PRDX4
gene geneOn this page
Also known as AOE37-2
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): 87 total
- Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈8% of expected missense variation)
- GTEx eGene: eQTL in 35 tissues, sQTL in 0 (q < 0.05)
- ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
- MANE Select transcript:
NM_006406 - Interaction hub: 2,358 STRING partners (top 5% of genes corpus-wide)
- Notable: 87 clinical variants but no curated precision-oncology (CIViC) evidence yet
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: 26 — 14 nonsense_mediated_decay, 11 protein_coding, 1 protein_coding_CDS_not_defined
MANE Select: ENST00000379341
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 3
ENST00000379341, ENST00000379331, ENST00000379349, ENST00000439422, ENST00000495599, ENST00000887283, ENST00000931168, ENST00000931169, ENST00000988484, ENST00000988485, ENST00000988486, ENST00000988487, ENST00000988489, ENST00001038760, ENST00001084463, ENST00001084470, ENST00001084471, ENST00001084474, ENST00001084476, ENST00001095693, ENST00001095694, ENST00001117752, ENST00001117753, ENST00001117754, ENST00001124129, ENST00001136491
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.
Highest expression (Bgee): body of pancreas, pancreas, tibia, adrenal tissue, islet of Langerhans.
Genetic regulation across tissues (GTEx eQTL / sQTL)
PRDX4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 35 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
showing 20 of 35 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Muscle Skeletal | eqtl | 2.5e-31 | -0.34 | X:23620988:A:G |
| Esophagus Muscularis | eqtl | 1.1e-17 | +0.34 | X:23661817:A:T |
| Skin Sun Exposed Lower leg | eqtl | 4.2e-17 | +0.14 | X:23666905:C:T |
| Nerve Tibial | eqtl | 7.1e-15 | +0.14 | X:23666905:C:T |
| Artery Tibial | eqtl | 1.4e-14 | +0.12 | X:23689710:G:A |
| Esophagus Mucosa | eqtl | 1.5e-14 | +0.14 | X:23679368:G:A |
| Thyroid | eqtl | 8.9e-12 | +0.14 | X:23681716:T:A |
| Brain Cerebellum | eqtl | 2.1e-11 | +0.30 | X:23679368:G:A |
| Colon Sigmoid | eqtl | 4.0e-11 | +0.19 | X:23681101:G:T |
| Colon Transverse | eqtl | 1.4e-09 | +0.12 | X:23671242:A:G |
| Brain Hippocampus | eqtl | 5.2e-08 | +0.22 | X:23683293:A:C |
| Brain Cerebellar Hemisphere | eqtl | 7.2e-08 | +0.19 | X:23666450:G:A |
| Esophagus Gastroesophageal Junction | eqtl | 6.7e-07 | +0.26 | X:23660381:C:CT |
| Adipose Subcutaneous | eqtl | 1.9e-06 | +0.12 | X:23689710:G:A |
| Brain Frontal Cortex BA9 | eqtl | 4.8e-06 | +0.20 | X:23666450:G:A |
| Brain Spinal cord cervical c-1 | eqtl | 2.1e-05 | +0.19 | X:23679368:G:A |
| Cells Cultured fibroblasts | eqtl | 2.7e-05 | +0.07 | X:23676359:A:T |
| Brain Nucleus accumbens basal ganglia | eqtl | 3.1e-05 | +0.17 | X:23668070:C:T |
| Brain Anterior cingulate cortex BA24 | eqtl | 5.4e-05 | +0.21 | X:23666450:G:A |
| Lung | eqtl | 9.9e-05 | +0.06 | X:23668070:C:T |
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
showing 100 of 295 tissues 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 |
| cardiac atrium | UBERON:0002081 | 96.94 | gold quality |
| right ovary | UBERON:0002118 | 96.83 | gold quality |
| left coronary artery | UBERON:0001626 | 96.81 | gold quality |
| gall bladder | UBERON:0002110 | 96.80 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 96.79 | gold quality |
| trachea | UBERON:0003126 | 96.78 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 96.77 | gold quality |
| skin of hip | UBERON:0001554 | 96.76 | gold quality |
| right coronary artery | UBERON:0001625 | 96.76 | gold quality |
| right adrenal gland | UBERON:0001233 | 96.75 | gold quality |
| rectum | UBERON:0001052 | 96.73 | gold quality |
| mucosa of sigmoid colon | UBERON:0004993 | 96.70 | gold quality |
| nasal cavity mucosa | UBERON:0001826 | 96.69 | gold quality |
| oral cavity | UBERON:0000167 | 96.68 | gold quality |
| coronary artery | UBERON:0001621 | 96.64 | gold quality |
| peritoneum | UBERON:0002358 | 96.64 | gold quality |
| omental fat pad | UBERON:0010414 | 96.64 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 96.63 | gold quality |
| left adrenal gland | UBERON:0001234 | 96.62 | gold quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 96.60 | gold quality |
| endocervix | UBERON:0000458 | 96.57 | gold quality |
| body of stomach | UBERON:0001161 | 96.57 | gold quality |
| left ovary | UBERON:0002119 | 96.57 | gold quality |
| mouth mucosa | UBERON:0003729 | 96.57 | gold quality |
| male germ cell | CL:0000015 | 96.53 | gold quality |
| ovary | UBERON:0000992 | 96.52 | gold quality |
| sperm | CL:0000019 | 96.47 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 96.47 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 96.38 | gold quality |
| calcaneal tendon | UBERON:0003701 | 96.30 | gold quality |
| adrenal gland | UBERON:0002369 | 96.28 | gold quality |
| pigmented layer of retina | UBERON:0001782 | 96.26 | gold quality |
| heart right ventricle | UBERON:0002080 | 96.24 | gold quality |
| superficial temporal artery | UBERON:0001614 | 96.22 | gold quality |
| uterus | UBERON:0000995 | 96.15 | gold quality |
| adrenal cortex | UBERON:0001235 | 96.08 | gold quality |
| ectocervix | UBERON:0012249 | 96.06 | gold quality |
| layer of synovial tissue | UBERON:0007616 | 96.04 | gold quality |
| synovial joint | UBERON:0002217 | 96.00 | gold quality |
| caput epididymis | UBERON:0004358 | 95.94 | gold quality |
| pericardium | UBERON:0002407 | 95.92 | gold quality |
| aorta | UBERON:0000947 | 95.90 | gold quality |
| adipose tissue | UBERON:0001013 | 95.89 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 95.89 | gold quality |
| left uterine tube | UBERON:0001303 | 95.88 | gold quality |
| stomach | UBERON:0000945 | 95.86 | gold quality |
| parietal pleura | UBERON:0002400 | 95.86 | gold quality |
| connective tissue | UBERON:0002384 | 95.82 | gold quality |
| body of uterus | UBERON:0009853 | 95.78 | gold quality |
| female reproductive system | UBERON:0000474 | 95.77 | gold quality |
| pylorus | UBERON:0001166 | 95.76 | gold quality |
| germinal epithelium of ovary | UBERON:0001304 | 95.75 | gold quality |
| epithelium of nasopharynx | UBERON:0001951 | 95.72 | gold quality |
| myocardium | UBERON:0002349 | 95.71 | gold quality |
| thoracic mammary gland | UBERON:0005200 | 95.69 | gold quality |
| right uterine tube | UBERON:0001302 | 95.68 | gold quality |
| myometrium | UBERON:0001296 | 95.64 | gold quality |
| mammary gland | UBERON:0001911 | 95.63 | gold quality |
| embryo | UBERON:0000922 | 95.62 | gold quality |
| bronchial epithelial cell | CL:0002328 | 95.53 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 95.50 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 95.49 | gold quality |
| tibial nerve | UBERON:0001323 | 95.46 | gold quality |
| colonic mucosa | UBERON:0000317 | 95.44 | gold quality |
| cardia of stomach | UBERON:0001162 | 95.44 | gold quality |
| heart | UBERON:0000948 | 95.38 | gold quality |
| cervix squamous epithelium | UBERON:0006922 | 95.38 | gold quality |
| fundus of stomach | UBERON:0001160 | 95.27 | gold quality |
| subcutaneous adipose tissue | UBERON:0002190 | 95.25 | gold quality |
| tibial artery | UBERON:0007610 | 95.13 | 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 |
HPA expression
RNA tissue specificity: Tissue enriched
showing 60 of 80 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Pancreas | tissue | 1142.7 | high |
| Liver | tissue | 258.9 | medium |
| Ovary | tissue | 111.0 | medium |
| Pituitary gland | tissue | 95.6 | |
| Placenta | tissue | 90.3 | medium |
| Testis | tissue | 89.5 | high |
| Salivary gland | tissue | 86.9 | low |
| Cervix | tissue | 77.3 | medium |
| Stomach 1 | tissue | 76.9 | medium |
| Rectum | tissue | 73.9 | low |
| Breast | tissue | 70.0 | medium |
| Colon | tissue | 68.1 | medium |
| Parathyroid gland | tissue | 65.0 | low |
| Urinary bladder | tissue | 64.5 | medium |
| Tonsil | tissue | 62.9 | low |
| Heart muscle | tissue | 62.7 | low |
| Fallopian tube | tissue | 62.1 | medium |
| Adipose tissue | tissue | 60.8 | medium |
| Gallbladder | tissue | 60.6 | medium |
| Duodenum | tissue | 60.2 | medium |
| Seminal vesicle | tissue | 59.6 | medium |
| Smooth muscle | tissue | 58.7 | low |
| Vagina | tissue | 57.2 | low |
| Prostate | tissue | 56.2 | low |
| Lymph node | tissue | 55.0 | medium |
| Adrenal gland | tissue | 52.7 | medium |
| Appendix | tissue | 50.8 | medium |
| Endometrium 1 | tissue | 49.6 | medium |
| Small intestine | tissue | 48.3 | medium |
| Esophagus | tissue | 46.2 | low |
| Choroid plexus | tissue | 45.4 | |
| Thyroid gland | tissue | 43.0 | medium |
| Frontal cortex | tissue | 38.9 | |
| Kidney | tissue | 37.5 | low |
| Caudate putamen | tissue | 36.7 | |
| Lung | tissue | 34.3 | medium |
| Skeletal muscle | tissue | 32.6 | medium |
| Bone marrow | tissue | 32.3 | low |
| Spleen | tissue | 31.2 | low |
| Skin 1 | tissue | 28.5 | medium |
| Retina | tissue | 27.9 | |
| Thymus | tissue | 24.7 | |
| Tongue | tissue | 23.6 | |
| Epididymis | tissue | 18.4 | medium |
| Locus coeruleus | tissue | 16.5 | |
| Nucleus accumbens | tissue | 15.7 | |
| Hippocampus | tissue | 11.7 | low |
| Cerebellum | tissue | 10.8 | low |
| Cerebral cortex | tissue | 9.9 | medium |
| Somatosensory cortex | tissue | 9.9 | |
| Retrosplenial and cingulate cortex | tissue | 9.8 | |
| Hippocampal formation | tissue | 9.7 | |
| Entorhinal cortex | tissue | 9.7 | |
| Temporal cortex | tissue | 9.7 | |
| Prefrontal cortex | tissue | 9.6 | |
| Occipital cortex | tissue | 9.5 | |
| Insular cortex | tissue | 9.3 | |
| Retrosplenial cortex | tissue | 9.0 | |
| Corpus callosum | tissue | 8.9 | |
| Motor cortex | tissue | 8.8 |
Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (97.4), Dorsal funiculus (white matter) (37.4), Lateral funiculus (white matter) (35.1), Anterior funiculus (white matter) (26.5), Nucleus raphe pallidus (25.7).
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): FOXO1, NRF1
Functional genomics
Regional missense constraint (gnomAD)
ENST00000379341 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈8% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD
| Region (GRCh38) | Missense obs / exp | o/e | Constrained |
|---|---|---|---|
| X:23,667,571–23,675,057 | 105 / 114.2 | 0.92 | no |
| X:23,675,058–23,679,182 | 2 / 16.5 | 0.12 | yes (p 3.5e-04) |
| X:23,679,183–23,686,332 | 73 / 76.5 | 0.95 | no |
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)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:1859815) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| oligozoospermia | 1 |
| testicular atrophy | 1 |
| oxidative stress | 1 |
| decreased testis weight | 1 |
| increased male germ cell apoptosis | 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 |
|---|---|---|---|
| Staphylococcus aureus subsp. aureus Mu50 | P0A0B5 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus MW2 | P0A0B6 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus NCTC 8325 | P0A0B7 | 100.0% | Diamond |
| Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 | P0A251 | 100.0% | Diamond |
| Salmonella enterica subsp. enterica serovar Typhi | P0A252 | 100.0% | Diamond |
| Escherichia coli K-12 | P0AE08 | 100.0% | Diamond |
| Escherichia coli CFT073 | P0AE09 | 100.0% | Diamond |
| Escherichia coli O157:H7 | P0AE10 | 100.0% | Diamond |
| Shigella flexneri | P0AE11 | 100.0% | Diamond |
| Candida albicans SC5314 | P0CU34 | 100.0% | Diamond |
| Mycobacterium tuberculosis variant bovis AF2122/97 | P65689 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus N315 | P99074 | 100.0% | Diamond |
| Mycobacterium tuberculosis CDC1551 | P9WIE0 | 100.0% | Diamond |
| Mycobacterium tuberculosis H37Rv | P9WIE1 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus USA300 | Q2FJN4 | 100.0% | Diamond |
| Macaca fascicularis | Q2PFZ3 | 100.0% | Diamond |
| Staphylococcus aureus RF122 | Q2YVK2 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus COL | Q5HIR5 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus MSSA476 | Q6GC91 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus MRSA252 | Q6GJR7 | 100.0% | Diamond |
| Triticum aestivum | P80602 | 99.5% | Diamond |
| Staphylococcus epidermidis RP62A | Q5HRY1 | 99.5% | Diamond |
| Staphylococcus epidermidis ATCC 12228 | Q8CMQ2 | 99.5% | Diamond |
| Hordeum vulgare | Q96468 | 99.5% | Diamond |
| Pongo abelii | Q5RC63 | 99.4% | Diamond |
| Myotis lucifugus | Q6B4U9 | 99.0% | Diamond |
| Spinacia oleracea | O24364 | 98.5% | Diamond |
| Helicobacter pylori 26695 | P21762 | 98.5% | Diamond |
| Helicobacter pylori J99 | P56876 | 98.5% | Diamond |
| Arabidopsis thaliana | Q96291 | 98.5% | Diamond |
| Methanococcus maripaludis C5 | A4FWZ9 | 97.2% | Diamond |
| Thermotoga petrophila RKU-1 | A5IIX7 | 97.2% | Diamond |
| Methanococcus maripaludis S2 | Q6LY19 | 97.2% | Diamond |
| Thermotoga maritima MSB8 | Q9WZR4 | 97.2% | Diamond |
| Bos taurus | Q5E947 | 97.0% | Diamond |
| Cricetulus griseus | Q8K3U7 | 96.5% | Diamond |
| Methanothermobacter thermautotrophicus str. Delta H | O26262 | 95.7% | Diamond |
| Methanothermobacter marburgensis str. Marburg | Q57109 | 95.7% | Diamond |
| Pyrococcus abyssi GE5 | Q9UZV4 | 94.4% | Diamond |
| Pyrococcus horikoshii OT3 | O58966 | 94.0% | 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 |
|---|---|---|
| PTCHD1-AS | ncRNA | 100873065 |
| PTCHD1 | protein-coding | 139411 |
| ACOT9 | protein-coding | 23597 |
| SAT1 | protein-coding | 6303 |
| APOO | protein-coding | 79135 |
| SAT1-DT | ncRNA | 105373148 |
| CXorf58 | protein-coding | 254158 |
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, H7C3T4, Q13162, 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)
- a hydroperoxide + [thioredoxin]-dithiol = an alcohol + [thioredoxin]-disulfide + H2O (RHEA:62620)
UniProt features (33 total): strand 12, helix 9, turn 4, disulfide bond 2, sequence conflict 2, signal peptide 1, chain 1, domain 1, active site 1
Structure
Experimental structures (PDB)
14 structures by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 2PN8 | Crystal structure of human peroxiredoxin 4 (thioredoxin peroxidase) | X-RAY DIFFRACTION | 1.8 |
| 3TJJ | Crystal structure of human peroxiredoxin IV C245A mutant in sulfenylated form | X-RAY DIFFRACTION | 1.91 |
| 3TJF | Crystal Structure of human peroxiredoxin IV C51A mutant in reduced form | X-RAY DIFFRACTION | 2.04 |
| 3TJK | Crystal Structure of human peroxiredoxin IV C245A mutant in reduced form | X-RAY DIFFRACTION | 2.09 |
| 3TKR | Crystal structure of full-length human peroxiredoxin 4 with T118E mutation | X-RAY DIFFRACTION | 2.1 |
| 3TKQ | Crystal structure of full-length human peroxiredoxin 4 with mixed conformation | X-RAY DIFFRACTION | 2.22 |
| 3TJG | Crystal Structure of human peroxiredoxin IV C51A mutant in oxidized form | X-RAY DIFFRACTION | 2.24 |
| 4RQX | Crystal structure of human peroxiredoxin 4(THIOREDOXIN PEROXIDASE) with MESNA | X-RAY DIFFRACTION | 2.26 |
| 3TJB | Crystal structure of wild-type human peroxiredoxin IV | X-RAY DIFFRACTION | 2.38 |
| 3TKS | Crystal structure of full-length human peroxiredoxin 4 in three different redox states | X-RAY DIFFRACTION | 2.4 |
| 3TKP | Crystal structure of full-length human peroxiredoxin 4 in the reduced form | X-RAY DIFFRACTION | 2.49 |
| 5HQP | Crystal structure of the ERp44-peroxiredoxin 4 complex | X-RAY DIFFRACTION | 2.6 |
| 8EKW | Cryo-EM structure of human PRDX4 | ELECTRON MICROSCOPY | 2.83 |
| 8EKY | Cryo-EM structure of the human PRDX4-ErP46 complex | ELECTRON MICROSCOPY | 3.47 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q13162-F1 | 84.59 | 0.72 |
Human Protein Atlas
Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers
Protein evidence: Evidence at protein level
Subcellular location (HPA, imaging): endoplasmic reticulum; cytosol
Antibody reliability (HPA): IH enhanced · 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.
Catalytic / active sites (1)
| Position | Role |
|---|---|
| 124 | cysteine sulfenic acid (-soh) intermediate |
Disulfide bonds (2)
| Type | Positions |
|---|---|
| Interchain (with c-245) | 124 |
| Interchain (with c-124) | 245 |
Function
Pathways and Gene Ontology
Reactome pathways
1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
3 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-6798695 | Neutrophil degranulation | curated |
| R-HSA-168256 | Immune System | — |
| R-HSA-168249 | Innate Immune System | — |
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 (5): response to oxidative stress (GO:0006979), I-kappaB phosphorylation (GO:0007252), hydrogen peroxide catabolic process (GO:0042744), cell redox homeostasis (GO:0045454), 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
2 top-level categories:
| Category | Pathways |
|---|---|
| Innate Immune System | 1 |
| Immune System | 1 |
GO top-level categories
27 GO namespaces:
| 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 |
| catabolic process | 1 |
| hydrogen peroxide metabolic process | 1 |
| cellular homeostasis | 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 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).
6 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| cytosol | CC | direct assay |
| endoplasmic reticulum | CC | direct assay |
| extracellular exosome | CC | high-throughput assay |
| nucleus | CC | high-throughput assay |
| molecular adaptor activity | MF | experiment |
| molecular sequestering activity | MF | direct assay |
Protein interactions and networks
STRING
showing 15 of 2,358 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| PRDX4 | GLUL | P15104 | 782 |
| PRDX4 | PRDX5 | P30044 | 753 |
| PRDX4 | TXN | P10599 | 696 |
| PRDX4 | SRXN1 | Q9BYN0 | 639 |
| PRDX4 | GPX7 | Q96SL4 | 638 |
| PRDX4 | GPX8 | Q8TED1 | 630 |
| PRDX4 | ERO1A | Q96HE7 | 618 |
| PRDX4 | TXNDC5 | Q8NBS9 | 574 |
| PRDX4 | TXNRD1 | Q16881 | 563 |
| PRDX4 | GPX4 | P36969 | 553 |
| PRDX4 | ERO1B | Q86YB8 | 550 |
| PRDX4 | GLRX | P35754 | 550 |
| PRDX4 | ERP44 | Q9BS26 | 539 |
| PRDX4 | TXN2 | Q99757 | 537 |
| PRDX4 | P4HB | P07237 | 531 |
IntAct
Human interaction partners of PRDX4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
28 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| ATXN1 | physical association | 0.670 | 3 |
| LBP | physical association | 0.600 | 4 |
| TBXA2R | physical association | 0.590 | 3 |
| PRDX1 | physical association | 0.570 | 2 |
| NR4A1 | physical association | 0.550 | 2 |
| PDIA6 | oxidoreductase activity electron transfer reaction | 0.520 | 2 |
| P4HB | oxidoreductase activity electron transfer reaction | 0.440 | 2 |
| PDIA3 | oxidoreductase activity electron transfer reaction | 0.440 | 2 |
| TXNDC5 | oxidoreductase activity electron transfer reaction | 0.440 | 2 |
| A1BG | physical association | 0.370 | 1 |
| ALG12 | physical association | 0.370 | 1 |
| APOB | physical association | 0.370 | 1 |
| CFHR1 | physical association | 0.370 | 1 |
| CFHR3 | physical association | 0.370 | 1 |
| CLIC1 | physical association | 0.370 | 1 |
| CYP27A1 | physical association | 0.370 | 1 |
| DUSP23 | physical association | 0.370 | 1 |
| EP300 | physical association | 0.370 | 1 |
| HDAC6 | physical association | 0.370 | 1 |
| MAP4K2 | physical association | 0.370 | 1 |
| MT-CO1 | physical association | 0.370 | 1 |
| PLG | physical association | 0.370 | 1 |
| PRDX2 | physical association | 0.370 | 1 |
| PRDX3 | physical association | 0.370 | 1 |
| RCHY1 | physical association | 0.370 | 1 |
| SULT2A1 | physical association | 0.370 | 1 |
| TTF2 | physical association | 0.370 | 1 |
| VTN | physical association | 0.370 | 1 |
BioGRID (314 interactions; top human partners by supporting records): PRDX1 (Two-hybrid; 11 records), AGR2 (Proximity Label-MS; 4 records), OTUD1 (Proximity Label-MS; 4 records), CUL3 (Affinity Capture-MS; 3 records), INS (Affinity Capture-MS; 3 records), TBXA2R (Two-hybrid; 3 records), AURKA (Affinity Capture-MS; 2 records), CCNF (Affinity Capture-MS; 2 records), CLIC1 (Affinity Capture-MS; 2 records), CTSB (Affinity Capture-MS; 2 records), CTSS (Affinity Capture-MS; 2 records), DPP4 (Affinity Capture-MS; 2 records), HDAC6 (Affinity Capture-MS; 2 records), HSPA5 (Affinity Capture-Western; 2 records), HUWE1 (Affinity Capture-MS; 2 records)
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 28 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 |
|---|---|---|---|
| protein folding | 5 | 18.5× | 2e-03 |
Disease & clinical
Genetic variants
Variant evidence for PRDX4: 87 ClinVar records (0 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation.
ClinVar
87 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 24 |
| Likely benign | 0 |
| Benign | 1 |
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 440):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| X:23671647–23671648 | donor_loss | 1.0000 | 5 |
| X:23674988–23674989 | acceptor_loss | 1.0000 | 6 |
| X:23675107–23675108 | donor_loss | 1.0000 | 5 |
| X:23682386 | acceptor_gain | 1.0000 | |
| X:23682393 | acceptor_gain | 1.0000 | |
| X:23682394–23682395 | acceptor_loss | 1.0000 | 5 |
| X:23682524 | donor_gain | 1.0000 | |
| X:23682527–23682528 | donor_loss | 1.0000 | 4 |
| X:23683659 | acceptor_gain | 1.0000 | |
| X:23683706–23683707 | donor_loss | 1.0000 | 4 |
AlphaMissense
895 missense substitutions predicted likely pathogenic (of 1,730 scored), across 186 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 |
|---|---|---|---|
| D151 | 8 | 0.997 | 0.999 |
| D179 | 8 | 0.996 | 0.999 |
| H156 | 8 | 0.994 | 0.999 |
| D218 | 8 | 0.993 | 0.998 |
| D119 | 8 | 0.988 | 0.997 |
| F122 | 8 | 0.988 | 1.000 |
| F120 | 8 | 0.986 | 1.000 |
| F115 | 8 | 0.976 | 0.998 |
| F138 | 8 | 0.976 | 0.999 |
| F267 | 8 | 0.976 | 0.995 |
| F131 | 8 | 0.963 | 0.997 |
| F203 | 8 | 0.958 | 0.998 |
| N217 | 8 | 0.951 | 0.999 |
| F235 | 8 | 0.942 | 0.996 |
| D206 | 8 | 0.940 | 0.997 |
| F98 | 8 | 0.920 | 0.996 |
| H197 | 8 | 0.865 | 0.985 |
| D239 | 8 | 0.860 | 0.971 |
| D226 | 8 | 0.818 | 0.963 |
| F113 | 8 | 0.811 | 0.994 |
HPA cancer prognostics
RNA cancer specificity: Low cancer specificity
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
6 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Kidney Renal Papillary Cell Carcinoma (TCGA) | unfavorable | 2.37e-07 |
| Kidney Renal Clear Cell Carcinoma (TCGA) | favorable | 7.58e-06 |
| Bladder Urothelial Carcinoma (TCGA) | unfavorable | 9e-05 |
| Kidney Chromophobe (TCGA) | unfavorable | 0.000291 |
| Liver Hepatocellular Carcinoma (TCGA) | unfavorable | 0.000553 |
| Breast Invasive Carcinoma (TCGA) | unfavorable | 0.000809 |
Disease associations
OMIM: gene MIM:300927 | disease phenotypes:
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL4295812 (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)
PharmGKB clinical annotations
1 annotations by evidence level (1 strongest → 4):
| Variant | Association | 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 |
Binding affinities (BindingDB)
2 measured of 2 human assays (4 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value |
|---|---|---|
| CHEMBL5565154 | IC50 | 350 nM |
| CHEMBL5653589 | KD | 1440 nM |
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 | increases expression, affects cotreatment | 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)
Via MONDO — disease-level, not drug-specific.
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for PRDX4 across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.