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
• GTEx eGene: eQTL in 20 tissues, sQTL in 1 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.98 (unconstrained)
• MANE Select transcript: NM_153182
• Notable: 99 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 30 — 23 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000394198

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

ENST00000394198, ENST00000333396, ENST00000360258, ENST00000503097, ENST00000503517, ENST00000506099, ENST00000506682, ENST00000507612, ENST00000514314, ENST00000894038, ENST00000894039, ENST00000894040, ENST00000894041, ENST00000894042, ENST00000894043, ENST00000894044, ENST00000936354, ENST00000936355, ENST00000936356, ENST00000944345, ENST00000944346, ENST00000944347, ENST00000944348, ENST00000944349, ENST00000977383, ENST00001036758, ENST00001036759, ENST00001036760, ENST00001112179, ENST00001138484

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.

Highest expression (Bgee): secondary oocyte, oocyte, lobe of thyroid gland, thyroid gland, oral cavity.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RIOX2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 21 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.1e-40	+0.41	3:98015083:G:A
Esophagus Mucosa	eqtl	2.0e-11	-0.15	3:97957309:C:G
Brain Frontal Cortex BA9	eqtl	5.1e-06	+0.38	3:97931871:A:G
Skin Sun Exposed Lower leg	eqtl	5.3e-06	-0.13	3:97957309:C:G
Whole Blood	eqtl	2.4e-05	+0.16	3:97874641:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.0e-04	-0.15	3:97822174:C:T
Muscle Skeletal	eqtl	2.1e-04	-0.11	3:97826055:C:T
Nerve Tibial	eqtl	2.5e-04	+0.16	3:97973519:C:G
Adipose Visceral Omentum	eqtl	3.5e-04	-0.12	3:97777811:A:G
Cells EBV-transformed lymphocytes	eqtl	4.1e-04	+0.17	3:97726625:T:C
Pancreas	eqtl	3.2e-03	-0.19	3:97840498:T:C
Esophagus Muscularis	eqtl	3.4e-03	-0.13	3:97785448:TTG:T
Artery Tibial	eqtl	5.7e-03	+0.41	3:97964652:G:A
Heart Left Ventricle	eqtl	6.5e-03	-0.13	3:97785448:TTG:T
Cells EBV-transformed lymphocytes	sqtl	1.3e-02	-1.49	3:97939859:T:C
Brain Cortex	eqtl	1.6e-02	-0.25	3:98703744:G:C
Brain Cerebellum	eqtl	2.0e-02	+0.22	3:97945881:C:T
Prostate	eqtl	3.4e-02	-0.93	3:98213254:A:G
Heart Atrial Appendage	eqtl	3.5e-02	-0.15	3:97965910:G:A
Adrenal Gland	eqtl	4.3e-02	+0.15	3:97874641:C:T

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

showing 100 of 295 tissues 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
gastrocnemius	UBERON:0001388	91.06	gold quality
tongue	UBERON:0001723	90.96	gold quality
calcaneal tendon	UBERON:0003701	90.95	gold quality
oviduct epithelium	UBERON:0004804	90.81	gold quality
pericardium	UBERON:0002407	90.75	gold quality
colonic epithelium	UBERON:0000397	90.68	gold quality
vagina	UBERON:0000996	90.58	gold quality
type B pancreatic cell	CL:0000169	90.57	silver quality
muscle of leg	UBERON:0001383	90.54	gold quality
penis	UBERON:0000989	90.51	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.48	gold quality
placenta	UBERON:0001987	90.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.40	gold quality
bronchial epithelial cell	CL:0002328	90.39	gold quality
lymph node	UBERON:0000029	90.32	gold quality
rectum	UBERON:0001052	90.26	gold quality
esophagus squamous epithelium	UBERON:0006920	90.26	gold quality
hair follicle	UBERON:0002073	90.23	gold quality
adipose tissue	UBERON:0001013	90.17	gold quality
islet of Langerhans	UBERON:0000006	90.16	gold quality
spinal cord	UBERON:0002240	90.09	gold quality
connective tissue	UBERON:0002384	90.05	gold quality
skin of abdomen	UBERON:0001416	89.90	gold quality
substantia nigra pars compacta	UBERON:0001965	89.80	gold quality
zone of skin	UBERON:0000014	89.72	gold quality
epithelium of esophagus	UBERON:0001976	89.66	gold quality
cardia of stomach	UBERON:0001162	89.65	gold quality
tonsil	UBERON:0002372	89.60	gold quality
epithelium of bronchus	UBERON:0002031	89.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.53	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.53	gold quality
squamous epithelium	UBERON:0006914	89.53	gold quality
bronchus	UBERON:0002185	89.52	gold quality
trigeminal ganglion	UBERON:0001675	89.51	gold quality
muscle organ	UBERON:0001630	89.47	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.44	gold quality
upper leg skin	UBERON:0004262	89.42	gold quality
body of tongue	UBERON:0011876	89.38	gold quality
mammary duct	UBERON:0001765	89.25	gold quality
peritoneum	UBERON:0002358	89.22	gold quality
omental fat pad	UBERON:0010414	89.21	gold quality
fallopian tube	UBERON:0003889	89.16	gold quality
esophagus	UBERON:0001043	89.15	gold quality
metanephros cortex	UBERON:0010533	89.15	gold quality
cauda epididymis	UBERON:0004360	89.09	gold quality
skin of leg	UBERON:0001511	89.06	gold quality
lateral globus pallidus	UBERON:0002476	89.05	gold quality
nucleus accumbens	UBERON:0001882	89.04	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.03	gold quality
epithelium of mammary gland	UBERON:0003244	88.98	gold quality
skeletal muscle tissue	UBERON:0001134	88.97	gold quality
corpus callosum	UBERON:0002336	88.97	gold quality
gingiva	UBERON:0001828	88.94	gold quality
caecum	UBERON:0001153	88.92	gold quality
pylorus	UBERON:0001166	88.92	gold quality
urinary bladder	UBERON:0001255	88.89	gold quality
colonic mucosa	UBERON:0000317	88.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.57	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.56	gold quality
tibial nerve	UBERON:0001323	88.53	gold quality
vermiform appendix	UBERON:0001154	88.52	gold quality
superficial temporal artery	UBERON:0001614	88.52	gold quality
trachea	UBERON:0003126	88.36	gold quality
mammary gland	UBERON:0001911	88.35	gold quality
thoracic mammary gland	UBERON:0005200	88.33	gold quality
sigmoid colon	UBERON:0001159	88.32	gold quality
amniotic fluid	UBERON:0000173	88.31	gold quality
superior vestibular nucleus	UBERON:0007227	88.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.21	gold quality
female reproductive system	UBERON:0000474	88.20	gold 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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thyroid gland	tissue	43.4	high
Corpus callosum	tissue	22.0
Nucleus accumbens	tissue	20.6
Locus coeruleus	tissue	20.4
Esophagus	tissue	18.3	not detected
Skeletal muscle	tissue	17.3	low
Skin 1	tissue	16.8	low
Salivary gland	tissue	16.4	not detected
Putamen	tissue	16.3
Hippocampus	tissue	15.9	not detected
Retina	tissue	15.6
Spinal cord	tissue	15.3
Choroid plexus	tissue	14.7
Placenta	tissue	14.6	high
Vagina	tissue	14.0	low
Pancreas	tissue	14.0	medium
Medulla oblongata	tissue	14.0
Tonsil	tissue	14.0	low
Postcentral gyrus	tissue	13.8
Appendix	tissue	13.6	medium
Caudate putamen	tissue	13.4
Lymph node	tissue	13.3	low
Midbrain	tissue	13.1
Substantia nigra	tissue	12.8
Adipose tissue	tissue	12.4	not detected
Breast	tissue	12.2	not detected
Ventral forebrain	tissue	12.2
Thalamus	tissue	11.7
Basal ganglia	tissue	11.6	not detected
Rectum	tissue	11.5	medium
Urinary bladder	tissue	11.5	high
Liver	tissue	11.4	not detected
Superior colliculi	tissue	11.1
Kidney	tissue	10.9	low
Pons	tissue	10.5
Tongue	tissue	10.5
Periaqueductal gray	tissue	10.5
Hippocampal formation	tissue	10.4
Parathyroid gland	tissue	10.1	not detected
Epididymis	tissue	10.0	not detected
Frontal cortex	tissue	9.9
Smooth muscle	tissue	9.7	low
Colon	tissue	9.6	medium
Fallopian tube	tissue	9.6	medium
Prostate	tissue	9.5	not detected
Septum	tissue	9.3
Cerebral cortex	tissue	9.0	low
Ovary	tissue	9.0	not detected
Seminal vesicle	tissue	9.0	low
Hypothalamus	tissue	9.0
Somatosensory cortex	tissue	9.0
Pituitary gland	tissue	8.9
Motor cortex	tissue	8.7
Occipital cortex	tissue	8.6
Stomach 1	tissue	8.4	high
Adrenal gland	tissue	8.4	low
Heart muscle	tissue	8.1	low
Spleen	tissue	7.9	not detected
Retrosplenial and cingulate cortex	tissue	7.9
Retrosplenial cortex	tissue	7.8

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Dorsal funiculus (white matter) (25.2), Lateral funiculus (white matter) (24.9), Anterior funiculus (white matter) (24.6), Cervical spinal cord, dorsal horn (24.4), Cervical spinal cord, central gray (24.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

Targeting RIOX2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 130 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 2.71e-08, LOEUF 0.978, missense Z 0.285 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000394198 — one region, missense o/e 1.01.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914264) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased neutrophil cell number	1
decreased inflammatory response	1
decreased airway responsiveness	1
abnormal immunoglobulin level	1
decreased macrophage cell number	1
decreased eosinophil cell number	1
abnormal circulating interferon-gamma level	1
abnormal circulating interleukin-4 level	1
decreased physiological sensitivity to xenobiotic	1

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
Pongo abelii	Q5R673	97.8%	Diamond
Drosophila persimilis	B4GUZ2	92.6%	Diamond
Drosophila pseudoobscura pseudoobscura	B5DUH6	92.6%	Diamond
Drosophila simulans	B4R4H1	87.5%	Diamond
Bos taurus	A5PK74	85.8%	Diamond
Drosophila sechellia	B4I100	84.5%	Diamond
Drosophila willistoni	B4NP88	77.7%	Diamond
Drosophila ananassae	B3MSI4	77.3%	Diamond
Drosophila mojavensis	B4L6Q5	75.8%	Diamond
Drosophila virilis	B4M7P8	75.8%	Diamond
Drosophila erecta	B3NU20	72.9%	Diamond
Drosophila yakuba	B4Q068	72.9%	Diamond
Culex quinquefasciatus	B0WMG3	72.1%	Diamond
Aedes aegypti	Q16W06	71.8%	Diamond
Gallus gallus	Q5ZMM1	62.3%	Diamond
Drosophila grimshawi	B4JMQ2	61.7%	Diamond
Branchiostoma floridae	C3XRY1	53.5%	Diamond
Dictyostelium discoideum	Q54K96	44.9%	Diamond
Brugia malayi	A8QFQ3	44.8%	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
CRYBG3	protein-coding	131544
EPHA6	protein-coding	285220
ARL6	protein-coding	84100
GABRR3	protein-coding	200959

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

Enzyme classification (BRENDA)

• EC 1.14.11.79 — protein-L-histidine (3S)-3-hydroxylase (BRENDA: 1 organisms, 5 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea)

• 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 (66 total): strand 22, helix 20, 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 by resolution:

PDB	Title	Method	Resolution (Å)
4BXF	60S ribosomal protein L27A histidine hydroxylase (MINA53 Y209C) in complex with MN(II) …	X-RAY DIFFRACTION	2.05
2XDV	Crystal Structure of the Catalytic Domain of FLJ14393	X-RAY DIFFRACTION	2.57
4BU2	60S ribosomal protein L27A histidine hydroxylase (MINA53) in complex with Ni(II) and …	X-RAY DIFFRACTION	2.78

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli; nucleoplasm

Antibody reliability (HPA): IH supported · IF supported

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)

Position	Role
179	Fe cation
181	Fe cation
240	Fe cation

Post-translational modifications (1)

Type	Positions
Phosphoserine	309

Mutagenesis-validated functional residues (1)

Position	Phenotype
179	abolishes demethylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-3214842	HDMs demethylate histones	curated
R-HSA-9629569	Protein hydroxylation	curated
R-HSA-3247509	Chromatin modifying enzymes	—
R-HSA-4839726	Chromatin organization	—
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—

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 (5): DNA-templated transcription (GO:0006351), protein hydroxylation (GO:0018126), 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

5 top-level categories:

Category	Pathways
Chromatin modifying enzymes	1
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Post-translational protein modification	1
Chromatin organization	1
Metabolism of proteins	1

GO top-level categories

29 GO namespaces:

Category	Terms
histone H3 demethylase activity	2
2-oxoglutarate-dependent dioxygenase activity	2
nuclear lumen	2
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
protein modification process	1
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
identical protein binding	MF	physical interaction
peptidyl-histidine dioxygenase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 474 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIOX2	LRP4	O75096	768
RIOX2	TYW5	A2RUC4	746
RIOX2	RPL27A	P46776	684
RIOX2	JMJD4	Q9H9V9	668
RIOX2	WNT7A	O00755	667
RIOX2	RPL8	P25120	650
RIOX2	JMJD8	Q96S16	629
RIOX2	KDM8	Q8N371	617
RIOX2	HSPBAP1	Q96EW2	613
RIOX2	LMX1B	O60663	605
RIOX2	OGFOD1	Q8N543	587
RIOX2	JMJD6	Q6NYC1	572
RIOX2	HIF1AN	Q9NWT6	535
RIOX2	JMJD7	P0C870	498
RIOX2	PGP	A6NDG6	438

IntAct

Human interaction partners of RIOX2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
LNX1	physical association	0.560	3
UIMC1	physical association	0.400	1
SPACA9	association	0.350	1

Disease & clinical

Genetic variants

Variant evidence for RIOX2: 99 ClinVar records (0 pathogenic / likely pathogenic).

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 1,092):

Position(s)	Effect	Δscore	Sites
3:97945233	donor_gain	1.0000
3:97945888	acceptor_loss	1.0000	2
3:97950896	acceptor_gain	1.0000
3:97950902–97950903	acceptor_gain	1.0000	2
3:97961587–97961588	donor_loss	1.0000	5
3:97961709–97961710	acceptor_loss	1.0000	6
3:97961711	acceptor_gain	1.0000
3:97961715	acceptor_gain	1.0000
3:97945796–97945797	donor_loss	0.9900	6
3:97945888–97945889	acceptor_loss	0.9900	4

AlphaMissense

753 missense substitutions predicted likely pathogenic (of 3,046 scored), across 202 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
M405	9	0.829	0.982
D181	8	0.990	0.996
H253	8	0.978	0.995
H179	8	0.975	0.997
H240	8	0.975	0.998
S257	8	0.935	0.998
D182	8	0.916	0.977
D99	8	0.913	0.967
H404	8	0.900	0.975
F81	8	0.861	0.969
F158	8	0.858	0.936
N399	8	0.851	0.943
F186	8	0.840	0.989
W196	7	0.990	0.998
K194	7	0.967	0.993
N165	7	0.966	0.996
E155	7	0.940	0.987
W59	7	0.929	0.964
F54	7	0.914	0.979
Q136	7	0.909	0.983

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (TCGA)	unfavorable	4.45e-05
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	0.000244
Thyroid Carcinoma (TCGA)	unfavorable	0.00034
Rectum Adenocarcinoma (TCGA)	favorable	0.000546

Disease associations

OMIM: gene MIM:612049 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465328 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

10 measured of 11 human assays (12 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5425339	IC50	500 nM
CHEMBL5428941	IC50	900 nM
CHEMBL5407378	IC50	1200 nM
CHEMBL5434665	IC50	1800 nM
CHEMBL5419332	IC50	1900 nM
CHEMBL5396670	IC50	2000 nM
CHEMBL5423565	IC50	2600 nM
CHEMBL5402035	IC50	2800 nM
CHEMBL5408048	IC50	5900 nM
CHEMBL5408058	IC50	8900 nM

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	affects cotreatment, increases expression, decreases expression	5
trichostatin A	affects cotreatment, increases expression, affects expression	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	increases expression, increases phosphorylation, decreases reaction	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	increases expression, increases phosphorylation, decreases reaction	1
bisphenol S	decreases methylation	1
Wortmannin	increases expression, decreases reaction	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)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RIOX2 across ~30M SureChEMBL compounds — explore on Sugi Predict.