RIOX2

Summary

RIOX2 (ribosomal oxygenase 2, HGNC:19441) is a protein-coding gene on chromosome 3q11.2, encoding Ribosomal oxygenase 2 (Q8IUF8). Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase.

MINA is a c-Myc (MYC; MIM 190080) target gene that may play a role in cell proliferation or regulation of cell growth. (Tsuneoka et al., 2002 [PubMed 12091391]; Zhang et al., 2005 [PubMed 15897898]).

Source: NCBI Gene 84864 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 99 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_153182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19441
Approved symbol	RIOX2
Name	ribosomal oxygenase 2
Location	3q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MINA53, FLJ14393, mdig, NO52, JMJD10
Ensembl gene	ENSG00000170854
Ensembl biotype	protein_coding
OMIM	612049
Entrez	84864

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000333396, ENST00000360258, ENST00000394198, ENST00000503097, ENST00000503517, ENST00000506099, ENST00000506682, ENST00000507612, ENST00000514314, ENST00000894038, ENST00000894039, ENST00000894040, ENST00000894041, ENST00000894042, ENST00000894043, ENST00000894044, ENST00000936354, ENST00000936355, ENST00000936356, ENST00000944345, ENST00000944346, ENST00000944347, ENST00000944348, ENST00000944349

RefSeq mRNA: 4 — MANE Select: NM_153182 NM_001042533, NM_001261829, NM_032778, NM_153182

CCDS: CCDS2929, CCDS43114

Canonical transcript exons

ENST00000394198 — 10 exons

Exon	Start	End
ENSE00001151417	97954392	97954495
ENSE00001164362	97967162	97967632
ENSE00001200827	97959051	97959179
ENSE00001200831	97961589	97961708
ENSE00001517741	97972381	97972431
ENSE00002049422	97941818	97945342
ENSE00003514069	97945798	97945887
ENSE00003518587	97950786	97950888
ENSE00003550521	97947361	97947449
ENSE00003623471	97949844	97950015

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6859 / max 292.1595, expressed in 1794 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43345	16.3955	1793
43344	0.1626	62
43342	0.0737	26
43343	0.0300	7
43339	0.0242	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.48	gold quality
oocyte	CL:0000023	96.62	gold quality
right lobe of thyroid gland	UBERON:0001119	95.95	gold quality
left lobe of thyroid gland	UBERON:0001120	95.50	gold quality
thyroid gland	UBERON:0002046	95.48	gold quality
oral cavity	UBERON:0000167	95.17	gold quality
buccal mucosa cell	CL:0002336	94.07	gold quality
medial globus pallidus	UBERON:0002477	93.67	gold quality
parotid gland	UBERON:0001831	93.30	gold quality
globus pallidus	UBERON:0001875	92.71	gold quality
body of pancreas	UBERON:0001150	92.45	gold quality
tendon of biceps brachii	UBERON:0008188	92.35	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.29	gold quality
superior surface of tongue	UBERON:0007371	92.21	gold quality
esophagus mucosa	UBERON:0002469	92.11	gold quality
epithelium of nasopharynx	UBERON:0001951	91.98	gold quality
pigmented layer of retina	UBERON:0001782	91.97	gold quality
tendon	UBERON:0000043	91.81	gold quality
mammalian vulva	UBERON:0000997	91.81	gold quality
saliva-secreting gland	UBERON:0001044	91.81	gold quality
minor salivary gland	UBERON:0001830	91.80	gold quality
gluteal muscle	UBERON:0002000	91.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.78	gold quality
mouth mucosa	UBERON:0003729	91.66	gold quality
biceps brachii	UBERON:0001507	91.56	gold quality
pharyngeal mucosa	UBERON:0000355	91.43	gold quality
tongue squamous epithelium	UBERON:0006919	91.41	gold quality
lower esophagus mucosa	UBERON:0035834	91.25	gold quality
pancreas	UBERON:0001264	91.11	gold quality
olfactory bulb	UBERON:0002264	91.11	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

130 targeting RIOX2, 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-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170

Literature-anchored findings (GeneRIF, showing 40)

• role in cell division (PMID:12091391)
• the elevated expression of Mina53 is a characteristic feature in colon cancer (PMID:14695334)
• Mina53 may have a role in progression of esophageal squamous cell carcinoma (PMID:15534111)
• Data suggests NO52 protein (MYC induced nuclear antigen) is directly involved in ribosome biogenesis, most likely during the assembly process of preribosomal particles. (PMID:15819408)
• The expression of mineral dust induced mRNA was detected in alveolar macrophages from coal miners but not from normal subjects. (PMID:15897898)
• Increased expression of Mina53 is associated with lymphoma (PMID:17786344)
• Mina53 is overexpressed in renal cell carcinoma tissue from patients with poor prognostic factors, suggesting that Mina53 overexpression is one of the factors for poor prognosis in renal cell carcinoma. (PMID:17803656)
• Mina53 was overexpressed in gastric carcinoma and associated with tumor proliferation and antioncogene inactivation. (PMID:18629780)
• The MINA protein alters histone H3 methylation contributes to the initiation or development of the human lung cancer. (PMID:19502796)
• Mina53 plays an important role in carcinogenesis and may be a target for cancer prevention. (PMID:19756735)
• favorable prognostic marker in early stage lung cancer (PMID:19914733)
• The single nucleotide polymorphism of the Mina gene is associated with the development of asthma in Chinese Han children. (PMID:21631300)
• Results imply that mdig is involved in the regulation of H3K9me3 to influence the heterochromatin structure of the genome and the expression of genes important for cell growth or transformation. (PMID:23965803)
• these data suggest that an increased expression of mdig is an important prognostic factor for poorer survival time of the breast cancer patients. (PMID:24309373)
• mina53 expression was gradually elevated during gastric carcinogenesis, and the overexpression of mina53 was correlated with different clinicopathological features between diffuse-type gastric carcinoma and intestinal-type gastric carcinoma cases. (PMID:24337011)
• results show mdig induction by arsenic is partially dependent on the JNK and STAT3 signaling pathways. (PMID:24434654)
• Increased expression of mdig in cancer tissues. (PMID:24505346)
• Mina53 can be used as a marker for pancreatic cancer (PMID:24522517)
• Mina: a Th2 response regulator meets TGFbeta. (PMID:25282476)
• in lung cancer tissues, upregulation of mdig expression accompanies with the downregulation of p27(KIP1) expression and in bronchial stump (PMID:25851349)
• Data suggest that mineral dust-induced gene protein (mdig) accomplishes its functions on chromatin, DNA repair and cell growth through interacting with the partner proteins. (PMID:26293673)
• Histone modifier genes (JMJD1C, RREB1, MINA, KDM7A) alter conotruncal heart phenotypes in 22q11.2 deletion syndrome. (PMID:26608785)
• Findings reveal the role of MINA in glioblastoma initiation and progression by controlling the cell-cycle progression through transcriptionally regulating cyclin and CDK expression via the demethylation of H3K9me3. (PMID:27292258)
• mdig directly interacts with c-myc and JAK1 in multiple myeloma (MM) cell lines, which contributes to hyperactivation of the IL-6-JAK-STAT3 signaling important for the pathogenesis of MM. (PMID:27833099)
• MDIG overexpression substantially promoted hepatocellular carcinoma cell proliferation, cell migration and spreading, whereas knockdown of MDIG would reverse above-mentioned effect. (PMID:28471446)
• Results indicate that mdig can inhibit the phosphorylation of GSK-3beta and promote the phosphorylation and destabilization of beta-catenin, in order to suppress the expression of slug, snail, and ZEB1 and the occurrence of EMT, and thereby inhibit the invasion and metastasis of non-small cell lung cancer (NSCLC). (PMID:29039479)
• RIOX2 transcripts were overexpressed in renal cell tumor subtypes compared to renal normal tissues. Higher RIOX2 transcript levels were associated with metastasis. (PMID:29099276)
• our findings revealed that Mina53 was an important indicator of prognosis in patients with stage III colorectal cancer treated with adjuvant chemotherapy. (PMID:29750310)
• MINA53 deficiency leads to glioblastoma cell apoptosis via inducing DNA replication stress and diminishing DNA damage response. (PMID:30333481)
• Mina53 regulates the differentiation and proliferation of leukemia cells. (PMID:30991463)
• Data indicate that in vitro histone demethylase MINA53 (MINA53) preferentially demethylates the histone substrate, H3K36me3. (PMID:31165872)
• Mdig promotes oncogenic gene expression through antagonizing repressive histone methylation markers. (PMID:31903140)
• Mina53 may play an important role in the occurrence of hepatocellular carcinoma and participate in the process of tumor growth as well as invasion and metastasis. (PMID:32306660)
• ZNF143-Mediated H3K9 Trimethylation Upregulates CDC6 by Activating MDIG in Hepatocellular Carcinoma. (PMID:32312832)
• Pathological and Prognostic Indications of the mdig Gene in Human Lung Cancer. (PMID:33423409)
• The mineral dust-induced gene, mdig, regulates angiogenesis and lymphangiogenesis in lung adenocarcinoma by modulating the expression of VEGF-A/C/D via EGFR and HIF-1alpha signaling. (PMID:33760153)
• Environmentally-induced mdig contributes to the severity of COVID-19 through fostering expression of SARS-CoV-2 receptor NRPs and glycan metabolism. (PMID:34335974)
• The bioinformatics analysis of RIOX2 gene in lung adenocarcinoma and squamous cell carcinoma. (PMID:34855761)
• The unfavorable clinical outcome of COVID-19 in smokers is mediated by H3K4me3, H3K9me3 and H3K27me3 histone marks. (PMID:35021853)
• Epigenomic reprogramming via HRP2-MINA dictates response to proteasome inhibitors in multiple myeloma with t(4;14) translocation. (PMID:35166240)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	riox2	ENSDARG00000036359
mus_musculus	Riox2	ENSMUSG00000022724
rattus_norvegicus	Riox2	ENSRNOG00000001680
drosophila_melanogaster	NO66	FBGN0266570
caenorhabditis_elegans	jmjc-1	WBGENE00020902

Paralogs (1): RIOX1 (ENSG00000170468)

Protein

Protein identifiers

Ribosomal oxygenase 2 — Q8IUF8 (reviewed: Q8IUF8)

Alternative names: 60S ribosomal protein L27a histidine hydroxylase, Bifunctional lysine-specific demethylase and histidyl-hydroxylase MINA, Histone lysine demethylase MINA, MYC-induced nuclear antigen, Mineral dust-induced gene protein, Nucleolar protein 52, Ribosomal oxygenase MINA

All UniProt accessions (5): A0A6M8YDW1, D6RCB6, Q8IUF8, H0Y8K4, H0Y9L8

UniProt curated annotations — full annotation on UniProt →

Function. Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase. Is involved in the demethylation of trimethylated ‘Lys-9’ on histone H3 (H3K9me3), leading to an increase in ribosomal RNA expression. Also catalyzes the hydroxylation of 60S ribosomal protein L27a on ‘His-39’. May play an important role in cell growth and survival. May be involved in ribosome biogenesis, most likely during the assembly process of pre-ribosomal particles.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Expressed in liver, skeletal muscle, heart, pancreas, and placenta. Not detected in brain, lung or kidney. Expressed in several lung cancer tissues, but is barely detected in the adjacent non-cancerous tissues. Also highly expressed in several esophageal squamous cell carcinoma (ESCC), and colon cancer tissues, and in various cancer cell lines.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Induction. Up-regulated in response to MYC, in alveolar macrophages from coal miners and in silica particle-treated A549 lung cancer cells.

Similarity. Belongs to the ROX family. MINA53 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8IUF8-1	1	yes
Q8IUF8-2	2
Q8IUF8-3	3
Q8IUF8-4	4

RefSeq proteins (4): NP_001035998, NP_001248758, NP_116167, NP_694822* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003347	JmjC_dom	Domain
IPR039994	NO66-like	Family
IPR046799	ROXA-like_wH	Domain

Pfam: PF08007, PF20514

Catalyzed reactions (Rhea), 2 shown:

• L-histidyl-[ribosomal protein uL15] + 2-oxoglutarate + O2 = (3S)-3-hydroxy-L-histidyl-[ribosomal protein uL15] + succinate + CO2 (RHEA:54024)
• L-histidyl-[protein] + 2-oxoglutarate + O2 = (3S)-3-hydroxy-L-histidyl-[protein] + succinate + CO2 (RHEA:54256)

UniProt features (64 total): strand 22, helix 18, splice variant 5, turn 5, sequence conflict 4, sequence variant 3, binding site 3, chain 1, domain 1, mutagenesis site 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4BXF	X-RAY DIFFRACTION	2.05
2XDV	X-RAY DIFFRACTION	2.57
4BU2	X-RAY DIFFRACTION	2.78

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUF8-F1	90.76	0.81

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 179; 181; 240

Post-translational modifications (1): 309

Mutagenesis-validated functional residues (1):

Position	Phenotype
179	abolishes demethylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones
R-HSA-9629569	Protein hydroxylation

MSigDB gene sets: 212 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RIBOSOME_BIOGENESIS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, NKX25_02, GCM_ZNF198, BEIER_GLIOMA_STEM_CELL_DN, BROWNE_HCMV_INFECTION_48HR_DN, BROWNE_HCMV_INFECTION_14HR_DN, WANG_TARGETS_OF_MLL_CBP_FUSION_DN, GOBP_CHROMATIN_REMODELING, DANG_BOUND_BY_MYC, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_PROTEIN_HYDROXYLATION, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN

GO Biological Process (3): ribosome biogenesis (GO:0042254), chromatin remodeling (GO:0006338), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (12): transcription corepressor activity (GO:0003714), histone demethylase activity (GO:0032452), histone H3K4 demethylase activity (GO:0032453), peptidyl-histidine dioxygenase activity (GO:0036139), identical protein binding (GO:0042802), metal ion binding (GO:0046872), histone H3K36 demethylase activity (GO:0051864), iron ion binding (GO:0005506), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), dioxygenase activity (GO:0051213)

GO Cellular Component (5): nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nucleolus (GO:0005730), cytosol (GO:0005829), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
histone H3 demethylase activity	2
2-oxoglutarate-dependent dioxygenase activity	2
nuclear lumen	2
cellular anatomical structure	2
ribonucleoprotein complex biogenesis	1
chromatin organization	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
protein demethylase activity	1
histone modifying activity	1
catalytic activity, acting on a protein	1
protein binding	1
cation binding	1
transition metal ion binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
dioxygenase activity	1
oxidoreductase activity	1
protein-containing complex	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIOX2	LRP4	O75096	783
RIOX2	TYW5	A2RUC4	743
RIOX2	RPL27A	P46776	714
RIOX2	JMJD4	Q9H9V9	703
RIOX2	WNT7A	O00755	670
RIOX2	RPL8	P25120	658
RIOX2	JMJD8	Q96S16	629
RIOX2	OGFOD1	Q8N543	604
RIOX2	KDM8	Q8N371	594
RIOX2	LMX1B	O60663	589
RIOX2	MYC	P01106	578
RIOX2	JMJD6	Q6NYC1	577
RIOX2	HSPBAP1	Q96EW2	560
RIOX2	JMJD7	P0C870	513
RIOX2	ORC5	O43913	499

IntAct

94 interactions, top by confidence:

A	B	Type	Score
SURF2	RPL5	psi-mi:“MI:0914”(association)	0.800
RIOX2	RIOX2	psi-mi:“MI:0915”(physical association)	0.740
HEXIM2	AHCYL1	psi-mi:“MI:0914”(association)	0.740
HIRIP3	CSNK2B	psi-mi:“MI:0914”(association)	0.730
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
RIOX2	LNX1	psi-mi:“MI:0915”(physical association)	0.560
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
THAP3	CASC3	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL8	ZBTB24	psi-mi:“MI:0914”(association)	0.530
C1orf174	AHCYL1	psi-mi:“MI:0914”(association)	0.530
SURF2	HEXIM1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
YJU2B	RCCD1	psi-mi:“MI:0914”(association)	0.530
RPL18	NAP1L1	psi-mi:“MI:0914”(association)	0.530
RBMX2	WDR46	psi-mi:“MI:0914”(association)	0.530
RPL13	RRP8	psi-mi:“MI:0914”(association)	0.530
ZSCAN5A	KDM1A	psi-mi:“MI:0914”(association)	0.530
RIOX2	tax	psi-mi:“MI:0915”(physical association)	0.490
tax	RIOX2	psi-mi:“MI:0915”(physical association)	0.490
NPM1	WDR46	psi-mi:“MI:0914”(association)	0.480
UIMC1	RIOX2	psi-mi:“MI:0915”(physical association)	0.400
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350

BioGRID (126): MINA (Two-hybrid), MINA (Affinity Capture-RNA), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS), MINA (Two-hybrid), EXOC7 (Co-fractionation), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS)

ESM2 similar proteins: A2AV36, A2RSX7, A2RUC4, A4IHY0, A6QQV6, A8E534, B2GUS6, B5XF11, E1C7T6, E9PYK3, F1RET2, P0C870, P0C872, P47823, P59723, P83006, Q08BV2, Q08BY5, Q0VCA8, Q0WVR4, Q3UDE2, Q3V3E1, Q58CU3, Q5BKC6, Q5EA24, Q5R673, Q5U4E8, Q5ZHV5, Q5ZIB9, Q66KI9, Q67XX3, Q67ZB6, Q6AXL5, Q6PCI6, Q7T0X7, Q7TMC8, Q8BFT6, Q8BGG7, Q8BK58, Q8BLR9

Diamond homologs: A3KP59, A5PK74, A8QFQ3, A8XEA2, B0WMG3, B3MSI4, B3NU20, B4GUZ2, B4I100, B4JMQ2, B4L6Q5, B4M7P8, B4NP88, B4Q068, B4R4H1, B5DUH6, C3XRY1, D3ZU57, O01658, Q16W06, Q54K96, Q5EA24, Q5R673, Q5ZMM1, Q7K4H4, Q8CD15, Q8CFC1, Q8IUF8, Q9H6W3, Q9JJF3, P27431, P44683

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 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
Peptide chain elongation	16	28.2×	2e-17
Viral mRNA Translation	16	28.2×	2e-17
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	16	27.9×	2e-17
Selenocysteine synthesis	16	26.7×	2e-17
Eukaryotic Translation Termination	16	26.7×	2e-17
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	16	26.2×	2e-17
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	16	26.2×	2e-17
Formation of a pool of free 40S subunits	16	24.9×	5e-17

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	17	30.9×	2e-18
ribosomal small subunit biogenesis	8	17.9×	3e-06
translation	16	16.1×	9e-13
negative regulation of translation	6	11.5×	2e-03
rRNA processing	7	9.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2067 predictions. Top by Δscore:

Variant	Effect	Δscore
3:97942283:GGCCA:G	acceptor_gain	1.0000
3:97945233:T:A	donor_gain	1.0000
3:97945343:C:CC	acceptor_gain	1.0000
3:97945793:CAAA:C	donor_loss	1.0000
3:97945794:AAAC:A	donor_loss	1.0000
3:97945795:AAC:A	donor_loss	1.0000
3:97945796:A:AG	donor_loss	1.0000
3:97945797:CC:C	donor_loss	1.0000
3:97945797:CCT:C	donor_gain	1.0000
3:97945886:TCC:T	acceptor_loss	1.0000
3:97945887:CC:C	acceptor_loss	1.0000
3:97945887:CCTT:C	acceptor_gain	1.0000
3:97945888:C:CA	acceptor_loss	1.0000
3:97945889:T:A	acceptor_loss	1.0000
3:97945890:T:TC	acceptor_gain	1.0000
3:97947359:A:AC	donor_gain	1.0000
3:97947360:C:CC	donor_gain	1.0000
3:97949902:AAAAT:A	donor_gain	1.0000
3:97949906:T:TA	donor_gain	1.0000
3:97949910:T:TA	donor_gain	1.0000
3:97950889:C:CC	acceptor_gain	1.0000
3:97950896:A:AC	acceptor_gain	1.0000
3:97950896:A:C	acceptor_gain	1.0000
3:97950902:C:CT	acceptor_gain	1.0000
3:97950902:C:T	acceptor_gain	1.0000
3:97950903:A:T	acceptor_gain	1.0000
3:97958025:CTGA:C	acceptor_gain	1.0000
3:97961583:TCTTA:T	donor_loss	1.0000
3:97961584:CTTA:C	donor_loss	1.0000
3:97961585:TTA:T	donor_loss	1.0000

AlphaMissense

3046 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:97954406:G:C	S257R	0.998
3:97954406:G:T	S257R	0.998
3:97954408:T:G	S257R	0.998
3:97954459:G:C	H240D	0.998
3:97959146:A:G	W196R	0.998
3:97959146:A:T	W196R	0.998
3:97961606:G:C	H179D	0.997
3:97961599:T:A	D181V	0.996
3:97961599:T:G	D181A	0.996
3:97961646:A:C	N165K	0.996
3:97961646:A:T	N165K	0.996
3:97954420:G:C	H253D	0.995
3:97954467:C:A	G237V	0.995
3:97954480:A:C	Y233D	0.995
3:97959144:C:A	W196C	0.995
3:97959144:C:G	W196C	0.995
3:97961598:A:C	D181E	0.995
3:97961598:A:T	D181E	0.995
3:97954470:C:A	R236I	0.994
3:97961599:T:C	D181G	0.994
3:97961600:C:G	D181H	0.994
3:97961651:A:G	S164P	0.994
3:97954467:C:T	G237E	0.993
3:97959145:C:G	W196S	0.993
3:97959151:T:A	K194I	0.993
3:97961614:A:G	L176P	0.993
3:97954468:C:G	G237R	0.992
3:97954468:C:T	G237R	0.992
3:97961590:T:A	E184V	0.992
3:97961604:A:C	H179Q	0.992

dbSNP variants (sampled 300 via entrez): RS1000068386 (3:97973544 G>A,T), RS1000069027 (3:97944780 A>T), RS1000323736 (3:97950088 C>T), RS1000490114 (3:97971281 C>A,T), RS1000843127 (3:97965609 T>C), RS1000844745 (3:97969777 G>A), RS1000874225 (3:97970191 T>C), RS1000956848 (3:97958383 T>C), RS1000960517 (3:97965925 T>A,C), RS1001039297 (3:97957024 G>A,T), RS1001061650 (3:97962836 T>G), RS1001113061 (3:97957280 C>T), RS1001305441 (3:97950967 T>C,G), RS1001335880 (3:97973926 G>T), RS1001468040 (3:97958615 T>C)

Disease associations

OMIM: gene MIM:612049 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465328 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 9 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.69	IC50	2050	nM	MOLIBRESIB

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-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178963: Inhibition of MINA (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	2.0500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression	5
trichostatin A	increases expression, affects expression, affects cotreatment	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
cobaltous chloride	decreases expression	2
Estradiol	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
1-nitropyrene	increases expression	1
nivalenol	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
arsenic trichloride	increases expression, increases phosphorylation, decreases reaction, affects reaction	1
perfluoro-n-nonanoic acid	increases expression	1
pyrazolanthrone	decreases reaction, increases expression, increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
stattic	decreases reaction, increases expression, increases phosphorylation	1
bisphenol S	decreases methylation	1
Wortmannin	decreases reaction, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5364267	Binding	Inhibition of N-terminal his6-tagged RIOX2 (26 to 465 residues) (unknown origin) expressed in Escherichia coli using RPL27A (31 to 49 residues) as substrate by SPE-MS analysis	5-Substituted Pyridine-2,4-dicarboxylate Derivatives Have Potential for Selective Inhibition of Human Jumonji-C Domain-Containing Protein 5. — J Med Chem

Clinical trials (associated diseases)

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