MARK3

Summary

MARK3 (microtubule affinity regulating kinase 3, HGNC:6897) is a protein-coding gene on chromosome 14q32.32-q32.33, encoding MAP/microtubule affinity-regulating kinase 3 (P27448). Serine/threonine-protein kinase.

The protein encoded by this gene is activated by phosphorylation and in turn is involved in the phosphorylation of tau proteins MAP2 and MAP4. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4140 — RefSeq curated summary.

At a glance

• Gene–disease (curated): visual impairment and progressive phthisis bulbi (Limited, GenCC)
• GWAS associations: 33
• Clinical variants (ClinVar): 117 total — 1 pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes — 45 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001128918

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6897
Approved symbol	MARK3
Name	microtubule affinity regulating kinase 3
Location	14q32.32-q32.33
Locus type	gene with protein product
Status	Approved
Aliases	CTAK1, KP78, PAR-1A
Ensembl gene	ENSG00000075413
Ensembl biotype	protein_coding
OMIM	602678
Entrez	4140

Gene structure

Transcript identifiers

Ensembl transcripts: 127 — 71 protein_coding, 27 nonsense_mediated_decay, 16 retained_intron, 13 protein_coding_CDS_not_defined

ENST00000216288, ENST00000303622, ENST00000335102, ENST00000416682, ENST00000429436, ENST00000440884, ENST00000553942, ENST00000554627, ENST00000555235, ENST00000556463, ENST00000556744, ENST00000558223, ENST00000558611, ENST00000558698, ENST00000558787, ENST00000558953, ENST00000559268, ENST00000559274, ENST00000559328, ENST00000560417, ENST00000560603, ENST00000560731, ENST00000561071, ENST00000561164, ENST00000561225, ENST00000561314, ENST00000676475, ENST00000676518, ENST00000676564, ENST00000676645, ENST00000676694, ENST00000676745, ENST00000676830, ENST00000676838, ENST00000676897, ENST00000676905, ENST00000676938, ENST00000676944, ENST00000677023, ENST00000677035, ENST00000677051, ENST00000677104, ENST00000677118, ENST00000677133, ENST00000677214, ENST00000677228, ENST00000677347, ENST00000677348, ENST00000677352, ENST00000677360, ENST00000677404, ENST00000677410, ENST00000677432, ENST00000677560, ENST00000677604, ENST00000677829, ENST00000677857, ENST00000677869, ENST00000677942, ENST00000678022, ENST00000678071, ENST00000678091, ENST00000678169, ENST00000678175, ENST00000678179, ENST00000678207, ENST00000678213, ENST00000678237, ENST00000678278, ENST00000678302, ENST00000678343, ENST00000678373, ENST00000678423, ENST00000678619, ENST00000678661, ENST00000678897, ENST00000678999, ENST00000679005, ENST00000679105, ENST00000679299, ENST00000679330, ENST00000873445, ENST00000873446, ENST00000873447, ENST00000873448, ENST00000873449, ENST00000873450, ENST00000873451, ENST00000873452, ENST00000873453, ENST00000873454, ENST00000873455, ENST00000873456, ENST00000873457, ENST00000912913, ENST00000912914, ENST00000912915, ENST00000912916, ENST00000912917, ENST00000912918, ENST00000912919, ENST00000912920, ENST00000912921, ENST00000912922, ENST00000912923, ENST00000912924, ENST00000912925, ENST00000912926, ENST00000912927, ENST00000912928, ENST00000912929, ENST00000969204, ENST00000969205, ENST00000969206, ENST00000969207, ENST00000969208, ENST00000969209, ENST00000969210, ENST00000969211, ENST00000969212, ENST00000969213, ENST00000969214, ENST00000969215, ENST00000969216, ENST00000969217, ENST00000969218, ENST00000969219

RefSeq mRNA: 7 — MANE Select: NM_001128918 NM_001128918, NM_001128919, NM_001128920, NM_001128921, NM_001411055, NM_001411056, NM_002376

CCDS: CCDS41993, CCDS45165, CCDS45166, CCDS45167, CCDS55947, CCDS91938, CCDS91940

Canonical transcript exons

ENST00000429436 — 18 exons

Exon	Start	End
ENSE00001601737	103465972	103466091
ENSE00001676776	103465557	103465793
ENSE00002441972	103502882	103503831
ENSE00002504628	103385415	103386080
ENSE00003476038	103467079	103467191
ENSE00003477170	103498502	103498528
ENSE00003486846	103405076	103405267
ENSE00003535025	103468033	103468186
ENSE00003564473	103466343	103466442
ENSE00003566551	103500156	103500200
ENSE00003573015	103491777	103492034
ENSE00003593641	103480387	103480490
ENSE00003602799	103428387	103428440
ENSE00003606505	103474993	103475210
ENSE00003608398	103462405	103462461
ENSE00003628041	103457142	103457212
ENSE00003676647	103448919	103448967
ENSE00003685453	103451918	103451983

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 97.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.3172 / max 305.8925, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141736	37.7573	1818
141737	0.6552	339
141739	0.4946	155
141738	0.4100	209

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	97.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.57	gold quality
cerebellar cortex	UBERON:0002129	97.54	gold quality
body of pancreas	UBERON:0001150	97.00	gold quality
apex of heart	UBERON:0002098	97.00	gold quality
cerebellum	UBERON:0002037	96.97	gold quality
lower esophagus mucosa	UBERON:0035834	96.70	gold quality
right adrenal gland cortex	UBERON:0035827	96.59	gold quality
cortical plate	UBERON:0005343	96.54	gold quality
left uterine tube	UBERON:0001303	96.47	gold quality
right lung	UBERON:0002167	96.41	gold quality
left adrenal gland	UBERON:0001234	96.36	gold quality
right atrium auricular region	UBERON:0006631	96.36	gold quality
left adrenal gland cortex	UBERON:0035825	96.33	gold quality
right adrenal gland	UBERON:0001233	96.31	gold quality
left ovary	UBERON:0002119	96.29	gold quality
heart left ventricle	UBERON:0002084	96.24	gold quality
colonic epithelium	UBERON:0000397	96.19	gold quality
body of stomach	UBERON:0001161	96.14	gold quality
cardiac ventricle	UBERON:0002082	96.06	gold quality
adrenal cortex	UBERON:0001235	95.93	gold quality
right ovary	UBERON:0002118	95.93	gold quality
right lobe of thyroid gland	UBERON:0001119	95.87	gold quality
upper lobe of left lung	UBERON:0008952	95.87	gold quality
monocyte	CL:0000576	95.86	gold quality
mucosa of stomach	UBERON:0001199	95.85	gold quality
adrenal gland	UBERON:0002369	95.79	gold quality
ventricular zone	UBERON:0003053	95.76	gold quality
left lobe of thyroid gland	UBERON:0001120	95.70	gold quality
ganglionic eminence	UBERON:0004023	95.67	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.58
E-CURD-135	no	748.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RBPJ, TP63

miRNA regulators (miRDB)

68 targeting MARK3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-142-3P	99.62	71.30	974

Literature-anchored findings (GeneRIF, showing 15)

• results show that LKB1 can direct the phosphorylation of the serine-threonine kinase PAR1A (PMID:12879020)
• identify sequence motifs required for stable C-TAK1 association and substrate phosphorylation (PMID:12941695)
• The C-TAK1/p78 constitutively associates with and phosphorylates KSR1 generating a 14-3-3 binding site. (PMID:15182702)
• Data show that the protein kinase Cdc25 C-associated kinase 1 (C-TAK1) is a binding partner and a substrate of Pim-1, and suggest a role for Pim-1 as a positive regulator at the G(2)/M transition of the cell cycle. (PMID:15319445)
• 14-3-3 binding to MARK3 is dependent on phosphorylation. (PMID:16968750)
• Class IIa histone deacetylases (HDACs) are subjected to signal-independent nuclear export that relies on their constitutive phosphorylation. EMK and C-TAK1, are identified as regulators of this process. (PMID:16980613)
• occurrence of an unusual TG 3’ splice site in intron 3 (PMID:17672918)
• identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain (PMID:17726107)
• interaction between Mitf and C-TAK1 was demonstrated. (PMID:20214879)
• We have shown that serum ALP levels modified the association of MARK3 with bone mineral density in osetoporosis for Chinese patients. (PMID:23894155)
• findings indicate that brain PP-1I associates with and is regulated by the associated protein kinases C-TAK1 and PFTK1 (PMID:25028520)
• Authors identified a regulatory switch controlled by MARK3 that couples microtubules to the actin cytoskeleton to establish epithelial cell polarity through ARHGEF2. (PMID:29089450)
• A non-synonymous homozygous variant (NM_001128918.2: c.1708C > G: p.Arg570Gly) in the MARK3 leads to visual impairment and progressive phthisis bulbi. (PMID:29771303)
• The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma. (PMID:35017636)
• Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women. (PMID:38715801)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mark3a	ENSDARG00000019345
danio_rerio	mark3b	ENSDARG00000026630
mus_musculus	Mark3	ENSMUSG00000007411
rattus_norvegicus	Mark3	ENSRNOG00000010330

Paralogs (3): MARK4 (ENSG00000007047), MARK2 (ENSG00000072518), MARK1 (ENSG00000116141)

Protein

Protein identifiers

MAP/microtubule affinity-regulating kinase 3 — P27448 (reviewed: P27448)

Alternative names: C-TAK1, Cdc25C-associated protein kinase 1, ELKL motif kinase 2, Protein kinase STK10, Ser/Thr protein kinase PAR-1, Serine/threonine-protein kinase p78

All UniProt accessions (36): P27448, A0A7I2V2E3, A0A7I2V2I9, A0A7I2V2J6, A0A7I2V2N8, A0A7I2V2U9, A0A7I2V3B9, A0A7I2V3C6, A0A7I2V3I9, A0A7I2V3K2, A0A7I2V3P5, A0A7I2V3Q1, A0A7I2V3X7, A0A7I2V409, A0A7I2V483, A0A7I2V4G7, A0A7I2V4K8, A0A7I2V4L1, A0A7I2V4T2, A0A7I2V4T5, A0A7I2V549, A0A7I2V5G3, A0A7I2V5H7, A0A7I2V5Z7, A0A7I2V602, A0A7I2V639, A0A7I2YQ84, A0A7I2YQ91, A0A7I2YQF4, A0A7I2YQF7, A0A7I2YQJ7, H0YIY6, H0YJI9, H0YKP9, H0YNV4, J3KNR0

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase. Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU. Phosphorylates CDC25C on ‘Ser-216’. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Regulates localization and activity of MITF by mediating its phosphorylation, promoting subsequent interaction between MITF and 14-3-3 and retention in the cytosol. Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1. Phosphorylates PKP2 and KSR1.

Subunit / interactions. Interacts with MAPT/TAU. Interacts with DLG5 (via coiled-coil domain). Interacts with STK3/MST2 and STK4/MST1 in the presence of DLG5. Interacts with YWHAB, YWHAG, YWHAQ and YWHAZ. Interacts with PKP2 (via N-terminus). Interacts with CDC25C. Interacts with KSR1.

Subcellular location. Cell membrane. Cell projection. Dendrite. Cytoplasm.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-564 by PRKCZ/aPKC inhibits the kinase activity.

Disease relevance. Visual impairment and progressive phthisis bulbi (VIPB) [MIM:618283] An autosomal recessive, progressive disease characterized by poor vision at birth and development of bilateral phthisis bulbi by adulthood. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by phosphorylation on Thr-211. Inhibited by phosphorylation on Thr-564.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
P27448-5	1	yes
P27448-2	2, CTAK75a
P27448-3	3
P27448-4	4
P27448-6	5, p58
P27448-7	6
P27448-8	7

RefSeq proteins (7): NP_001122390, NP_001122391, NP_001122392, NP_001122393, NP_001397984, NP_001397985, NP_002367 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001772	KA1_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015940	UBA	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR028375	KA1/Ssp2_C	Homologous_superfamily
IPR049508	MARK1-4_cat	Domain

Pfam: PF00069, PF00627, PF02149

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 (84 total): modified residue 20, helix 17, strand 9, sequence conflict 8, compositionally biased region 7, splice variant 6, sequence variant 4, domain 3, region of interest 3, binding site 2, turn 2, chain 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
8UOJ	X-RAY DIFFRACTION	1.6
8UOI	X-RAY DIFFRACTION	1.8
8UOK	X-RAY DIFFRACTION	1.85
3FE3	X-RAY DIFFRACTION	1.9
8UOL	X-RAY DIFFRACTION	1.9
7P1L	X-RAY DIFFRACTION	1.95
9VGR	X-RAY DIFFRACTION	2
8UOH	X-RAY DIFFRACTION	2.15
9YSQ	X-RAY DIFFRACTION	2.4
9YR9	X-RAY DIFFRACTION	2.4
9VFO	X-RAY DIFFRACTION	2.5
2QNJ	X-RAY DIFFRACTION	2.7
9ZZW	X-RAY DIFFRACTION	2.76
9VIR	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27448-F1	69.25	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): 178 (proton acceptor)

Ligand- & substrate-binding residues (2): 62–70; 85

Post-translational modifications (20): 42, 211, 368, 374, 376, 380, 383, 400, 419, 469, 540, 543, 549, 564, 583, 598, 601, 643, 384, 407

Mutagenesis-validated functional residues (1):

Position	Phenotype
211	prevents phosphorylation and activation by stk11/lkb1 complex.

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-5673000	RAF activation
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-5675221	Negative regulation of MAPK pathway
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9656223	Signaling by RAF1 mutants
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-5683057	MAPK family signaling cascades
R-HSA-5684996	MAPK1/MAPK3 signaling
R-HSA-6802949	Signaling by RAS mutants
R-HSA-6802957	Oncogenic MAPK signaling
R-HSA-9730414	MITF-M-regulated melanocyte development

MSigDB gene sets: 230 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, KYNG_DNA_DAMAGE_DN, GOBP_HIPPO_SIGNALING, BILD_SRC_ONCOGENIC_SIGNATURE, YY1_Q6, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_NOT_BY_GAMMA_IN_WS, ONKEN_UVEAL_MELANOMA_UP, YY1_02, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_CTBP1

GO Biological Process (6): microtubule cytoskeleton organization (GO:0000226), protein phosphorylation (GO:0006468), regulation of G2/M transition of mitotic cell cycle (GO:0010389), negative regulation of hippo signaling (GO:0035331), intracellular signal transduction (GO:0035556), negative regulation of protein localization to nucleus (GO:1900181)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein phosphatase binding (GO:0019903), tau protein binding (GO:0048156), tau-protein kinase activity (GO:0050321), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), dendrite (GO:0030425), extracellular exosome (GO:0070062), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Oncogenic MAPK signaling	6
RAF/MAP kinase cascade	3
Signaling by RAS mutants	1
MITF-M-regulated melanocyte development	1
Disease	1
MAPK1/MAPK3 signaling	1
Signal Transduction	1
MAPK family signaling cascades	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular anatomical structure	2
protein kinase activity	2
cytoskeleton organization	1
microtubule-based process	1
phosphorylation	1
protein modification process	1
G2/M transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
hippo signaling	1
regulation of hippo signaling	1
negative regulation of intracellular signal transduction	1
signal transduction	1
protein localization to nucleus	1
regulation of protein localization to nucleus	1
negative regulation of protein localization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
phosphatase binding	1
cytoskeletal protein binding	1
protein serine/threonine kinase activity	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
cytoplasm	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
extracellular vesicle	1

Protein interactions and networks

STRING

1320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MARK3	MAP4	P27816	841
MARK3	CDC25C	P30307	802
MARK3	F2R	P25116	782
MARK3	GRIK4	Q16099	764
MARK3	PKP2	Q99959	600
MARK3	EPRS1	P07814	577
MARK3	RSPO2	Q6UXX9	503
MARK3	YWHAZ	P29213	501
MARK3	PTPRK	Q15262	497
MARK3	YWHAG	P35214	481
MARK3	PARD3	Q8TEW0	436
MARK3	ZBTB40	Q9NUA8	434
MARK3	TFCP2	Q12800	430
MARK3	CDC7	O00311	429
MARK3	AXIN1	O15169	415
MARK3	SMOC1	Q9H4F8	415

IntAct

210 interactions, top by confidence:

A	B	Type	Score
YWHAZ	MARK3	psi-mi:“MI:0914”(association)	0.940
MARK3	YWHAZ	psi-mi:“MI:0915”(physical association)	0.940
YWHAZ	MARK3	psi-mi:“MI:0915”(physical association)	0.940
MARK3	YWHAZ	psi-mi:“MI:0407”(direct interaction)	0.940
MARK3	YWHAB	psi-mi:“MI:0915”(physical association)	0.920
MARK3	YWHAG	psi-mi:“MI:0915”(physical association)	0.920
YWHAG	MARK3	psi-mi:“MI:0915”(physical association)	0.920
MARK3	YWHAH	psi-mi:“MI:0915”(physical association)	0.910
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
MARK3	YWHAE	psi-mi:“MI:0914”(association)	0.790
MARK3	YWHAE	psi-mi:“MI:0915”(physical association)	0.790
SFN	MARK3	psi-mi:“MI:0915”(physical association)	0.720
MARK3	SFN	psi-mi:“MI:0915”(physical association)	0.720
	TOMM70	psi-mi:“MI:0914”(association)	0.690
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
NUAK2	PPP1R12A	psi-mi:“MI:0914”(association)	0.640
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610

BioGRID (405): Crtc2 (Biochemical Activity), CAPZA1 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), CNBP (Affinity Capture-MS), DLG5 (Affinity Capture-MS), HNRNPDL (Affinity Capture-MS), MTCL1 (Affinity Capture-MS), ALYREF (Affinity Capture-MS), YWHAZ (Affinity Capture-MS), MARK3 (Biochemical Activity), MARK3 (Affinity Capture-MS), MARK3 (Affinity Capture-MS), MARK3 (Two-hybrid), MARK3 (Affinity Capture-MS), MARK3 (Proximity Label-MS)

ESM2 similar proteins: A1Z8N1, B0UYF2, B3MG58, B3NSE1, B4GAP7, B4HNS0, B4J913, B4KR05, B4LPX5, B4MYA4, B4P624, B4QBN2, D4AYW0, O18868, O18965, O95259, P15385, P22459, P22462, P27448, P57789, Q02280, Q03141, Q05037, Q0P5V9, Q14721, Q14B80, Q17NV8, Q28527, Q291H8, Q2KNE5, Q5BKX6, Q60603, Q61423, Q63472, Q7PIR5, Q8BUW1, Q8IRI6, Q8NCM2, Q920E3

Diamond homologs: A0AUV4, A1A5Q6, A2KF29, A2XFF4, A8WYE4, B2DD29, B7XHR6, B8BBT7, C0HKC8, C0HKC9, F1QGZ6, O08678, O08679, O22932, O22971, O65554, O74536, O94168, P27448, P52497, P54645, P54646, P57059, P92958, Q00372, Q02723, Q03141, Q05512, Q09137, Q0D4B2, Q0JI49, Q13131, Q19469, Q28948, Q2QY53, Q2RAX3, Q2V452, Q38997, Q54DF2, Q54TA3

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
STK11	“up-regulates activity”	MARK3	phosphorylation
PRKCZ	down-regulates	MARK3	phosphorylation
PIM1	down-regulates	MARK3	phosphorylation
PIM	down-regulates	MARK3	phosphorylation
MARK3	“down-regulates activity”	TNK1	phosphorylation
MARK3	“up-regulates activity”	ARHGEF2	phosphorylation
MARK3	“up-regulates activity”	CDC25B	phosphorylation
MARK3	“down-regulates activity”	CDC25B	phosphorylation
MARK3	“down-regulates activity”	KSR1	phosphorylation
MARK3	“down-regulates activity”	CDC25C	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 168 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
Activation of BAD and translocation to mitochondria	7	49.8×	7e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	44.0×	1e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	44.0×	1e-08
Activation of BH3-only proteins	7	32.5×	1e-07
RHO GTPases activate PKNs	9	26.7×	7e-09
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	24.3×	5e-05
Intrinsic Pathway for Apoptosis	7	19.2×	4e-06
Downstream signal transduction	5	17.8×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	11	5.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	80
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
599409	NM_001128918.3(MARK3):c.1708C>G (p.Arg570Gly)	Pathogenic

SpliceAI

3682 predictions. Top by Δscore:

Variant	Effect	Δscore
14:103385695:G:GT	donor_gain	1.0000
14:103405062:A:AG	acceptor_gain	1.0000
14:103405062:AT:A	acceptor_gain	1.0000
14:103405062:ATGCT:A	acceptor_gain	1.0000
14:103405063:T:G	acceptor_gain	1.0000
14:103405063:T:TA	acceptor_gain	1.0000
14:103405066:T:A	acceptor_gain	1.0000
14:103405069:A:AG	acceptor_gain	1.0000
14:103405070:T:G	acceptor_gain	1.0000
14:103405073:CAG:C	acceptor_loss	1.0000
14:103405074:A:AC	acceptor_loss	1.0000
14:103405074:A:AG	acceptor_gain	1.0000
14:103405075:G:GA	acceptor_gain	1.0000
14:103405075:GC:G	acceptor_gain	1.0000
14:103405075:GCA:G	acceptor_gain	1.0000
14:103405075:GCAC:G	acceptor_gain	1.0000
14:103405075:GCACA:G	acceptor_gain	1.0000
14:103405263:GAGAG:G	donor_gain	1.0000
14:103405265:GAG:G	donor_gain	1.0000
14:103405265:GAGG:G	donor_loss	1.0000
14:103405266:AGGT:A	donor_loss	1.0000
14:103405268:G:GA	donor_loss	1.0000
14:103428439:AGGT:A	donor_loss	1.0000
14:103428441:G:GA	donor_loss	1.0000
14:103428442:T:G	donor_loss	1.0000
14:103451896:C:CA	acceptor_gain	1.0000
14:103451898:T:TA	acceptor_gain	1.0000
14:103451913:CGCAG:C	acceptor_loss	1.0000
14:103451914:GCAGT:G	acceptor_loss	1.0000
14:103451915:CA:C	acceptor_loss	1.0000

AlphaMissense

4971 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:103405190:T:G	Y56D	1.000
14:103405209:T:A	I62N	1.000
14:103405211:G:A	G63S	1.000
14:103405211:G:C	G63R	1.000
14:103405211:G:T	G63C	1.000
14:103405212:G:A	G63D	1.000
14:103405212:G:C	G63A	1.000
14:103405212:G:T	G63V	1.000
14:103405217:G:A	G65R	1.000
14:103405217:G:C	G65R	1.000
14:103405217:G:T	G65W	1.000
14:103405218:G:A	G65E	1.000
14:103405218:G:C	G65A	1.000
14:103405218:G:T	G65V	1.000
14:103405222:T:A	N66K	1.000
14:103405222:T:G	N66K	1.000
14:103405223:T:A	F67I	1.000
14:103405223:T:C	F67L	1.000
14:103405223:T:G	F67V	1.000
14:103405224:T:C	F67S	1.000
14:103405224:T:G	F67C	1.000
14:103405225:T:A	F67L	1.000
14:103405225:T:G	F67L	1.000
14:103405226:G:C	A68P	1.000
14:103405227:C:A	A68E	1.000
14:103405227:C:T	A68V	1.000
14:103405232:G:C	V70L	1.000
14:103405232:G:T	V70L	1.000
14:103405233:T:A	V70E	1.000
14:103405233:T:C	V70A	1.000

dbSNP variants (sampled 300 via entrez): RS1000029942 (14:103405136 C>T), RS1000031944 (14:103424952 AT>A,ATT), RS1000032848 (14:103490938 C>T), RS1000058050 (14:103484128 G>A), RS1000089339 (14:103443344 A>G), RS1000122868 (14:103459681 T>TG), RS1000125714 (14:103464340 C>G,T), RS1000148722 (14:103502068 G>A,C,T), RS1000155379 (14:103459853 T>A), RS1000183625 (14:103426745 A>C), RS1000215537 (14:103418047 T>C), RS1000228215 (14:103502938 T>C), RS1000250498 (14:103425239 CTATTTATTTATTATT>C), RS1000286608 (14:103461597 A>C,G), RS1000329699 (14:103421348 A>G)

Disease associations

OMIM: gene MIM:602678 | disease phenotypes: MIM:618283

GenCC curated gene-disease

Disease	Classification	Inheritance
visual impairment and progressive phthisis bulbi	Limited	Autosomal recessive

Mondo (1): visual impairment and progressive phthisis bulbi (MONDO:0032655)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000508	Ptosis
HP:0000540	Hypermetropia
HP:0000667	Phthisis bulbi
HP:0003577	Congenital onset
HP:0007663	Reduced visual acuity
HP:0007720	Flat cornea

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST004521_15	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_262	Autism spectrum disorder or schizophrenia	6.000000e-09
GCST004608_195	Granulocyte percentage of myeloid white cells	7.000000e-31
GCST004625_147	Monocyte count	3.000000e-50
GCST004630_156	Mean corpuscular hemoglobin	2.000000e-14
GCST005194_69	Coronary artery disease	2.000000e-06
GCST005951_9	Body mass index	4.000000e-09
GCST005977_13	Monocyte count	4.000000e-12
GCST006288_164	Heel bone mineral density	6.000000e-16
GCST006288_331	Heel bone mineral density	2.000000e-18
GCST006288_436	Heel bone mineral density	3.000000e-34
GCST006624_109	Systolic blood pressure	5.000000e-21
GCST006979_1015	Heel bone mineral density	5.000000e-104
GCST006988_73	Blond vs. brown/black hair color	1.000000e-09
GCST007267_34	Systolic blood pressure	2.000000e-17
GCST007691_21	Femoral neck bone mineral density	5.000000e-16
GCST008839_376	Height	9.000000e-17
GCST009379_196	Type 2 diabetes	3.000000e-08
GCST009462_67	Optic disc size	5.000000e-09
GCST010302_1	Cutaneous melanoma or hair colour	1.000000e-16
GCST010320_26	PR interval	3.000000e-09
GCST010321_43	PR interval	1.000000e-10
GCST010703_23	Brain morphology (MOSTest)	2.000000e-09
GCST010866_59	Coronary artery disease	3.000000e-09
GCST90000025_203	Appendicular lean mass	6.000000e-26
GCST90002388_142	Lymphocyte count	2.000000e-11
GCST90002390_279	Mean corpuscular hemoglobin	3.000000e-20
GCST90002394_485	Monocyte percentage of white cells	2.000000e-105
GCST90002396_626	Mean reticulocyte volume	4.000000e-09
GCST90002397_372	Mean spheric corpuscular volume	6.000000e-14

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0005091	monocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004340	body mass index
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0003924	hair color
EFO:0007785	femoral neck bone mineral density
EFO:0004462	PR interval
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5600 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

45 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 164,131 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL3426621	RIPASUDIL	3	870
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL2386889	SCH-900776	2	740
CHEMBL253969	OSI-632	2	1,150
CHEMBL3039513	DECERNOTINIB	2
CHEMBL3115681	NARAZACICLIB	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL3545396	BMS-690514	2
CHEMBL362558	LY-2090314	2
CHEMBL402548	DANUSERTIB	2
CHEMBL475251	R-406	2
CHEMBL495727	AT-9283	2
CHEMBL564829	MILCICLIB	2
CHEMBL565612	SOTRASTAURIN	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — MARK subfamily

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
PCC0208017	Inhibition	8.74	pIC50
PCC0105003	Inhibition	8.57	pIC50
compound 17d [PMID: 23099093]	Inhibition	7.92	pIC50
compound 14 [PMID: 34333981]	Inhibition	5.4	pIC50

Binding affinities (BindingDB)

14 measured of 14 human assays (14 total across all organisms); most potent 14 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[(1R)-3,3-difluoro-2-[[4-[7-(4-fluorophenyl)imidazo[1,2-b]pyridazin-3-yl]thiophene-2-carbonyl]amino]cyclohexyl]azanium	IC50	0.5 nM	US-8592425: Imidazo[1,2-a]pyridines and imidazo[1,2-b]pyridazines as mark inhibitors
Staurosporine	KD	1.7 nM
N-[(6S)-6-amino-2,2-difluorocyclohexyl]-4-imidazo[1,2-b]pyridazin-3-ylthiophene-2-carboxamide	IC50	15 nM	US-8592425: Imidazo[1,2-a]pyridines and imidazo[1,2-b]pyridazines as mark inhibitors
N-[(6R)-6-amino-2,2-difluorocyclohexyl]-4-imidazo[1,2-b]pyridazin-3-yl-5-methylthiophene-2-carboxamide	IC50	20 nM	US-8592425: Imidazo[1,2-a]pyridines and imidazo[1,2-b]pyridazines as mark inhibitors
N-[(6R)-6-amino-2,2-difluorocyclohexyl]-5-ethyl-4-(7-methylimidazo[1,2-b]pyridazin-3-yl)thiophene-2-carboxamide	IC50	140 nM	US-8592425: Imidazo[1,2-a]pyridines and imidazo[1,2-b]pyridazines as mark inhibitors
PKC-412	KD	190 nM
2-[(3,5-difluoro-4-hydroxyphenyl)amino]-5,7-dimethyl-8-(3-methylbutyl)-5,6,7,8-tetrahydropteridin-6-one	IC50	340 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
N-[(6S)-6-amino-2,2-difluorocyclohexyl]-5-chloro-4-imidazo[1,2-a]pyridin-3-yl-1,3-thiazole-2-carboxamide	IC50	720 nM	US-8592425: Imidazo[1,2-a]pyridines and imidazo[1,2-b]pyridazines as mark inhibitors
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
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

473 potent at pChembl≥5 of 485 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.53	IC50	0.297	nM	STAUROSPORINE
9.42	IC50	0.38	nM	STAUROSPORINE
9.40	Ki	0.3981	nM	CHEMBL1980995
9.36	IC50	0.438	nM	STAUROSPORINE
9.30	IC50	0.5	nM	CHEMBL3648448
9.30	Kd	0.5	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL4532781
9.00	IC50	1	nM	CHEMBL4569508
9.00	Ki	1	nM	CHEMBL2000724
8.92	IC50	1.2	nM	CHEMBL3884319
8.89	IC50	1.3	nM	CHEMBL4550486
8.70	IC50	2	nM	CHEMBL4528550
8.62	IC50	2.4	nM	CHEMBL4552799
8.52	IC50	3	nM	CHEMBL4562217
8.52	IC50	3	nM	CHEMBL5305160
8.52	Kd	3	nM	STAUROSPORINE
8.40	Ki	3.981	nM	SP-600125
8.30	IC50	5	nM	CHEMBL4593028
8.30	IC50	5	nM	CHEMBL4552628
8.22	Kd	6	nM	CHEMBL4576489
8.22	IC50	6	nM	CHEMBL4550702
8.20	Ki	6.31	nM	CHEMBL1993661
8.10	Ki	7.943	nM	CHEMBL1241473
8.05	IC50	9	nM	CHEMBL4579339
8.05	IC50	9	nM	CHEMBL4571737
8.00	IC50	10	nM	CHEMBL3884318
8.00	IC50	10	nM	CHEMBL3883979
8.00	IC50	10	nM	CHEMBL4543195
8.00	IC50	10	nM	CHEMBL4569165
7.96	Kd	11	nM	CHEMBL4875028
7.92	IC50	12	nM	CHEMBL2207198
7.92	Kd	12	nM	TAE-684
7.90	Ki	12.59	nM	CENISERTIB
7.89	Kd	13	nM	CHEMBL4465866
7.89	IC50	13	nM	CHEMBL4547786
7.85	IC50	14	nM	CHEMBL3884535
7.82	IC50	15	nM	CHEMBL3648449
7.82	IC50	15	nM	CHEMBL4557345
7.82	IC50	15	nM	CHEMBL4578265
7.80	Kd	16	nM	UCN-01
7.80	Ki	15.85	nM	CHEMBL1983111
7.80	Ki	15.85	nM	TAE-684
7.72	IC50	19	nM	CHEMBL3884344
7.70	IC50	20	nM	CHEMBL2207208
7.70	IC50	20	nM	CHEMBL3648447
7.70	Ki	19.95	nM	GO-6976
7.68	Kd	21	nM	MIDOSTAURIN
7.66	IC50	22	nM	CHEMBL4589674
7.62	IC50	24	nM	CHEMBL4544609
7.62	IC50	24	nM	CHEMBL5557426

PubChem BioAssay actives

153 with measured affinity, of 1714 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
N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-5-methyl-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0003	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	1715285: Inhibition of human MARK3 using KKKVSRSGLYRSPSMPENLNRPR as substrate by [gamma-33P]-ATP assay	ic50	0.0003	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0010	uM
N-[(1R,2R)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0010	uM
2-anilino-7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethylpyrrolo[2,3-d]pyrimidin-6-one	1335988: Inhibition of full length human MARK3 using biotin labeled peptide substrate by HTRF based assay	ic50	0.0012	uM
N-[(1R,2S)-2-aminocyclohexyl]-5-methyl-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0013	uM
N-[(1R,2S)-2-aminocyclopentyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0020	uM
N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-5-methyl-4-pyrazolo[1,5-a]pyrimidin-3-ylthiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0024	uM
N-[(1R,2R)-2-aminocyclopentyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0030	uM
7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethyl-2-[3-(pyrrolidin-1-ylmethyl)anilino]pyrrolo[2,3-d]pyrimidin-6-one	1992916: Inhibition of MARK3 (unknown origin)	ic50	0.0030	uM
4-[6-[4-(2-methoxyethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0050	uM
N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methylthiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0050	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	1526308: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MARK3 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0060	uM
4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0060	uM
N-(1-cyclopropyl-2-hydroxyethyl)-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0090	uM
N-[(1R,2S)-2-hydroxycyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0090	uM
7-[(1S)-1-(3-hydroxyphenyl)ethyl]-5,5-dimethyl-2-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidin-6-one	1335988: Inhibition of full length human MARK3 using biotin labeled peptide substrate by HTRF based assay	ic50	0.0100	uM
7-[(1S)-4-amino-2,3-dihydro-1H-inden-1-yl]-2-anilino-5,5-dimethylpyrrolo[2,3-d]pyrimidin-6-one	1335988: Inhibition of full length human MARK3 using biotin labeled peptide substrate by HTRF based assay	ic50	0.0100	uM
N-[(1R,2R)-2-hydroxycyclopentyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0100	uM
N-(3-amino-4,4,4-trifluorobutyl)-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0100	uM
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]cyclohexanecarboxamide	1760722: Binding affinity to wild-type human full length MARK3 (M1 to L729 residues) expressed in bacterial expression system by measuring active site-directed competition binding based Kinomescan method	kd	0.0110	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	624863: Binding constant for MARK3 kinase domain	kd	0.0120	uM
N-[3-[[5-cyclopropyl-2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide	718688: Inhibition of MARK3	ic50	0.0120	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	1526308: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MARK3 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0130	uM
4-[6-(1-methylimidazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0130	uM
7-cyclohexyl-5,5-dimethyl-2-(3-piperazin-1-ylanilino)pyrrolo[2,3-d]pyrimidin-6-one	1335988: Inhibition of full length human MARK3 using biotin labeled peptide substrate by HTRF based assay	ic50	0.0140	uM
4-[6-(2,3-dihydro-1-benzofuran-6-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0150	uM
N-(3-amino-4,4-difluorobutyl)-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0150	uM
(2S,3R,4R,6R,18S)-18-hydroxy-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	1425069: 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	0.0160	uM
N-[(1S)-1-(2-anilino-5,5-dimethyl-6-oxopyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydro-1H-inden-4-yl]methanesulfonamide	1335988: Inhibition of full length human MARK3 using biotin labeled peptide substrate by HTRF based assay	ic50	0.0190	uM
N-[3-[[5-cyclopropyl-2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide	718688: Inhibition of MARK3	ic50	0.0200	uM
Midostaurin	435659: Binding constant for full-length MARK3	kd	0.0210	uM
N-(3-amino-4-fluorobutyl)-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0220	uM
N-methyl-3-(3,12,13,23-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1(16),2,4,6,8,10,14,17,19,21-decaen-23-yl)propan-1-amine;dihydrochloride	2075600: Inhibition of human MARK3 using ATPKKLNRTLSVA as substrate in presence of ATP	ic50	0.0240	uM
N-[(1R,2R)-2-hydroxycyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0240	uM
7-[(1S)-2,3-dihydro-1H-inden-1-yl]-5,5-dimethyl-2-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidin-6-one	1335988: Inhibition of full length human MARK3 using biotin labeled peptide substrate by HTRF based assay	ic50	0.0270	uM
N-[7-chloro-6-[1-[(3R,4R)-4-hydroxy-3-methyloxolan-3-yl]piperidin-4-yl]isoquinolin-3-yl]spiro[2.2]pentane-2-carboxamide	2020514: Inhibition of recombinant human full length MARK3 expressed in insect cells using CHKtide as substrate preincubated with compound for 15 mins followed by substrate addition and measured after 15 mins in the presence of ATP by scintillation based radiometric LeadHunter assay	ic50	0.0290	uM
N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide	1992916: Inhibition of MARK3 (unknown origin)	ic50	0.0360	uM
5,5-dimethyl-7-[(1S)-1-phenylethyl]-2-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidin-6-one	1335988: Inhibition of full length human MARK3 using biotin labeled peptide substrate by HTRF based assay	ic50	0.0370	uM
4-[6-(1-benzofuran-6-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0380	uM
N-[(1R,2S)-2-hydroxycyclopentyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0430	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	507609: Binding affinity to MARK3	kd	0.0490	uM
7’-[(2S)-butan-2-yl]-2’-(pyridin-3-ylamino)spiro[cyclopropane-1,5’-pyrrolo[2,3-d]pyrimidine]-6’-one	1336442: Inhibition of MARK3 (unknown origin)	ic50	0.0600	uM
7-[(1S)-1-(4-fluorophenyl)ethyl]-5,5-dimethyl-2-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidin-6-one	1336442: Inhibition of MARK3 (unknown origin)	ic50	0.0610	uM
4-(6-pyridin-3-ylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0700	uM
4-[6-(1-methylindol-6-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0740	uM
2-anilino-5,5-dimethyl-7-[(2S)-3-methylbutan-2-yl]pyrrolo[2,3-d]pyrimidin-6-one	1335988: Inhibition of full length human MARK3 using biotin labeled peptide substrate by HTRF based assay	ic50	0.0800	uM
7-[(2S)-butan-2-yl]-5,5-dimethyl-2-[4-(5-methyl-1H-1,2,4-triazol-3-yl)anilino]pyrrolo[2,3-d]pyrimidin-6-one	1336442: Inhibition of MARK3 (unknown origin)	ic50	0.0800	uM
7-[(2S)-butan-2-yl]-5,5-dimethyl-2-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidin-6-one	1336442: Inhibition of MARK3 (unknown origin)	ic50	0.0820	uM
4-[6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637033: Inhibition of full-length recombinant human GST-tagged MARK3 expressed in baculovirus expression system using biotinylated-Cdc25C peptide substrate measured after 2 hrs by HTRF assay	ic50	0.0990	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, increases expression	3
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
beta-lapachone	increases expression, decreases expression	1
arsenite	affects binding, decreases reaction	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
K 7174	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
PCI 5002	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	increases phosphorylation	1
Dibutyl Phthalate	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Hydralazine	affects cotreatment, increases expression	1
Lead	affects splicing	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Silver	increases expression	1
Tetradecanoylphorbol Acetate	affects cotreatment, decreases expression	1
Thiram	increases expression	1

ChEMBL screening assays

387 unique, capped per target: 386 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004128	Binding	Inhibition of MARK3 at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL1963756	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MARK3	PubChem BioAssay data set

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1NQ	Abcam K-562 MARK3 KO	Cancer cell line	Female
CVCL_D2KB	Abcam Raji MARK3 KO	Cancer cell line	Male
CVCL_SX15	HAP1 MARK3 (-) 1	Cancer cell line	Male
CVCL_SX16	HAP1 MARK3 (-) 2	Cancer cell line	Male
CVCL_SX17	HAP1 MARK3 (-) 3	Cancer cell line	Male
CVCL_UQ92	Abcam Jurkat MARK3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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