MATK

Summary

MATK (megakaryocyte-associated tyrosine kinase, HGNC:6906) is a protein-coding gene on chromosome 19p13.3, encoding Megakaryocyte-associated tyrosine-protein kinase (P42679). Could play a significant role in the signal transduction of hematopoietic cells.

The protein encoded by this gene has amino acid sequence similarity to Csk tyrosine kinase and has the structural features of the CSK subfamily: SRC homology SH2 and SH3 domains, a catalytic domain, a unique N terminus, lack of myristylation signals, lack of a negative regulatory phosphorylation site, and lack of an autophosphorylation site. This protein is thought to play a significant role in the signal transduction of hematopoietic cells. It is able to phosphorylate and inactivate Src family kinases, and may play an inhibitory role in the control of T-cell proliferation. This protein might be involved in signaling in some cases of breast cancer. Three alternatively spliced transcript variants that encode different isoforms have been described for this gene.

Source: NCBI Gene 4145 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 75 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_139355

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6906
Approved symbol	MATK
Name	megakaryocyte-associated tyrosine kinase
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HYLTK, CTK, HYL, Lsk, CHK, HHYLTK, DKFZp434N1212, MGC1708, MGC2101
Ensembl gene	ENSG00000007264
Ensembl biotype	protein_coding
OMIM	600038
Entrez	4145

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 24 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000310132, ENST00000395040, ENST00000395045, ENST00000585778, ENST00000587180, ENST00000588983, ENST00000590028, ENST00000590493, ENST00000590821, ENST00000590849, ENST00000590980, ENST00000591059, ENST00000592300, ENST00000592612, ENST00000619596, ENST00000874393, ENST00000874394, ENST00000874395, ENST00000874396, ENST00000874397, ENST00000874398, ENST00000923599, ENST00000923600, ENST00000923601, ENST00000923602, ENST00000923603, ENST00000923604

RefSeq mRNA: 3 — MANE Select: NM_139355 NM_002378, NM_139354, NM_139355

CCDS: CCDS12113, CCDS12114, CCDS42468

Canonical transcript exons

ENST00000310132 — 14 exons

Exon	Start	End
ENSE00000664298	3783814	3784033
ENSE00000875993	3784338	3784451
ENSE00000875996	3783126	3783219
ENSE00000875997	3781607	3781672
ENSE00000875998	3779698	3779797
ENSE00000875999	3779533	3779617
ENSE00000876002	3779378	3779451
ENSE00000876003	3778992	3779187
ENSE00000951594	3778509	3778595
ENSE00002307506	3785064	3785286
ENSE00002770053	3786169	3786381
ENSE00002801673	3777973	3778422
ENSE00003480927	3784825	3784884
ENSE00003690443	3784124	3784239

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 97.80.

FANTOM5 (CAGE): breadth broad, TPM avg 7.6433 / max 313.2340, expressed in 754 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178338	4.5685	603
178339	1.7027	502
178337	0.9624	149
178336	0.2563	90
178340	0.1534	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.80	gold quality
cingulate cortex	UBERON:0003027	93.64	gold quality
anterior cingulate cortex	UBERON:0009835	93.58	gold quality
right frontal lobe	UBERON:0002810	93.18	gold quality
amygdala	UBERON:0001876	91.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.67	gold quality
prefrontal cortex	UBERON:0000451	91.51	gold quality
nucleus accumbens	UBERON:0001882	90.65	gold quality
frontal cortex	UBERON:0001870	89.76	gold quality
putamen	UBERON:0001874	89.72	gold quality
neocortex	UBERON:0001950	89.70	gold quality
caudate nucleus	UBERON:0001873	89.49	gold quality
cerebral cortex	UBERON:0000956	88.88	gold quality
telencephalon	UBERON:0001893	88.65	gold quality
Ammon’s horn	UBERON:0001954	88.16	gold quality
cervix squamous epithelium	UBERON:0006922	87.25	gold quality
temporal lobe	UBERON:0001871	87.22	gold quality
blood	UBERON:0000178	87.15	gold quality
forebrain	UBERON:0001890	86.39	gold quality
Brodmann (1909) area 10	UBERON:0013541	86.28	gold quality
primary visual cortex	UBERON:0002436	86.09	gold quality
occipital lobe	UBERON:0002021	84.67	gold quality
superior frontal gyrus	UBERON:0002661	84.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.18	gold quality
brain	UBERON:0000955	83.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.32	gold quality
central nervous system	UBERON:0001017	83.11	gold quality
postcentral gyrus	UBERON:0002581	83.05	gold quality
parietal lobe	UBERON:0001872	82.79	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-CURD-84	yes	493.58
E-HCAD-4	yes	112.88
E-HCAD-1	yes	82.35
E-CURD-122	yes	51.77
E-MTAB-6701	yes	35.33
E-MTAB-9467	yes	30.55
E-MTAB-10287	yes	29.07
E-HCAD-10	yes	28.68
E-CURD-88	yes	20.11
E-CURD-46	yes	18.42
E-HCAD-9	yes	18.42
E-MTAB-8410	yes	14.26
E-MTAB-10553	yes	12.44
E-CURD-112	yes	11.09
E-MTAB-9067	yes	9.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

5 targeting MATK, 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-7155-5P	98.65	66.14	1290
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-4800-3P	88.42	63.07	35
HSA-MIR-4750-5P	80.79	59.79	18

Literature-anchored findings (GeneRIF, showing 14)

• ERBB2 binds to the SH2 domain of CHK and inhibits cell growth in human breast tumor cell lines (PMID:12122014)
• Overexpression of the Csk homologous kinase facilitates phosphorylation of akt/protein kinase b in breast neoplasms (PMID:12429987)
• CHK Leu223 stabilizes the movement of the alphaC-helix of the protein tyrosine kinase (PMID:12782282)
• Loss of CHK expression is associated with human brain tumors (PMID:15329911)
• Nuclear multi-lobulation in late S phase, which is dependent on polymerization and depolymerization of microtubules, may be involved in nuclear Chk-induced inhibition of proliferation. (PMID:15748901)
• striking functional differences between the Csk and Chk SH2 domains and revealed functional similarities between the Chk and Src SH2 domains (PMID:15890649)
• This study describes for the first time the Src-independent actions of CHK and provides novel insights into CHK function in neural cells. (PMID:16168623)
• Matk/CHK is not functionally redundant with Csk, and this tyrosine kinase plays an important role as a regulator of immunologic responses (PMID:16574955)
• Findings indicate that the importance of the N-terminal domain to Chk-induced tyrosine phosphorylation in the nucleus, and implicate that nuclear tyrosine-phosphorylated proteins may contribute to inhibition of cell proliferation. (PMID:16707123)
• Progesterone increases MATK in mast cells and reducs cell proliferation. (PMID:17492661)
• These results reveal a potentially important role for CHK in Src activation and tumorigenicity in colon cancer cells. (PMID:17934522)
• CHK is capable of inhibiting the CXCL12-CXCR4 pathway in neuroblastoma. (PMID:18292939)
• After IGF-I stimulation, CTK is recruited to IGF-IR and its recruitment facilitates CTK’s subsequent association with phospho-SHPS-1. (PMID:21799000)
• CSK-homologous kinase (CHK/MATK) is a potential colorectal cancer tumour suppressor gene epigenetically silenced by promoter methylation. (PMID:33767439)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	matk	ENSDARG00000074670
mus_musculus	Matk	ENSMUSG00000004933
rattus_norvegicus	Matk	ENSRNOG00000020431

Paralogs (32): FGR (ENSG00000000938), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Megakaryocyte-associated tyrosine-protein kinase — P42679 (reviewed: P42679)

Alternative names: CSK homologous kinase, Hematopoietic consensus tyrosine-lacking kinase, Protein kinase HYL, Tyrosine-protein kinase CTK

All UniProt accessions (10): P42679, F1T0G6, K7EKC4, K7EKS5, K7ENL8, K7EPP2, K7EQV3, K7EQY5, K7ERY4, K7ES68

UniProt curated annotations — full annotation on UniProt →

Function. Could play a significant role in the signal transduction of hematopoietic cells. May regulate tyrosine kinase activity of SRC-family members in brain by specifically phosphorylating their C-terminal regulatory tyrosine residue which acts as a negative regulatory site. It may play an inhibitory role in the control of T-cell proliferation.

Subunit / interactions. Interacts with KIT.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Expressed in various myeloid cell lines, detected in brain and lung.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P42679-1	1	yes
P42679-2	2
P42679-3	3

RefSeq proteins (3): NP_002369, NP_647611, NP_647612* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035027	Csk-like_SH2	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (35 total): strand 13, domain 3, sequence variant 3, sequence conflict 3, helix 3, splice variant 2, binding site 2, chain 1, turn 1, region of interest 1, compositionally biased region 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3US4	X-RAY DIFFRACTION	1.5
1JWO	X-RAY DIFFRACTION	2.5
1X6G	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42679-F1	84.24	0.63

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): 352 (proton acceptor)

Ligand- & substrate-binding residues (2): 241–249; 262

Post-translational modifications (1): 501

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8863795	Downregulation of ERBB2 signaling
R-HSA-1227986	Signaling by ERBB2
R-HSA-162582	Signal Transduction
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 212 (showing top): RORA1_01, RIZKI_TUMOR_INVASIVENESS_3D_DN, GNF2_ZAP70, MUELLER_PLURINET, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, AMIT_EGF_RESPONSE_120_HELA, GNF2_IL2RB, ZHU_CMV_ALL_DN, ALCALA_APOPTOSIS, GNF2_PTPN4, GAVIN_FOXP3_TARGETS_CLUSTER_P3, BLALOCK_ALZHEIMERS_DISEASE_DN, chr19p13, GOMF_PROTEIN_KINASE_ACTIVITY, RUTELLA_RESPONSE_TO_HGF_UP

GO Biological Process (2): protein phosphorylation (GO:0006468), positive regulation of cell population proliferation (GO:0008284)

GO Molecular Function (8): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by ERBB2	1
Signaling by Receptor Tyrosine Kinases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
phosphorylation	1
protein modification process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
protein kinase activity	1
protein tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MATK	SLAMF1	Q13291	875
MATK	CD48	P09326	816
MATK	PSMA7	O14818	791
MATK	RPS16	P17008	778
MATK	PTPRC	P08575	765
MATK	CD34	P28906	761
MATK	ABCG1	P45844	713
MATK	RPL32	P02433	680
MATK	MPP3	Q13368	671
MATK	ITGAM	P11215	669
MATK	IL7R	P16871	659
MATK	APOA1	P02647	633
MATK	ITGA2B	P08514	632
MATK	KITLG	P21583	623
MATK	ABCA1	O95477	620

IntAct

35 interactions, top by confidence:

A	B	Type	Score
MATK	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.620
LRRK2	MATK	psi-mi:“MI:0407”(direct interaction)	0.620
MATK	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.590
MATK	ERBB2	psi-mi:“MI:0914”(association)	0.590
MATK	KLK6	psi-mi:“MI:0915”(physical association)	0.560
MATK	BACE2	psi-mi:“MI:0915”(physical association)	0.560
CSK	MATK	psi-mi:“MI:0914”(association)	0.530
HSP90AB1	MATK	psi-mi:“MI:0915”(physical association)	0.520
MATK	FRS3	psi-mi:“MI:0915”(physical association)	0.490
MATK	PTK2B	psi-mi:“MI:0914”(association)	0.460
MATK	AR	psi-mi:“MI:0407”(direct interaction)	0.440
MATK	MET	psi-mi:“MI:0407”(direct interaction)	0.440
MATK	LRRK1	psi-mi:“MI:0407”(direct interaction)	0.440
MATK	NOC3L	psi-mi:“MI:0915”(physical association)	0.400
MATK	YWHAE	psi-mi:“MI:0915”(physical association)	0.400
SFN	MATK	psi-mi:“MI:0915”(physical association)	0.400
MATK	CDC37	psi-mi:“MI:0915”(physical association)	0.400
CACNA1A	MATK	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (48): MATK (Two-hybrid), MATK (Two-hybrid), MATK (Biochemical Activity), MATK (Affinity Capture-MS), MATK (Reconstituted Complex), MATK (Reconstituted Complex), MATK (Reconstituted Complex), MATK (Two-hybrid), MATK (Affinity Capture-Western), SIRPA (Affinity Capture-Western), MATK (Co-localization), SIRPA (Reconstituted Complex), SIRPA (Biochemical Activity), EGFR (Affinity Capture-Western), ERBB2 (Affinity Capture-Western)

ESM2 similar proteins: P00523, P00524, P00525, P00526, P00530, P00541, P00542, P00543, P05480, P06239, P06240, P07332, P08103, P08631, P09769, P12931, P13115, P13116, P14085, P14234, P14238, P15054, P16277, P16879, P23049, P25020, P31693, P41242, P41243, P42679, P42682, P42683, P50545, P51451, P53668, P53669, P55144, P55146, P63185, Q01621

Diamond homologs: A0JNB0, A1A5H8, A1Y2K1, F1LM93, F1RDG9, G5EE56, O45539, P00519, P00520, P00521, P00522, P00523, P00524, P00525, P00526, P00527, P00528, P00544, P03949, P05480, P06239, P06240, P06241, P07947, P07948, P08103, P08630, P08631, P09324, P09769, P10447, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P14234, P15054

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MATK	“down-regulates activity”	LYN	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2406 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3778418:AGTGA:A	acceptor_gain	1.0000
19:3778419:GTGA:G	acceptor_gain	1.0000
19:3778420:TGA:T	acceptor_gain	1.0000
19:3778421:GA:G	acceptor_gain	1.0000
19:3778422:ACT:A	acceptor_loss	1.0000
19:3778423:C:CC	acceptor_gain	1.0000
19:3778593:CTT:C	acceptor_gain	1.0000
19:3778596:C:CC	acceptor_gain	1.0000
19:3778986:GCTCA:G	donor_loss	1.0000
19:3778987:CTCAC:C	donor_loss	1.0000
19:3778988:TCACC:T	donor_loss	1.0000
19:3778989:CAC:C	donor_loss	1.0000
19:3778990:A:AC	donor_gain	1.0000
19:3778990:AC:A	donor_gain	1.0000
19:3778990:ACC:A	donor_gain	1.0000
19:3778990:ACCC:A	donor_gain	1.0000
19:3778991:C:CC	donor_gain	1.0000
19:3778991:C:CG	donor_loss	1.0000
19:3778991:CC:C	donor_gain	1.0000
19:3778991:CCC:C	donor_gain	1.0000
19:3778991:CCCC:C	donor_gain	1.0000
19:3778991:CCCCG:C	donor_gain	1.0000
19:3779183:CGTGC:C	acceptor_gain	1.0000
19:3779185:TGC:T	acceptor_gain	1.0000
19:3779185:TGCC:T	acceptor_loss	1.0000
19:3779186:GC:G	acceptor_gain	1.0000
19:3779187:CC:C	acceptor_gain	1.0000
19:3779188:C:CC	acceptor_gain	1.0000
19:3779194:G:C	acceptor_gain	1.0000
19:3779194:G:GC	acceptor_gain	1.0000

AlphaMissense

3271 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3779021:A:G	W390R	1.000
19:3779021:A:T	W390R	1.000
19:3779754:C:A	K262N	1.000
19:3779754:C:G	K262N	1.000
19:3784032:A:G	W122R	1.000
19:3784032:A:T	W122R	1.000
19:3778531:C:T	G421E	0.999
19:3778561:C:T	G411E	0.999
19:3778562:C:A	G411W	0.999
19:3778571:A:G	W408R	0.999
19:3778571:A:T	W408R	0.999
19:3779019:C:A	W390C	0.999
19:3779019:C:G	W390C	0.999
19:3779079:G:C	D370E	0.999
19:3779079:G:T	D370E	0.999
19:3779080:T:A	D370V	0.999
19:3779080:T:C	D370G	0.999
19:3779080:T:G	D370A	0.999
19:3779082:G:C	S369R	0.999
19:3779082:G:T	S369R	0.999
19:3779084:T:G	S369R	0.999
19:3779118:G:C	N357K	0.999
19:3779118:G:T	N357K	0.999
19:3779120:T:C	N357D	0.999
19:3779133:G:C	D352E	0.999
19:3779133:G:T	D352E	0.999
19:3779134:T:A	D352V	0.999
19:3779134:T:C	D352G	0.999
19:3779134:T:G	D352A	0.999
19:3779137:C:G	R351P	0.999

dbSNP variants (sampled 300 via entrez): RS1000125410 (19:3802932 T>C), RS1000224708 (19:3803330 C>A,T), RS1000378758 (19:3782452 C>T), RS1000413517 (19:3787436 C>T), RS1000499039 (19:3802583 C>G), RS1000575373 (19:3798946 T>C), RS1000829966 (19:3792772 C>T), RS1000944138 (19:3792926 C>G), RS1001002082 (19:3803423 A>C,G), RS1001099477 (19:3777707 G>A), RS1001159447 (19:3798436 T>C), RS1001167938 (19:3788846 C>A,T), RS1001241565 (19:3789113 G>A,C), RS1001352311 (19:3783553 GTC>G), RS1001508902 (19:3798878 T>A)

Disease associations

OMIM: gene MIM:600038 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_352	Obesity-related traits	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005109	energy expenditure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4175 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 97,603 (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
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL535	SUNITINIB	4	79,020
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL1084546	PF-00562271	1	399
CHEMBL1908397	KW-2449	1	622
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Csk family

ChEMBL bioactivities

61 potent at pChembl≥5 of 62 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	Ki	39.81	nM	ILORASERTIB
7.30	Ki	50.12	nM	CHEMBL1993661
7.20	Ki	63.1	nM	CENISERTIB
7.10	Ki	79.43	nM	CHEMBL1978448
7.10	Ki	79.43	nM	CHEMBL1991395
7.00	Ki	100	nM	PF-00562271
6.90	Ki	125.9	nM	CHEMBL1978099
6.80	Ki	158.5	nM	CHEMBL1998585
6.80	Ki	158.5	nM	CHEMBL1988838
6.70	Ki	199.5	nM	CHEMBL1973540
6.60	Ki	251.2	nM	CHEMBL2004716
6.58	Kd	260	nM	STAUROSPORINE
6.50	Ki	316.2	nM	CHEMBL1987034
6.50	Ki	316.2	nM	CHEMBL1989708
6.50	Ki	316.2	nM	CHEMBL422897
6.41	IC50	392	nM	STAUROSPORINE
6.40	Ki	398.1	nM	CHEMBL539474
6.40	Ki	398.1	nM	CHEMBL1964692
6.40	Ki	398.1	nM	CHEMBL243088
6.31	IC50	492	nM	STAUROSPORINE
6.30	Ki	501.2	nM	CHEMBL244378
6.30	Ki	501.2	nM	SP-600125
6.20	Ki	631	nM	CHEMBL1988594
6.20	Ki	631	nM	CHEMBL271381
6.20	Ki	631	nM	CHEMBL1983111
6.10	Ki	794.3	nM	CHEMBL1969372
6.10	Ki	794.3	nM	CHEMBL1985092
6.10	Ki	794.3	nM	CHEMBL196363
6.01	Kd	970	nM	LESTAURTINIB
6.00	Ki	1000	nM	CHEMBL2005886
6.00	Ki	1000	nM	CHEMBL1980896
6.00	Ki	1000	nM	CHEMBL2004544
6.00	Ki	1000	nM	CHEMBL1984162
6.00	Ki	1000	nM	CHEMBL17370
5.90	Ki	1259	nM	CHEMBL1970104
5.89	IC50	1300	nM	STAUROSPORINE
5.89	Kd	1300	nM	AST-487
5.80	Ki	1585	nM	CHEMBL246970
5.80	Ki	1585	nM	CHEMBL1991674
5.80	Ki	1585	nM	CHEMBL1966143
5.80	Ki	1585	nM	CHEMBL1991429
5.80	Ki	1585	nM	CHEMBL508928
5.80	Ki	1585	nM	CHEMBL1990885
5.80	Ki	1585	nM	CHEMBL1965507
5.80	Ki	1585	nM	CHEMBL1979883
5.80	Ki	1585	nM	CHEMBL404367
5.77	Kd	1700	nM	FEDRATINIB
5.70	Ki	1995	nM	CHEMBL1983449
5.70	Ki	1995	nM	CHEMBL1968103
5.70	Ki	1995	nM	CHEMBL2006715

PubChem BioAssay actives

13 with measured affinity, of 220 total; 9 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	624864: Binding constant for CTK kinase domain	kd	0.2600	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	507891: Binding affinity to CTK	kd	0.9700	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624864: Binding constant for CTK kinase domain	kd	1.3000	uM
Fedratinib	624864: Binding constant for CTK kinase domain	kd	1.7000	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	624864: Binding constant for CTK kinase domain	kd	2.8000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624864: Binding constant for CTK kinase domain	kd	3.0000	uM
Bosutinib	624864: Binding constant for CTK kinase domain	kd	5.8000	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	624864: Binding constant for CTK kinase domain	kd	6.2000	uM
Sunitinib	624864: Binding constant for CTK kinase domain	kd	7.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects cotreatment, decreases expression	3
Estradiol	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
GW 506033X	decreases reaction, increases expression, increases response to substance	1
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
terbufos	increases methylation	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Fonofos	increases methylation	1
Lead	affects expression	1
Lipopolysaccharides	increases response to substance, decreases reaction, affects reaction, increases expression	1
Parathion	increases methylation	1
Plant Extracts	decreases expression	1
Potassium Dichromate	increases expression	1

ChEMBL screening assays

138 unique, capped per target: 137 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1040684	Binding	Residual activity of MATK at 0.1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL1963689	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MATK	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3AV	Abcam HEK293T MATK KO	Transformed cell line	Female
CVCL_SX34	HAP1 MATK (-) 1	Cancer cell line	Male
CVCL_SX35	HAP1 MATK (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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