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 — automated summary from GO annotations (Alliance of Genome Resources).

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
• GTEx eGene: eQTL in 41 tissues, sQTL in 2 (q < 0.05)
• ChEMBL bioactivity: 17 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 95.6% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.01 (unconstrained)
• MANE Select transcript: NM_018343
• Interaction hub: 1,986 STRING partners (top 8% of genes corpus-wide)
• Notable: 92 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 18 — 10 protein_coding, 6 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000283109

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 1, TSL 4: 1

ENST00000283109, ENST00000508447, ENST00000508991, ENST00000510384, ENST00000511012, ENST00000511293, ENST00000511920, ENST00000902084, ENST00000924329, ENST00000924330, ENST00000924331, ENST00000996015, ENST00000996016, ENST00001019121, ENST00001019122, ENST00001088548, ENST00001088549, ENST00001138077

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.

Highest expression (Bgee): oocyte, secondary oocyte, calcaneal tendon, ganglionic eminence, stromal cell of endometrium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RIOK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 41 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 43 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	1.5e-39	-0.32	5:97161137:T:TAG
Cells Cultured fibroblasts	eqtl	5.1e-35	-0.27	5:97161137:T:TAG
Artery Tibial	eqtl	2.7e-19	-0.24	5:97161137:T:TAG
Adipose Subcutaneous	eqtl	1.1e-12	-0.22	5:97161137:T:TAG
Brain Hypothalamus	eqtl	6.4e-12	-0.45	5:97161137:T:TAG
Brain Cortex	eqtl	9.9e-12	-0.48	5:97161137:T:TAG
Nerve Tibial	eqtl	2.6e-11	-0.18	5:97161137:T:TAG
Artery Aorta	eqtl	1.7e-09	-0.17	5:97171092:T:C
Heart Left Ventricle	eqtl	2.8e-07	-0.17	5:97161137:T:TAG
Thyroid	eqtl	3.6e-07	-0.15	5:97161137:T:TAG
Esophagus Mucosa	eqtl	5.7e-07	+0.15	5:97181292:A:T
Skin Sun Exposed Lower leg	eqtl	1.0e-06	-0.13	5:97171092:T:C
Brain Nucleus accumbens basal ganglia	eqtl	2.4e-06	-0.35	5:97161137:T:TAG
Brain Frontal Cortex BA9	eqtl	2.7e-06	-0.35	5:97161137:T:TAG
Adipose Visceral Omentum	eqtl	1.1e-05	+0.15	5:97184902:C:T
Brain Hippocampus	eqtl	1.3e-05	-0.33	5:97161137:T:TAG
Brain Anterior cingulate cortex BA24	eqtl	1.4e-05	-0.40	5:97161137:T:TAG
Brain Cerebellum	eqtl	2.0e-05	-0.29	5:97161137:T:TAG
Brain Cerebellar Hemisphere	eqtl	4.1e-05	-0.25	5:97161137:T:TAG
Breast Mammary Tissue	eqtl	5.2e-05	-0.16	5:97161137:T:TAG

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
62717	21.9749	1795

Top tissues by expression

showing 100 of 283 tissues 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
adenohypophysis	UBERON:0002196	85.45	gold quality
right adrenal gland cortex	UBERON:0035827	85.40	gold quality
right atrium auricular region	UBERON:0006631	85.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.27	gold quality
thoracic aorta	UBERON:0001515	85.23	gold quality
colonic epithelium	UBERON:0000397	85.18	gold quality
left adrenal gland cortex	UBERON:0035825	85.18	gold quality
ascending aorta	UBERON:0001496	85.14	gold quality
monocyte	CL:0000576	85.10	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.10	gold quality
leukocyte	CL:0000738	85.02	gold quality
heart left ventricle	UBERON:0002084	85.00	gold quality
body of uterus	UBERON:0009853	84.95	gold quality
adrenal gland	UBERON:0002369	84.93	gold quality
lower esophagus	UBERON:0013473	84.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.91	gold quality
left uterine tube	UBERON:0001303	84.89	gold quality
minor salivary gland	UBERON:0001830	84.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.79	gold quality
mononuclear cell	CL:0000842	84.78	gold quality
left coronary artery	UBERON:0001626	84.75	gold quality
pituitary gland	UBERON:0000007	84.62	gold quality
esophagus	UBERON:0001043	84.59	gold quality
cardiac ventricle	UBERON:0002082	84.57	gold quality
aorta	UBERON:0000947	84.54	gold quality
left lobe of thyroid gland	UBERON:0001120	84.50	gold quality
right lobe of thyroid gland	UBERON:0001119	84.45	gold quality
transverse colon	UBERON:0001157	84.43	gold quality
esophagus mucosa	UBERON:0002469	84.37	gold quality
popliteal artery	UBERON:0002250	84.25	gold quality
stomach	UBERON:0000945	84.24	gold quality
tibial artery	UBERON:0007610	84.24	gold quality
endocervix	UBERON:0000458	83.93	gold quality
biceps brachii	UBERON:0001507	83.92	gold quality
colon	UBERON:0001155	83.89	gold quality
large intestine	UBERON:0000059	83.87	gold quality
thyroid gland	UBERON:0002046	83.86	gold quality
heart	UBERON:0000948	83.78	gold quality
vagina	UBERON:0000996	83.74	gold quality
right coronary artery	UBERON:0001625	83.65	gold quality
cartilage tissue	UBERON:0002418	83.65	gold quality
tendon	UBERON:0000043	83.63	gold quality
adrenal cortex	UBERON:0001235	83.61	gold quality
adipose tissue	UBERON:0001013	83.59	gold quality
intestine	UBERON:0000160	83.55	gold quality
spleen	UBERON:0002106	83.53	gold quality
mouth mucosa	UBERON:0003729	83.50	gold quality
connective tissue	UBERON:0002384	83.47	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.46	gold quality
muscle organ	UBERON:0001630	83.41	gold quality
skeletal muscle organ	UBERON:0014892	83.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.40	gold quality
peripheral nervous system	UBERON:0000010	83.37	gold quality
tibial nerve	UBERON:0001323	83.37	gold quality
coronary artery	UBERON:0001621	83.37	gold quality
upper lobe of left lung	UBERON:0008952	83.23	gold quality
ectocervix	UBERON:0012249	83.21	gold quality
granulocyte	CL:0000094	83.07	gold quality
cardiac atrium	UBERON:0002081	83.01	gold quality
tibia	UBERON:0000979	82.92	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	82.85	gold quality
metanephros cortex	UBERON:0010533	82.79	gold quality
skin of abdomen	UBERON:0001416	82.70	gold quality
upper lobe of lung	UBERON:0008948	82.53	gold quality
right lung	UBERON:0002167	82.42	gold quality
saliva-secreting gland	UBERON:0001044	82.36	gold quality
tonsil	UBERON:0002372	82.32	gold quality
apex of heart	UBERON:0002098	82.27	gold quality
right uterine tube	UBERON:0001302	82.26	gold quality
right testis	UBERON:0004534	82.26	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pons	tissue	24.6
Thalamus	tissue	23.6
Superior colliculi	tissue	23.3
Midbrain	tissue	21.9
Septum	tissue	21.5
Cerebellum	tissue	21.1	high
Putamen	tissue	21.0
Substantia nigra	tissue	21.0
Cerebral cortex	tissue	20.6	low
Somatosensory cortex	tissue	20.6
Medulla oblongata	tissue	20.5
Hippocampal formation	tissue	20.5
Spinal cord	tissue	20.3
Bone marrow	tissue	20.3	high
Hypothalamus	tissue	19.5
Caudate putamen	tissue	19.5
Periaqueductal gray	tissue	19.2
Frontal cortex	tissue	19.0
Basal ganglia	tissue	18.6	medium
Ventral forebrain	tissue	18.3
Entorhinal cortex	tissue	18.2
Retina	tissue	18.0
Olfactory bulb	tissue	17.9
Temporal cortex	tissue	17.8
Corpus callosum	tissue	17.6
Postcentral gyrus	tissue	17.0
Motor cortex	tissue	16.8
Amygdala	tissue	16.8
Occipital cortex	tissue	16.8
Choroid plexus	tissue	16.5
Retrosplenial and cingulate cortex	tissue	16.4
Prefrontal cortex	tissue	15.7
Retrosplenial cortex	tissue	15.4
Pancreas	tissue	15.3	medium
Nucleus accumbens	tissue	15.1
Insular cortex	tissue	14.7
Locus coeruleus	tissue	14.4
Pituitary gland	tissue	14.2
Breast	tissue	13.8	high
Adrenal gland	tissue	13.8	medium
Skeletal muscle	tissue	13.7	low
Liver	tissue	13.6	not detected
Lymph node	tissue	13.3	high
Tongue	tissue	13.3
Ovary	tissue	13.2	high
Thymus	tissue	12.7
Tonsil	tissue	12.7	high
Appendix	tissue	12.7	high
Colon	tissue	12.5	medium
Adipose tissue	tissue	12.3	not detected
Urinary bladder	tissue	12.3	medium
Spleen	tissue	12.2	not detected
Duodenum	tissue	12.2	high
Hippocampus	tissue	12.1	not detected
Vagina	tissue	11.8	medium
Rectum	tissue	11.8	medium
Epididymis	tissue	11.7	medium
Stomach 1	tissue	11.6	high
Placenta	tissue	11.4	high
Testis	tissue	10.9	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar cortex (21.9), Dorsal hippocampus (20.5), Ventral spinal cord (20.3), Corpus callosum, genu (white matter) (19.8), Dorsal spinal cord (19.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting RIOK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 92 miRNAs:

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

gnomAD constraint: pLI 2.7e-08, LOEUF 1.01, missense Z 1.47 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000283109 — one region, missense o/e 0.87. DepMap (CRISPR cell-line fitness): dependent in 95.6% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): U-87 MG (-1.972), NCI-H82 (-1.694), MJ (-1.67), HEL 92.1.7 (-1.666), Set-2 (-1.506), SW579 (-1.439), TE-10 (-1.42), NCI-H209 (-1.381), KLE (-1.363), UOK101 (-1.319), JM1 (-1.307), SK-N-SH (-1.296), KP-N-YN (-1.268), SNU-668 (-1.267), SK-N-AS (-1.26).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914295) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 28 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased hematocrit	1
increased monocyte cell number	1
decreased neutrophil cell number	1
abnormal immune system morphology	1
abnormal hematopoietic system physiology	1
anemia	1
abnormal CD4-positive, alpha beta T cell morphology	1
decreased hemoglobin content	1
decreased erythrocyte cell number	1
increased circulating alanine transaminase level	1
increased hematopoietic stem cell number	1
increased circulating aspartate transaminase level	1
increased circulating bilirubin level	1
abnormal CD4-positive, alpha-beta T cell physiology	1
increased NK T cell number	1
abnormal interleukin secretion	1
abnormal circulating interleukin level	1
increased physiological sensitivity to xenobiotic	1
decreased erythroid progenitor cell number	1
abnormal bone marrow cell physiology	1
increased susceptibility to xenobiotic induced morbidity/mortality	1
prenatal lethality, complete penetrance	1
preweaning lethality, incomplete penetrance	1
embryonic lethality prior to organogenesis	1
prenatal lethality prior to heart atrial septation	1

+3 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Stenotrophomonas maltophilia K279a	B2FR65	97.6%	Diamond
Stenotrophomonas maltophilia R551-3	B4SLP5	97.6%	Diamond
Dictyostelium discoideum	Q54T05	61.9%	Diamond
Schizosaccharomyces pombe 972h-	Q9P7W5	54.2%	Diamond
Saccharomyces cerevisiae S288C	P40160	48.9%	Diamond
Methanocaldococcus jannaschii DSM 2661	Q58473	37.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC01340	ncRNA	102546227
LIX1	protein-coding	167410
LNPEP	protein-coding	4012
LIX1-AS1	ncRNA	101926893
ERAP1	protein-coding	51752

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)

• 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 by resolution:

PDB	Title	Method	Resolution (Å)
6FDM	Human Rio2 kinase structure	X-RAY DIFFRACTION	2.1
5DHF	Crystal Structure of hRio2 NES Peptide in complex with CRM1-Ran-RanBP1	X-RAY DIFFRACTION	2.29
6HK6	Human RIOK2 bound to inhibitor	X-RAY DIFFRACTION	2.35
7VBT	Crystal structure of RIOK2 in complex with CQ211	X-RAY DIFFRACTION	2.54
6FDO	Rio2 structure	X-RAY DIFFRACTION	2.6
6FDN	Rio2 structure	X-RAY DIFFRACTION	2.9
9F81	Crystal structure of RIOK2 with a covalent compound GCL 47	X-RAY DIFFRACTION	3.02
7WU0	Cryo-EM structure of a human pre-40S ribosomal subunit - State RRP12-B3	ELECTRON MICROSCOPY	3.3
6G18	Cryo-EM structure of a late human pre-40S ribosomal subunit - State C	ELECTRON MICROSCOPY	3.6
6G51	Cryo-EM structure of a late human pre-40S ribosomal subunit - State D	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Atypical kinases, Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane

Antibody reliability (HPA): IH uncertain · IF approved

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)

Position	Role
228	proton acceptor

Ligand- & substrate-binding residues (1)

Position	Role
123	ATP

Post-translational modifications (14)

Type	Positions
Phosphoserine	380, 382, 385, 390, 412, 417, 442, 548, 332, 335, 337, 350, 362
Phosphotyrosine	445

Mutagenesis-validated functional residues (10)

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

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol	curated
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72312	rRNA processing	—
R-HSA-8868773	rRNA processing in the nucleus 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 (7): regulation of mitotic metaphase/anaphase transition (GO:0030071), maturation of SSU-rRNA (GO:0030490), ribosomal small subunit biogenesis (GO:0042274), 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

3 top-level categories:

Category	Pathways
rRNA processing in the nucleus and cytosol	1
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

34 GO namespaces:

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
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
anion 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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
maturation of SSU-rRNA	BP	mutant phenotype
positive regulation of rRNA processing	BP	direct assay
positive regulation of ribosomal small subunit export from nucleus	BP	mutant phenotype
regulation of mitotic metaphase/anaphase transition	BP	mutant phenotype
ribosomal small subunit biogenesis	BP	mutant phenotype
cytoplasm	CC	mutant phenotype
preribosome, small subunit precursor	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,986 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIOK2	LTV1	Q96GA3	866
RIOK2	BYSL	Q13895	850
RIOK2	TSR1	Q2NL82	840
RIOK2	NOB1	Q9ULX3	838
RIOK2	PNO1	Q9NRX1	803
RIOK2	RPS19	P39019	799
RIOK2	RIOK3	O14730	772
RIOK2	RRP12	Q5JTH9	751
RIOK2	NMD3	Q96D46	712
RIOK2	RPS3	P23396	625
RIOK2	RCL1	Q9Y2P8	604
RIOK2	LSG1	Q9H089	602
RIOK2	DHX15	O43143	600
RIOK2	NOP14	P78316	598
RIOK2	BMS1	Q14692	591

IntAct

Human interaction partners of RIOK2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
BYSL	association	0.530	1
CSNK2A1	phosphorylation reaction	0.440	1
GFUS	physical association	0.370	1
RELA	physical association	0.370	1
RPRD1A	physical association	0.370	1
SMAD3	physical association	0.370	1
MACROH2A1	association	0.350	1
VPS26A	association	0.350	1

BioGRID (148 interactions; top human partners by supporting records): BYSL (Affinity Capture-MS; 6 records), TSR1 (Co-fractionation; 4 records), FAM19A3 (Affinity Capture-MS; 2 records), HECTD1 (Affinity Capture-MS; 2 records), MTOR (Affinity Capture-Western; 2 records), PARP1 (Proximity Label-MS; 2 records), PIP4K2C (Affinity Capture-MS; 2 records), RELA (Affinity Capture-MS; 2 records), ABCF3 (Affinity Capture-MS), ABT1 (Affinity Capture-MS), ACACA (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), AKR7L (Affinity Capture-MS), AMY2A (Affinity Capture-MS), ANAPC15 (Affinity Capture-MS)

SIGNOR signaling

showing 1 of 3 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for RIOK2: 92 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 43 predictions of 807):

Position(s)	Effect	Δscore	Sites
5:97163226–97163227	acceptor_loss	1.0000	5
5:97165049–97165050	donor_loss	1.0000	5
5:97165148	acceptor_loss	1.0000
5:97168758–97168759	donor_loss	1.0000	5
5:97171204–97171205	donor_loss	1.0000	5
5:97171398–97171399	acceptor_loss	1.0000	4
5:97173173–97173174	donor_loss	1.0000	5
5:97173264–97173265	acceptor_loss	1.0000	5
5:97177293	acceptor_loss	1.0000	3
5:97177730–97177731	donor_loss	1.0000	5

AlphaMissense

1,216 missense substitutions predicted likely pathogenic (of 3,671 scored), across 288 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M188	9	0.937	0.992
M27	9	0.900	0.988
M250	9	0.883	0.995
M25	9	0.826	0.958
D246	8	0.998	0.999
D228	8	0.997	1.000
D265	8	0.995	0.999
H226	8	0.993	0.998
D81	8	0.989	0.996
F132	8	0.989	0.999
N233	8	0.989	0.999
H30	8	0.984	0.998
H184	8	0.978	0.994
D140	8	0.957	0.988
H125	8	0.955	0.998
F247	8	0.953	0.992
N29	8	0.951	0.994
F262	8	0.944	0.995
D297	8	0.942	0.970
H255	8	0.940	0.989

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	unfavorable	0.00072
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.000769

Disease associations

OMIM: gene MIM:617754 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

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

Mondo (1): (MONDO:0018393)

GWAS associations

2 associations:

Study	Trait	p-value
GCST008708_1	Chronic mountain sickness	7e-6
GCST009391_2148	Metabolite levels	7e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 143,912 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

17 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL1789941	RUXOLITINIB	4	12,161
CHEMBL535	SUNITINIB	4	80,232
CHEMBL522892	DOVITINIB	3	5,162
CHEMBL603469	LESTAURTINIB	3
CHEMBL1908391	MASITINIB	3	2,941
CHEMBL521851	PICTILISIB	2	6,322
CHEMBL475251	R-406	2	787
CHEMBL1721885	SU-014813	2	375
CHEMBL230011	TG100-115	2	1,586
CHEMBL572878	TOZASERTIB	2	3,128
CHEMBL574738	AST-487	1	468
CHEMBL296468	BMS-387032	1	2,127
CHEMBL4647810	ELIMUSERTIB	1	316
CHEMBL1908397	KW-2449	1	655

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — RIO2 subfamily

Binding affinities (BindingDB)

57 measured of 126 human assays (129 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
CEP-701	KD	3.4 nM
Staurosporine, 8	IC50	6.5 nM
CHEMBL5174723	KD	7.3 nM
CHEMBL5199096	KD	8.4 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
CHEMBL5190698	KD	18 nM
CHEMBL5399070	KD	19 nM
CHEMBL5184015	KD	48 nM
CHEMBL5417058	KD	48 nM
CHEMBL5192566	KD	49 nM
CHEMBL5417476	KD	53 nM
CHEMBL5439857	KD	56 nM
CHEMBL5406944	KD	62 nM
CHEMBL5190197	KD	63 nM
CHEMBL5194039	KD	63 nM
CHEMBL6145816	IC50	98 nM
PKC-412	KD	110 nM
CHEMBL5190993	KD	120 nM
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	KD	120 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
CHEMBL5172767	IC50	139 nM
CHEMBL5527885	KD	140 nM
CHEMBL5416400	KD	165 nM
CHEMBL5174394	KD	200 nM
CHEMBL5187692	KD	235 nM
2-[(3R)-3-methylmorpholin-4-yl]-4-(1-methyl-1H-pyrazol-5-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridine	IC50	330 nM
CHEMBL5184335	KD	385 nM
CHEMBL4744041	KD	430 nM
CHEMBL5189953	KD	455 nM
CHEMBL5177849	KD	575 nM
CHEMBL1908397	KD	650 nM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	KD	740 nM
(9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-di(metheno)dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione	IC50	743 nM
CHEMBL5205288	KD	810 nM
CHEMBL5188981	KD	840 nM
CHEMBL4754904	IC50	860 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CHEMBL4749658	IC50	1900 nM
3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol	KD	2400 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
SUNITINIB MALATE	KD	3500 nM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide	KD	3900 nM	US-20250129067: PLATELET-DERIVED GROWTH FACTOR RECEPTOR (PDGFR) ALPHA INHIBITORS AND USES THEREOF
CHEMBL4754518	IC50	4500 nM
CHEMBL4744511	IC50	4800 nM
CHEMBL4781866	IC50	5200 nM
CHEMBL4750817	IC50	5300 nM
CHEMBL4777902	IC50	7500 nM

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

82 with measured affinity, of 451 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	2213153: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant	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	2213153: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant	kd	0.0970	uM
(E)-1-(4-fluorophenyl)-4-[4-[4-[8-(6-methoxy-3-pyridinyl)-4-oxo-5H-triazolo[4,5-c]quinolin-1-yl]-2-(trifluoromethyl)phenyl]piperazin-1-yl]but-2-ene-1,4-dione	2213189: Inhibition of RIOK2 (unknown origin) ATPase activity incubated for 2 hrs in presence of ATP by ADP-Glo assay	ic50	0.0980	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
5-[(E)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	2213153: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant	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
(2S)-2-(6-methoxynaphthalen-2-yl)-N-(4-methyl-2-pyridinyl)propanamide	2213153: Binding affinity to RIOK2 (unknown origin) assessed as dissociation constant	kd	0.5200	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

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
Particulate Matter	decreases expression, increases abundance, affects 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	affects cotreatment, increases abundance, increases expression	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	increases abundance, increases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RIOK2 across ~30M SureChEMBL compounds — explore on Sugi Predict.