PRDX4

Summary

PRDX4 (peroxiredoxin 4, HGNC:17169) is a protein-coding gene on chromosome Xp22.11, encoding Peroxiredoxin-4 (Q13162). Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.

The protein encoded by this gene is an antioxidant enzyme and belongs to the peroxiredoxin family. The protein is localized to the cytoplasm. Peroxidases of the peroxiredoxin family reduce hydrogen peroxide and alkyl hydroperoxides to water and alcohol with the use of reducing equivalents derived from thiol-containing donor molecules. This protein has been found to play a regulatory role in the activation of the transcription factor NF-kappaB.

Source: NCBI Gene 10549 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 86 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17169
Approved symbol	PRDX4
Name	peroxiredoxin 4
Location	Xp22.11
Locus type	gene with protein product
Status	Approved
Aliases	AOE37-2
Ensembl gene	ENSG00000123131
Ensembl biotype	protein_coding
OMIM	300927
Entrez	10549

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000379331, ENST00000379341, ENST00000379349, ENST00000439422, ENST00000495599, ENST00000887283, ENST00000931168, ENST00000931169

RefSeq mRNA: 1 — MANE Select: NM_006406 NM_006406

CCDS: CCDS14206

Canonical transcript exons

ENST00000379341 — 7 exons

Exon	Start	End
ENSE00000836235	23682396	23682526
ENSE00000836236	23683671	23683705
ENSE00001828273	23686285	23686397
ENSE00001858070	23667493	23667811
ENSE00003495943	23671529	23671646
ENSE00003512837	23674990	23675106
ENSE00003789100	23679165	23679287

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 155.0809 / max 1791.9174, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195764	128.2859	1820
195765	26.7844	1787
195761	0.0106	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.47	gold quality
pancreas	UBERON:0001264	98.99	gold quality
tibia	UBERON:0000979	98.93	gold quality
adrenal tissue	UBERON:0018303	98.81	gold quality
islet of Langerhans	UBERON:0000006	98.62	gold quality
parotid gland	UBERON:0001831	98.52	gold quality
stromal cell of endometrium	CL:0002255	98.48	gold quality
type B pancreatic cell	CL:0000169	98.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.33	gold quality
right testis	UBERON:0004534	98.28	gold quality
left testis	UBERON:0004533	98.25	gold quality
adult organism	UBERON:0007023	98.20	gold quality
cartilage tissue	UBERON:0002418	98.17	gold quality
liver	UBERON:0002107	97.75	gold quality
decidua	UBERON:0002450	97.74	gold quality
periodontal ligament	UBERON:0008266	97.68	gold quality
testis	UBERON:0000473	97.67	gold quality
placenta	UBERON:0001987	97.53	gold quality
right lobe of liver	UBERON:0001114	97.50	gold quality
corpus epididymis	UBERON:0004359	97.49	gold quality
seminal vesicle	UBERON:0000998	97.40	gold quality
saliva-secreting gland	UBERON:0001044	97.19	gold quality
pituitary gland	UBERON:0000007	97.17	gold quality
ventricular zone	UBERON:0003053	97.11	gold quality
right atrium auricular region	UBERON:0006631	97.03	gold quality
endometrium	UBERON:0001295	97.02	gold quality
ascending aorta	UBERON:0001496	97.02	gold quality
thoracic aorta	UBERON:0001515	97.00	gold quality
minor salivary gland	UBERON:0001830	96.97	gold quality
adenohypophysis	UBERON:0002196	96.96	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-HCAD-32	yes	1048.25
E-CURD-88	yes	131.52
E-HCAD-4	yes	69.01
E-HCAD-1	yes	64.28
E-MTAB-9467	yes	63.56
E-CURD-46	yes	61.46
E-CURD-122	yes	57.48
E-MTAB-8410	yes	42.04
E-HCAD-11	yes	26.28
E-HCAD-6	yes	18.08
E-CURD-112	yes	16.09
E-MTAB-10553	yes	15.64
E-MTAB-10042	yes	13.49
E-HCAD-31	no	21.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, NRF1

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• PRDX4 interacts with and regulates TBXA2R. (PMID:17644091)
• Peroxiredoxin IV forms complex structures within the ER, consistent with the formation of homodecamers (PMID:18052930)
• These results suggested that Prx IV involved in the 16alpha-OHE1-induced proliferation of MCF-7 cells has a proliferative effect and may be related to cancer development or progression. (PMID:18272409)
• data suggested that TRAIL suppressed the PRDX4 gene at the transcriptional level and that downregulation of PRDX4 might facilitate cell death induced by TRAIL (PMID:19364504)
• PRDX4 has a pivotal protective function against diabetes progression in this type 1 diabetes mellitus model (PMID:20446767)
• These results suggest that Prdx-1 and Prdx-4 are essential for preventing respiratory syncytial virus-induced oxidative damage in a subset of nuclear intermediate filament and actin binding proteins in epithelial cells. (PMID:20610706)
• PRDXs exhibit differential expression in prostate tumors, with PRDX3 and 4 consistently upregulated. (PMID:21031435)
• Here, the authors demonstrate that several members of the protein disulphide isomerase family are able to directly reduce this PrxIV disulphide and in the process become oxidized. (PMID:21057456)
• Elevated serum levels of the antioxidant Prx4 were associated with an increased disease severity and adverse outcome of critically ill patients with sepsis. (PMID:21283059)
• strong reduction in PRDX4 expression levels in APL correlates with increased trimethylation of histone 3 lysine residue 27 and 4 at the transcriptional start site of PRDX4, indicative of a bivalent histone code involved in transcriptional silencing. (PMID:21283726)
• Srx-Prx IV axis is critical for lung cancer maintenance and metastasis, suggesting that targeting the Srx-Prx IV axis may provide unique effective strategies for cancer prevention and treatment. (PMID:21487000)
• Data show that Keap1 and PRDX IV were overexpressed in the TNBC cohort. (PMID:21693047)
• A proteomic approach for identification and localization of the pericellular components of chondrocytes (PMID:21698479)
• Overexpression of PRDX4 and P4HA2 was significantly associated with lymphatic metastasis in oral cavity squamous cell carcinoma (PMID:21859152)
• This study solved crystal structures of human Prx4 in three different redox forms and characterized the reaction features of Prx4 with hydrogen peroxide. (PMID:21916849)
• Crystal structure of reduced and of oxidized peroxiredoxin IV enzyme reveals a stable oxidized decamer and a non-disulfide-bonded intermediate in the catalytic cycle (PMID:21994946)
• Prdx4 inhibits G-CSF-induced signalling and proliferation in myeloid progenitors. (PMID:22045733)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• 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)
• data suggest that PRDX4 can be a novel target for glioblastoma multiforme therapies in the future (PMID:22916164)
• 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)
• Elevated serum Prx4 levels are associated with a significantly higher risk of incident cardiovascular disease (CVD) events or CVD mortality and all-cause mortality after adjustment for clinical risk factors. (PMID:23316297)
• expression of Prxs I and IV, both at mRNA and protein levels, was associated with light chain secretion quantified by ELISA. (PMID:23737084)
• Remarkably, the Prx4-dependent formation of native disulfide bonds was accelerated when PDI was combined with ERp46 or P5, suggesting that PDIs work synergistically to increase the rate and fidelity of oxidative protein folding. (PMID:23949117)
• Data indicate that protein disulfide isomerase (PDI) and ERp44 dynamically localize Ero1alpha and peroxiredoxin 4 in early secretory compartment (ESC). (PMID:23979138)
• expression of PRDX4 in PCOS ovaries appeared to be mediated through oxidative stress in GCs. We reported that the deficiency of antioxidant PRDX4 was associated with pathophysiological mechanism of PCOS. (PMID:24098506)
• peroxiredoxin IV recycling in the endoplasmic reticulum is much less efficient than in the cytosol or mitochondria, leading to the protection of peroxiredoxin IV from hyperoxidation. (PMID:24403061)
• The structure and function of PRDX4 as well as its sensitivity to hyperoxidation. [Review] (PMID:24450625)
• Prx4 is a circulating antioxidant and is independently associated with increased risk of cardiovascular and all-cause mortality in T2DM. (PMID:24586984)
• there is a significant difference in concentration of Prx4 between cardiac arrest patients with good and poor outcome (PMID:24617620)
• Findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes (PMID:24893865)
• these data suggest an important role of Prdx4 in maintaining insulin levels and improving the ER folding capacity also under conditions of a high insulin requirement. (PMID:25122762)
• An off-pathway reaction in the Prx4-mediated oxidative protein folding. (PMID:25137134)
• Positive Prx 4 expression is significantly correlated with recurrence and shorter disease-free survival in patients with early-stage lung squamous cell carcinoma. (PMID:26261544)
• Prdx4 expression was closely related to follicular development and has aprominent role in protecting human and mouse granulosa cells from reactive oxygen species damage. (PMID:26917265)
• levels of peroxiredoxin 4 are higher in patients with prediabetes, but are similar in subjects with and without insulin resistance, which suggests that the main factor for its increased levels is hyperglycaemia and not insulin sensitivity state. (PMID:27303935)
• Results show that ERp44 binds the oxidized but not the reduced form of Prx4; the ERp44-Prx4 complex is formed via thiol-disulfide interchange reactions, and its crystal structure reveals a redox-dependent recognition. (PMID:27642162)
• Significant reduction in mRNA and protein levels of PrdxIV was observed in HEK293 cells overexpressing pathologically relevant recombinant mutant GNE protein (D207V and V603L) compared with vector control. Downregulation of PrdxIV keep the ER in a reduced (redox) state that may contribute to misfolding and aggregation of proteins in GNE myopathy. (PMID:28895049)
• Hepatocellular carcinoma (HCC) tumors with low expression of PRDX4 had higher ROS levels, malignancy, and associated with reduced overall survival. In HCC cell lines, its knockdown led to increased intracellular ROS level and suppressed cell proliferation, inducing cell death. These results indicate that PRDX4 has an inhibitory effect in the initiation of HCC, but a dual (inhibitory or promoting) role in the progression. (PMID:29687726)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prdx4	ENSDARG00000069013
mus_musculus	Prdx4	ENSMUSG00000025289
rattus_norvegicus	Prdx4	ENSRNOG00000003763
drosophila_melanogaster	Prx4	FBGN0040308
caenorhabditis_elegans		WBGENE00011110

Paralogs (4): PRDX1 (ENSG00000117450), PRDX6 (ENSG00000117592), PRDX3 (ENSG00000165672), PRDX2 (ENSG00000167815)

Protein

Protein identifiers

Peroxiredoxin-4 — Q13162 (reviewed: Q13162)

Alternative names: Antioxidant enzyme AOE372, Peroxiredoxin IV, Thioredoxin peroxidase AO372, Thioredoxin-dependent peroxide reductase A0372, Thioredoxin-dependent peroxiredoxin 4

All UniProt accessions (5): A6NG45, A6NJJ0, Q13162, H7C3T4, V9HW63

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 and as sensor of hydrogen peroxide-mediated signaling events. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.

Subunit / interactions. Homodimer; disulfide-linked, upon oxidation. 5 homodimers assemble to form a ring-like decamer. Can form heterodimers with PRDX1.

Subcellular location. Cytoplasm. Endoplasmic reticulum.

Post-translational modifications. 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.

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.

RefSeq proteins (1): NP_006397* (*=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

Enzyme classification (BRENDA):

• EC 1.11.1.24 — thioredoxin-dependent peroxiredoxin (BRENDA: 72 organisms, 110 substrates, 31 inhibitors, 72 Km, 50 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
H2O2	0.0004–11.7	23
CUMENE HYDROPEROXIDE	0.0066–0.191	8
THIOREDOXIN	0.001–0.0794	7
TERT-BUTYL HYDROPEROXIDE	—	5
THIOREDOXIN A	0.0009–0.0122	5
THIOREDOXIN B	0.0022–0.0208	5
T-BUTYL HYDROPEROXIDE	0.072–0.193	4
THIOREDOXIN Q	0.0007–0.0028	4
REDUCED THIOREDOXIN	0.0024–0.004	2
REDUCED THIOREDOXIN A	0.0079–0.0087	2
ETHYL HYDROPEROXIDE	0.0045	1
LINOLEIC ACID HYDROPEROXIDE	0.117	1
TRYPAREDOXIN 2	0.0319	1

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (31 total): strand 11, helix 8, turn 4, disulfide bond 2, sequence conflict 2, signal peptide 1, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
2PN8	X-RAY DIFFRACTION	1.8
3TJJ	X-RAY DIFFRACTION	1.91
3TJF	X-RAY DIFFRACTION	2.04
3TJK	X-RAY DIFFRACTION	2.09
3TKR	X-RAY DIFFRACTION	2.1
3TKQ	X-RAY DIFFRACTION	2.22
3TJG	X-RAY DIFFRACTION	2.24
4RQX	X-RAY DIFFRACTION	2.26
3TJB	X-RAY DIFFRACTION	2.38
3TKS	X-RAY DIFFRACTION	2.4
3TKP	X-RAY DIFFRACTION	2.49
5HQP	X-RAY DIFFRACTION	2.6
8EKW	ELECTRON MICROSCOPY	2.83
8EKY	ELECTRON MICROSCOPY	3.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13162-F1	84.59	0.72

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): 124 (cysteine sulfenic acid (-soh) intermediate)

Disulfide bonds (2): 124, 245

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 302 (showing top): MODULE_93, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GRUETZMANN_PANCREATIC_CANCER_DN, BASSO_B_LYMPHOCYTE_NETWORK, GOCC_SECRETORY_GRANULE, MODULE_151, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, KYNG_DNA_DAMAGE_DN, GOBP_MALE_GAMETE_GENERATION, CEBPB_01

GO Biological Process (11): response to oxidative stress (GO:0006979), I-kappaB phosphorylation (GO:0007252), spermatogenesis (GO:0007283), male gonad development (GO:0008584), extracellular matrix organization (GO:0030198), hydrogen peroxide catabolic process (GO:0042744), cell redox homeostasis (GO:0045454), protein maturation (GO:0051604), negative regulation of male germ cell proliferation (GO:2000255), reactive oxygen species metabolic process (GO:0072593), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (10): thioredoxin peroxidase activity (GO:0008379), identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), molecular sequestering activity (GO:0140313), 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 (8): extracellular region (GO:0005576), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
molecular_function	3
cellular anatomical structure	3
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
response to stress	1
protein phosphorylation	1
canonical NF-kappaB signal transduction	1
developmental process involved in reproduction	1
male gamete generation	1
gonad development	1
development of primary male sexual characteristics	1
extracellular structure organization	1
external encapsulating structure organization	1
catabolic process	1
hydrogen peroxide metabolic process	1
cellular homeostasis	1
gene expression	1
protein metabolic process	1
male germ cell proliferation	1
negative regulation of germ cell proliferation	1
negative regulation of reproductive process	1
regulation of male germ cell proliferation	1
metabolic process	1
cellular detoxification	1
thioredoxin-dependent peroxiredoxin activity	1
protein binding	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
cellular oxidant detoxification	1
catalytic activity	1
peroxidase activity	1
peroxiredoxin activity	1
endomembrane system	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDX4	TXNDC5	Q8NBS9	891
PRDX4	TXN	P10599	816
PRDX4	GLUL	P15104	804
PRDX4	ERP44	Q9BS26	771
PRDX4	PRDX5	P30044	770
PRDX4	GPX3	P22352	706
PRDX4	SRXN1	Q9BYN0	683
PRDX4	GPX7	Q96SL4	629
PRDX4	ERO1A	Q96HE7	627
PRDX4	TXNRD1	Q16881	581
PRDX4	ERO1B	Q86YB8	578
PRDX4	GLRX	P35754	577
PRDX4	GPX8	Q8TED1	573
PRDX4	ATP5F1B	P06576	561
PRDX4	TXN2	Q99757	550

IntAct

148 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ATXN1	PRDX4	psi-mi:“MI:0915”(physical association)	0.670
LBP	PRDX4	psi-mi:“MI:0915”(physical association)	0.600
PRDX4	LBP	psi-mi:“MI:0915”(physical association)	0.600
LBP	PRDX4	psi-mi:“MI:0403”(colocalization)	0.600
PRDX4	TBXA2R	psi-mi:“MI:0915”(physical association)	0.590
PRDX4	TBXA2R	psi-mi:“MI:0407”(direct interaction)	0.590
PRDX1	PRDX4	psi-mi:“MI:0915”(physical association)	0.570
PRDX4	PRDX1	psi-mi:“MI:0915”(physical association)	0.570
NR4A1	PRDX4	psi-mi:“MI:0915”(physical association)	0.550
PRDX4	NR4A1	psi-mi:“MI:0915”(physical association)	0.550
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
PDIA6	PRDX4	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.520
PDIA6	PRDX4	psi-mi:“MI:0403”(colocalization)	0.520
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460
TXNDC5	PRDX4	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
PDIA3	PRDX4	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440

BioGRID (305): PRDX4 (Affinity Capture-MS), PRDX4 (Affinity Capture-RNA), PRDX4 (Affinity Capture-RNA), PRDX4 (Affinity Capture-RNA), PRDX4 (Affinity Capture-MS), PRDX4 (Affinity Capture-MS), PRDX4 (Affinity Capture-MS), PRDX4 (Proximity Label-MS), PRDX4 (Proximity Label-MS), PRDX4 (Affinity Capture-MS), PRDX4 (Affinity Capture-MS), PRDX4 (Affinity Capture-MS), PRDX4 (Affinity Capture-MS), PRDX4 (Affinity Capture-MS), PRDX4 (Affinity Capture-MS)

ESM2 similar proteins: A0A061AE05, A4FWZ9, A6UPH7, F3YDF1, F4IAG2, F7D4X9, O08807, O26262, O29969, O42411, O42412, O42449, O88967, O93937, P05990, P07259, P14312, P32112, P35705, P45876, P48822, P49896, P50249, P53537, P54813, P55869, P80602, Q09794, Q13162, Q27772, Q2QEI3, Q57109, Q6L240, Q6LY19, Q6U6H1, Q73RS4, Q7S8A6, Q804E1, Q8KBN8, Q8RCY5

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Detoxification of Reactive Oxygen Species	7	17.7×	8e-05
FCERI mediated MAPK activation	5	14.5×	7e-04
Signaling by FGFR1 in disease	5	12.3×	1e-03
mRNA 3’-end processing	5	8.3×	4e-03
Signaling by BRAF and RAF1 fusions	5	7.2×	8e-03
mRNA Polyadenylation	8	5.9×	1e-03
Processing of Capped Intron-Containing Pre-mRNA	7	4.8×	8e-03
mRNA Splicing - Major Pathway	9	4.1×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
hydrogen peroxide catabolic process	5	24.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

847 predictions. Top by Δscore:

Variant	Effect	Δscore
X:23667738:TGGAC:T	donor_gain	1.0000
X:23667739:GGACA:G	donor_gain	1.0000
X:23667807:GAAGA:G	donor_gain	1.0000
X:23667810:GA:G	donor_gain	1.0000
X:23667812:G:GG	donor_gain	1.0000
X:23671527:A:AG	acceptor_gain	1.0000
X:23671528:G:GA	acceptor_gain	1.0000
X:23671642:GATTT:G	donor_gain	1.0000
X:23671643:ATTT:A	donor_gain	1.0000
X:23671644:TTT:T	donor_gain	1.0000
X:23671645:TT:T	donor_gain	1.0000
X:23671645:TTGT:T	donor_loss	1.0000
X:23671646:TGTA:T	donor_loss	1.0000
X:23671647:G:GG	donor_gain	1.0000
X:23671648:TAA:T	donor_loss	1.0000
X:23671649:AA:A	donor_loss	1.0000
X:23674985:TTCAG:T	acceptor_loss	1.0000
X:23674986:TCAG:T	acceptor_loss	1.0000
X:23674987:CAGC:C	acceptor_loss	1.0000
X:23674988:A:AG	acceptor_gain	1.0000
X:23674988:A:T	acceptor_loss	1.0000
X:23674989:G:GA	acceptor_gain	1.0000
X:23674989:G:T	acceptor_loss	1.0000
X:23674989:GC:G	acceptor_gain	1.0000
X:23674989:GCA:G	acceptor_gain	1.0000
X:23674989:GCAC:G	acceptor_gain	1.0000
X:23674989:GCACA:G	acceptor_gain	1.0000
X:23675065:G:GA	donor_gain	1.0000
X:23675102:GCCTG:G	donor_gain	1.0000
X:23675106:GGTC:G	donor_loss	1.0000

AlphaMissense

1730 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:23671645:T:C	F120L	1.000
X:23674990:C:A	F120L	1.000
X:23674990:C:G	F120L	1.000
X:23674994:T:C	F122L	1.000
X:23674996:T:A	F122L	1.000
X:23674996:T:G	F122L	1.000
X:23675000:T:C	C124R	1.000
X:23675001:G:A	C124Y	1.000
X:23675002:T:G	C124W	1.000
X:23675010:A:T	E127V	1.000
X:23675076:C:T	S149F	1.000
X:23682491:T:A	V232D	1.000
X:23683685:T:A	W249R	1.000
X:23683685:T:C	W249R	1.000
X:23671549:T:A	W88R	0.999
X:23671549:T:C	W88R	0.999
X:23671562:C:A	A92D	0.999
X:23671622:T:A	V112D	0.999
X:23671633:T:G	Y116D	0.999
X:23671637:C:A	P117Q	0.999
X:23671640:T:C	L118P	0.999
X:23674992:C:T	T121I	0.999
X:23675007:C:T	T126I	0.999
X:23675011:A:C	E127D	0.999
X:23675011:A:T	E127D	0.999
X:23675043:T:C	F138S	0.999
X:23675070:C:A	A147E	0.999
X:23675074:C:G	C148W	0.999
X:23675075:T:C	S149P	0.999
X:23675076:C:A	S149Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000057586 (X:23669993 T>C), RS1000229469 (X:23669324 C>T), RS1000450838 (X:23677777 C>T), RS1000802169 (X:23678074 C>T), RS1000887249 (X:23684460 A>G,T), RS1001033050 (X:23681108 T>C), RS1001466557 (X:23667130 T>C), RS1001514364 (X:23668574 T>C), RS1001516651 (X:23677806 CAAAA>C,CAA,CAAA,CAAAAA), RS1001569139 (X:23677103 A>G), RS1001779997 (X:23685097 T>G), RS1001863856 (X:23668986 C>T), RS1001906171 (X:23675246 T>C), RS1002051881 (X:23678536 A>G), RS1002073393 (X:23676533 A>G)

Disease associations

OMIM: gene MIM:300927 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295812 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs518329	Dosage	3	docetaxel	Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs518329	PRDX4	3	0.25	1	docetaxel

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.52	Kd	30.49	nM	CHEMBL5653589
7.52	ED50	30.49	nM	CHEMBL5653589
5.56	Kd	2733	nM	CHEMBL3752910
5.56	ED50	2733	nM	CHEMBL3752910
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 17 total; 3 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149064: Binding affinity to human PRDX4 incubated for 45 mins by Kinobead based pull down assay	kd	0.0305	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149064: Binding affinity to human PRDX4 incubated for 45 mins by Kinobead based pull down assay	kd	2.7330	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178893: Inhibition of PRDX4 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
bisphenol A	affects expression, decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Aerosols	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Cadmium	decreases expression, increases abundance, increases expression	2
Doxorubicin	affects expression, increases expression	2
Hydrogen Peroxide	affects cotreatment, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
moringin	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
16-hydroxyestrone	increases expression	1
gallium nitrate	decreases expression	1
gossypol acetic acid	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
dibenzo(a,l)pyrene	decreases expression	1
cyfluthrin	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CD 437	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
chromium histidinate	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118781	Binding	Binding affinity to PRDX4 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

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3ET	Abcam HEK293T PRDX4 KO	Transformed cell line	Female
CVCL_E2HK	HAP1 PRDX4 (-) 1	Cancer cell line	Male
CVCL_E2HL	HAP1 PRDX4 (-) 2	Cancer cell line	Male
CVCL_E2HM	HAP1 PRDX4 (-) 3	Cancer cell line	Male
CVCL_E2HN	HAP1 PRDX4 (-) 4	Cancer cell line	Male
CVCL_E2HP	HAP1 PRDX4 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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