2 (unknown origin)	ic50	0.6000	uM
methyl N-[4-[5-[(2S)-2-amino-2,4-dimethylpentoxy]-6-chloro-2-pyridinyl]-2-pyridinyl]carbamate	1904670: Inhibition of MYLK2 (unknown origin)	ic50	0.6500	uM
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethyl)phenyl]ethanone	702097: Inhibition of MLCK2	ic50	0.7010	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	624705: Binding constant for MYLK2 kinase domain	kd	0.9600	uM
Erlotinib	435415: Binding constant for MYLK2 kinase domain	kd	0.9700	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	435415: Binding constant for MYLK2 kinase domain	kd	0.9800	uM
Momelotinib	2183912: Inhibition of MYLK2 (unknown origin)	ic50	1.0000	uM
5-cyclopropyl-4-N-[2-(1H-imidazol-5-yl)ethyl]-2-N-[3-methyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyrimidine-2,4-diamine	1823797: Inhibition of full length recombinant human MYLK2 using KKLNRTLSFAEPG as substrate incubated for 40 mins in presence of [gamma-33P-ATP] by radiometric scintillation assay	ic50	1.1190	uM
Sorafenib	256623: Average Binding Constant for MYLK2; NA=Not Active at 10 uM	kd	1.3000	uM
Axitinib	624705: Binding constant for MYLK2 kinase domain	kd	1.3000	uM
methyl N-[4-[5-[(2S)-2-amino-2,4-dimethylpentoxy]-6-methyl-2-pyridinyl]-2-pyridinyl]carbamate	1904670: Inhibition of MYLK2 (unknown origin)	ic50	1.8000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256623: Average Binding Constant for MYLK2; NA=Not Active at 10 uM	kd	1.8000	uM
Gefitinib	435415: Binding constant for MYLK2 kinase domain	kd	1.9000	uM
Pazopanib	435415: Binding constant for MYLK2 kinase domain	kd	2.0000	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624705: Binding constant for MYLK2 kinase domain	kd	2.3000	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	624705: Binding constant for MYLK2 kinase domain	kd	2.8000	uM
Fedratinib	624705: Binding constant for MYLK2 kinase domain	kd	3.0000	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	624705: Binding constant for MYLK2 kinase domain	kd	3.5000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624705: Binding constant for MYLK2 kinase domain	kd	4.0000	uM
2-N-(3,5-dichlorophenyl)-4-N-[4-(dimethylamino)cyclohexyl]-5-(3-methyl-1,2-oxazol-5-yl)pyrimidine-2,4-diamine	720967: Inhibition of MYLK2 (unknown origin) in presence of ATP	ic50	4.8600	uM
2-(3,5-dichloroanilino)-4-[[4-(dimethylamino)cyclohexyl]amino]-N-(1-methylpiperidin-4-yl)pyrimidine-5-carboxamide	720967: Inhibition of MYLK2 (unknown origin) in presence of ATP	ic50	8.2700	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
ML 9	decreases activity	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Amiodarone	increases expression	1
Atrazine	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

196 unique, capped per target: 196 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1041154	Binding	Residual activity of MYLK2 at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8QZ	Ubigene HCT 116 MYLK2 KO	Cancer cell line	Male
CVCL_E0IN	Ubigene HeLa MYLK2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy