RIOK2

Summary

RIOK2 (RIO kinase 2, HGNC:18999) is a protein-coding gene on chromosome 5q15, encoding Serine/threonine-protein kinase RIO2 (Q9BVS4). Serine/threonine-protein kinase involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. It is a common-essential gene (DepMap: required in 95.6% of cancer cell lines).

Predicted to enable protein kinase activity. Involved in several processes, including positive regulation of rRNA processing; positive regulation of ribosomal small subunit export from nucleus; and regulation of mitotic metaphase/anaphase transition. Located in cytoplasm. Part of preribosome, small subunit precursor.

Source: NCBI Gene 55781 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 92 total
• Druggable target: yes — 17 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 95.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_018343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18999
Approved symbol	RIOK2
Name	RIO kinase 2
Location	5q15
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11159
Ensembl gene	ENSG00000058729
Ensembl biotype	protein_coding
OMIM	617754
Entrez	55781

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000283109, ENST00000508447, ENST00000508991, ENST00000510384, ENST00000511012, ENST00000511293, ENST00000511920, ENST00000902084, ENST00000924329, ENST00000924330, ENST00000924331

RefSeq mRNA: 2 — MANE Select: NM_018343 NM_001159749, NM_018343

CCDS: CCDS4089, CCDS54884

Canonical transcript exons

ENST00000283109 — 10 exons

Exon	Start	End
ENSE00000908295	97173175	97173263
ENSE00000908296	97171206	97171397
ENSE00000908297	97168760	97168852
ENSE00000908298	97167467	97167991
ENSE00000908299	97165051	97165147
ENSE00001159839	97183126	97183247
ENSE00001175067	97177116	97177291
ENSE00001229156	97160867	97163225
ENSE00003509929	97177732	97177848
ENSE00003656941	97179055	97179193

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 94.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.9749 / max 598.3145, expressed in 1795 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62717	21.9749	1795

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.87	gold quality
secondary oocyte	CL:0000655	94.36	gold quality
calcaneal tendon	UBERON:0003701	92.43	gold quality
ganglionic eminence	UBERON:0004023	92.14	gold quality
stromal cell of endometrium	CL:0002255	91.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.18	gold quality
adrenal tissue	UBERON:0018303	90.37	gold quality
ventricular zone	UBERON:0003053	90.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.53	gold quality
cortical plate	UBERON:0005343	89.40	gold quality
body of pancreas	UBERON:0001150	88.95	gold quality
mucosa of transverse colon	UBERON:0004991	88.27	gold quality
islet of Langerhans	UBERON:0000006	87.74	gold quality
gastrocnemius	UBERON:0001388	87.68	gold quality
pancreas	UBERON:0001264	87.55	gold quality
muscle of leg	UBERON:0001383	87.32	gold quality
embryo	UBERON:0000922	86.33	gold quality
left ovary	UBERON:0002119	86.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.22	gold quality
descending thoracic aorta	UBERON:0002345	86.04	gold quality
right lobe of liver	UBERON:0001114	85.95	gold quality
right ovary	UBERON:0002118	85.94	gold quality
omental fat pad	UBERON:0010414	85.92	gold quality
right adrenal gland	UBERON:0001233	85.87	gold quality
peritoneum	UBERON:0002358	85.86	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.67	gold quality
ovary	UBERON:0000992	85.63	gold quality
body of stomach	UBERON:0001161	85.57	gold quality
left adrenal gland	UBERON:0001234	85.54	gold quality
rectum	UBERON:0001052	85.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	637.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting RIOK2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
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-6758-5P	100.00	66.21	1470
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4760-5P	99.80	69.88	1619

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 11)

• Results show that the protein kinase human Rio2 (hRio2) is part of a late 40S preribosomal particle in human cells. (PMID:19564402)
• Plk1-mediated phosphorylation of Rio2 regulates metaphase-anaphase transition during mitotic progression. (PMID:21880710)
• reduced expression of RIOK1 or RIOK2 disrupted Akt signaling and caused cell cycle exit, apoptosis, and chemosensitivity in glioblastoma cells (PMID:23459592)
• As RIO2 is involved in the biosynthesis of the ribosome and cell cycle regulation, our selective ligand may be useful for the delineation of the biological role of this kinase. (PMID:25891899)
• These results suggested that RIOK2 and NOB1 may be potential targets in the treatment of Non-small cell lung cancer (NSCLC), and miR145 may be considered a therapeutic inhibitor of both genes. (PMID:29749434)
• Results describe three atomic structures of RIO2 kinase showing that it forms homodimer in vitro. Upon self-association, each protomer ATP-binding pocket is partially remodeled. The homodimerization is mediated by key residues previously shown to be responsible for ATP binding and catalysis. This data reveals an intricate mechanism where identical residues are involved in substrate binding and oligomeric state formation. (PMID:31390939)
• RIOK2 is negatively regulated by miR-4744 and promotes glioma cell migration/invasion through epithelial-mesenchymal transition. (PMID:32125767)
• BYSL contributes to tumor growth by cooperating with the mTORC2 complex in gliomas. (PMID:33628587)
• RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit. (PMID:34125833)
• Identification of RIOK2 as a master regulator of human blood cell development. (PMID:34937919)
• RIOK2 Contributes to Cell Growth and Protein Synthesis in Human Oral Squamous Cell Carcinoma. (PMID:36661680)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	riok2	ENSDARG00000035264
mus_musculus	Riok2	ENSMUSG00000116564
rattus_norvegicus	Riok2	ENSRNOG00000012692
drosophila_melanogaster	RIOK2	FBGN0039306
caenorhabditis_elegans	riok-2	WBGENE00013688

Paralogs (3): RIOK3 (ENSG00000101782), RIOK1 (ENSG00000124784), ATMIN (ENSG00000166454)

Protein

Protein identifiers

Serine/threonine-protein kinase RIO2 — Q9BVS4 (reviewed: Q9BVS4)

Alternative names: RIO kinase 2

All UniProt accessions (4): Q9BVS4, D6RB96, H0Y8R4, H0Y919

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in export of the 40S pre-ribosome particles (pre-40S) from the nucleus to the cytoplasm. Its kinase activity is required for the release of NOB1, PNO1 and LTV1 from the late pre-40S and the processing of 18S-E pre-rRNA to the mature 18S rRNA. Regulates the timing of the metaphase-anaphase transition during mitotic progression, and its phosphorylation, most likely by PLK1, regulates this function.

Subunit / interactions. Associated with late 40S pre-ribosomal particles. Interacts with PLK1 (via its N-terminus).

Subcellular location. Cytoplasm.

Post-translational modifications. Autophosphorylated (in vitro). Phosphorylation at Ser-335, Ser-380, Ser-548 by PLK1 affects the timing of the metaphase-anaphase transition.

Similarity. Belongs to the protein kinase superfamily. RIO-type Ser/Thr kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BVS4-1	1	yes
Q9BVS4-2	2

RefSeq proteins (2): NP_001153221, NP_060813* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000687	RIO_kinase	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015285	RIO2_wHTH_N	Domain
IPR018934	RIO_dom	Domain
IPR018935	RIO_kinase_CS	Conserved_site
IPR030484	Rio2	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF01163, PF09202

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 (72 total): helix 15, modified residue 14, strand 14, sequence variant 11, mutagenesis site 10, turn 2, chain 1, domain 1, splice variant 1, short sequence motif 1, active site 1, binding site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6FDM	X-RAY DIFFRACTION	2.1
5DHF	X-RAY DIFFRACTION	2.29
6HK6	X-RAY DIFFRACTION	2.35
7VBT	X-RAY DIFFRACTION	2.54
6FDO	X-RAY DIFFRACTION	2.6
6FDN	X-RAY DIFFRACTION	2.9
9F81	X-RAY DIFFRACTION	3.02
7WU0	ELECTRON MICROSCOPY	3.3
6G18	ELECTRON MICROSCOPY	3.6
6G51	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BVS4-F1	67.80	0.32

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): 228 (proton acceptor)

Ligand- & substrate-binding residues (1): 123

Post-translational modifications (14): 380, 382, 385, 390, 412, 417, 442, 445, 548, 332, 335, 337, 350, 362

Mutagenesis-validated functional residues (10):

Position	Phenotype
123	abolishes autophosphorylation; impairs release of pre-40s trans-acting factors and rrna processing; when associated with
246	abolishes autophosphorylation; impairs release of pre-40s trans-acting factors and rrna processing; when associated with
335	does not affect autophosphorylation activity; when associated with a-380 and a-548. does not affect the timing of metaph
335	increases time spent in metaphase; when associated with d-380 and d-548.
380	does not affect autophosphorylation activity; when associated with a-335 and a-548. does not affect the timing of metaph
380	increases time spent in metaphase; when associated with d-335 and d-548.
400	nuclear relocalization; when associated with a-403.
403	nuclear relocalization; when associated with a-400.
548	does not affect autophosphorylation activity; when associated with a-335 and a-380. does not affect the timing of metaph
548	increases time spent in metaphase; when associated with d-335 and d-380.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 165 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_MATURATION_OF_SSU_RRNA, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_NUCLEAR_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_CHROMOSOME_SEGREGATION, GOBP_REGULATION_OF_NUCLEOCYTOPLASMIC_TRANSPORT, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (8): regulation of mitotic metaphase/anaphase transition (GO:0030071), maturation of SSU-rRNA (GO:0030490), ribosomal small subunit biogenesis (GO:0042274), protein autophosphorylation (GO:0046777), positive regulation of ribosomal small subunit export from nucleus (GO:2000208), positive regulation of rRNA processing (GO:2000234), protein phosphorylation (GO:0006468), ribosome biogenesis (GO:0042254)

GO Molecular Function (10): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), preribosome, small subunit precursor (GO:0030688)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
rRNA processing	2
ribonucleoprotein complex biogenesis	2
protein kinase activity	2
metaphase/anaphase transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of metaphase/anaphase transition of cell cycle	1
ribosomal small subunit biogenesis	1
ribosome biogenesis	1
protein phosphorylation	1
ribosomal small subunit export from nucleus	1
positive regulation of ribosomal subunit export from nucleus	1
regulation of ribosomal small subunit export from nucleus	1
positive regulation of RNA metabolic process	1
regulation of rRNA processing	1
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
preribosome	1

Protein interactions and networks

STRING

2573 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIOK2	LTV1	Q96GA3	943
RIOK2	BYSL	Q13895	942
RIOK2	TSR1	Q2NL82	937
RIOK2	PNO1	Q9NRX1	902
RIOK2	NOB1	Q9ULX3	894
RIOK2	RRP12	Q5JTH9	842
RIOK2	RIOK3	O14730	775
RIOK2	BMS1	Q14692	764
RIOK2	RIOK1	Q9BRS2	725
RIOK2	NMD3	Q96D46	723
RIOK2	XPO1	O14980	699
RIOK2	RPS10	P46783	675
RIOK2	RPS3	P23396	667
RIOK2	LSG1	Q9H089	658
RIOK2	DHX15	O43143	647

IntAct

76 interactions, top by confidence:

A	B	Type	Score
NUP50	KPNA3	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SRPK1	SNRPC	psi-mi:“MI:0914”(association)	0.640
BYSL	PARN	psi-mi:“MI:0914”(association)	0.640
	RIOK2	psi-mi:“MI:0915”(physical association)	0.560
RIOK2	BYSL	psi-mi:“MI:0914”(association)	0.530
MINK1	CNOT1	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
MYO1C	TMOD1	psi-mi:“MI:0914”(association)	0.530
GHITM	MFN2	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
CSNK2A1	RIOK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RIOK2	SMAD3	psi-mi:“MI:0915”(physical association)	0.370
RELA	RIOK2	psi-mi:“MI:0915”(physical association)	0.370
RIOK2	GFUS	psi-mi:“MI:0915”(physical association)	0.370
RIOK2	RPRD1A	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Cep120	TBC1D31	psi-mi:“MI:0914”(association)	0.350
VPS16	TTC31	psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
TAFA3	FUOM	psi-mi:“MI:0914”(association)	0.350
GRB7	RIOK3	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
RIOK2	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
BYSL	RPS3A	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350

BioGRID (145): TSR1 (Co-fractionation), RIOK2 (Proximity Label-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS), RIOK2 (Affinity Capture-MS)

ESM2 similar proteins: A1ZAJ2, A8WRG3, A8XQD5, E7F187, G5EEM9, G5EFD2, I2HAA0, O01583, O01991, O43166, O43314, O45818, O60333, O80528, O82486, O88658, P24583, P43125, P50526, P91309, P91682, Q06685, Q10003, Q11186, Q14149, Q17BU3, Q28WQ1, Q4R8E0, Q5R9Y9, Q5REW0, Q60575, Q60L58, Q61T02, Q640I9, Q6GQT0, Q6NSI8, Q6P158, Q7PHR1, Q7YZT6, Q8C0T5

Diamond homologs: A5UAM9, A5UG81, A6VQT5, B0RTE2, B0U358, B2FR65, B2I5R8, B2SLU1, B4SLP5, O86224, P58551, Q2P6W5, Q3BWM9, Q4QNS8, Q4URM8, Q5H410, Q65R39, Q6LVM6, Q7MPR5, Q87C81, Q87T74, Q8DDZ1, Q8PBX3, Q8PNH3, Q9BVS4, Q9CLD5, Q9CQS5, Q9KVB9, Q9PBJ1, Q9UYB9, P40160, Q54T05, Q58473, Q95Q34, Q9P7W5, O30245, Q57886, D4GYY1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PLK1	“up-regulates activity”	RIOK2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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
Eukaryotic Translation Initiation	6	24.7×	4e-06
Cap-dependent Translation Initiation	6	24.7×	4e-06
SARS-CoV-1 modulates host translation machinery	6	24.7×	4e-06
Formation of the ternary complex, and subsequently, the 43S complex	8	23.0×	4e-07
Eukaryotic Translation Elongation	6	22.3×	7e-06
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	6	21.8×	8e-06
Translation initiation complex formation	8	20.3×	6e-07
Ribosomal scanning and start codon recognition	8	20.3×	6e-07

GO biological processes:

GO term	Partners	Fold	FDR
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	5	34.8×	7e-05
ribosomal small subunit biogenesis	8	18.8×	7e-06
cytoplasmic translation	8	15.3×	2e-05
translation	8	8.5×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1384 predictions. Top by Δscore:

Variant	Effect	Δscore
5:97163223:TTCC:T	acceptor_loss	1.0000
5:97163226:C:CC	acceptor_gain	1.0000
5:97163226:C:CG	acceptor_loss	1.0000
5:97163227:T:A	acceptor_loss	1.0000
5:97165044:TACTT:T	donor_loss	1.0000
5:97165045:ACTTA:A	donor_loss	1.0000
5:97165046:CT:C	donor_loss	1.0000
5:97165047:TTACT:T	donor_loss	1.0000
5:97165048:TA:T	donor_loss	1.0000
5:97165049:A:AC	donor_gain	1.0000
5:97165050:C:CT	donor_gain	1.0000
5:97165050:CT:C	donor_gain	1.0000
5:97165050:CTG:C	donor_gain	1.0000
5:97165050:CTGG:C	donor_gain	1.0000
5:97165050:CTGGA:C	donor_gain	1.0000
5:97165143:CATCT:C	acceptor_gain	1.0000
5:97165146:CT:C	acceptor_gain	1.0000
5:97165148:C:CC	acceptor_gain	1.0000
5:97165148:CTAAA:C	acceptor_loss	1.0000
5:97167989:CTC:C	acceptor_gain	1.0000
5:97167990:TC:T	acceptor_gain	1.0000
5:97167991:CC:C	acceptor_gain	1.0000
5:97167992:C:CC	acceptor_gain	1.0000
5:97168755:CAAA:C	donor_loss	1.0000
5:97168756:AAACC:A	donor_loss	1.0000
5:97168757:AAC:A	donor_loss	1.0000
5:97168758:A:AT	donor_loss	1.0000
5:97168759:C:CA	donor_loss	1.0000
5:97171204:A:AC	donor_gain	1.0000
5:97171205:C:CC	donor_gain	1.0000

AlphaMissense

3671 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:97171289:A:C	F232L	1.000
5:97171289:A:T	F232L	1.000
5:97171291:A:G	F232L	1.000
5:97171302:T:A	D228V	1.000
5:97177166:A:G	W150R	1.000
5:97177166:A:T	W150R	1.000
5:97179162:A:T	V33D	1.000
5:97168839:C:G	D265H	0.999
5:97171238:C:A	Q249H	0.999
5:97171238:C:G	Q249H	0.999
5:97171247:A:C	D246E	0.999
5:97171247:A:T	D246E	0.999
5:97171248:T:A	D246V	0.999
5:97171248:T:C	D246G	0.999
5:97171248:T:G	D246A	0.999
5:97171249:C:G	D246H	0.999
5:97171284:A:G	L234P	0.999
5:97171286:A:C	N233K	0.999
5:97171286:A:T	N233K	0.999
5:97171288:T:C	N233D	0.999
5:97171301:A:C	D228E	0.999
5:97171301:A:T	D228E	0.999
5:97171302:T:C	D228G	0.999
5:97171302:T:G	D228A	0.999
5:97171303:C:G	D228H	0.999
5:97171314:A:G	L224P	0.999
5:97173214:C:G	R183P	0.999
5:97173215:G:T	R183S	0.999
5:97173238:A:T	V175D	0.999
5:97177141:G:T	A158D	0.999

dbSNP variants (sampled 300 via entrez): RS1000092017 (5:97185099 A>G), RS1000123404 (5:97184954 C>A,G), RS1000449841 (5:97174313 G>C), RS1000500450 (5:97174607 T>A,C,G), RS1000509148 (5:97160526 C>A,G,T), RS1000690652 (5:97166967 G>A,T), RS1000698878 (5:97167369 T>C,G), RS1000701141 (5:97174345 G>A), RS1001123959 (5:97166742 G>T), RS1001368713 (5:97172701 A>G), RS1001426337 (5:97179583 C>T), RS1001780151 (5:97165978 A>G), RS1001930198 (5:97168654 C>A,T), RS1001991177 (5:97161248 A>G), RS1002020244 (5:97160864 G>A)

Disease associations

OMIM: gene MIM:617754 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Limited	Autosomal recessive

Mondo (1): (MONDO:0018393)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008708_1	Chronic mountain sickness	7.000000e-06
GCST009391_2148	Metabolite levels	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010143	chronic mountain sickness
EFO:0010551	xanthurenate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL6000 (SINGLE PROTEIN), CHEMBL6195604 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

17 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 139,815 (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
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL1908391	MASITINIB	3	2,808
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL230011	TG100-115	2	1,504
CHEMBL475251	R-406	2	762
CHEMBL521851	PICTILISIB	2	6,071
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1908397	KW-2449	1	622
CHEMBL296468	BMS-387032	1	2,075
CHEMBL4647810	ELIMUSERTIB	1	297
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 — RIO2 subfamily

ChEMBL bioactivities

83 potent at pChembl≥5 of 88 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.21	Kd	6.1	nM	CHEMBL5172767
8.14	Kd	7.3	nM	CHEMBL5174723
8.14	Kd	7.3	nM	CHEMBL5172767
8.08	Kd	8.4	nM	CHEMBL5199096
7.75	Kd	18	nM	CHEMBL5190698
7.72	Kd	19	nM	CHEMBL5399070
7.32	Kd	47.5	nM	CHEMBL5184015
7.32	Kd	48	nM	CHEMBL5417058
7.31	Kd	49	nM	CHEMBL5192566
7.31	Kd	49	nM	SUNITINIB
7.28	Kd	53	nM	CHEMBL5417476
7.25	Kd	56	nM	CHEMBL5439857
7.25	IC50	56	nM	CHEMBL5172767
7.21	Kd	62	nM	CHEMBL5406944
7.20	Kd	63	nM	CHEMBL5190197
7.20	Kd	63	nM	CHEMBL5194039
7.01	Kd	97	nM	MIDOSTAURIN
7.01	IC50	98	nM	CHEMBL6145816
6.92	Kd	120	nM	CHEMBL5190993
6.89	Kd	130	nM	CHEMBL2348353
6.89	IC50	130	nM	CHEMBL4858983
6.86	IC50	139	nM	CHEMBL5172767
6.85	Kd	140	nM	CHEMBL4781866
6.85	Kd	140	nM	CHEMBL5527885
6.85	Kd	140	nM	SU-014813
6.82	Kd	150	nM	CHEMBL4781866
6.80	Kd	160	nM	CHEMBL4781866
6.78	Kd	165	nM	CHEMBL5416400
6.70	Kd	200	nM	CHEMBL5174394
6.70	Kd	200	nM	CHEMBL2094383
6.63	Kd	235	nM	CHEMBL5187692
6.62	Kd	240	nM	CHEMBL2348350
6.60	Kd	250	nM	TOZASERTIB
6.58	Kd	260	nM	DOVITINIB
6.42	Kd	385	nM	CHEMBL5184335
6.41	Kd	390	nM	STAUROSPORINE
6.34	Kd	455	nM	CHEMBL5189953
6.28	Kd	520	nM	CHEMBL4754518
6.26	Kd	550	nM	AST-487
6.24	Kd	575	nM	CHEMBL5177849
6.21	Kd	610	nM	PAZOPANIB
6.18	Kd	660	nM	ELIMUSERTIB
6.17	Kd	670	nM	PICTILISIB
6.11	Kd	770	nM	PI-103
6.11	Kd	770	nM	PLX-4720
6.09	Kd	810	nM	CHEMBL5205288
6.08	Kd	840	nM	CHEMBL5188981
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n

PubChem BioAssay actives

74 with measured affinity, of 375 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
8-(6-methoxy-3-pyridinyl)-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.0061	uM
1-(3-chloro-4-piperazin-1-ylphenyl)-8-(6-methoxy-3-pyridinyl)-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.0073	uM
8-(6-methoxy-3-pyridinyl)-1-(3-methyl-4-piperazin-1-ylphenyl)-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.0084	uM
1-(3-fluoro-4-piperazin-1-ylphenyl)-8-(6-methoxy-3-pyridinyl)-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.0180	uM
8-(6-methoxy-3-pyridinyl)-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]-5H-pyrazolo[4,5-c]quinolin-4-one	1977525: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant by KINOMEscan assay	kd	0.0190	uM
1-(3-methoxy-4-piperazin-1-ylphenyl)-8-(6-methoxy-3-pyridinyl)-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.0475	uM
8-(6-methoxy-3-pyridinyl)-3-methyl-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]-5H-imidazo[4,5-c]quinoline-2,4-dione	1977525: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant by KINOMEscan assay	kd	0.0480	uM
8-(6-methoxy-3-pyridinyl)-5-methyl-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.0490	uM
Sunitinib	508063: Binding affinity to RIOK2	kd	0.0490	uM
8-(6-methoxy-3-pyridinyl)-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]-5H-imidazo[1,2-a]quinoxalin-4-one	1977525: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant by KINOMEscan assay	kd	0.0530	uM
8-(6-methoxy-3-pyridinyl)-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]-5H-imidazo[1,5-a]quinoxalin-4-one	1977525: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant by KINOMEscan assay	kd	0.0560	uM
8-(6-methoxy-3-pyridinyl)-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]-5H-imidazo[4,5-c]quinolin-4-one	1977525: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant by KINOMEscan assay	kd	0.0620	uM
8-(6-methoxy-3-pyridinyl)-1-[4-(4-methylpiperazin-1-yl)phenyl]-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.0630	uM
8-(6-methoxy-3-pyridinyl)-1-(4-piperazin-1-ylphenyl)-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.0630	uM
Midostaurin	508063: Binding affinity to RIOK2	kd	0.0970	uM
1-(4-methoxyphenyl)-8-(6-methoxy-3-pyridinyl)-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.1200	uM
5-(dimethylamino)-2-(pyridin-2-yldiazenyl)phenol;methanesulfonic acid	1766474: Inhibition of RIOK2 in human VCaP cells after 48 hrs by Western blotting analysis	ic50	0.1300	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	625111: Binding constant for RIOK2 kinase domain	kd	0.1400	uM
N-(4-methyl-2-pyridinyl)-2-naphthalen-2-ylacetamide	1685593: Binding affinity to RIOK2 (unknown origin)	kd	0.1400	uM
8-(6-methoxy-3-pyridinyl)-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]-5H-pyrrolo[1,2-a]quinoxalin-4-one	1977525: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant by KINOMEscan assay	kd	0.1650	uM
N-(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)-N-methylbenzamide	1910805: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant	kd	0.2000	uM
1-[(E)-2-(1,3-thiazol-2-yl)ethenyl]naphthalen-2-ol	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.2000	uM
1-(1,3-thiazol-2-yldiazenyl)naphthalen-2-ol	1977520: Binding affinity to human RIOK2 assessed as dissociation constant by KINOMEscan assay	kd	0.2000	uM
8-(6-methoxy-3-pyridinyl)-1-(4-phenylphenyl)-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.2350	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625111: Binding constant for RIOK2 kinase domain	kd	0.2500	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	625111: Binding constant for RIOK2 kinase domain	kd	0.2600	uM
8-(6-ethoxy-3-pyridinyl)-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.3850	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	625111: Binding constant for RIOK2 kinase domain	kd	0.3900	uM
1-(4-chlorophenyl)-8-(6-methoxy-3-pyridinyl)-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.4550	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625111: Binding constant for RIOK2 kinase domain	kd	0.5500	uM
8-(6-methoxy-3-pyridinyl)-1-[4-piperazin-1-yl-2-(trifluoromethyl)phenyl]-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.5750	uM
Pazopanib	625111: Binding constant for RIOK2 kinase domain	kd	0.6100	uM
(3R)-3-methyl-4-[4-(2-methylpyrazol-3-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridin-2-yl]morpholine	1652484: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system by Kinomescan method	kd	0.6600	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	625111: Binding constant for RIOK2 kinase domain	kd	0.6700	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	625111: Binding constant for RIOK2 kinase domain	kd	0.7700	uM
3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenol	625111: Binding constant for RIOK2 kinase domain	kd	0.7700	uM
8-(6-methoxy-3-pyridinyl)-1-(4-methylphenyl)-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.8100	uM
1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]-8-pyridin-3-yl-5H-triazolo[4,5-c]quinolin-4-one	1910807: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system assessed as dissociation constant by KINOMEscan assay	kd	0.8400	uM
2-[4-[(1E)-1-hydroxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]ethanol	625111: Binding constant for RIOK2 kinase domain	kd	1.2000	uM
Ruxolitinib	625111: Binding constant for RIOK2 kinase domain	kd	1.2000	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	625111: Binding constant for RIOK2 kinase domain	kd	1.5000	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	625111: Binding constant for RIOK2 kinase domain	kd	1.5000	uM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide	625111: Binding constant for RIOK2 kinase domain	kd	1.7000	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	625111: Binding constant for RIOK2 kinase domain	kd	2.0000	uM
N-[[2-methyl-4-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]phenyl]methyl]-3-propan-2-yloxyazetidine-1-carboxamide	1696278: Binding affinity to wild-type human partial length RIOK2 (M1 to D313 residues) expressed in mammalian expression system by Kinomescan method	kd	2.4000	uM
Fedratinib	625111: Binding constant for RIOK2 kinase domain	kd	2.6000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625111: Binding constant for RIOK2 kinase domain	kd	3.4000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625111: Binding constant for RIOK2 kinase domain	kd	5.0000	uM
N-(4-chloro-2-pyridinyl)-2-naphthalen-2-ylacetamide	1685587: Displacement of tracer K5 from N-terminal nanoluciferase-tagged RIOK2 (unknown origin) expressed in HEK293 cells measured after 2 hrs by NanoBRET assay	ic50	5.0000	uM
N-(4-methoxy-2-pyridinyl)-2-naphthalen-2-ylacetamide	1685587: Displacement of tracer K5 from N-terminal nanoluciferase-tagged RIOK2 (unknown origin) expressed in HEK293 cells measured after 2 hrs by NanoBRET assay	ic50	5.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
methylparaben	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
hydroquinone	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
MT19c compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Formaldehyde	decreases expression	1

ChEMBL screening assays

156 unique, capped per target: 156 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1052945	Binding	Inhibition of RIOK2 assessed as enzyme activity at 1 uM relative to untreated control	Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline. — J Med Chem

Clinical trials (associated diseases)

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