MOK

Summary

MOK (MOK protein kinase, HGNC:9833) is a protein-coding gene on chromosome 14q32.31, encoding MAPK/MAK/MRK overlapping kinase (Q9UQ07). Able to phosphorylate several exogenous substrates and to undergo autophosphorylation. It is a selective cancer dependency (DepMap: 10.9% of cell lines).

This gene belongs to the MAP kinase superfamily. The gene was found to be regulated by caudal type transcription factor 2 (Cdx2) protein. The encoded protein, which is localized to epithelial cells in the intestinal crypt, may play a role in growth arrest and differentiation of cells of upper crypt and lower villus regions. Multiple alternatively spliced transcript variants encoding different isoforms have been observed for this gene.

Source: NCBI Gene 5891 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 93 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.9% of screened cell lines
• MANE Select transcript: NM_014226

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9833
Approved symbol	MOK
Name	MOK protein kinase
Location	14q32.31
Locus type	gene with protein product
Status	Approved
Aliases	RAGE1, STK30
Ensembl gene	ENSG00000080823
Ensembl biotype	protein_coding
OMIM	605762
Entrez	5891

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 15 protein_coding, 10 nonsense_mediated_decay, 9 protein_coding_CDS_not_defined, 8 retained_intron

ENST00000361847, ENST00000517537, ENST00000517966, ENST00000518045, ENST00000518399, ENST00000518482, ENST00000518686, ENST00000519058, ENST00000519477, ENST00000519569, ENST00000519877, ENST00000520046, ENST00000520238, ENST00000520252, ENST00000520266, ENST00000521249, ENST00000521388, ENST00000521493, ENST00000521766, ENST00000521937, ENST00000521966, ENST00000522093, ENST00000522534, ENST00000522537, ENST00000522867, ENST00000522874, ENST00000523169, ENST00000523231, ENST00000523485, ENST00000524019, ENST00000524120, ENST00000524207, ENST00000524214, ENST00000524370, ENST00000557823, ENST00000559138, ENST00000559512, ENST00000559838, ENST00000561150, ENST00000562292, ENST00000899019, ENST00000899020

RefSeq mRNA: 9 — MANE Select: NM_014226 NM_001272011, NM_001330234, NM_001353827, NM_001353828, NM_001353829, NM_001353830, NM_001353831, NM_001353832, NM_014226

CCDS: CCDS61552, CCDS81854, CCDS9971

Canonical transcript exons

ENST00000361847 — 12 exons

Exon	Start	End
ENSE00002090783	102304962	102305164
ENSE00002115313	102228836	102229366
ENSE00003465433	102229457	102229657
ENSE00003503276	102251917	102251995
ENSE00003511493	102265823	102265912
ENSE00003563772	102231707	102231821
ENSE00003572348	102283478	102283592
ENSE00003614832	102232535	102232708
ENSE00003642516	102251756	102251804
ENSE00003668101	102263546	102263616
ENSE00003676550	102233688	102233789
ENSE00003684357	102250812	102250990

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 98.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.0387 / max 255.5398, expressed in 1654 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145036	8.9781	1534
145025	1.4068	256
145014	1.0981	499
145013	1.0107	457
145037	0.8674	517
145015	0.1771	83
145012	0.0960	26
145021	0.0710	12
145027	0.0627	31
145016	0.0416	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.13	gold quality
left testis	UBERON:0004533	97.04	gold quality
right testis	UBERON:0004534	96.85	gold quality
testis	UBERON:0000473	94.78	gold quality
epithelium of bronchus	UBERON:0002031	93.12	gold quality
adenohypophysis	UBERON:0002196	92.95	gold quality
cortical plate	UBERON:0005343	92.77	gold quality
bronchial epithelial cell	CL:0002328	92.66	gold quality
bronchus	UBERON:0002185	92.30	gold quality
pituitary gland	UBERON:0000007	91.71	gold quality
sural nerve	UBERON:0015488	91.33	gold quality
right lobe of thyroid gland	UBERON:0001119	91.19	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.17	gold quality
left lobe of thyroid gland	UBERON:0001120	91.03	gold quality
thyroid gland	UBERON:0002046	90.35	gold quality
right frontal lobe	UBERON:0002810	89.81	gold quality
left ovary	UBERON:0002119	88.52	gold quality
right ovary	UBERON:0002118	88.39	gold quality
nucleus accumbens	UBERON:0001882	88.23	gold quality
ventricular zone	UBERON:0003053	88.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.11	gold quality
apex of heart	UBERON:0002098	87.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.95	gold quality
metanephros cortex	UBERON:0010533	87.93	gold quality
caudate nucleus	UBERON:0001873	87.68	gold quality
right atrium auricular region	UBERON:0006631	87.54	gold quality
cingulate cortex	UBERON:0003027	87.29	gold quality
anterior cingulate cortex	UBERON:0009835	87.10	gold quality
endocervix	UBERON:0000458	87.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.82	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	30.03
E-GEOD-137537	yes	20.80
E-CURD-114	yes	11.39
E-ANND-3	yes	10.91
E-GEOD-124858	no	221.55
E-MTAB-6142	no	136.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2

miRNA regulators (miRDB)

15 targeting MOK, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-5699-5P	97.36	67.03	1014
HSA-MIR-6836-3P	97.08	64.99	712
HSA-MIR-196B-3P	85.79	67.95	91

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• RAGE was demonstrated in all 8 yolk sac tumors and 21 of 26 embryonal carcinomas. In yolk sac tumors, RAGE reactivity was diffusely present throughout the tumors. In embryonal carcinomas, RAGE was identified only in yolk sac components (PMID:12777992)
• identification of MOK, a member of the mitogen-activated protein kinase superfamily, as one of the genes induced by a caudal-related homeobox transcription factor, Cdx2 (PMID:15327990)
• May provide suitable targets for immunotherapy of renal cell carcinoma. (PMID:15900605)
• Compared RAGE and PAX-2 staining in metastatic clear renal cell carcinoma. (PMID:18685487)
• POLL is under genetic selection in Sub-Saharan African populations. (PMID:19060005)
• The RAGE pathway may play an important role in STAT3 induction in glioma-associated macrophages and microglia, a process that may be mediated through S100B. (PMID:21264954)
• PBMNC from type 2 diabetics were more sensitive to innate immune stimulation with LPS and monoclonal agonist anti-TLR4 than were cells from ND. The actions of LPS, anti-TLR4 and anti-RAGE potentiated the production of IL-6 and TNF-alpha in both groups. (PMID:21377387)
• Our results suggest that RAGE may be important in tumor invasion and could be a potential predictor for the prognosis of hepatocellular carcinoma patients. (PMID:21717246)
• the expressions of ICK/MAK/MOK proteins in the intestinal tract can be differentially and dynamically regulated, implicating a significant functional diversity within this group of protein kinases. (PMID:24244486)
• The findings indicate a statistically significant association of p.Gly82Ser polymorphism in RAGE with DR in T2DM patients. (PMID:24529564)
• our results suggest MOK promoter hypomethylation is a common event and contributes to MOK overexpression in acute myeloid leukemia (PMID:25755699)
• RAGE silencing deters CML-AGE induced inflammation and TLR4 expression in endothelial cells. (PMID:33639133)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mok	ENSMUSG00000056458
rattus_norvegicus	Mok	ENSRNOG00000007850
caenorhabditis_elegans	F52B5.2	WBGENE00009921

Paralogs (19): MAPK9 (ENSG00000050748), MAPK6 (ENSG00000069956), NLK (ENSG00000087095), SRPK1 (ENSG00000096063), MAPK1 (ENSG00000100030), MAPK3 (ENSG00000102882), MAPK8 (ENSG00000107643), MAPK10 (ENSG00000109339), MAK (ENSG00000111837), MAPK14 (ENSG00000112062), CILK1 (ENSG00000112144), SRPK2 (ENSG00000135250), MAPK4 (ENSG00000141639), MAPK13 (ENSG00000156711), MAPK7 (ENSG00000166484), MAPK15 (ENSG00000181085), SRPK3 (ENSG00000184343), MAPK11 (ENSG00000185386), MAPK12 (ENSG00000188130)

Protein

Protein identifiers

MAPK/MAK/MRK overlapping kinase — Q9UQ07 (reviewed: Q9UQ07)

Alternative names: MOK protein kinase, Renal tumor antigen 1

All UniProt accessions (11): Q9UQ07, E5RFX9, E5RHT7, E5RHY4, E5RI85, H0YBV8, H0YKX6, H0YLZ5, H0YM36, H0YMY9, H3BNF8

UniProt curated annotations — full annotation on UniProt →

Function. Able to phosphorylate several exogenous substrates and to undergo autophosphorylation. Negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner.

Subcellular location. Cytoplasm. Cell projection. Cilium. Nucleus.

Tissue specificity. Expressed in heart, brain, lung, kidney, and pancreas, and at very low levels in placenta, liver and skeletal muscle. Detected in retina.

Post-translational modifications. Autophosphorylated.

Activity regulation. Phosphorylation appears to increase the enzymatic activity.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UQ07-1	1	yes
Q9UQ07-2	2
Q9UQ07-3	3, RAGE-1 ORF5, RAGE-2 ORF5, RAGE-3 ORF5
Q9UQ07-4	4, RAGE-4 ORF3
Q9UQ07-5	5
Q9UQ07-6	6

RefSeq proteins (9): NP_001258940, NP_001317163, NP_001340756, NP_001340757, NP_001340758, NP_001340759, NP_001340760, NP_001340761, NP_055041* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050117	MAPK	Family

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (25 total): splice variant 7, sequence variant 7, region of interest 2, sequence conflict 2, compositionally biased region 2, binding site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UQ07-F1	76.98	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): 128 (proton acceptor)

Ligand- & substrate-binding residues (2): 10–18; 33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): MORF_RAGE, YAGI_AML_WITH_INV_16_TRANSLOCATION, LU_IL4_SIGNALING, KYNG_DNA_DAMAGE_DN, KYNG_DNA_DAMAGE_BY_4NQO, YOKOE_CANCER_TESTIS_ANTIGENS, AAACCAC_MIR140, XU_RESPONSE_TO_TRETINOIN_DN, MORF_FANCG, GOBP_REGULATION_OF_CELL_CYCLE, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, MORF_PML, RFX1_02, MORF_IKBKG, MORF_MT4

GO Biological Process (16): intracellular signal transduction (GO:0035556), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), epidermal growth factor receptor signaling pathway (GO:0007173), positive regulation of macrophage chemotaxis (GO:0010759), positive regulation of telomere maintenance (GO:0032206), regulation of stress-activated MAPK cascade (GO:0032872), cellular response to amino acid starvation (GO:0034198), stress-activated MAPK cascade (GO:0051403), regulation of cytoskeleton organization (GO:0051493), regulation of cell cycle (GO:0051726), response to epidermal growth factor (GO:0070849), caveolin-mediated endocytosis (GO:0072584), regulation of Golgi inheritance (GO:0090170), positive regulation of macrophage proliferation (GO:0120041), regulation of early endosome to late endosome transport (GO:2000641)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), MAP kinase activity (GO:0004707), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphatase binding (GO:0019902)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), cilium (GO:0005929), ciliary base (GO:0097546), early endosome (GO:0005769), late endosome (GO:0005770), Golgi apparatus (GO:0005794), caveola (GO:0005901), focal adhesion (GO:0005925), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
regulation of cellular process	2
MAPK cascade	2
protein kinase activity	2
protein serine/threonine kinase activity	2
intracellular membrane-bounded organelle	2
endosome	2
signal transduction	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
ERBB signaling pathway	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
telomere maintenance	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
regulation of MAPK cascade	1
stress-activated MAPK cascade	1
regulation of stress-activated protein kinase signaling cascade	1
cellular response to starvation	1
response to amino acid starvation	1
stress-activated protein kinase signaling cascade	1
cytoskeleton organization	1
regulation of organelle organization	1
cell cycle	1
response to growth factor	1
endocytosis	1
Golgi inheritance	1
regulation of Golgi organization	1
macrophage proliferation	1
positive regulation of leukocyte proliferation	1

Protein interactions and networks

STRING

941 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOK	MAGEA1	P43355	780
MOK	CDC37	Q16543	603
MOK	MBP	P02686	547
MOK	TARDBP	Q13148	486
MOK	PRAME	P78395	430
MOK	CD80	P33681	427
MOK	GAGE4	P0DSO3	420
MOK	HSPA4	P34932	391
MOK	HSPA8	P11142	369
MOK	SMIM19	Q96E16	363
MOK	SHC2	P98077	358
MOK	IFT46	Q9NQC8	338
MOK	MAGED4B	Q96JG8	323
MOK	OR8B12	Q8NGG6	311
MOK	CTAG1A	P78358	308

IntAct

22 interactions, top by confidence:

A	B	Type	Score
MOK	H1-3	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
S100P	MOK	psi-mi:“MI:0915”(physical association)	0.400
PRP4K	MOK	psi-mi:“MI:0915”(physical association)	0.400
ANXA2	MOK	psi-mi:“MI:0915”(physical association)	0.400
CLPB	MOK	psi-mi:“MI:0915”(physical association)	0.400
DGKD	MOK	psi-mi:“MI:0915”(physical association)	0.400
ECHDC1	MOK	psi-mi:“MI:0915”(physical association)	0.400
MOK	ACTB	psi-mi:“MI:0915”(physical association)	0.400
MOK	SDF4	psi-mi:“MI:0915”(physical association)	0.400
MOK	CDC37	psi-mi:“MI:0915”(physical association)	0.400
MOK	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
IMPDH1	LCMT2	psi-mi:“MI:0914”(association)	0.350
CAMK2D	SETD1A	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
CAMK2A	SMCHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): HIST1H1D (Affinity Capture-MS), PNPO (Affinity Capture-MS), NAA50 (Affinity Capture-MS), MOK (Affinity Capture-MS), PNPO (Affinity Capture-MS), HIST1H1D (Affinity Capture-MS), MOK (Affinity Capture-MS), NAA50 (Affinity Capture-MS), MOK (Affinity Capture-MS), MOK (Proximity Label-MS), MOK (Proximity Label-MS), MOK (Proximity Label-MS), MOK (Proximity Label-MS), MOK (Proximity Label-MS), MOK (Positive Genetic)

ESM2 similar proteins: F1QGZ6, G4NEB8, O35099, O35942, O54785, O54863, O54992, O64816, O96017, P45985, P47809, P49187, P51955, P53350, P53351, P53666, P53670, P53671, P53779, P62205, P70032, Q07192, Q07832, Q13163, Q21029, Q28GW8, Q2TA25, Q32L23, Q3SZW1, Q5HZ38, Q5R4L1, Q61241, Q61831, Q62673, Q62862, Q63651, Q6DE87, Q6NU47, Q6NU98, Q8BPM2

Diamond homologs: A2X6X1, A2XFC8, A2XUW1, A2YCH5, A8WIP6, B0Y8W7, B3WFY8, G4N0Z0, G4NH08, G5EFV5, O04160, O23145, O42376, O42781, O80345, P16892, P18266, P20793, P20794, P21127, P23573, P24788, P27638, P38615, P39073, P43288, P43289, P43294, P46892, P47812, P49841, P51136, P51137, P51138, P51139, P54665, P54666, Q00532, Q00859, Q03957

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3109 predictions. Top by Δscore:

Variant	Effect	Δscore
14:102232606:CAT:C	acceptor_gain	1.0000
14:102232608:T:TC	acceptor_gain	1.0000
14:102232611:CG:C	acceptor_gain	1.0000
14:102232612:G:C	acceptor_gain	1.0000
14:102232612:G:GC	acceptor_gain	1.0000
14:102232615:C:CT	acceptor_gain	1.0000
14:102232616:A:T	acceptor_gain	1.0000
14:102232628:CATTG:C	acceptor_gain	1.0000
14:102232630:T:C	acceptor_gain	1.0000
14:102232630:T:TC	acceptor_gain	1.0000
14:102232632:G:C	acceptor_gain	1.0000
14:102232632:G:GC	acceptor_gain	1.0000
14:102233684:TTACT:T	donor_loss	1.0000
14:102233685:TACTG:T	donor_loss	1.0000
14:102233686:A:AC	donor_gain	1.0000
14:102233686:AC:A	donor_loss	1.0000
14:102233687:C:CA	donor_gain	1.0000
14:102233687:CT:C	donor_gain	1.0000
14:102233687:CTG:C	donor_gain	1.0000
14:102233687:CTGT:C	donor_gain	1.0000
14:102233687:CTGTT:C	donor_gain	1.0000
14:102233785:GCAGA:G	acceptor_gain	1.0000
14:102233786:CAGA:C	acceptor_gain	1.0000
14:102233786:CAGAC:C	acceptor_gain	1.0000
14:102233790:C:CC	acceptor_gain	1.0000
14:102250986:TCCTG:T	acceptor_gain	1.0000
14:102250987:CCTGC:C	acceptor_gain	1.0000
14:102250988:CTG:C	acceptor_gain	1.0000
14:102250991:C:CC	acceptor_gain	1.0000
14:102265917:CG:C	acceptor_gain	1.0000

AlphaMissense

2742 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:102283501:T:A	K33N	0.999
14:102283501:T:G	K33N	0.999
14:102250846:A:G	W186R	0.998
14:102250846:A:T	W186R	0.998
14:102250967:G:C	D145E	0.998
14:102250967:G:T	D145E	0.998
14:102250968:T:A	D145V	0.998
14:102283555:A:C	F15L	0.998
14:102283555:A:T	F15L	0.998
14:102283557:A:G	F15L	0.998
14:102250906:A:G	W166R	0.997
14:102250906:A:T	W166R	0.997
14:102250968:T:C	D145G	0.997
14:102250968:T:G	D145A	0.997
14:102251777:T:A	K130N	0.997
14:102251777:T:G	K130N	0.997
14:102251784:T:A	D128V	0.997
14:102251784:T:G	D128A	0.997
14:102251787:C:A	R127I	0.997
14:102250841:G:C	S187R	0.996
14:102250841:G:T	S187R	0.996
14:102250843:T:G	S187R	0.996
14:102250899:C:G	R168P	0.996
14:102250969:C:G	D145H	0.996
14:102251766:A:T	I134K	0.996
14:102251768:A:C	N133K	0.996
14:102251768:A:T	N133K	0.996
14:102251784:T:C	D128G	0.996
14:102263590:A:G	L80P	0.996
14:102283502:T:A	K33I	0.996

dbSNP variants (sampled 300 via entrez): RS1000017027 (14:102257848 G>A,C), RS1000043280 (14:102302845 C>A), RS1000075652 (14:102302970 T>G), RS1000099179 (14:102265328 C>T), RS1000115952 (14:102280218 A>C,G), RS1000123869 (14:102238629 C>A), RS1000146268 (14:102290183 T>C), RS1000176671 (14:102224991 G>A,T), RS1000252044 (14:102283075 CAATGGATCATAAAATCA>C), RS1000265965 (14:102230461 T>C), RS1000266143 (14:102274273 G>A,T), RS1000307653 (14:102271912 T>G), RS1000310616 (14:102252573 T>C), RS1000324286 (14:102268211 T>C), RS1000330732 (14:102235794 T>G)

Disease associations

OMIM: gene MIM:605762 | disease phenotypes: MIM:252940

GenCC curated gene-disease

Mondo (1): mucopolysaccharidosis type 3D (MONDO:0009658)

Orphanet (2): Mucopolysaccharidosis type 3 (Orphanet:581), Sanfilippo syndrome type D (Orphanet:79272)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007656_14	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	1.000000e-11
GCST009257_7	Caudate nucleus volume	3.000000e-06
GCST90002404_355	Red cell distribution width	6.000000e-29

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004830	caudate nucleus volume
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295983 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — RCK family

ChEMBL bioactivities

32 potent at pChembl≥5 of 44 total, top 32 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	Kd	2	nM	CHEMBL5879765
8.52	Kd	3	nM	CHEMBL6005155
8.10	Kd	8	nM	CHEMBL5796991
8.00	Kd	10	nM	CHEMBL5881386
7.96	Kd	11	nM	CHEMBL5971800
7.89	Kd	13	nM	CHEMBL5758869
7.80	Kd	16	nM	CHEMBL6042160
7.66	Kd	22	nM	CHEMBL6044780
7.60	Kd	25	nM	CHEMBL5859519
7.57	Kd	27	nM	CHEMBL6040216
7.54	Kd	29	nM	CHEMBL5778641
7.50	Kd	32	nM	CHEMBL5975898
7.50	Kd	32	nM	CHEMBL5888873
7.47	Kd	34	nM	CHEMBL5854141
7.47	Kd	34	nM	CHEMBL5993424
7.33	Kd	47	nM	CHEMBL5755226
7.27	Kd	54	nM	CHEMBL5881976
7.25	Kd	56	nM	CHEMBL5810909
7.14	Kd	72	nM	CHEMBL5832403
7.12	Kd	76	nM	CHEMBL5863353
7.10	Kd	80	nM	CHEMBL5750595
7.09	Kd	81	nM	CHEMBL5896875
7.05	Kd	89	nM	CHEMBL6055437
6.91	Kd	122	nM	CHEMBL5800530
6.91	Kd	122	nM	CHEMBL5861457
6.86	Kd	137	nM	CHEMBL5964098
6.78	Kd	168	nM	CHEMBL6046917
5.93	IC50	1180	nM	CHEMBL5396715
5.89	Kd	1300	nM	CHEMBL5944537
5.87	Kd	1340	nM	CHEMBL5991110
5.72	Kd	1900	nM	CHEMBL5890011
5.24	Kd	5800	nM	CHEMBL5844499

PubChem BioAssay actives

1 with measured affinity, of 17 total; 1 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
2-[3-[2-[[(3S)-1-(cyclopropanecarbonyl)piperidin-3-yl]amino]pyrimidin-4-yl]-2-naphthalen-2-ylimidazol-4-yl]acetonitrile	2031920: Inhibition of MOK (unknown origin) assessed as incorporation of 33P-ATP	ic50	1.1800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Tretinoin	decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
thifluzamide	increases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	decreases expression	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation, increases expression	1
Vinblastine	affects response to substance	1

ChEMBL screening assays

26 unique, capped per target: 26 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4191067	Binding	Inhibition of recombinant human MOK (1 to 343 residues) at 1 uM using RSRSRSRSRSRSRSR as substrate after 40 mins in presence of [gamma-33P]ATP by scintillation counting method	Discovery of pyrazolopyrimidine derivatives as novel inhibitors of ataxia telangiectasia and rad3 related protein (ATR). — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1XD	Abcam HeLa MOK KO	Cancer cell line	Female
CVCL_SY74	HAP1 MOK (-) 1	Cancer cell line	Male
CVCL_SY75	HAP1 MOK (-) 2	Cancer cell line	Male
CVCL_SY76	HAP1 MOK (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05648851	Not specified	COMPLETED	A Natural History Study of Sanfilippo Syndrome Type D