MYLK4

Summary

MYLK4 (myosin light chain kinase family member 4, HGNC:27972) is a protein-coding gene on chromosome 6p25.2, encoding Myosin light chain kinase family member 4 (Q86YV6).

Predicted to enable myosin light chain kinase activity. Predicted to be involved in signal transduction. Predicted to be located in membrane. Predicted to be active in cytoplasm.

Source: NCBI Gene 340156 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 132 total
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001012418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27972
Approved symbol	MYLK4
Name	myosin light chain kinase family member 4
Location	6p25.2
Locus type	gene with protein product
Status	Approved
Aliases	SgK085
Ensembl gene	ENSG00000145949
Ensembl biotype	protein_coding
Entrez	340156

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000274643, ENST00000647417, ENST00000698899, ENST00000698900, ENST00000866488, ENST00000866489, ENST00000941557, ENST00000941558, ENST00000941559, ENST00000941560

RefSeq mRNA: 2 — MANE Select: NM_001012418 NM_001012418, NM_001347872

CCDS: CCDS34330, CCDS93849

Canonical transcript exons

ENST00000274643 — 13 exons

Exon	Start	End
ENSE00000973234	2678220	2678372
ENSE00001134408	2675047	2675125
ENSE00001161249	2679280	2679408
ENSE00001339373	2671276	2671348
ENSE00001486271	2680221	2680291
ENSE00001486275	2683021	2683162
ENSE00001486276	2685296	2685405
ENSE00001486278	2685483	2685576
ENSE00001486279	2688851	2688956
ENSE00001486281	2692784	2692859
ENSE00001486283	2749136	2749406
ENSE00001855144	2750736	2750922
ENSE00003891285	2663637	2667899

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 92.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5035 / max 143.0859, expressed in 53 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71369	0.1453	14
71365	0.1064	15
71371	0.1031	34
71367	0.0871	11
71366	0.0616	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	92.96	gold quality
deltoid	UBERON:0001476	91.47	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.58	gold quality
buccal mucosa cell	CL:0002336	83.73	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.70	gold quality
skeletal muscle tissue	UBERON:0001134	82.37	gold quality
body of tongue	UBERON:0011876	81.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.44	gold quality
muscle tissue	UBERON:0002385	79.14	gold quality
quadriceps femoris	UBERON:0001377	78.14	gold quality
muscle of leg	UBERON:0001383	77.86	gold quality
vastus lateralis	UBERON:0001379	77.83	gold quality
gastrocnemius	UBERON:0001388	77.06	gold quality
tongue	UBERON:0001723	73.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.12	gold quality
palpebral conjunctiva	UBERON:0001812	68.64	gold quality
tibia	UBERON:0000979	63.31	silver quality
minor salivary gland	UBERON:0001830	63.14	gold quality
right atrium auricular region	UBERON:0006631	63.11	gold quality
cardiac atrium	UBERON:0002081	62.78	gold quality
skin of hip	UBERON:0001554	62.59	silver quality
lower lobe of lung	UBERON:0008949	62.57	silver quality
right coronary artery	UBERON:0001625	62.42	gold quality
skin of leg	UBERON:0001511	61.46	gold quality
monocyte	CL:0000576	61.20	gold quality
tibial artery	UBERON:0007610	61.20	gold quality
popliteal artery	UBERON:0002250	61.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	61.12	gold quality
leukocyte	CL:0000738	60.86	gold quality
mouth mucosa	UBERON:0003729	60.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

182 targeting MYLK4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 2)

• First identification, named SgK085 and classified as one of four myosin light chain kinases in a comprehensive analysis of protein kinases encoded by the human genome. (PMID:12471243)
• MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma. (PMID:33980265)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mylk4b	ENSDARG00000055412
danio_rerio	mylk4a	ENSDARG00000091260
mus_musculus	Mylk4	ENSMUSG00000044951
rattus_norvegicus	Mylk4	ENSRNOG00000070083

Paralogs (22): CAMKK1 (ENSG00000004660), CAMK1G (ENSG00000008118), CAMK2B (ENSG00000058404), CAMK2A (ENSG00000070808), MYLK2 (ENSG00000101306), CAMKK2 (ENSG00000110931), STK11 (ENSG00000118046), STK33 (ENSG00000130413), PNCK (ENSG00000130822), DCLK1 (ENSG00000133083), CAMK1 (ENSG00000134072), MYLK3 (ENSG00000140795), CAMK2D (ENSG00000145349), 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 family member 4 — Q86YV6 (reviewed: Q86YV6)

Alternative names: Sugen kinase 85

All UniProt accessions (3): A0A2R8Y4U5, A0A8V8TMV3, Q86YV6

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. Sequence incomplete.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q86YV6-1	1	yes
Q86YV6-2	2

RefSeq proteins (2): NP_001012418, NP_001334801 (=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

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (39 total): helix 15, sequence variant 8, strand 8, turn 2, binding site 2, chain 1, domain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2X4F	X-RAY DIFFRACTION	2.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YV6-F1	79.96	0.66

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): 227 (proton acceptor)

Ligand- & substrate-binding residues (2): 112–120; 135

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, chr6p25, ATGTTTC_MIR494, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GTATTAT_MIR3693P, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, CTTTGCA_MIR527, MIR616_5P, MIR371B_5P, MIR373_5P, MIR6867_5P

GO Biological Process (2): signal transduction (GO:0007165), protein phosphorylation (GO:0006468)

GO Molecular Function (9): myosin light chain kinase activity (GO:0004687), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), 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 (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phosphorylation	1
protein modification process	1
protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1527 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYLK4	STAMBPL1	Q96FJ0	416
MYLK4	MYH7B	A7E2Y1	385
MYLK4	CIART	Q8N365	385
MYLK4	CSNK2A2	P19784	350
MYLK4	MYL6B	P14649	350
MYLK4	MYBPC2	Q14324	348
MYLK4	TNNT1	P13805	337
MYLK4	TNNI1	P19237	337
MYLK4	COQ10B	Q9H8M1	333
MYLK4	CTNNAL1	Q9UBT7	330
MYLK4	CFAP61	Q8NHU2	319
MYLK4	MYL12A	P19105	318
MYLK4	SPCS3	P12280	311
MYLK4	MRPS18B	Q9Y676	292
MYLK4	MYL3	P08590	287

IntAct

9 interactions, top by confidence:

A	B	Type	Score
HSP90AB1	MYLK4	psi-mi:“MI:0915”(physical association)	0.740
MYLK4	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
MYLK4	OGDH	psi-mi:“MI:0915”(physical association)	0.400
CDC37	MYLK4	psi-mi:“MI:0915”(physical association)	0.400
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
MYLK4	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
MYLK4	AP3D1	psi-mi:“MI:0914”(association)	0.350
MYLK4	ZMPSTE24	psi-mi:“MI:0914”(association)	0.350

BioGRID (110): HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), HSP90AB3P (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), CDC37 (Affinity Capture-MS), SUPT20H (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), HSP90AB3P (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), MYLK4 (Proximity Label-MS), HSP90AA5P (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS)

ESM2 similar proteins: O08605, O43293, O54784, O74536, O88764, P00518, P07934, P08414, P13234, P13286, P15735, P18653, P18654, P23443, P31325, P51812, P54645, P67998, P67999, Q00168, Q13131, Q13555, Q15349, Q16566, Q16816, Q2KJ16, Q2LZZ7, Q4G050, Q58D94, Q5EG47, Q5RDH5, Q5SUV5, Q6DGS3, Q6TJY3, Q7SY49, Q7TPS0, Q86YV6, Q8BHI9, Q8BSK8, Q8C050

Diamond homologs: A0A2I0BVG8, A0A509AFG4, A0A509AHB6, A0A509ALV6, A0A509AQE6, A0A5K1K8H0, A2XFF4, A8X6H4, B8BBT7, E9PT87, F4JBP3, O15865, O22932, O61267, O70150, O80673, P05986, P08414, P13234, P18654, P22216, P22517, P25323, P27466, P28582, P34101, P40376, P51812, P53681, P53684, P62343, P62344, P62345, P92958, P93759, Q00771, Q09170, Q0D715, Q0VD22, Q10KY3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3104 predictions. Top by Δscore:

Variant	Effect	Δscore
6:2678214:CGTTA:C	donor_loss	1.0000
6:2678215:GTTA:G	donor_loss	1.0000
6:2678216:TTA:T	donor_loss	1.0000
6:2678217:TACCT:T	donor_loss	1.0000
6:2678219:C:CA	donor_loss	1.0000
6:2678219:CCT:C	donor_gain	1.0000
6:2678348:C:CT	acceptor_gain	1.0000
6:2678348:C:T	acceptor_gain	1.0000
6:2678349:A:T	acceptor_gain	1.0000
6:2678368:TAAGT:T	acceptor_gain	1.0000
6:2678369:AAGTC:A	acceptor_gain	1.0000
6:2678370:AGT:A	acceptor_gain	1.0000
6:2678370:AGTCT:A	acceptor_gain	1.0000
6:2678371:GT:G	acceptor_gain	1.0000
6:2678371:GTCT:G	acceptor_gain	1.0000
6:2678373:C:CC	acceptor_gain	1.0000
6:2678373:CTGGA:C	acceptor_loss	1.0000
6:2679272:CTACT:C	donor_loss	1.0000
6:2679274:ACT:A	donor_loss	1.0000
6:2679275:CTC:C	donor_loss	1.0000
6:2679276:TCA:T	donor_loss	1.0000
6:2679277:CAC:C	donor_loss	1.0000
6:2679278:A:AC	donor_gain	1.0000
6:2679278:ACAG:A	donor_gain	1.0000
6:2679279:C:CC	donor_gain	1.0000
6:2679279:CA:C	donor_gain	1.0000
6:2679279:CAG:C	donor_gain	1.0000
6:2679279:CAGC:C	donor_gain	1.0000
6:2679404:TGTAT:T	acceptor_gain	1.0000
6:2679406:TAT:T	acceptor_gain	1.0000

AlphaMissense

2609 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:2679308:A:G	W287R	1.000
6:2679308:A:T	W287R	1.000
6:2679360:A:C	F269L	1.000
6:2679360:A:T	F269L	1.000
6:2679362:A:G	F269L	1.000
6:2680239:T:A	D247V	1.000
6:2679298:C:T	G290E	0.999
6:2679299:C:A	G290W	0.999
6:2679299:C:G	G290R	0.999
6:2679299:C:T	G290R	0.999
6:2679313:T:G	D285A	0.999
6:2679314:C:A	D285Y	0.999
6:2679314:C:G	D285H	0.999
6:2679328:A:T	V280D	0.999
6:2679361:A:G	F269S	0.999
6:2680227:G:T	A251D	0.999
6:2680238:A:C	D247E	0.999
6:2680238:A:T	D247E	0.999
6:2680239:T:C	D247G	0.999
6:2680239:T:G	D247A	0.999
6:2680240:C:G	D247H	0.999
6:2680283:A:C	N232K	0.999
6:2680283:A:T	N232K	0.999
6:2683021:C:A	K229N	0.999
6:2683021:C:G	K229N	0.999
6:2683025:A:G	L228P	0.999
6:2683027:G:C	D227E	0.999
6:2683027:G:T	D227E	0.999
6:2683028:T:A	D227V	0.999
6:2683028:T:G	D227A	0.999

dbSNP variants (sampled 300 via entrez): RS1000002472 (6:2753577 A>G), RS1000005670 (6:2758011 G>A), RS1000062455 (6:2672939 A>G), RS1000074406 (6:2707383 T>C), RS1000078615 (6:2678978 A>G), RS1000108335 (6:2758312 T>C), RS1000133697 (6:2671506 A>G), RS1000141572 (6:2747623 G>T), RS1000163769 (6:2741695 T>C), RS1000196822 (6:2742001 C>T), RS1000229383 (6:2700925 T>C), RS1000245246 (6:2760291 A>G), RS1000307918 (6:2745562 G>A), RS1000338828 (6:2694842 A>G), RS1000341857 (6:2700678 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002209_5	Orthostatic hypotension	9.000000e-06
GCST006485_6	Telomere length	2.000000e-06
GCST006979_489	Heel bone mineral density	1.000000e-11
GCST009514_2	Recurrence of mild malaria attacks	5.000000e-08
GCST010043_134	Asthma	2.000000e-08
GCST012207_4	Shigella-associated diarrhea	6.000000e-06
GCST90000025_514	Appendicular lean mass	4.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004952	disease recurrence
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5426 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 119,422 (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
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL521851	PICTILISIB	2	6,071
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1908397	KW-2449	1	622
CHEMBL296468	BMS-387032	1	2,075

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
compound 17 [PMID: 36111834]	Inhibition	6.58	pIC50

Binding affinities (BindingDB)

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

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 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
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
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

69 potent at pChembl≥5 of 69 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CHEMBL5574990
8.40	IC50	4	nM	CHEMBL5569176
8.22	IC50	6	nM	CHEMBL5569603
8.22	IC50	6	nM	CHEMBL5564156
7.89	IC50	13	nM	CHEMBL5565459
7.82	Kd	15	nM	SUNITINIB
7.77	IC50	17	nM	CHEMBL5575519
7.57	IC50	27	nM	CHEMBL5542886
7.54	Kd	29	nM	LESTAURTINIB
7.50	Kd	32	nM	SU-014813
7.40	IC50	40	nM	CHEMBL5579785
7.34	IC50	46	nM	CHEMBL5574107
7.32	IC50	47.7	nM	STAUROSPORINE
7.28	IC50	52.9	nM	STAUROSPORINE
7.26	IC50	54.5	nM	STAUROSPORINE
7.26	IC50	55	nM	CHEMBL5742882
7.26	IC50	55	nM	CHEMBL5852177
7.26	IC50	55	nM	CHEMBL5748469
7.18	IC50	66	nM	CHEMBL5174830
7.17	IC50	68	nM	CHEMBL5571334
7.10	Kd	80	nM	DOVITINIB
7.07	IC50	85	nM	CHEMBL5573038
6.89	Kd	130	nM	FEDRATINIB
6.77	Kd	170	nM	KW-2449
6.64	Kd	230	nM	ENZASTAURIN
6.57	IC50	270	nM	CHEMBL5174830
6.37	Kd	430	nM	CHEMBL4564337
6.36	IC50	440	nM	CHEMBL5575113
6.36	Kd	440	nM	NINTEDANIB
6.33	Kd	470	nM	STAUROSPORINE
6.26	IC50	550	nM	NETARSUDIL-M1
6.26	IC50	550	nM	CHEMBL5917940
6.26	IC50	550	nM	CHEMBL5918426
6.26	IC50	550	nM	CHEMBL5852987
6.26	IC50	550	nM	CHEMBL6062242
6.26	IC50	550	nM	CHEMBL6003919
6.26	IC50	550	nM	CHEMBL5873976
6.26	IC50	550	nM	CHEMBL5847068
6.26	IC50	550	nM	CHEMBL5881257
6.26	IC50	550	nM	CHEMBL5776811
6.26	IC50	550	nM	CHEMBL5741032
6.26	IC50	550	nM	CHEMBL5748469
6.21	Kd	620	nM	CHEMBL2425628
6.19	Kd	640	nM	MIDOSTAURIN
6.16	Kd	700	nM	CHEMBL4799297
6.16	Kd	700	nM	BMS-345541
6.11	Kd	780	nM	PICTILISIB
6.09	Kd	810	nM	R-406
6.06	Kd	870	nM	CHEMBL1908395
6.00	IC50	1000	nM	TP-030-1

PubChem BioAssay actives

45 with measured affinity, of 231 total; 33 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
N-(6-piperazin-1-yl-3-pyridinyl)-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-amine	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0020	uM
4-(2-morpholin-4-ylquinazolin-6-yl)-N-(4-piperazin-1-ylphenyl)pyrimidin-2-amine	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0040	uM
4-(2-morpholin-4-ylquinazolin-6-yl)-N-(1-piperidin-4-ylpyrazol-4-yl)pyrimidin-2-amine	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0060	uM
N-(1-piperidin-4-ylpyrazol-4-yl)-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-amine	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0060	uM
2-[(1S,4S)-5-[5-[[5-fluoro-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-yl]amino]-2-pyridinyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]ethanol	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0130	uM
Sunitinib	435691: Binding constant for SgK085 kinase domain	kd	0.0150	uM
2-[4-[4-[[5-fluoro-4-(2-morpholin-4-ylquinazolin-6-yl)pyrimidin-2-yl]amino]pyrazol-1-yl]piperidin-1-yl]ethanol	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0170	uM
N-(4-piperazin-1-ylphenyl)-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-amine	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0270	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	508083: Binding affinity to SgK085	kd	0.0290	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	435691: Binding constant for SgK085 kinase domain	kd	0.0320	uM
2-[4-[5-[[4-[2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]quinazolin-6-yl]pyrimidin-2-yl]amino]-2-pyridinyl]piperidin-1-yl]ethanol	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0400	uM
N-(4-morpholin-4-ylphenyl)-4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-amine	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0460	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	2198336: Inhibition of human MYLK4 using KKRPQRRYSNVF as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assay	ic50	0.0477	uM
4-[[4-(2-morpholin-4-ylquinazolin-6-yl)pyrimidin-2-yl]amino]-N-propan-2-ylbenzamide	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0680	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435691: Binding constant for SgK085 kinase domain	kd	0.0800	uM
N-propan-2-yl-5-[[4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-yl]amino]pyridine-2-carboxamide	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.0850	uM
Fedratinib	624809: Binding constant for MYLK4 kinase domain	kd	0.1300	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624809: Binding constant for MYLK4 kinase domain	kd	0.1700	uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione	624809: Binding constant for MYLK4 kinase domain	kd	0.2300	uM
5-(6-bromo-5-methoxy-1H-indol-3-yl)-2-(1H-pyrrol-2-yl)-1,3-oxazole	1541237: Binding affinity to wild-type human partial length MYLK4 (V79 to S380 residues) expressed in bacterial expression system by active-site directed competition binding assay based Kinomescan method	kd	0.4300	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624809: Binding constant for MYLK4 kinase domain	kd	0.4400	uM
N-propan-2-yl-4-[[4-(2-pyrrolidin-1-ylquinazolin-6-yl)pyrimidin-2-yl]amino]benzamide	2094979: Inhibition of MYLK4 (unknown origin) in presence of ATP	ic50	0.4400	uM
(4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone	769494: Binding affinity to SgK085 (unknown origin)	kd	0.6200	uM
Midostaurin	435691: Binding constant for SgK085 kinase domain	kd	0.6400	uM
N’-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine	624809: Binding constant for MYLK4 kinase domain	kd	0.7000	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	624809: Binding constant for MYLK4 kinase domain	kd	0.7800	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624809: Binding constant for MYLK4 kinase domain	kd	0.8100	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624809: Binding constant for MYLK4 kinase domain	kd	0.8700	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624809: Binding constant for MYLK4 kinase domain	kd	1.5000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435691: Binding constant for SgK085 kinase domain	kd	2.2000	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	624809: Binding constant for MYLK4 kinase domain	kd	2.4000	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	624809: Binding constant for MYLK4 kinase domain	kd	3.4000	uM
5-amino-N-[[4-(3-cyclohexylpropylcarbamoyl)phenyl]methyl]-1-phenylpyrazole-4-carboxamide	1527590: Inhibition of MYLK4 (unknown origin) expressed in human HEK293 cells incubated for 2 hrs followed by NanoBRET NanoGlo Substrate addition by NanoBRET assay	ic50	10.0000	uM

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, increases methylation	2
Benzo(a)pyrene	decreases expression, increases methylation	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
pentanal	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Methapyrilene	decreases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Asbestos, Crocidolite	decreases methylation	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	increases expression	1

ChEMBL screening assays

113 unique, capped per target: 113 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1051352	Binding	Binding constant for SgK085 kinase domain	A quantitative analysis of kinase inhibitor selectivity. — Nat Biotechnol

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea