MIOX

Summary

MIOX (myo-inositol oxygenase, HGNC:14522) is a protein-coding gene on chromosome 22q13.33, encoding Inositol oxygenase (Q9UGB7).

Enables ferric iron binding activity and inositol oxygenase activity. Involved in inositol catabolic process. Predicted to be located in cytoplasm and inclusion body.

Source: NCBI Gene 55586 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_017584

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14522
Approved symbol	MIOX
Name	myo-inositol oxygenase
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100253
Ensembl biotype	protein_coding
OMIM	606774
Entrez	55586

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000216075, ENST00000395732, ENST00000395733, ENST00000451761, ENST00000899223

RefSeq mRNA: 1 — MANE Select: NM_017584 NM_017584

CCDS: CCDS14092

Canonical transcript exons

ENST00000216075 — 10 exons

Exon	Start	End
ENSE00000657697	50487662	50487742
ENSE00000657699	50487886	50488048
ENSE00000657701	50488275	50488342
ENSE00000657708	50489397	50489446
ENSE00000657711	50489532	50489644
ENSE00000878900	50487385	50487465
ENSE00001690311	50489748	50490648
ENSE00001944909	50486859	50486912
ENSE00003502465	50489228	50489295
ENSE00003545925	50489040	50489149

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 99.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5111 / max 529.2042, expressed in 12 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193004	0.5111	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.85	gold quality
adult organism	UBERON:0007023	98.62	gold quality
adult mammalian kidney	UBERON:0000082	96.16	gold quality
renal medulla	UBERON:0000362	93.15	gold quality
kidney	UBERON:0002113	90.87	gold quality
cortex of kidney	UBERON:0001225	88.46	gold quality
metanephros cortex	UBERON:0010533	83.54	gold quality
left lobe of thyroid gland	UBERON:0001120	80.08	gold quality
thyroid gland	UBERON:0002046	79.06	gold quality
right lobe of thyroid gland	UBERON:0001119	78.02	gold quality
pancreatic ductal cell	CL:0002079	77.06	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.93	gold quality
gall bladder	UBERON:0002110	73.49	gold quality
metanephros	UBERON:0000081	70.86	gold quality
upper arm skin	UBERON:0004263	69.44	gold quality
left ventricle myocardium	UBERON:0006566	67.84	gold quality
cardiac muscle of right atrium	UBERON:0003379	67.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.53	gold quality
vena cava	UBERON:0004087	65.84	gold quality
nasal cavity epithelium	UBERON:0005384	65.42	gold quality
trabecular bone tissue	UBERON:0002483	64.83	gold quality
layer of synovial tissue	UBERON:0007616	63.08	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	62.53	gold quality
endothelial cell	CL:0000115	62.30	gold quality
thymus	UBERON:0002370	60.94	gold quality
oocyte	CL:0000023	60.41	gold quality
body of pancreas	UBERON:0001150	60.36	gold quality
cerebellar vermis	UBERON:0004720	60.25	gold quality
pharyngeal mucosa	UBERON:0000355	59.88	gold quality
quadriceps femoris	UBERON:0001377	59.79	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	3254.69
E-GEOD-131882	yes	2910.40
E-ANND-3	yes	5.87
E-CURD-135	no	2420.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting MIOX, 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-4487	99.96	64.58	1252
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-8055	97.62	66.09	1023

Literature-anchored findings (GeneRIF, showing 13)

• myo-inositol oxygenase (MIOX) (PMID:11716759)
• Molecular cloning and characterization of myo-inositol oxygenase as a 33kDa protein. (PMID:15504367)
• expression of MIOX is up-regulated by a positive feedback mechanism where xylitol, one of the products of MI catabolism via the glucuronate-xylulose pathway, induces an overexpression of MIOX (PMID:15778219)
• results demonstrated that the polymorphism (rs761745) in the promoter region of myo-inositol oxygenase(MIOX) gene may be associated with the development of type 1 diabetes mellitus in our studied population (PMID:19896870)
• Data suggest that MIOX expression/activity is up-regulated in kidneys tubules during oxidative stress (as in obesity and diabetic nephropathy); up-regulation of MIOX activity is related to phosphorylation of serine/threonine residues. (PMID:26578517)
• these findings highlight the epigenetic regulation of MIOX in the pathogenesis of diabetic tubulopathy. (PMID:28208054)
• Our results suggest that serum MIOX levels do not change in polycystic ovary syndrome. It was, therefore, concluded that myoinositol deficiency observed in PCOS was not related to the level of MIOX enzyme which cleaves myoinositol. (PMID:29187000)
• increased MIOX expression in the kidney contributes to tubular damage in DN (Diabetic Nephropathy). The concentration of MIOX in the serum and urine may serve as a new biomarker for the early diagnosis of DN. (PMID:30504713)
• MIOX-induced oxidant stress and tunicamycin-induced endoplasmic reticulum stress are interlinked, and both of the events may feed into each other to amplify the tubulointerstitial injury. (PMID:30539651)
• Myo-inositol Oxygenase (MIOX) Overexpression Drives the Progression of Renal Tubulointerstitial Injury in Diabetes. (PMID:32169892)
• Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA. (PMID:35338333)
• Myo-inositol oxygenase (MIOX) accelerated inflammation in the model of infection-induced cardiac dysfunction by NLRP3 inflammasome. (PMID:37249295)
• MIOX inhibits autophagy to regulate the ROS -driven inhibition of STAT3/c-Myc-mediated epithelial-mesenchymal transition in clear cell renal cell carcinoma. (PMID:37977044)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	miox	ENSDARG00000002764
mus_musculus	Miox	ENSMUSG00000022613
rattus_norvegicus	Miox	ENSRNOG00000008694
drosophila_melanogaster	Miox	FBGN0036262
caenorhabditis_elegans		WBGENE00016920

Protein

Protein identifiers

Inositol oxygenase — Q9UGB7 (reviewed: Q9UGB7)

Alternative names: Aldehyde reductase-like 6, Kidney-specific protein 32, Myo-inositol oxygenase, Renal-specific oxidoreductase

All UniProt accessions (3): Q9UGB7, A6PVH2, A6PVH4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Kidney specific.

Cofactor. Binds 2 iron ions per subunit.

Pathway. Polyol metabolism; myo-inositol degradation into D-glucuronate; D-glucuronate from myo-inositol: step 1/1.

Similarity. Belongs to the myo-inositol oxygenase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UGB7-1	1	yes
Q9UGB7-2	2

RefSeq proteins (1): NP_060054* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007828	Inositol_oxygenase	Family

Pfam: PF05153

Enzyme classification (BRENDA):

• EC 1.13.99.1 — inositol oxygenase (BRENDA: 13 organisms, 18 substrates, 63 inhibitors, 21 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MYO-INOSITOL	2.105–45	15
INOSITOL	0.2–22.1	4
O2	0.0095–0.06	2

Catalyzed reactions (Rhea), 1 shown:

• myo-inositol + O2 = D-glucuronate + H2O + H(+) (RHEA:23696)

UniProt features (44 total): helix 17, binding site 12, sequence conflict 4, strand 4, splice variant 2, turn 2, chain 1, modified residue 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2IBN	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGB7-F1	93.82	0.87

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 (12): 29; 220–221; 220; 253; 85–87; 98; 123; 124; 124; 127; 141–142; 194

Post-translational modifications (1): 33

Mutagenesis-validated functional residues (1):

Position	Phenotype
127	strongly reduced enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1855183	Synthesis of IP2, IP, and Ins in the cytosol
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism

MSigDB gene sets: 59 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_POLYOL_CATABOLIC_PROCESS, PAX2_01, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GOBP_INOSITOL_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, HNF1_C, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_NAD_P_H, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, GOBP_ALCOHOL_CATABOLIC_PROCESS, GOBP_ALCOHOL_METABOLIC_PROCESS, GOCC_INCLUSION_BODY, chr22q13, E4BP4_01

GO Biological Process (1): inositol catabolic process (GO:0019310)

GO Molecular Function (7): alcohol dehydrogenase (NADP+) activity (GO:0008106), ferric iron binding (GO:0008199), oxidoreductase activity, acting on NAD(P)H (GO:0016651), inositol oxygenase activity (GO:0050113), iron ion binding (GO:0005506), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), inclusion body (GO:0016234)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Inositol phosphate metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
cellular anatomical structure	2
inositol metabolic process	1
polyol catabolic process	1
alcohol dehydrogenase [NAD(P)+] activity	1
iron ion binding	1
oxidoreductase activity	1
monooxygenase activity	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen	1
transition metal ion binding	1
catalytic activity	1
cation binding	1
cytoplasm	1

Protein interactions and networks

STRING

940 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIOX	AKR1A1	P14550	837
MIOX	AKR1B10	O60218	808
MIOX	ADM2	Q7Z4H4	794
MIOX	MAPK8IP2	Q13387	769
MIOX	AKR1B1	P15121	750
MIOX	PARVB	Q9HBI1	720
MIOX	GDPGP1	Q6ZNW5	717
MIOX	ISYNA1	Q9NPH2	702
MIOX	UGDH	O60701	615
MIOX	SOX10	P56693	496
MIOX	UMOD	P07911	474
MIOX	SLC2A13	Q96QE2	467
MIOX	IMPA1	P29218	451
MIOX	RPL3L	Q92901	443
MIOX	MYL11	Q96A32	435

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MIOX	PBLD	psi-mi:“MI:0915”(physical association)	0.400
MIOX	MIOX	psi-mi:“MI:0915”(physical association)	0.370
MIOX	CCT6A	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): MIOX (Two-hybrid), PBLD (Affinity Capture-MS), UBR4 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), KCMF1 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), TMEM160 (Affinity Capture-MS), MYO10 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), RMDN3 (Affinity Capture-MS)

ESM2 similar proteins: A4IHS2, A7MBE4, A9JS49, O54820, O55096, O70310, O80585, O82200, O82427, P30419, P31717, P42898, Q05B52, Q08DJ7, Q0MQB7, Q10RZ1, Q28CM7, Q295E6, Q3UDE2, Q4FZU1, Q4R7D0, Q4V8T0, Q54GH4, Q561S0, Q5I598, Q5R5N9, Q5RAF3, Q5REY9, Q5Z8T3, Q60HE5, Q6AYQ3, Q75HE6, Q803R5, Q8BGB8, Q8H1S0, Q8K1Q0, Q8K224, Q8L799, Q8WN98, Q99KK7

Diamond homologs: A7MBE4, O82200, Q4V8T0, Q54GH4, Q5REY9, Q5Z8T3, Q8H1S0, Q8L799, Q8WN98, Q9FJU4, Q9QXN4, Q9QXN5, Q9UGB7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1160 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50487461:ACACG:A	donor_gain	1.0000
22:50487462:CACG:C	donor_gain	1.0000
22:50487463:ACG:A	donor_gain	1.0000
22:50487463:ACGGT:A	donor_loss	1.0000
22:50487464:CG:C	donor_gain	1.0000
22:50487465:GG:G	donor_gain	1.0000
22:50487466:G:GG	donor_gain	1.0000
22:50487660:A:AG	acceptor_gain	1.0000
22:50487661:G:GG	acceptor_gain	1.0000
22:50487661:GTCA:G	acceptor_gain	1.0000
22:50487880:C:CA	acceptor_gain	1.0000
22:50487881:GCCA:G	acceptor_loss	1.0000
22:50487884:A:AG	acceptor_gain	1.0000
22:50487884:AGCAT:A	acceptor_gain	1.0000
22:50487885:G:GA	acceptor_gain	1.0000
22:50487885:GC:G	acceptor_gain	1.0000
22:50487885:GCA:G	acceptor_gain	1.0000
22:50487885:GCAT:G	acceptor_gain	1.0000
22:50487885:GCATG:G	acceptor_gain	1.0000
22:50487976:G:GT	donor_gain	1.0000
22:50488029:G:GT	donor_gain	1.0000
22:50488044:CAAGG:C	donor_gain	1.0000
22:50488045:AAGG:A	donor_gain	1.0000
22:50488046:AGG:A	donor_gain	1.0000
22:50488047:GG:G	donor_gain	1.0000
22:50488047:GGG:G	donor_gain	1.0000
22:50488048:GG:G	donor_gain	1.0000
22:50488049:G:GG	donor_gain	1.0000
22:50488049:G:T	donor_gain	1.0000
22:50488049:GT:G	donor_loss	1.0000

AlphaMissense

1897 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50488305:A:T	D124V	0.999
22:50488000:C:G	H98D	0.998
22:50488305:A:C	D124A	0.998
22:50488306:C:A	D124E	0.998
22:50488306:C:G	D124E	0.998
22:50487971:A:G	D88G	0.997
22:50488000:C:A	H98N	0.997
22:50488301:C:G	H123D	0.997
22:50489553:C:G	H220D	0.997
22:50487961:G:C	D85H	0.996
22:50487963:T:A	D85E	0.996
22:50487963:T:G	D85E	0.996
22:50487972:C:A	D88E	0.996
22:50487972:C:G	D88E	0.996
22:50488002:T:A	H98Q	0.996
22:50488002:T:G	H98Q	0.996
22:50489752:T:C	F252L	0.996
22:50489754:C:A	F252L	0.996
22:50489754:C:G	F252L	0.996
22:50489757:C:A	D253E	0.996
22:50489757:C:G	D253E	0.996
22:50489769:G:C	K257N	0.996
22:50489769:G:T	K257N	0.996
22:50487707:C:G	H48D	0.995
22:50488305:A:G	D124G	0.995
22:50489056:A:T	D142V	0.995
22:50489756:A:G	D253G	0.995
22:50487962:A:C	D85A	0.994
22:50487962:A:T	D85V	0.994
22:50488293:G:A	G120E	0.994

dbSNP variants (sampled 300 via entrez): RS1000256103 (22:50491085 C>A,T), RS1000347587 (22:50485686 G>A), RS1000363279 (22:50487117 G>A), RS1000756854 (22:50488107 A>C,G), RS1000782721 (22:50485475 T>C,G), RS1000836734 (22:50488685 C>T), RS1001659172 (22:50489446 G>A), RS1001688711 (22:50485007 T>C), RS1002181517 (22:50485161 T>C), RS1002313175 (22:50489354 T>G), RS1002404458 (22:50484884 G>A,C), RS1002743030 (22:50485869 C>G,T), RS1002923554 (22:50485997 C>T), RS1004418909 (22:50486605 G>C), RS1004847214 (22:50484918 C>T)

Disease associations

OMIM: gene MIM:606774 | 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: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
propionaldehyde	decreases expression	1
sodium arsenite	increases expression	1
tebuconazole	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Cadmium	affects expression	1
Cisplatin	increases expression	1
Estradiol	increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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