Details for: RIOX2

Gene ID: 84864

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: RIOX2

Ensembl ID: ENSG00000170854

Description: ribosomal oxygenase 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • epithelial cell CL0000066
    CSI 5.28
    rCSI 8.11%
    PRS 83.21
  • placental villous trophoblast CL2000060
    CSI 4.76
    rCSI 7.35%
    PRS 92.11
  • secretory cell CL0000151
    CSI 3.66
    rCSI 3.82%
    PRS 92.85
  • ON-bipolar cell CL0000749
    CSI 3.41
    rCSI 5.07%
    PRS 92.4
  • ionocyte CL0005006
    CSI 3.03
    rCSI 3.24%
    PRS 94.71
  • early lymphoid progenitor CL0000936
    CSI 3.03
    rCSI 2.66%
    PRS 96.01
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.94
    rCSI 6.6%
    PRS 84.3
  • mucosal invariant T cell CL0000940
    CSI 2.91
    rCSI 2.35%
    PRS 96.87
  • acinar cell CL0000622
    CSI 2.86
    rCSI 4.19%
    PRS 96.97
  • renal alpha-intercalated cell CL0005011
    CSI 2.85
    rCSI 3.81%
    PRS 95.73
  • fibroblast of lung CL0002553
    CSI 2.81
    rCSI 2.61%
    PRS 94.95
  • neural crest cell CL0011012
    CSI 2.65
    rCSI 2.09%
    PRS 88.57
  • multi-ciliated epithelial cell CL0005012
    CSI 2.58
    rCSI 2.58%
    PRS 88.95
  • rod bipolar cell CL0000751
    CSI 2.48
    rCSI 4.46%
    PRS 89.91
  • myeloid leukocyte CL0000766
    CSI 2.38
    rCSI 2.2%
    PRS 94.86
  • pulmonary ionocyte CL0017000
    CSI 2.23
    rCSI 2.71%
    PRS 96.06
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.2
    rCSI 2.73%
    PRS 81.97
  • ciliated epithelial cell CL0000067
    CSI 2.19
    rCSI 1.93%
    PRS 86.68
  • extravillous trophoblast CL0008036
    CSI 2.17
    rCSI 2.69%
    PRS 92.39
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.91
    rCSI 2.47%
    PRS 85.01
  • retinal bipolar neuron CL0000748
    CSI 1.81
    rCSI 3.39%
    PRS 87.36
  • glioblast CL0000030
    CSI 1.72
    rCSI 2.74%
    PRS 87.63
  • retinal pigment epithelial cell CL0002586
    CSI 1.62
    rCSI 3.22%
    PRS 91.03
  • suprabasal keratinocyte CL4033013
    CSI 1.38
    rCSI 2.25%
    PRS 68.31
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.21
    rCSI 1.46%
    PRS 76.18
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.04
    rCSI 2.63%
    PRS 89.73
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.69
    rCSI 2.47%
    PRS 82.24
  • direct pathway medium spiny neuron CL4023026
    CSI 0.25
    rCSI 6.08%
    PRS 81.91

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [RIOX2](/details-gene/84864) (Ribosomal Oxygenase 2) is a protein-coding gene located on chromosome 3q11.2. It functions as a histone demethylase and a ribosomal oxygenase, implicating it in the dual regulation of chromatin structure and ribosome biogenesis. Functionally, [RIOX2](/details-gene/84864) is involved in processes such as [chromatin remodeling](/details-go/GO:0006338), [negative regulation of transcription](/details-go/GO:0045892), and [ribosome biogenesis](/details-go/GO:0042254). Its expression profile indicates a fundamental role in cellular activity, with high significance observed across a wide variety of cell types. **Overall**, it is most significant in [epithelial cells](/details-cell/CL0000066), [placental villous trophoblasts](/details-cell/CL2000060), and [secretory cells](/details-cell/CL0000151), suggesting a key function in tissues characterized by high rates of proliferation, secretion, and metabolic activity. Several studies have identified [RIOX2](/details-gene/84864) (also known as MINA, NO66, or MDIG) as a Myc target gene and have linked its overexpression to proliferation in various cancers ([Link](https://doi.org/10.1074/jbc.m204458200), [Link](https://doi.org/10.1038/sj.onc.1208668)). ## Cellular Roles and Expression Landscape The expression pattern of [RIOX2](/details-gene/84864) underscores its importance in a broad range of biological contexts. The **Overall** analysis reveals its highest significance in [epithelial cells](/details-cell/CL0000066) (CSI: 5.28), which are often characterized by rapid turnover and barrier function. High significance is also noted in specialized cells like [placental villous trophoblasts](/details-cell/CL2000060) (CSI: 4.76), critical for fetal development, and various [secretory cells](/details-cell/CL0000151) (CSI: 3.66), including [acinar cells](/details-cell/CL0000622) (CSI: 2.86), indicating a role in protein production and export. Beyond epithelial and secretory lineages, [RIOX2](/details-gene/84864) shows relevance in the nervous system, with notable significance in retinal [ON-bipolar cells](/details-cell/CL0000749) and glial [astrocytes of the cerebral cortex](/details-cell/CL0002605). Furthermore, its expression in [early lymphoid progenitors](/details-cell/CL0000936), [mucosal invariant T cells](/details-cell/CL0000940), and [myeloid leukocytes](/details-cell/CL0000766) suggests a role in the development and function of the immune system. This widespread, yet distinct, expression pattern in metabolically active or proliferating cells is consistent with its documented functions in both ribosome assembly and transcriptional regulation, two fundamental processes that support cell growth and function. ## Pathways and Molecular Function [RIOX2](/details-gene/84864) is a bifunctional enzyme with well-defined roles in both the nucleus and cytoplasm. Its primary molecular functions include [histone demethylase activity](/details-go/GO:0032452), specifically targeting H3K36 and H3K4 ([GO:0051864](https://www.ebi.ac.uk/QuickGO/term/GO:0051864), [GO:0032453](https://www.ebi.ac.uk/QuickGO/term/GO:0032453)), and [peptidyl-histidine dioxygenase activity](/details-go/GO:0036139). In the nucleus, primarily within the [nucleoplasm](/details-go/GO:0005654) and as part of [transcription regulator complexes](/details-go/GO:0005667), [RIOX2](/details-gene/84864) acts as a JmjC domain-containing histone demethylase. This activity is central to its role in [chromatin organization](/details-reactome/R-HSA-4839726) and the [negative regulation of dna-templated transcription](/details-go/GO:0045892). One study demonstrated that [RIOX2](/details-gene/84864) can suppress the formation of tri-methylated lysine 9 on histone H3 (H3K9me3), a mark typically associated with heterochromatin and gene silencing ([Link](https://doi.org/10.4161/cc.8.13.8927)). This suggests it acts as a transcriptional corepressor by modifying the chromatin landscape. Concurrently, [RIOX2](/details-gene/84864) is highly active in the [nucleolus](/details-go/GO:0005730), the primary site of [ribosome biogenesis](/details-go/GO:0042254). Its function as a 60S ribosomal protein L27a histidine hydroxylase is part of the [post-translational protein modification](/details-reactome/R-HSA-597592) pathway. This enzymatic activity is crucial for the maturation of the 60S ribosomal subunit, directly linking [RIOX2](/details-gene/84864) to the cell's protein synthesis capacity. This dual functionality allows [RIOX2](/details-gene/84864) to potentially coordinate gene expression programs with the translational machinery required to execute them, a critical nexus for controlling cell growth and proliferation. ## Research Directions The established links between [RIOX2](/details-gene/84864), cell proliferation, and cancer progression provide a strong foundation for future investigation. Its overexpression has been reported as a negative prognostic factor in multiple malignancies, including esophageal, colon, and lung cancer ([Link](https://doi.org/10.1158/1078-0432.ccr-03-0543), [Link](https://doi.org/10.1016/s0002-9440(10)63111-2), [Link](https://doi.org/10.1038/sj.onc.1208668)). Based on its known functions, several testable hypotheses can be proposed: 1. **Hypothesis 1:** The dual enzymatic activities of [RIOX2](/details-gene/84864) are coordinately regulated to drive tumorigenesis. In cancer cells, its ribosomal hydroxylase function is upregulated to meet the high demand for protein synthesis, while its histone demethylase activity is targeted to specific gene promoters to silence tumor suppressors and activate oncogenic pathways. 2. **Hypothesis 2:** [RIOX2](/details-gene/84864) acts as an epigenetic dependency in certain cancers by maintaining a repressive chromatin state at key developmental or tumor suppressor loci. Its inhibition would lead to the re-expression of these genes, triggering cell cycle arrest or apoptosis. **Proposed Experimental Approach:** To test Hypothesis 2, one could employ a multi-omics approach in a relevant cancer cell line where [RIOX2](/details-gene/84864) is highly expressed, such as a lung adenocarcinoma line. * First, perform CRISPR-Cas9-mediated knockout or CRISPRi-mediated knockdown of [RIOX2](/details-gene/84864). * Subsequently, conduct parallel RNA-sequencing (RNA-seq) to identify differentially expressed genes and Chromatin Immunoprecipitation sequencing (ChIP-seq) for histone marks modulated by [RIOX2](/details-gene/84864) (e.g., H3K9me3). * Integrating these datasets would reveal genes that are both transcriptionally upregulated upon [RIOX2](/details-gene/84864) loss and show a corresponding decrease in repressive histone marks at their regulatory regions. This would directly identify the gene targets of its corepressor activity and elucidate the mechanism behind its pro-tumorigenic role. **Therapeutic Potential:** Given its enzymatic nature (oxygenase/demethylase) and its consistent overexpression in various cancers, [RIOX2](/details-gene/84864) represents a compelling therapeutic target. **Inhibition**, rather than activation, would be the desired therapeutic strategy. Its JmjC domain is a structurally defined pocket amenable to the development of small molecule inhibitors, a strategy that has proven successful for other histone demethylases. However, its broad expression in healthy, highly metabolic tissues (e.g., [epithelial cells](/details-cell/CL0000066)) suggests that systemic inhibition could lead to on-target toxicity. Therefore, the development of tumor-targeted delivery systems or inhibitors with a favorable therapeutic window would be crucial for clinical translation.

Genular Protein ID: 3081642574

Symbol: RIOX2_HUMAN

Name: 60S ribosomal protein L27a histidine hydroxylase

UniProtKB Accession Codes:

Q8IUF8 D3DN35 Q6AHW4 Q6SKS0 Q8IU69 Q8IUF6 Q8IUF7 Q96C17 Q96KB0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 16 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 16 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 12 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 2 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 Reactome 2 RefSeq 5 Rhea 6 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12091391

Title: A novel myc target gene, mina53, that is involved in cell proliferation.

PubMed ID: 12091391

DOI: 10.1074/jbc.m204458200

PubMed ID: 14742713

Title: NO66, a highly conserved dual location protein in the nucleolus and in a special type of synchronously replicating chromatin.

PubMed ID: 14742713

DOI: 10.1091/mbc.e03-08-0623

PubMed ID: 15897898

Title: The human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer.

PubMed ID: 15897898

DOI: 10.1038/sj.onc.1208668

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 14695334

Title: Increased expression of a Myc target gene Mina53 in human colon cancer.

PubMed ID: 14695334

DOI: 10.1016/s0002-9440(10)63111-2

PubMed ID: 15534111

Title: Mina53 as a potential prognostic factor for esophageal squamous cell carcinoma.

PubMed ID: 15534111

DOI: 10.1158/1078-0432.ccr-03-0543

PubMed ID: 15819408

Title: Protein NO52 -- a constitutive nucleolar component sharing high sequence homologies to protein NO66.

PubMed ID: 15819408

DOI: 10.1016/j.ejcb.2004.12.022

PubMed ID: 17317935

Title: Immunohistochemical expression of Mina53 and Ki67 proteins in human primary gingival squamous cell carcinoma.

PubMed ID: 17317935

DOI: 10.2739/kurumemedj.53.71

PubMed ID: 19502796

Title: Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3.

PubMed ID: 19502796

DOI: 10.4161/cc.8.13.8927

PubMed ID: 19608861

Title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

PubMed ID: 19608861

DOI: 10.1126/science.1175371

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23103944

Title: Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans.

PubMed ID: 23103944

DOI: 10.1038/nchembio.1093

Sequence Information:

  • Length: 465
  • Mass: 52800
  • Checksum: B59F8AE9C802FEB0
  • Sequence:
    • MPKKAKPTGS GKEEGPAPCK QMKLEAAGGP SALNFDSPSS LFESLISPIK TETFFKEFWE 
QKPLLIQRDD PALATYYGSL FKLTDLKSLC SRGMYYGRDV NVCRCVNGKK KVLNKDGKAH 
FLQLRKDFDQ KRATIQFHQP QRFKDELWRI QEKLECYFGS LVGSNVYITP AGSQGLPPHY 
DDVEVFILQL EGEKHWRLYH PTVPLAREYS VEAEERIGRP VHEFMLKPGD LLYFPRGTIH 
QADTPAGLAH STHVTISTYQ NNSWGDFLLD TISGLVFDTA KEDVELRTGI PRQLLLQVES 
TTVATRRLSG FLRTLADRLE GTKELLSSDM KKDFIMHRLP PYSAGDGAEL STPGGKLPRL 
DSVVRLQFKD HIVLTVLPDQ DQSDEAQEKM VYIYHSLKNS RETHMMGNEE ETEFHGLRFP 
LSHLDALKQI WNSPAISVKD LKLTTDEEKE SLVLSLWTEC LIQVV