MINK1

Summary

MINK1 (misshapen like kinase 1, HGNC:17565) is a protein-coding gene on chromosome 17p13.2, encoding Misshapen-like kinase 1 (Q8N4C8). Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking.

This gene encodes a serine/threonine kinase belonging to the germinal center kinase (GCK) family. The protein is structurally similar to the kinases that are related to NIK and may belong to a distinct subfamily of NIK-related kinases within the GCK family. Studies of the mouse homolog indicate an up-regulation of expression in the course of postnatal mouse cerebral development and activation of the cJun N-terminal kinase (JNK) and the p38 pathways.

Source: NCBI Gene 50488 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 211 total
• Druggable target: yes — 47 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_153827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17565
Approved symbol	MINK1
Name	misshapen like kinase 1
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	B55, MINK, ZC3, MAP4K6, YSK2
Ensembl gene	ENSG00000141503
Ensembl biotype	protein_coding
OMIM	609426
Entrez	50488

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 22 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay

ENST00000347992, ENST00000355280, ENST00000453408, ENST00000571207, ENST00000571526, ENST00000572304, ENST00000572330, ENST00000572629, ENST00000574453, ENST00000574871, ENST00000575511, ENST00000576037, ENST00000577021, ENST00000664602, ENST00000902221, ENST00000902222, ENST00000902223, ENST00000902224, ENST00000902225, ENST00000902226, ENST00000902227, ENST00000902228, ENST00000902229, ENST00000902230, ENST00000961648, ENST00000961649, ENST00000961650, ENST00000961651, ENST00000961652, ENST00000961653, ENST00000961654

RefSeq mRNA: 5 — MANE Select: NM_153827 NM_001024937, NM_001321236, NM_015716, NM_153827, NM_170663

CCDS: CCDS45588, CCDS45589, CCDS45590

Canonical transcript exons

ENST00000355280 — 32 exons

Exon	Start	End
ENSE00001213221	4892402	4892512
ENSE00001675208	4833340	4833640
ENSE00003461399	4885911	4885965
ENSE00003464106	4887110	4887179
ENSE00003464497	4884912	4885002
ENSE00003474326	4895075	4895242
ENSE00003476100	4895698	4895832
ENSE00003478976	4890951	4891124
ENSE00003482764	4895350	4895493
ENSE00003503660	4896674	4896813
ENSE00003514918	4886451	4886626
ENSE00003543327	4897204	4898061
ENSE00003546309	4896429	4896588
ENSE00003546929	4889647	4889763
ENSE00003547046	4887580	4887790
ENSE00003558776	4892149	4892234
ENSE00003572497	4894174	4894311
ENSE00003578136	4885483	4885613
ENSE00003587958	4891456	4891716
ENSE00003587983	4881132	4881257
ENSE00003590314	4884363	4884473
ENSE00003594060	4878317	4878382
ENSE00003604262	4893434	4893597
ENSE00003615948	4886120	4886198
ENSE00003637817	4894525	4894633
ENSE00003638950	4896193	4896342
ENSE00003652153	4880984	4881040
ENSE00003659044	4892656	4892768
ENSE00003671132	4896003	4896103
ENSE00003678300	4893988	4894093
ENSE00003684319	4892979	4893067
ENSE00003692223	4890517	4890735

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.4355 / max 639.6168, expressed in 1821 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158947	35.1894	1817
158949	0.9927	486
158946	0.5349	278
158950	0.3699	175
158948	0.2977	129
158954	0.0509	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	99.04	gold quality
lower esophagus mucosa	UBERON:0035834	98.54	gold quality
skin of leg	UBERON:0001511	98.31	gold quality
skin of abdomen	UBERON:0001416	98.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.96	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.93	gold quality
nipple	UBERON:0002030	97.92	gold quality
olfactory bulb	UBERON:0002264	97.90	gold quality
esophagus mucosa	UBERON:0002469	97.84	gold quality
inferior vagus X ganglion	UBERON:0005363	97.81	gold quality
ventral tegmental area	UBERON:0002691	97.77	gold quality
ileal mucosa	UBERON:0000331	97.63	gold quality
pharyngeal mucosa	UBERON:0000355	97.62	gold quality
zone of skin	UBERON:0000014	97.59	gold quality
cervix squamous epithelium	UBERON:0006922	97.53	gold quality
entorhinal cortex	UBERON:0002728	97.40	gold quality
right frontal lobe	UBERON:0002810	97.40	gold quality
left ovary	UBERON:0002119	97.38	gold quality
right ovary	UBERON:0002118	97.36	gold quality
cerebellar hemisphere	UBERON:0002245	97.35	gold quality
pancreatic ductal cell	CL:0002079	97.34	gold quality
medulla oblongata	UBERON:0001896	97.34	gold quality
cerebellar cortex	UBERON:0002129	97.32	gold quality
inferior olivary complex	UBERON:0002127	97.27	gold quality
upper arm skin	UBERON:0004263	97.10	gold quality
parietal lobe	UBERON:0001872	97.06	gold quality
cerebellum	UBERON:0002037	97.06	gold quality
sural nerve	UBERON:0015488	97.05	gold quality
nucleus accumbens	UBERON:0001882	96.98	gold quality
mucosa of transverse colon	UBERON:0004991	96.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

125 targeting MINK1, 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-4262	100.00	73.26	3931
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-495-3P	99.96	72.81	4197

Literature-anchored findings (GeneRIF, showing 11)

• Analysis of the coding region of the NIK gene in progressive supranuclear palsy (PSP) patients through single strand conformation polymorphism and direct sequencing does not support a pathogenic role of the NIK gene in PSP. (PMID:12668260)
• results suggest that human Misshapen/NIKs-related kinase beta (hMINK beta) plays an important role in cytoskeleton reorganization, cell adhesion, and cell motility(hMINKbeta) (PMID:15469942)
• MINK interaction with Rap2 plays a critical role in maintaining the morphological integrity of dendrites and synaptic transmission. (PMID:21048137)
• MINK1 interacts with and phosphorylates PRICKLE1 and PRICKLE2. (PMID:22037766)
• Misshapen-like kinase 1 (MINK1) is a novel component of striatin-interacting phosphatase and kinase (STRIPAK) and is required for the completion of cytokinesis. (PMID:22665485)
• MINK plays a functional role in the IRES-mediated translation of EV71 viral RNA and may provide a potential target for the development of specific antiviral strategies against EV71 infection (PMID:25747578)
• Results find MINK1 interacting with full-length and truncated APC. Its is negatively regulated by APC independently of b-catenin. MINK1 localizes to cell-cell junctions and enhances cell adhesion and proliferation. (PMID:31160382)
• LncRNA SNHG14 contributes to proinflammatory cytokine production in rheumatoid arthritis via the regulation of the miR-17-5p/MINK1-JNK pathway. (PMID:34529319)
• The serine/threonine kinase MINK1 directly regulates the function of promigratory proteins. (PMID:35971817)
• Multi-Omic Investigations of a 17-19 Translocation Links MINK1 Disruption to Autism, Epilepsy and Osteoporosis. (PMID:36012658)
• MINK1 deficiency stimulates nucleus pulposus cell pyroptosis and exacerbates intervertebral disc degeneration. (PMID:38723371)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mink1	ENSDARG00000035360
mus_musculus	Mink1	ENSMUSG00000020827
rattus_norvegicus	Mink1	ENSRNOG00000033508
drosophila_melanogaster	msn	FBGN0010909
caenorhabditis_elegans		WBGENE00003247

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Protein

Protein identifiers

Misshapen-like kinase 1 — Q8N4C8 (reviewed: Q8N4C8)

Alternative names: GCK family kinase MiNK, MAPK/ERK kinase kinase kinase 6, Misshapen/NIK-related kinase, Mitogen-activated protein kinase kinase kinase kinase 6

All UniProt accessions (6): A0A590UJE1, Q8N4C8, I3L1U1, I3L203, I3L2I2, I3L4T2

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking. Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway. Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration.

Subunit / interactions. Interacts with TANC1. Interacts with RAP2A. Isoform 4 interacts with NCK1.

Subcellular location. Cytoplasm. Postsynaptic density. Cell projection. Axon. Dendrite Golgi apparatus.

Tissue specificity. Expressed in the brain, isoform 2 is more abundant than isoform 1. Isoform 3 is ubiquitously expressed. Isoform 1 is most abundant in the skeletal muscle. Isoform 4 is ubiquitously expressed with relative high levels in brain, skeletal muscle, pancreas and testis.

Post-translational modifications. Autophosphorylated.

Induction. Activated after Ras induction via a mechanism involving reactive oxygen species.

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8N4C8-1	3, MINK-alpha	yes
Q8N4C8-2	1, MiNK-1, MINK-delta
Q8N4C8-3	2, MiNK-2, MINK-gamma
Q8N4C8-4	4, MINK-beta
Q8N4C8-5	5, MINK-eta

RefSeq proteins (5): NP_001020108, NP_001308165, NP_056531, NP_722549, NP_733763 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001180	CNH_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR051700	STE20_Ser-Thr_kinase	Family

Pfam: PF00069, PF00780

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 (45 total): compositionally biased region 13, modified residue 12, sequence variant 6, region of interest 5, splice variant 3, domain 2, binding site 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4C8-F1	64.32	0.24

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): 153 (proton acceptor)

Ligand- & substrate-binding residues (2): 31–39; 54

Post-translational modifications (12): 324, 326, 501, 509, 641, 701, 754, 763, 777, 778, 782, 891

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 245 (showing top): GOBP_DENDRITE_DEVELOPMENT, GGGACCA_MIR133A_MIR133B, TGCGCANK_UNKNOWN, GAANYNYGACNY_UNKNOWN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, NKX25_02, AREB6_03, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, KYNG_DNA_DAMAGE_DN, GOBP_NEUROGENESIS, AATGGAG_MIR136, RODRIGUES_NTN1_TARGETS_DN, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_CELL_ADHESION, ONKEN_UVEAL_MELANOMA_UP

GO Biological Process (19): MAPK cascade (GO:0000165), regulation of cell-matrix adhesion (GO:0001952), protein phosphorylation (GO:0006468), JNK cascade (GO:0007254), chemical synaptic transmission (GO:0007268), brain development (GO:0007420), regulation of cell-cell adhesion (GO:0022407), actin cytoskeleton organization (GO:0030036), regulation of cell migration (GO:0030334), regulation of MAPK cascade (GO:0043408), positive regulation of JNK cascade (GO:0046330), protein autophosphorylation (GO:0046777), neuron projection morphogenesis (GO:0048812), dendrite morphogenesis (GO:0048813), positive regulation of p38MAPK cascade (GO:1900745), regulation of AMPA receptor activity (GO:2000311), intracellular signal transduction (GO:0035556), regulation of JNK cascade (GO:0046328), positive regulation of intracellular signal transduction (GO:1902533)

GO Molecular Function (8): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), postsynaptic density (GO:0014069), axon (GO:0030424), dendrite (GO:0030425), extracellular exosome (GO:0070062), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular Senescence	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
MAPK cascade	2
regulation of intracellular signal transduction	2
JNK cascade	2
positive regulation of MAPK cascade	2
intracellular anatomical structure	2
protein kinase activity	2
cytoplasm	2
neuron projection	2
intracellular signaling cassette	1
cell-matrix adhesion	1
regulation of cell-substrate adhesion	1
phosphorylation	1
protein modification process	1
anterograde trans-synaptic signaling	1
central nervous system development	1
animal organ development	1
head development	1
regulation of cell adhesion	1
cell-cell adhesion	1
cytoskeleton organization	1
actin filament-based process	1
cell migration	1
regulation of cell motility	1
regulation of JNK cascade	1
protein phosphorylation	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
dendrite development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
p38MAPK cascade	1
regulation of p38MAPK cascade	1
AMPA glutamate receptor activity	1
regulation of transmembrane transporter activity	1
regulation of neurotransmitter receptor activity	1
signal transduction	1
regulation of MAPK cascade	1
positive regulation of signal transduction	1
intracellular signal transduction	1

Protein interactions and networks

STRING

1510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MINK1	ARPP19	P56211	916
MINK1	ENSA	O43768	897
MINK1	STRN	O43815	888
MINK1	CHRNE	Q04844	825
MINK1	PPP2CA	P05323	786
MINK1	PPP2R3A	Q06190	769
MINK1	PPP2R2A	P50409	718
MINK1	NCK1	P16333	714
MINK1	PPP2R3B	Q9Y5P8	696
MINK1	PPP2R2D	Q66LE6	695
MINK1	PPP2R5D	Q14738	668
MINK1	CIP2A	Q8TCG1	659
MINK1	PPP2R1A	P30153	655
MINK1	PPP2R5A	Q15172	642
MINK1	MOB4	Q9Y3A3	601

IntAct

79 interactions, top by confidence:

A	B	Type	Score
CNOT6L	CNOT1	psi-mi:“MI:0914”(association)	0.810
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
TSEN15	TSEN54	psi-mi:“MI:0914”(association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MINK1	MAP4K4	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
HSF1	IER5	psi-mi:“MI:0915”(physical association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
MINK1	RAP2A	psi-mi:“MI:0915”(physical association)	0.550
MINK1	HSF1	psi-mi:“MI:0407”(direct interaction)	0.540
MINK1	CNOT1	psi-mi:“MI:0914”(association)	0.530
NCK1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
FANCD2OS	CNOT1	psi-mi:“MI:0914”(association)	0.530
TEX264	PER1	psi-mi:“MI:0914”(association)	0.530
SLC9A8	ZNF432	psi-mi:“MI:0914”(association)	0.530
ATG14	CETN2	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
STRN	MAP4K4	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
MINK1	YWHAE	psi-mi:“MI:0915”(physical association)	0.470
SFN	MINK1	psi-mi:“MI:0915”(physical association)	0.470

BioGRID (240): MAP4K4 (Affinity Capture-MS), MINK1 (Affinity Capture-MS), MINK1 (Affinity Capture-MS), MINK1 (Co-fractionation), MINK1 (Affinity Capture-MS), NCK1 (Two-hybrid), MINK1 (Proximity Label-MS), MINK1 (Proximity Label-MS), MINK1 (Affinity Capture-MS), MINK1 (Affinity Capture-MS), MINK1 (Affinity Capture-MS), MINK1 (Affinity Capture-MS), MINK1 (Affinity Capture-MS), MINK1 (Affinity Capture-RNA), MINK1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0R4IZ84, A0A1L8H8C0, A0A1L8HFX9, A2RUV4, F1LP90, F5HSE3, O43310, O60237, O75167, O88453, P41110, P61406, Q12830, Q1LVF3, Q2HJG4, Q2PFD7, Q3TLH4, Q5RAK6, Q5ZMS6, Q66HC1, Q6A0A2, Q6NRP6, Q6NZL0, Q6P1U3, Q6PKG0, Q75N33, Q7TN02, Q7TPM1, Q7YZA2, Q7Z6E9, Q80TN7, Q80XI3, Q86UR5, Q86US8, Q8IVL0, Q8IVL1, Q8K0V4, Q8N4C8, Q90YL3, Q90YY5

Diamond homologs: A0A8I5ZNK2, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A8XJW8, B0LT89, F1LP90, F1NBT0, G5EEN4, G5EFU0, G5EGQ3, H2L099, O00506, O14047, O14305, O23304, O24527, O54748, O61122, O61125, O75011, O75914, O88506, O88643, O95747, O95819, O96013, P08458, P35465, P83510, Q03497, Q08E52, Q0IHQ8, Q12851, Q13043, Q13153

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
KRAS	up-regulates	MINK1
MINK1	“down-regulates activity”	SMAD1	phosphorylation
MINK1	“up-regulates activity”	NLRP3	phosphorylation
MINK1	up-regulates	KCNH2	binding
MINK1	“up-regulates activity”	PRICKLE1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	88.1×	5e-12
Activation of BAD and translocation to mitochondria	7	87.4×	9e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	77.1×	2e-10
Activation of BH3-only proteins	7	57.0×	2e-09
Downstream signal transduction	7	43.7×	1e-08
RHO GTPases activate PKNs	7	36.4×	4e-08
Intrinsic Pathway for Apoptosis	7	33.6×	6e-08
HSF1 activation	5	31.2×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	23.5×	4e-04
cellular response to heat	5	22.1×	4e-04
ephrin receptor signaling pathway	5	22.1×	4e-04
MAPK cascade	8	15.7×	3e-05
Ras protein signal transduction	5	13.2×	3e-03
intracellular protein localization	8	10.7×	3e-04
positive regulation of neuron projection development	6	10.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	161
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

6093 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4878312:CCTAG:C	acceptor_loss	1.0000
17:4878313:CTAGG:C	acceptor_loss	1.0000
17:4878315:A:AG	acceptor_gain	1.0000
17:4878315:A:AT	acceptor_loss	1.0000
17:4878315:AG:A	acceptor_gain	1.0000
17:4878316:G:GG	acceptor_gain	1.0000
17:4878316:GG:G	acceptor_gain	1.0000
17:4878396:TGTGG:T	donor_gain	1.0000
17:4878397:GTGGA:G	donor_gain	1.0000
17:4881038:G:GT	donor_gain	1.0000
17:4881128:TTAG:T	acceptor_loss	1.0000
17:4881129:TAG:T	acceptor_loss	1.0000
17:4881130:A:AG	acceptor_gain	1.0000
17:4881130:A:C	acceptor_loss	1.0000
17:4881131:G:GG	acceptor_gain	1.0000
17:4881131:GGAC:G	acceptor_gain	1.0000
17:4881256:GG:G	donor_gain	1.0000
17:4881257:GG:G	donor_gain	1.0000
17:4881258:G:GG	donor_gain	1.0000
17:4881259:T:A	donor_loss	1.0000
17:4884341:C:A	acceptor_gain	1.0000
17:4884342:G:A	acceptor_gain	1.0000
17:4884345:A:AG	acceptor_gain	1.0000
17:4884346:C:G	acceptor_gain	1.0000
17:4884352:T:TA	acceptor_gain	1.0000
17:4884353:G:A	acceptor_gain	1.0000
17:4884361:A:AG	acceptor_gain	1.0000
17:4884361:AGCT:A	acceptor_gain	1.0000
17:4884362:G:GA	acceptor_gain	1.0000
17:4884362:GCTG:G	acceptor_gain	1.0000

AlphaMissense

8715 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4878332:T:C	F25L	1.000
17:4878333:T:C	F25S	1.000
17:4878334:T:A	F25L	1.000
17:4878334:T:G	F25L	1.000
17:4878353:G:C	G32R	1.000
17:4878368:G:A	G37R	1.000
17:4878368:G:C	G37R	1.000
17:4878369:G:A	G37E	1.000
17:4880984:G:C	G42R	1.000
17:4880990:C:G	H44D	1.000
17:4880994:T:A	V45D	1.000
17:4881002:G:A	G48R	1.000
17:4881002:G:C	G48R	1.000
17:4881002:G:T	G48W	1.000
17:4881003:G:A	G48E	1.000
17:4881003:G:T	G48V	1.000
17:4881009:T:C	L50P	1.000
17:4881012:C:A	A51D	1.000
17:4881015:C:A	A52D	1.000
17:4881018:T:A	I53N	1.000
17:4881018:T:C	I53T	1.000
17:4881018:T:G	I53S	1.000
17:4881033:T:A	V58D	1.000
17:4881148:T:G	I66S	1.000
17:4881160:T:G	I70S	1.000
17:4881169:T:C	L73P	1.000
17:4881171:A:G	K74E	1.000
17:4881172:A:T	K74I	1.000
17:4881173:A:C	K74N	1.000
17:4881173:A:T	K74N	1.000

dbSNP variants (sampled 300 via entrez): RS1000008448 (17:4863904 C>T), RS1000072161 (17:4867728 C>G,T), RS1000126161 (17:4869206 G>C), RS1000132201 (17:4859096 G>C), RS1000144356 (17:4858119 A>C), RS1000153034 (17:4896768 C>A,T), RS1000269667 (17:4880431 G>GC), RS1000286439 (17:4862392 C>A,T), RS1000295191 (17:4894711 G>A), RS1000368772 (17:4833900 C>A), RS1000392351 (17:4850519 G>C,T), RS1000397648 (17:4894982 T>C), RS1000406755 (17:4875570 T>G), RS1000444521 (17:4864154 C>T), RS1000571487 (17:4863366 T>C)

Disease associations

OMIM: gene MIM:609426 | disease phenotypes: MIM:601462

GenCC curated gene-disease

Mondo (2): 7p22.1 microduplication syndrome (MONDO:0017792), congenital myasthenic syndrome (MONDO:0018940)

Orphanet (2): 7p22.1 microduplication syndrome (Orphanet:314034), Congenital myasthenic syndrome (Orphanet:590)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004627_167	Lymphocyte count	1.000000e-14
GCST004632_1	Lymphocyte percentage of white cells	4.000000e-10
GCST007354_18	Intracranial aneurysm	2.000000e-12
GCST009597_193	Multiple sclerosis	9.000000e-06
GCST010320_24	PR interval	3.000000e-10
GCST010321_55	PR interval	9.000000e-10
GCST90002388_483	Lymphocyte count	1.000000e-25
GCST90002389_219	Lymphocyte percentage of white cells	7.000000e-15
GCST90002399_279	Neutrophil percentage of white cells	7.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004462	PR interval
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3430890 (PROTEIN COMPLEX), CHEMBL5518 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

47 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 563,480 (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
CHEMBL180022	NERATINIB	4	9,404
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL377300	BRIVANIB	3	1,721
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL1614707	MUBRITINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1938400	PF-03715455	2
CHEMBL1967878	CENISERTIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MSN subfamily

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
PF-03715455	Inhibition	8.22	pIC50
PF06260933	Inhibition	8.1	pIC50
pexmetinib	Inhibition	7.59	pIC50

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(4-fluorophenyl)-3-pyridin-4-yl-1-(2,4,6-trichlorophenyl)pyrazol-5-amine	IC50	33 nM	US-9416123: Kinase modulators for the treatment of cancer
SCH772984	IC50	580 nM
GEFITINIB	IC50	2300 nM	US-9416123: Kinase modulators for the treatment of cancer

ChEMBL bioactivities

451 potent at pChembl≥5 of 460 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.63	IC50	0.235	nM	STAUROSPORINE
9.35	IC50	0.451	nM	STAUROSPORINE
9.33	IC50	0.47	nM	STAUROSPORINE
9.31	IC50	0.49	nM	STAUROSPORINE
9.24	IC50	0.581	nM	STAUROSPORINE
9.00	Kd	1	nM	STAUROSPORINE
8.90	Ki	1.259	nM	CHEMBL379975
8.89	IC50	1.3	nM	CHEMBL4746566
8.50	Ki	3.162	nM	CHEMBL1986943
8.49	Kd	3.2	nM	BOSUTINIB
8.44	IC50	3.6	nM	CHEMBL5999390
8.44	Kd	3.6	nM	LESTAURTINIB
8.40	Ki	3.981	nM	CHEMBL1998159
8.40	Ki	3.981	nM	CHEMBL1991674
8.30	Ki	5.012	nM	CHEMBL1996980
8.22	IC50	6	nM	CHEMBL4568087
8.22	IC50	6	nM	PF-03715455
8.20	Ki	6.31	nM	CHEMBL1976936
8.20	Ki	6.31	nM	CHEMBL1992220
8.20	Ki	6.31	nM	CHEMBL1997846
8.20	Ki	6.31	nM	CHEMBL2005509
8.11	Kd	7.8	nM	AST-487
8.10	IC50	8	nM	CHEMBL3754515
8.10	Ki	7.943	nM	SOTRASTAURIN
8.10	Ki	7.943	nM	CHEMBL2006439
8.10	Ki	7.943	nM	CHEMBL1986855
8.04	Kd	9.1	nM	DOVITINIB
8.00	Ki	10	nM	DOVITINIB
8.00	Ki	10	nM	CHEMBL1982271
7.96	IC50	11	nM	REBASTINIB
7.90	IC50	12.59	nM	CHEMBL4471729
7.90	Ki	12.59	nM	CHEMBL1983589
7.90	Ki	12.59	nM	CHEMBL2005718
7.90	Ki	12.59	nM	CHEMBL2005216
7.89	IC50	13	nM	CHEMBL4569508
7.80	IC50	15.85	nM	CHEMBL3754283
7.80	Ki	15.85	nM	CHEMBL1980253
7.80	Ki	15.85	nM	CHEMBL1994669
7.75	Kd	18	nM	GALUNISERTIB
7.70	Kd	20	nM	CHEMBL3990456
7.70	Ki	19.95	nM	CHEMBL1998432
7.70	Ki	19.95	nM	CHEMBL1970903
7.70	Ki	19.95	nM	CHEMBL1973720
7.70	Ki	19.95	nM	CHEMBL1991063
7.66	IC50	22	nM	CHEMBL4550702
7.66	IC50	22	nM	BOSUTINIB
7.60	Kd	25	nM	KW-2449
7.60	Ki	25.12	nM	CHEMBL1970142
7.60	Ki	25.12	nM	CHEMBL2006778
7.60	Ki	25.12	nM	CHEMBL1967116

PubChem BioAssay actives

88 with measured affinity, of 918 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
(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	1715272: Inhibition of human MINK1 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0002	uM
2-[4-[6-amino-5-(4-chlorophenyl)-3-pyridinyl]phenoxy]-2-methylpropanoic acid	1686959: Inhibition of MINK (unknown origin) in presence of 10 uM ATP	ic50	0.0013	uM
Bosutinib	624813: Binding constant for MINK kinase domain	kd	0.0032	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	507622: Binding affinity to MINK	kd	0.0036	uM
1-[3-tert-butyl-1-(3-chloro-4-hydroxyphenyl)pyrazol-5-yl]-3-[[2-[[3-[2-(2-hydroxyethylsulfanyl)phenyl]-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea	639697: Inhibition of MINK	ic50	0.0060	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637109: Inhibition of recombinant human His-tagged MINK1 catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0060	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624813: Binding constant for MINK kinase domain	kd	0.0078	uM
5-(6-amino-3-pyridinyl)-3-(4-chlorophenyl)pyridin-2-amine	1271358: Inhibition of MINK (unknown origin) in presence of ATP (Km)	ic50	0.0080	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	624813: Binding constant for MINK kinase domain	kd	0.0091	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168217: Inhibition of human wild type MINK using RBER-CHKtide as substrate preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.0110	uM
5-bromo-2-(2-fluoro-4-pyridinyl)-1,7-naphthyridin-8-amine	1633853: Inhibition of human full length MINK1(1-1332)-G5-Avi-6His-Flag expressed in baculovirus-infected sf21 cells using His6-SMAD1 as substrate preincubated for 30 mins followed by substrate addition and measured after 120 mins by ADP-Glo Reagent based method	ic50	0.0126	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637109: Inhibition of recombinant human His-tagged MINK1 catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0130	uM
4-[6-amino-5-(4-methylsulfonylphenyl)-3-pyridinyl]phenol	1633853: Inhibition of human full length MINK1(1-1332)-G5-Avi-6His-Flag expressed in baculovirus-infected sf21 cells using His6-SMAD1 as substrate preincubated for 30 mins followed by substrate addition and measured after 120 mins by ADP-Glo Reagent based method	ic50	0.0158	uM
4-[2-(6-methyl-2-pyridinyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide	1425077: 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	0.0180	uM
2-amino-2-cyclohexyl-N-[2-(1-methylpyrazol-4-yl)-9-oxo-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl]acetamide	1425077: 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	0.0200	uM
4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637109: Inhibition of recombinant human His-tagged MINK1 catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0220	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624813: Binding constant for MINK kinase domain	kd	0.0250	uM
Sunitinib	507622: Binding affinity to MINK	kd	0.0290	uM
Neratinib	624813: Binding constant for MINK kinase domain	kd	0.0290	uM
4-[6-amino-5-(4-cyanophenyl)-3-pyridinyl]-N-propan-2-ylbenzamide	1633853: Inhibition of human full length MINK1(1-1332)-G5-Avi-6His-Flag expressed in baculovirus-infected sf21 cells using His6-SMAD1 as substrate preincubated for 30 mins followed by substrate addition and measured after 120 mins by ADP-Glo Reagent based method	ic50	0.0398	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	636471: Inhibition of MINK	ic50	0.0400	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1425077: 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	0.0410	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	624813: Binding constant for MINK kinase domain	kd	0.0690	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624813: Binding constant for MINK kinase domain	kd	0.0810	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624813: Binding constant for MINK kinase domain	kd	0.0820	uM
3-tert-butyl-N-[(5R)-2-[2-(3,5-dimethyl-1-propan-2-ylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]-1,2,4-oxadiazole-5-carboxamide	1763495: Inhibition of human MINK1	ic50	0.0907	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624813: Binding constant for MINK kinase domain	kd	0.1000	uM
22-fluoro-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	1823470: Inhibition of MINK1 (unknown origin) at 1 uM by kinome scan method	ic50	0.1150	uM
N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methylthiophene-2-carboxamide	1637109: Inhibition of recombinant human His-tagged MINK1 catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.1400	uM
6-(2-fluoro-4-pyridinyl)pyrido[3,2-d]pyrimidin-4-amine	1633848: Inhibition of human 6His-TEV-Avi-MINK1(1 to 328)-GNS expressed in baculovirus-infected sf21 cells using LRRKtide as substrate preincubated for 30 mins followed by substrate addition and measured after 75 to 90 mins by ADP-Glo Reagent based method	ic50	0.1500	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	1526284: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MINK1 (unknown origin) (1 to 314 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.1580	uM
Midostaurin	507622: Binding affinity to MINK	kd	0.1700	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624813: Binding constant for MINK kinase domain	kd	0.1800	uM
2-[8-amino-2-(2-fluoro-4-pyridinyl)-1,7-naphthyridin-5-yl]propan-2-ol	1633848: Inhibition of human 6His-TEV-Avi-MINK1(1 to 328)-GNS expressed in baculovirus-infected sf21 cells using LRRKtide as substrate preincubated for 30 mins followed by substrate addition and measured after 75 to 90 mins by ADP-Glo Reagent based method	ic50	0.1995	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	1425077: 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	0.2090	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	1526284: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MINK1 (unknown origin) (1 to 314 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.2280	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	624813: Binding constant for MINK kinase domain	kd	0.2500	uM
(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-ol	624813: Binding constant for MINK kinase domain	kd	0.3100	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	624813: Binding constant for MINK kinase domain	kd	0.3100	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	624813: Binding constant for MINK kinase domain	kd	0.3300	uM
N-[4-chloro-3-(trifluoromethyl)phenyl]-4-[6-[4-(4-methylpiperazin-1-yl)phenyl]thieno[2,3-d]pyrimidin-4-yl]piperazine-1-carboxamide	1779551: Inhibition of human MINK	ic50	0.3354	uM
1-[4-[4-methyl-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenyl]piperazine	1665335: Inhibition of MINK (unknown origin)	ic50	0.3360	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	1425077: 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	0.3480	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	624813: Binding constant for MINK kinase domain	kd	0.5400	uM
Axitinib	624813: Binding constant for MINK kinase domain	kd	0.5600	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624813: Binding constant for MINK kinase domain	kd	0.6000	uM
5-(4-methylsulfonylphenyl)-3-[6-(trifluoromethyl)-3-pyridinyl]pyridin-2-amine	2085289: Inhibition of human MINK1	ic50	0.7400	uM
(3S)-1-[2-oxo-2-[4-(4-pyrimidin-2-ylphenyl)piperazin-1-yl]ethyl]-N-(3-pyridin-4-yl-1H-indazol-5-yl)pyrrolidine-3-carboxamide	1800457: Selectivity screening from Article 10.1038/nchembio.1629: “A unique inhibitor binding site in ER K1/2 is associated with slow binding kinetics”	ic50	0.9420	uM
2-[4-[(1E)-1-hydroxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]ethanol	624813: Binding constant for MINK kinase domain	kd	1.0000	uM
Momelotinib	2183908: Inhibition of MINK1 (unknown origin)	ic50	1.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	increases expression, decreases reaction, decreases expression, affects cotreatment	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
takinib	decreases activity	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation	1
titanium dioxide	increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	decreases expression	1
candoxin	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cadmium	increases expression	1
Caffeine	affects phosphorylation	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	increases expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Piroxicam	decreases reaction, increases expression	1

ChEMBL screening assays

338 unique, capped per target: 335 binding, 2 toxicity, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3362675	Binding	Inhibition of human KCNQ1/MINK expressed in CHO cells by electrophysiology	Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120). — Bioorg Med Chem Lett
CHEMBL5258220	Toxicity	Inhibition of KCNQ1/MINK (unknown origin) at 10 uM	Discovery of VU2957 (Valiglurax): An mGlu4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson’s Disease. — ACS Med Chem Lett
CHEMBL1963795	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MINK	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SY38	HAP1 MINK1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01203592	PHASE1	COMPLETED	Efficacy of Albuterol in the Treatment of Congenital Myasthenic Syndromes
NCT06436742	PHASE1	RECRUITING	A Phase 1b Study to Investigate Safety and Tolerability of ARGX-119 in Adult Participants With DOK7-Congenital Myasthenic Syndromes (CMS)
NCT07226726	PHASE1	RECRUITING	Patients With Congenital Myasthenic Syndrome Will be Treated With Mesenchymal Stem Cell Exosome Solution
NCT00872950	Not specified	APPROVED_FOR_MARKETING	3,4-Diaminopyridine Use in Lambert-Eaton Myasthenic Syndrome(LEMS) and Congenital Myasthenic Syndromes (CMS)
NCT01403402	Not specified	RECRUITING	Congenital Muscle Disease Study of Patient and Family Reported Medical Information
NCT01474980	Not specified	COMPLETED	Pregnancy Outcomes in Congenital Myasthenie Syndrome
NCT02012933	Not specified	NO_LONGER_AVAILABLE	3,4-Diaminopyridine for Lambert-Eaton Myasthenic Syndrome (LEMS) and Congenital Myasthenia (CM)
NCT02189720	Not specified	APPROVED_FOR_MARKETING	Expanded Access Study Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS),Congenital Myasthenic Syndrome
NCT03062631	Not specified	NO_LONGER_AVAILABLE	Treatment Use of 3,4 Diaminopyridine in Congenital Myasthenia
NCT05408702	Not specified	COMPLETED	Exercise in Autoimmune Myasthenia Gravis and Myasthenic Syndromes
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06078553	Not specified	RECRUITING	A Natural History Study in Participants With Congenital Myasthenic Syndromes (CMS) Due to Mutations in DOK7, MUSK, AGRN, or LRP4