PRDX3

Summary

PRDX3 (peroxiredoxin 3, HGNC:9354) is a protein-coding gene on chromosome 10q26.11, encoding Thioredoxin-dependent peroxide reductase, mitochondrial (P30048). Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.

This gene encodes a mitochondrial protein with antioxidant function. The protein is similar to the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase, and it can rescue bacterial resistance to alkylhydroperoxide in E. coli that lack the C22 subunit. The human and mouse genes are highly conserved, and they map to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian homologs suggest that these genes consist of a family that is responsible for the regulation of cellular proliferation, differentiation and antioxidant functions. This family member can protect cells from oxidative stress, and it can promote cell survival in prostate cancer. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1, 3, 13 and 22.

Source: NCBI Gene 10935 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia, autosomal recessive 32 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 66 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 22
• Druggable target: yes
• MANE Select transcript: NM_006793

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9354
Approved symbol	PRDX3
Name	peroxiredoxin 3
Location	10q26.11
Locus type	gene with protein product
Status	Approved
Aliases	MER5, AOP-1, SP-22
Ensembl gene	ENSG00000165672
Ensembl biotype	protein_coding
OMIM	604769
Entrez	10935

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 retained_intron

ENST00000298510, ENST00000463322, ENST00000494433, ENST00000865257, ENST00000865258, ENST00000865259, ENST00000865260, ENST00000865261, ENST00000865262, ENST00000865263, ENST00000938897, ENST00000938898, ENST00000938899, ENST00000938900

RefSeq mRNA: 2 — MANE Select: NM_006793 NM_001302272, NM_006793

CCDS: CCDS7611

Canonical transcript exons

ENST00000298510 — 7 exons

Exon	Start	End
ENSE00001095351	119177021	119177153
ENSE00001095353	119172382	119172485
ENSE00001095354	119174451	119174592
ENSE00001095356	119169177	119169342
ENSE00001095359	119173737	119173872
ENSE00001123443	119167720	119168533
ENSE00001123450	119178755	119178812

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 154.2814 / max 1240.9486, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111679	154.2814	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.59	gold quality
right adrenal gland cortex	UBERON:0035827	99.49	gold quality
right adrenal gland	UBERON:0001233	99.45	gold quality
left adrenal gland	UBERON:0001234	99.35	gold quality
left adrenal gland cortex	UBERON:0035825	99.30	gold quality
adrenal cortex	UBERON:0001235	99.28	gold quality
heart right ventricle	UBERON:0002080	99.14	gold quality
biceps brachii	UBERON:0001507	99.12	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.06	gold quality
adrenal gland	UBERON:0002369	99.03	gold quality
oocyte	CL:0000023	98.88	gold quality
islet of Langerhans	UBERON:0000006	98.86	gold quality
gastrocnemius	UBERON:0001388	98.82	gold quality
secondary oocyte	CL:0000655	98.78	gold quality
vastus lateralis	UBERON:0001379	98.78	gold quality
right lobe of liver	UBERON:0001114	98.76	gold quality
muscle of leg	UBERON:0001383	98.71	gold quality
quadriceps femoris	UBERON:0001377	98.69	gold quality
muscle organ	UBERON:0001630	98.67	gold quality
diaphragm	UBERON:0001103	98.66	gold quality
left ventricle myocardium	UBERON:0006566	98.65	gold quality
adult mammalian kidney	UBERON:0000082	98.61	gold quality
myocardium	UBERON:0002349	98.61	gold quality
rectum	UBERON:0001052	98.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.52	gold quality
choroid plexus epithelium	UBERON:0003911	98.45	gold quality
heart left ventricle	UBERON:0002084	98.40	gold quality
renal medulla	UBERON:0000362	98.37	gold quality
cardiac ventricle	UBERON:0002082	98.37	gold quality
skeletal muscle tissue	UBERON:0001134	98.29	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7606	yes	884.27
E-HCAD-4	yes	141.56
E-MTAB-9067	yes	20.46
E-HCAD-13	yes	11.82
E-MTAB-6379	no	1775.16
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, FOXM1, FOXO3, HIF1A, MYC, NRF1

miRNA regulators (miRDB)

49 targeting PRDX3, 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-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-501-5P	98.77	68.88	1328

Literature-anchored findings (GeneRIF, showing 40)

• Protein levels of Prx-III, a mitochondrial protein were significantly decreased in Alzheimer Disease and Down Syndrome. (PMID:11771746)
• Proteomics analysis of cellular response to oxidative stress. Evidence for in vivo overoxidation of peroxiredoxins at their active site (PMID:11904290)
• PRDX3 is a c-Myc target gene that is requried to maintain normal mitochondrial function. c-Myc directly activates expression of a mitochondrial peroxiredoxin that is required for Myc-mediated transformation. (PMID:12011429)
• 2-Cys Prxs act in a mutually nonredundant and sometimes stress-specific fashion to protect human cells from oxidant injury. The substantial resistance of human cells to hydroperoxides may result in part from the additive action of multiple Prxs (PMID:12080185)
• LZK was associated directly with the IKK complex through the kinase domain, and that AOP-1 was recruited to the IKK complex through the binding to LZK. (PMID:12492477)
• Mitochondrial thioredoxin reductase and peroxiredoxin III are overexpressed in hepatocellular carcinomas. (PMID:12530083)
• The level of peroxiredoxin 3 is decreased in the frontal cortex of patients with Down syndrome and Pick’s disease. (PMID:12650976)
• Peroxiredoxin III is a critical regulator of the abundance of mitochondrial H(2)O(2), which itself promotes apoptosis in cooperation with other mediators of apoptotic signaling (PMID:15280382)
• findings indicate that RPK118 is a PRDX3-binding protein that may be involved in transporting PRDX3 from the cytoplasm to its mitochondrial site of function or to other membrane structures via endosome trafficking. (PMID:15750338)
• The additive protection by Trx2 and GSH shows that Trx2 and GSH systems are both functionally important at low oxidative stress conditions. (PMID:17548047)
• Finally, the expression level of beta-globin and GATA-1 was dramatically increased in Prdx III O/E cell line. (PMID:17574212)
• Present throughout lens and localized to mitochondria in lens epithelial cells. Induction is acute response of lens to increased H2O2. Important role in lens H2O2-detoxification, mitochondrial maintenance, and possibly cataract formation. (PMID:17893648)
• FOXO3A mediates Prx III expression, and this may play a critical role in the resistance to oxidative stress in cardiac fibroblasts (PMID:18195003)
• coexpression of AOP-1 inhibited TNNI3K kinase activity (PMID:18205602)
• Our results show that mitochondrial PRDX-depleted cells are more prone to oxidative damages and apoptosis induced by MPP(+), a complex I inhibitor which provides an experimental paradigm of Parkinson’s disease. (PMID:18262354)
• Significantly decreased expression of Prx-2, -3, and -5 in FED may suggest an alteration in the ability of endothelial cells to withstand oxidant-induced damage and may be closely related to the pathogenesis of this disease. (PMID:18378575)
• As a result of increased Prdx3 transgene expression, mitochondria from transgenic mice produce a significantly reduced amount of hydrogen peroxide and cells from transgenic (PRDX3) mice have increased resistance to stress-induced cell death and apoptosis. (PMID:18778410)
• Report the effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells. (PMID:19135121)
• Srx plays a crucial role in the reactivation of sulfinic mitochondrial Prx III and that its mitochondrial translocation is critical in maintaining the balance between mitochondrial H(2)O(2) production and elimination (PMID:19176523)
• Conclude that Prx II and III are upregulated in response to the development of cervical cancer. (PMID:19424615)
• We found that Prx 3 displayed strong reactivity with H(2)O(2), with a competitive kinetic approach generating a second order rate constant of 2 x 10(7) M(-1) s(-1). This is higher than typical thiols and similar to values for other mammalian 2-Cys Prxs (PMID:19462976)
• Prx3 knockdown resulted in a 50% decrease in D3-mediated whole-cell deiodination. (PMID:19819956)
• Peroxiredoxin III has a significant role in cell cycle regulation and could be a potential proliferation marker in breast cancer. (PMID:20043069)
• Peroxiredoxin III was significantly up-regulated in cervical cancer tissues. (PMID:20718351)
• Prx3, which resides within mitochondria, were reacted with a selection of hydroperoxides generated by gamma-radiolysis or singlet oxygen, on free amino acids, peptides and proteins. (PMID:20840079)
• Both thioredoxin 2 and glutaredoxin 2 contribute to the reduction of the mitochondrial 2-Cys peroxiredoxin Prx3. (PMID:20929858)
• PRDXs exhibit differential expression in prostate tumors, with PRDX3 and 4 consistently upregulated. (PMID:21031435)
• The interaction between genetic variations in the PRDX3 gene and dietary fat intake is important for modulation of BMI and obesity risk. (PMID:21127481)
• Paraneoplastic autoimmune reaction against retinal pigment epithelium, with PRDX3 as the putative antigen, may be a cause of acute exudative polymorphous vitelliform maculopathy (AEPVM). (PMID:21220625)
• Model for the exceptional reactivity of peroxiredoxins 2 and 3 with hydrogen peroxide: a kinetic and computational study. (PMID:21385867)
• Cullin 4B protein ubiquitin ligase targets peroxiredoxin III for degradation. (PMID:21795677)
• Report nuclear factor E2-related factor 2 dependent overexpression of sulfiredoxin and peroxiredoxin III in human lung cancer. (PMID:22016591)
• The results indicated that overexpression of PRDX3 was associated with 94.9% hepatocellular carcinoma, and correlated with poor differentiation (P<0.05), which suggest that PRDX3 has substantial clinical impact on the progression of hepatocarcinoma. (PMID:22344546)
• Reverse phase protein arrays verified that the overexpression of both PRDX3 and PRDX4 in prostate tumor samples is negatively correlated with the presence of the TMPRSS2-ERG gene fusion. (PMID:22424448)
• Single nucleotide polymorphisms in the PRDX3 and RPS19 is associated with HPV persistence and cervical precancer/cancer. (PMID:22496757)
• the effects of PRDX3 in PCa progression may be caused by the regulation function of miR-23b, and consequently, miR-23b may be involved in the response of PCa cells to hypoxia stress (PMID:22710126)
• A fraction of FOXM1 coexists in the cytoplasm with mitochondrial peroxiredoxin 3. (PMID:23018647)
• Drug resistance formation was accompanied by a significant increase in the expression of PRDX1, PRDX2, PRDX3, PRDX6 genes in all cancer cell strains, which confirms the importance of redox-dependent mechanisms into development of cisplatin resistance. (PMID:23113308)
• Medulloblastoma tumors exhibit decreased expression of miR-383 but elevated expression of PRDX3. Up-regulation of miR-383 knocks down the expression of PRDX3, inhibits cell proliferation and promotes apoptosis. (PMID:23157748)
• these results indicate that two placental proteins, Prx3 and Prx4, may act as new placental immune targets. Production of antibodies against peroxiredoxins 3 and 4 may introduce a new autoimmune hypothesis in recurrent pregnancy loss. (PMID:23190175)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prdx3	ENSDARG00000032102
mus_musculus	Prdx3	ENSMUSG00000024997
rattus_norvegicus	Prdx3	ENSRNOG00000010958
drosophila_melanogaster	Prx3	FBGN0038519

Paralogs (4): PRDX1 (ENSG00000117450), PRDX6 (ENSG00000117592), PRDX4 (ENSG00000123131), PRDX2 (ENSG00000167815)

Protein

Protein identifiers

Thioredoxin-dependent peroxide reductase, mitochondrial — P30048 (reviewed: P30048)

Alternative names: Antioxidant protein 1, HBC189, Peroxiredoxin III, Peroxiredoxin-3, Protein MER5 homolog, Thioredoxin-dependent peroxiredoxin 3

All UniProt accessions (2): P30048, A0A384MTR2

UniProt curated annotations — full annotation on UniProt →

Function. Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides. Acts synergistically with MAP3K13 to regulate the activation of NF-kappa-B in the cytosol. Required for the maintenance of physical strength.

Subunit / interactions. Homodimer; disulfide-linked, upon oxidation. 6 homodimers assemble to form a ring-like dodecamer. Interacts with NEK6. Interacts with LRRK2. Interacts with MAP3K13. Interacts with RPS6KC1 (via PX domain).

Subcellular location. Mitochondrion. Cytoplasm. Early endosome.

Post-translational modifications. Phosphorylated by LRRK2; phosphorylation reduces perodixase activity. The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) and sulphonic acid (C(P)-SO3H) instead of its condensation to a disulfide bond. S-palmitoylated.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 32 (SCAR32) [MIM:619862] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR32 is characterized by the onset of gait ataxia in the second or third decades of life. Other classic features include upper limb ataxia, oculomotor signs, dysphagia, and dysarthria. Some patients may have hyper- or hypokinetic movement abnormalities. Brain imaging shows cerebellar atrophy. Atrophy can extend to the brainstem and medullary olives. The disease is caused by variants affecting the gene represented in this entry. Corneal dystrophy, punctiform and polychromatic pre-Descemet (PPPCD) [MIM:619871] An autosomal dominant corneal dystrophy characterized by the presence of punctiform, multicolored opacities in the posterior stroma, immediately anterior to Descemet membrane. Affected individuals are typically asymptomatic. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this typical 2-Cys peroxiredoxin, C(R) is provided by the other dimeric subunit to form an intersubunit disulfide. The disulfide is subsequently reduced by thioredoxin.

Similarity. Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P30048-1	1	yes
P30048-2	2

RefSeq proteins (2): NP_001289201, NP_006784* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000866	AhpC/TSA	Domain
IPR013766	Thioredoxin_domain	Domain
IPR019479	Peroxiredoxin_C	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR050217	Peroxiredoxin	Family

Pfam: PF00578, PF10417

Catalyzed reactions (Rhea), 1 shown:

• a hydroperoxide + [thioredoxin]-dithiol = an alcohol + [thioredoxin]-disulfide + H2O (RHEA:62620)

UniProt features (41 total): sequence variant 8, strand 8, helix 8, modified residue 4, mutagenesis site 3, turn 2, disulfide bond 2, transit peptide 1, chain 1, splice variant 1, domain 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5UCX	X-RAY DIFFRACTION	2.4
5JCG	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30048-F1	85.80	0.77

Functional residue map

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

Catalytic / active sites (1): 108 (cysteine sulfenic acid (-soh) intermediate)

Post-translational modifications (4): 83, 91, 91, 146

Disulfide bonds (2): 108, 229

Mutagenesis-validated functional residues (3):

Position	Phenotype
136	forms obligate homodimers under reducing and oxidizing conditions; does not form dodecamer rings under reducing conditio
139	forms predominantly dodecamer rings.
146	impairs phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3299685	Detoxification of Reactive Oxygen Species

MSigDB gene sets: 347 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MATTIOLI_MGUS_VS_PCL, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, MORF_HDAC2, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, TTGCWCAAY_CEBPB_02

GO Biological Process (16): maternal placenta development (GO:0001893), response to oxidative stress (GO:0006979), mitochondrion organization (GO:0007005), positive regulation of cell population proliferation (GO:0008284), myeloid cell differentiation (GO:0030099), response to lipopolysaccharide (GO:0032496), negative regulation of kinase activity (GO:0033673), cellular response to oxidative stress (GO:0034599), cellular response to reactive oxygen species (GO:0034614), response to hydrogen peroxide (GO:0042542), hydrogen peroxide catabolic process (GO:0042744), negative regulation of apoptotic process (GO:0043066), cell redox homeostasis (GO:0045454), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), regulation of mitochondrial membrane potential (GO:0051881), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (11): thioredoxin peroxidase activity (GO:0008379), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), NADH-dependent peroxiredoxin activity (GO:0102039), peroxidase activity (GO:0004601), protein binding (GO:0005515), antioxidant activity (GO:0016209), oxidoreductase activity (GO:0016491), peroxiredoxin activity (GO:0051920), thioredoxin-dependent peroxiredoxin activity (GO:0140824)

GO Cellular Component (9): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular response to chemical stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
response to reactive oxygen species	2
peroxiredoxin activity	2
cytoplasm	2
placenta development	1
developmental process involved in reproduction	1
anatomical structure development	1
maternal process involved in female pregnancy	1
response to stress	1
organelle organization	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
hemopoiesis	1
cell differentiation	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
kinase activity	1
negative regulation of phosphorylation	1
negative regulation of catalytic activity	1
regulation of kinase activity	1
response to oxidative stress	1
cellular response to chemical stress	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
catabolic process	1
hydrogen peroxide metabolic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cellular homeostasis	1
regulation of membrane potential	1
cellular detoxification	1
thioredoxin-dependent peroxiredoxin activity	1
kinase binding	1
protein binding	1
cysteine-type endopeptidase regulator activity involved in apoptotic process	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1

Protein interactions and networks

STRING

4137 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDX3	FANCG	O15287	888
PRDX3	PRDX5	P30044	825
PRDX3	TXNRD2	Q9NNW7	808
PRDX3	CYCS	P00001	778
PRDX3	PINK1	Q9BXM7	771
PRDX3	TXN2	Q99757	766
PRDX3	ATOX1	O00244	761
PRDX3	TXNRD1	Q16881	759
PRDX3	TXN	P10599	755
PRDX3	SRXN1	Q9BYN0	696
PRDX3	F5H3C5	F5H3C5	678
PRDX3	SOD2	P04179	678
PRDX3	PARK7	Q99497	649
PRDX3	GLRX2	Q9NS18	642
PRDX3	PRKN	O60260	635

IntAct

217 interactions, top by confidence:

A	B	Type	Score
LRRK2	PRDX3	psi-mi:“MI:0915”(physical association)	0.800
PRDX3	LRRK2	psi-mi:“MI:0915”(physical association)	0.800
GORASP2	PRDX3	psi-mi:“MI:0915”(physical association)	0.740
PRDX3	GORASP2	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HNRNPCL1	HNRNPC	psi-mi:“MI:0914”(association)	0.670
BIRC2	HTRA2	psi-mi:“MI:0914”(association)	0.650
PRDX3	ZNF77	psi-mi:“MI:0915”(physical association)	0.560
PCNA	POM121C	psi-mi:“MI:0914”(association)	0.550
PRDX3	PRDX3	psi-mi:“MI:0407”(direct interaction)	0.550
PRDX3	PRDX3	psi-mi:“MI:0915”(physical association)	0.550
PRDX3	OPA1	psi-mi:“MI:0914”(association)	0.530
P/V	IRS4	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
PRDX2	PRDX3	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (382): GORASP2 (Two-hybrid), PRDX3 (Affinity Capture-MS), PRDX3 (Affinity Capture-MS), BIRC2 (Affinity Capture-MS), OPA1 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), XIAP (Affinity Capture-MS), PRDX3 (Two-hybrid), PRDX3 (Affinity Capture-RNA), PRDX3 (Co-fractionation), PRDX3 (Co-fractionation), PRDX3 (Co-fractionation), PRDX3 (Affinity Capture-MS), PRDX3 (Affinity Capture-MS), PRDX3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4J8, A6H784, D3ZS74, D4A6D7, E9QBI7, O42899, O43819, O60341, O75880, P00258, P10109, P23833, P24483, P30048, P38072, Q05B51, Q0VCH8, Q12931, Q2KHU5, Q2NKY8, Q2TBI4, Q3ULF4, Q4VAE3, Q5EA41, Q5REY3, Q5RH02, Q5SUC9, Q69ZP3, Q6DKK2, Q6PI78, Q6ZQ88, Q7ZUC7, Q8BMS4, Q8JZQ2, Q8LAL0, Q8N490, Q8VCL2, Q920A7, Q95N00, Q96HS1

Diamond homologs: A0A0K3AUJ9, A0A2Z5VKM8, A0R1V9, A2BJD9, A3DKL1, A5IIX7, A8A9P0, K0J4Q8, O08807, O24364, O34564, O67024, O74887, P0A0B5, P0A0B6, P0A0B7, P0A251, P0A252, P0AE08, P0AE09, P0AE10, P0AE11, P0CB50, P0CU34, P19476, P20108, P21762, P23161, P26830, P30048, P32119, P34760, P35700, P35704, P35705, P48822, P49537, P51272, P52552, P56876

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LRRK2	“down-regulates activity”	PRDX3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 205 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.

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	13.0×	2e-03
autophagosome maturation	6	12.7×	2e-03
mRNA stabilization	5	11.0×	8e-03
JNK cascade	6	9.8×	4e-03
G1/S transition of mitotic cell cycle	8	9.7×	7e-04
cellular response to oxidative stress	9	8.4×	7e-04
mitochondrion organization	8	7.3×	3e-03
response to ethanol	8	7.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	42
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1686990	NM_006793.5(PRDX3):c.604G>A (p.Asp202Asn)	Pathogenic
1686991	NM_006793.5(PRDX3):c.340dup (p.Ala114fs)	Pathogenic
1686994	NM_006793.5(PRDX3):c.37-2A>G	Pathogenic
1686995	NM_006793.5(PRDX3):c.568G>C (p.Asp190His)	Pathogenic
2443837	NM_006793.5(PRDX3):c.658C>T (p.Gln220Ter)	Pathogenic
2446414	NM_006793.5(PRDX3):c.489C>G (p.Asp163Glu)	Pathogenic
4686789	NM_006793.5(PRDX3):c.619C>T (p.Arg207Ter)	Pathogenic
1686992	NM_006793.5(PRDX3):c.508C>T (p.Arg170Ter)	Likely pathogenic
3025412	NM_006793.5(PRDX3):c.717+1G>A	Likely pathogenic

SpliceAI

877 predictions. Top by Δscore:

Variant	Effect	Δscore
10:119168534:C:CC	acceptor_gain	1.0000
10:119168534:CTGA:C	acceptor_loss	1.0000
10:119168535:T:C	acceptor_loss	1.0000
10:119169326:C:CT	acceptor_gain	1.0000
10:119169329:T:TC	acceptor_gain	1.0000
10:119169341:CT:C	acceptor_gain	1.0000
10:119172481:CCATT:C	acceptor_gain	1.0000
10:119172482:CATTC:C	acceptor_gain	1.0000
10:119172484:TT:T	acceptor_gain	1.0000
10:119172485:TCTAA:T	acceptor_loss	1.0000
10:119172486:C:CC	acceptor_gain	1.0000
10:119172491:C:CT	acceptor_gain	1.0000
10:119173731:CCATA:C	donor_loss	1.0000
10:119173732:CATAC:C	donor_loss	1.0000
10:119173733:ATAC:A	donor_loss	1.0000
10:119173734:TAC:T	donor_loss	1.0000
10:119173735:A:AC	donor_gain	1.0000
10:119173735:ACCTT:A	donor_loss	1.0000
10:119173736:C:CC	donor_gain	1.0000
10:119173736:CCTTT:C	donor_gain	1.0000
10:119173868:AGGTG:A	acceptor_gain	1.0000
10:119173869:GGTG:G	acceptor_gain	1.0000
10:119173870:GTG:G	acceptor_gain	1.0000
10:119173871:TG:T	acceptor_gain	1.0000
10:119173873:C:CC	acceptor_gain	1.0000
10:119174449:A:AC	donor_gain	1.0000
10:119174450:C:CA	donor_gain	1.0000
10:119174450:CAA:C	donor_gain	1.0000
10:119174450:CAAAT:C	donor_gain	1.0000
10:119178750:CTCA:C	donor_loss	1.0000

AlphaMissense

1668 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:119169195:C:A	W233C	0.999
10:119169195:C:G	W233C	0.999
10:119169197:A:G	W233R	0.999
10:119169197:A:T	W233R	0.999
10:119172382:C:A	R184I	0.999
10:119172382:C:G	R184T	0.999
10:119173757:A:G	W143R	0.999
10:119173757:A:T	W143R	0.999
10:119173862:A:G	C108R	0.999
10:119173866:A:C	F106L	0.999
10:119173866:A:T	F106L	0.999
10:119173868:A:G	F106L	0.999
10:119173872:G:C	F104L	0.999
10:119173872:G:T	F104L	0.999
10:119174452:A:G	F104L	0.999
10:119169207:G:C	C229W	0.998
10:119169209:A:G	C229R	0.998
10:119169331:A:T	I188K	0.998
10:119173766:G:C	H140D	0.998
10:119173781:C:G	D135H	0.998
10:119173787:A:G	S133P	0.998
10:119173789:A:T	V132D	0.998
10:119173792:G:T	A131E	0.998
10:119173803:A:C	C127W	0.998
10:119173819:A:G	F122S	0.998
10:119173852:T:A	E111V	0.998
10:119173860:A:C	C108W	0.998
10:119173861:C:T	C108Y	0.998
10:119169196:C:G	W233S	0.997
10:119169208:C:T	C229Y	0.997

dbSNP variants (sampled 300 via entrez): RS1000056372 (10:119179269 A>G), RS1000086979 (10:119178954 G>C), RS1000696596 (10:119170661 C>T), RS1000864425 (10:119168807 C>G), RS1000935516 (10:119174312 C>A), RS1001013551 (10:119172476 A>C,G), RS1001368158 (10:119174005 G>A), RS1001418703 (10:119174351 T>C), RS1001656512 (10:119175786 T>TTC), RS1001680771 (10:119179565 T>G), RS1001941250 (10:119177460 C>A), RS1001995381 (10:119177289 G>A,T), RS1002071828 (10:119177875 A>T), RS1002133269 (10:119171798 TA>T,TAA), RS1002204141 (10:119170290 G>A)

Disease associations

OMIM: gene MIM:604769 | disease phenotypes: MIM:213200, MIM:619862, MIM:619871

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia, autosomal recessive 32	Strong	Autosomal recessive
corneal dystrophy, punctiform and polychromatic pre-descemet	Strong	Autosomal dominant
cerebellar ataxia	Strong	Autosomal recessive

Mondo (4): autosomal recessive cerebellar ataxia (MONDO:0015244), spinocerebellar ataxia, autosomal recessive 32 (MONDO:0859245), corneal dystrophy, punctiform and polychromatic pre-descemet (MONDO:0859248), cerebellar ataxia (MONDO:0000437)

Orphanet (1): Autosomal recessive cerebellar ataxia (Orphanet:1172)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000338	Hypomimic face
HP:0000473	Torticollis
HP:0000508	Ptosis
HP:0000640	Gaze-evoked nystagmus
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002067	Bradykinesia
HP:0002070	Limb ataxia
HP:0002174	Postural tremor
HP:0003474	Somatic sensory dysfunction
HP:0003621	Juvenile onset
HP:0007338	Hypermetric saccades
HP:0007366	Atrophy/Degeneration affecting the brainstem
HP:0011462	Young adult onset
HP:0034327	Posterior corneal stroma punctiform multicolored opacities
HP:0040129	Abnormal nerve conduction velocity
HP:0045084	Limb myoclonus

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004860_17	Alcoholic chronic pancreatitis	6.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295742 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.78	Kd	164.5	nM	CHEMBL3752910
6.78	ED50	164.5	nM	CHEMBL3752910
5.34	Kd	4562	nM	CHEMBL5653589
5.34	ED50	4562	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 11 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149063: Binding affinity to human PRDX3 incubated for 45 mins by Kinobead based pull down assay	kd	0.1645	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149063: Binding affinity to human PRDX3 incubated for 45 mins by Kinobead based pull down assay	kd	4.5622	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance, affects cotreatment	5
Hydrogen Peroxide	affects response to substance, affects expression, decreases expression, increases oxidation	5
Arsenic Trioxide	increases cleavage, increases expression, increases oxidation, affects response to substance, affects binding (+4 more)	4
bisphenol A	affects expression, decreases expression, increases expression	3
chromium hexavalent ion	decreases expression, increases oxidation	3
bisphenol S	affects cotreatment, decreases methylation, increases expression, affects expression	3
Vorinostat	increases expression, decreases expression	3
Arsenic	increases abundance, increases expression, decreases expression	3
Auranofin	affects cotreatment, increases expression, increases reaction, increases oxidation	3
Dinitrochlorobenzene	decreases expression, increases oxidation	3
Paraquat	affects cotreatment, increases expression, increases oxidation	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
chloropicrin	affects expression, decreases expression	2
Acetaminophen	affects cotreatment, decreases expression	2
Lipopolysaccharides	decreases expression, increases expression, increases reaction, affects cotreatment	2
Quercetin	affects cotreatment, increases expression	2
Rotenone	increases expression	2
1-Methyl-4-phenylpyridinium	increases expression, affects response to substance	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
chlorophyllin	decreases expression	1
geraniol	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
arsenite	affects binding, decreases reaction, increases reaction	1
sulforaphane	affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118650	Binding	Binding affinity to PRDX3 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TG48	HAP1 PRDX3 (-) 1	Cancer cell line	Male
CVCL_TG49	HAP1 PRDX3 (-) 2	Cancer cell line	Male
CVCL_TG50	HAP1 PRDX3 (-) 3	Cancer cell line	Male
CVCL_TG51	HAP1 PRDX3 (-) 4	Cancer cell line	Male
CVCL_TG52	HAP1 PRDX3 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	PHASE4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT01970098	PHASE3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	PHASE3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	PHASE3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	PHASE3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	PHASE3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	PHASE3	RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT00034242	PHASE2	COMPLETED	High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538	PHASE2	COMPLETED	Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016	PHASE2	COMPLETED	A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440	PHASE2	COMPLETED	Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655	PHASE2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669	PHASE2	COMPLETED	Effect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05125666	PHASE2	UNKNOWN	Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274	PHASE2	NOT_YET_RECRUITING	Stemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT00683943	PHASE1	COMPLETED	Lithium Treatment for Patients With Spinocerebellar Ataxia Type I
NCT02287064	PHASE1	UNKNOWN	An Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias
NCT05157802	PHASE1	ACTIVE_NOT_RECRUITING	Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT01104649	PHASE2/PHASE3	COMPLETED	Efficacy of Riluzole in Hereditary Cerebellar Ataxia
NCT02960893	PHASE2/PHASE3	COMPLETED	Trial in Adult Participants With Spinocerebellar Ataxia (SCA)
NCT00244361	PHASE1/PHASE2	COMPLETED	Effectiveness of Rituximab in Pediatric OMS Patients.
NCT01649687	PHASE1/PHASE2	COMPLETED	Treatment of Cerebellar Ataxia With Mesenchymal Stem Cells
NCT01958177	PHASE1/PHASE2	UNKNOWN	Clinical Study to Evaluate the Safety and Efficacy BMMNC in Cerebellar Ataxia
NCT02829268	PHASE1/PHASE2	COMPLETED	A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome
NCT00001324	Not specified	COMPLETED	PET Scan to Study Brain Control of Human Movement
NCT00006492	Not specified	COMPLETED	Gluten-Free Diet in Patients With Gluten Sensitivity and Cerebellar Ataxia
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00272272	Not specified	COMPLETED	Fall Prevention in a Geriatric Nursing Home Setting Using the Music of Nolwenn Leroy
NCT00654251	Not specified	COMPLETED	Measuring Neurological Impairment and Functional Visual Assessment In Spinocerebellar Ataxias
NCT00692861	Not specified	COMPLETED	Autoimmunity in Neurologic Complications of Celiac Disease
NCT01037777	Not specified	COMPLETED	RISCA : Prospective Study of Individuals at Risk for SCA1, SCA2, SCA3, SCA6, SCA7
NCT01307176	Not specified	COMPLETED	Exercise Training Program for Cerebellar Ataxia
NCT01428531	Not specified	COMPLETED	Special Drug Use Investigation for Arixtra® (Fondaparinux) Venous Thromboembolism Treatment