PRDX1

Summary

PRDX1 (peroxiredoxin 1, HGNC:9352) is a protein-coding gene on chromosome 1p34.1, encoding Peroxiredoxin-1 (Q06830). Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.

This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. Four transcript variants encoding the same protein have been identified for this gene.

Source: NCBI Gene 5052 — RefSeq curated summary.

At a glance

• Gene–disease (curated): methylmalonic aciduria and homocystinuria type cblC (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 79 total — 2 pathogenic
• Phenotypes (HPO): 65
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_181697

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9352
Approved symbol	PRDX1
Name	peroxiredoxin 1
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	NKEFA
Ensembl gene	ENSG00000117450
Ensembl biotype	protein_coding
OMIM	176763
Entrez	5052

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 31 protein_coding

ENST00000262746, ENST00000319248, ENST00000372079, ENST00000424390, ENST00000447184, ENST00000676549, ENST00000909388, ENST00000909389, ENST00000909390, ENST00000909391, ENST00000909392, ENST00000909393, ENST00000909394, ENST00000909395, ENST00000909396, ENST00000909397, ENST00000914629, ENST00000914630, ENST00000914631, ENST00000914632, ENST00000914633, ENST00000914634, ENST00000914635, ENST00000914636, ENST00000914637, ENST00000914638, ENST00000914639, ENST00000914640, ENST00000914641, ENST00000914642, ENST00000914643

RefSeq mRNA: 4 — MANE Select: NM_181697 NM_001202431, NM_002574, NM_181696, NM_181697

CCDS: CCDS522

Canonical transcript exons

ENST00000319248 — 6 exons

Exon	Start	End
ENSE00000771101	45514873	45514995
ENSE00001456858	45511051	45511414
ENSE00001456866	45521829	45521884
ENSE00003630916	45515654	45515807
ENSE00003648037	45518938	45519054
ENSE00003788073	45514507	45514637

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 458.1037 / max 2962.1246, expressed in 1824 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12131	456.5687	1824
201497	0.4827	266
12137	0.4147	99
12134	0.4108	141
12132	0.1171	61
12136	0.0878	40
12133	0.0219	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.68	gold quality
left lobe of thyroid gland	UBERON:0001120	99.67	gold quality
nasal cavity epithelium	UBERON:0005384	99.66	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.65	gold quality
palpebral conjunctiva	UBERON:0001812	99.64	gold quality
esophagus mucosa	UBERON:0002469	99.61	gold quality
ganglionic eminence	UBERON:0004023	99.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.61	gold quality
thyroid gland	UBERON:0002046	99.60	gold quality
spinal cord	UBERON:0002240	99.57	gold quality
metanephros cortex	UBERON:0010533	99.57	gold quality
gingiva	UBERON:0001828	99.54	gold quality
gingival epithelium	UBERON:0001949	99.53	gold quality
oral cavity	UBERON:0000167	99.52	gold quality
epithelium of nasopharynx	UBERON:0001951	99.51	gold quality
lower esophagus mucosa	UBERON:0035834	99.51	gold quality
islet of Langerhans	UBERON:0000006	99.50	gold quality
nasal cavity mucosa	UBERON:0001826	99.49	gold quality
esophagus	UBERON:0001043	99.48	gold quality
right adrenal gland	UBERON:0001233	99.46	gold quality
right atrium auricular region	UBERON:0006631	99.46	gold quality
tongue squamous epithelium	UBERON:0006919	99.46	gold quality
esophagus squamous epithelium	UBERON:0006920	99.44	gold quality
right adrenal gland cortex	UBERON:0035827	99.44	gold quality
cardiac atrium	UBERON:0002081	99.43	gold quality
pharyngeal mucosa	UBERON:0000355	99.41	gold quality
left adrenal gland	UBERON:0001234	99.41	gold quality
epithelium of esophagus	UBERON:0001976	99.41	gold quality
embryo	UBERON:0000922	99.40	gold quality
right lung	UBERON:0002167	99.40	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	2718.98
E-MTAB-8205	yes	1798.71
E-MTAB-8894	yes	1688.38
E-HCAD-5	yes	1649.26
E-MTAB-9067	yes	1068.74
E-HCAD-4	yes	610.12
E-HCAD-1	yes	227.28
E-CURD-122	yes	47.99
E-CURD-112	yes	42.24
E-MTAB-5061	yes	25.96
E-MTAB-10553	yes	20.92
E-GEOD-125970	yes	18.23
E-GEOD-83139	yes	12.71
E-MTAB-10042	yes	10.80
E-GEOD-135922	yes	6.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, IRF6, JUN, NFE2L2, NFKB, TCF23

miRNA regulators (miRDB)

14 targeting PRDX1, 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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-581	98.39	67.42	835
HSA-MIR-4432	97.80	67.87	705

Literature-anchored findings (GeneRIF, showing 40)

• Protein levels of Prx-I and Prx-II were significantly increased 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)
• regulation of activity by Cdc2-mediated phosphorylation (PMID:11986303)
• 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)
• Data show that peroxiredoxin I (Prx I)activity decreased gradually during catalysis, coincident with the conversion of Prx I to a more acidic species. (PMID:12161445)
• No detectable changes in expression of peroxiredoxin 1 are observed in postmortem cerebellum or frontal cortex of patients with Down syndrome, Alzheimer or Pick’s disease. (PMID:12650976)
• results show that the sulfinic form of peroxiredoxin I, produced during the exposure of cells to H2O2, is rapidly reduced to the catalytically active thiol form (PMID:12714748)
• Prx I and Trx expression is increased in lung cancer cells following hypoxia and in human lung cancer tissues (PMID:14703116)
• results show that sestrins, a family of proteins whose expression is modulated by p53, are required for regeneration of peroxiredoxins containing Cys-SO(2)H (PMID:15105503)
• mammalian sulfiredoxin reactivates hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine (PMID:15448164)
• Prx I and Prx II are induced at the early and late stage of differentiation of normal human epidermal keratinocytes. (PMID:15864612)
• expression in squamous cell carcinoma of the tongue indicates tumors with a high potential for recurrence (PMID:15955662)
• Prdx1 is activated by histone deacetylase inhibitor FK228, which causes apoptosis induction in esophageal cancer cells (PMID:16278420)
• Our findings collectively suggest that non-classical secretion of Prx-I is induced by TGF-beta1, which is constitutively activated by furin in A549 cells. (PMID:16677601)
• Aspartate-187 of peroxiredoxin (Prx) I is the catalytic residue responsible for ATP hydrolysis in the cysteinesulfinic acid reduction of Prx by human sulfiredoxin. (PMID:17176052)
• The human prx1 promoter was cloned and nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) was identified as a key transcription factor. (PMID:17234762)
• Human Prdx1 and Prdx2 possess unique functions and regulatory mechanisms and that Cys(83) bestows a distinctive identity to Prdx1. (PMID:17519234)
• Cytoplasmic perocyredoxin 1 inhibited NF-kappaB activation and nuclear translocation. (PMID:17603937)
• peroxiredoxin 1, but not NF-E2-related factor 2, has a role in non-small cell lung cancer recurrence and progression (PMID:17606720)
• In the normal human ciliary body, PRDX I, II and III were immunolocalized to the non-pigmented epithelial cells and ciliary muscle fibers. It suggests that 2-Cys PRDXs may have physiological functions to protect cells in human ciliary body. (PMID:17707450)
• hippocampal neurons transfected with wild type Prx1 exhibit increased Abeta resistance (PMID:17761673)
• Loss of PRDX1 is associated with esophageal squamous cell carcinoma (PMID:17786348)
• Cell survival-enhancing property of Prx1 has been attributed to its antioxidant activity, the reactive oxygen species-scavenging activity of Prx1 was not essential for AR stimulation; Prx1 itself was oxidized and inactivated by hypoxia/reoxygenation. (PMID:17909037)
• 2.6 A crystal structure of the human Srx-PrxI complex (PMID:18172504)
• The observation that PrxI is involved in suppressing genome instability and protecting against cell death potentially provides a better understanding of the consequences of PrxI dysfunction in human cells. (PMID:18281480)
• Prx1 may possess unique functions and regulatory mechanisms in NSCLC which are not shared with Prx2, and that Prx1 may serve as a new prognostic biomarker and therapeutic target in NSCLC. (PMID:18413821)
• These findings suggest a negative role of Prx-1 in ASK1-induced apoptosis. (PMID:18501712)
• PSB7, PRDX1, and SRP9 up-regulation as candidate biomarkers of colon cancer is discovered (PMID:18549262)
• peroxiredoxin (Prx) I and Prx II are specific targets of HDAC6 (PMID:18606987)
• We showed that Prx I, PDGF-A, and PDGFR-alpha follow the same expression pattern during carcinoma ex pleomorphic adenoma progression. (PMID:18992915)
• Ets regulates PRDX1 expression through their interaction with HMGB1 protein. (PMID:19016754)
• Report the effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells. (PMID:19135121)
• Prx II is more susceptible than Prx I to hyperoxidation and that the majority of the hyperoxidized Prx II formation is reversible. However, the hyperoxidized Prx I showed much less reversibility (PMID:19286652)
• Prx I is overexpressed in oncocytes regardless of salivary gland lesion where they appear. Results suggest that Prx I expression in oncocytes is related to ability to decompose mitochondrial-derived H(2)O(2) to provide a protective role. (PMID:19298244)
• Prx I functions to block propagation of Nox-derived ROS signaling to the p38 MAPK/caspase/cell death cascade during TRAIL treatment and also provides a molecular mechanism by which Prx I contributes to TRAIL resistance in liver cancers. (PMID:19406930)
• The high expressions of Prx1, Trx1 and HIF-1alpha were related to invasion and lymph node metastasis in papillary thyroid carcinoma. (PMID:19558833)
• Results show Prx1 increases the affinity of androgen receptor to dihydrotestosterone (DHT) and decreases the rate of DHT dissociation from the occupied receptor. (PMID:19737972)
• Studies present the 2.1 A crystal structure of human Srx in complex with PrxI, ATP, and Mg(2+). (PMID:19812042)
• Prdx 1 was found to be the strongest overexpressed protein in malignant ovarian tumors among the selected proteins. Prdx 1 expression (>50% positive cancer cells) was significantly correlated with poor overall survival in ovarian serous carcinomas. (PMID:19902980)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	prdx1	ENSDARG00000058734
mus_musculus	Prdx1	ENSMUSG00000028691
rattus_norvegicus	Prdx1	ENSRNOG00000017194
rattus_norvegicus	Prdx1l1	ENSRNOG00000017695
drosophila_melanogaster	Prx6c	FBGN0033518
drosophila_melanogaster	Prx6b	FBGN0033520
drosophila_melanogaster	CG12896	FBGN0033521

Paralogs (4): PRDX6 (ENSG00000117592), PRDX4 (ENSG00000123131), PRDX3 (ENSG00000165672), PRDX2 (ENSG00000167815)

Protein

Protein identifiers

Peroxiredoxin-1 — Q06830 (reviewed: Q06830)

Alternative names: Natural killer cell-enhancing factor A, Proliferation-associated gene protein, Thioredoxin peroxidase 2, Thioredoxin-dependent peroxide reductase 2, Thioredoxin-dependent peroxiredoxin 1

All UniProt accessions (4): A0A0A0MRQ5, A0A0A0MSI0, A0A384NPQ2, Q06830

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. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation.

Subunit / interactions. Homodimer; disulfide-linked, upon oxidation. 5 homodimers assemble to form a ring-like decamer. Interacts with GDPD5; forms a mixed-disulfide with GDPD5. Interacts with SESN1 and SESN2. Interacts with FAM107A.

Subcellular location. Cytoplasm. Melanosome.

Post-translational modifications. Phosphorylated on Thr-90 during the M-phase, which leads to a more than 80% decrease in enzymatic activity. Acetylation increases reducing activity and resistance to superoxidation. Deacetylated by HDAC6 which decreases reducing activity. The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) instead of its condensation to a disulfide bond. It can be reactivated by forming a transient disulfide bond with sulfiredoxin SRXN1, which reduces the cysteine sulfinic acid in an ATP- and Mg-dependent manner.

Induction. Constitutively expressed in most human cells; is induced to higher levels upon serum stimulation in untransformed and transformed cells.

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 (4): NP_001189360, NP_002565, NP_859047, NP_859048* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000866	AhpC/TSA	Domain
IPR013766	Thioredoxin_domain	Domain
IPR019479	Peroxiredoxin_C	Domain
IPR024706	Peroxiredoxin_AhpC-typ	Family
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 (50 total): modified residue 10, strand 10, helix 9, sequence conflict 4, cross-link 3, mutagenesis site 3, disulfide bond 2, turn 2, initiator methionine 1, chain 1, domain 1, sequence variant 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
8Z54	X-RAY DIFFRACTION	1.45
8X71	X-RAY DIFFRACTION	1.58
8X73	X-RAY DIFFRACTION	1.61
9LNH	X-RAY DIFFRACTION	1.63
9B7A	X-RAY DIFFRACTION	1.71
7WET	X-RAY DIFFRACTION	1.76
9VGT	X-RAY DIFFRACTION	1.79
8Z56	X-RAY DIFFRACTION	1.81
7WEU	X-RAY DIFFRACTION	1.81
9LG0	X-RAY DIFFRACTION	1.81
8Z55	X-RAY DIFFRACTION	1.83
8Z57	X-RAY DIFFRACTION	1.96
3HY2	X-RAY DIFFRACTION	2.1
4XCS	X-RAY DIFFRACTION	2.1
9DEX	X-RAY DIFFRACTION	2.3
8Z58	X-RAY DIFFRACTION	2.4
2RII	X-RAY DIFFRACTION	2.6
7LJ1	X-RAY DIFFRACTION	2.97

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06830-F1	97.29	0.97

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

Post-translational modifications (13): 32, 35, 35, 90, 136, 197, 7, 120, 185, 2, 7, 16, 27

Disulfide bonds (2): 52, 173

Mutagenesis-validated functional residues (3):

Position	Phenotype
90	abolishes phosphorylation by cdk1; 30% reduction in enzymatic activity.
90	87% reduction in enzymatic activity.
197	reduces acetylation.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3000471	Scavenging by Class B Receptors
R-HSA-3299685	Detoxification of Reactive Oxygen Species
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes

MSigDB gene sets: 527 (showing top): MODULE_93, SHEPARD_BMYB_MORPHOLINO_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, KAAB_FAILED_HEART_ATRIUM_DN, XU_GH1_AUTOCRINE_TARGETS_UP, MODULE_151, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_ERYTHROCYTE_HOMEOSTASIS, HSIAO_HOUSEKEEPING_GENES

GO Biological Process (16): skeletal system development (GO:0001501), response to oxidative stress (GO:0006979), canonical NF-kappaB signal transduction (GO:0007249), cell population proliferation (GO:0008283), removal of superoxide radicals (GO:0019430), natural killer cell activation (GO:0030101), regulation of stress-activated MAPK cascade (GO:0032872), erythrocyte homeostasis (GO:0034101), natural killer cell mediated cytotoxicity (GO:0042267), hydrogen peroxide catabolic process (GO:0042744), leukocyte activation (GO:0045321), cell redox homeostasis (GO:0045454), fibroblast proliferation (GO:0048144), regulation of non-canonical NF-kappaB signal transduction (GO:1901222), response to reactive oxygen species (GO:0000302), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (10): RNA binding (GO:0003723), peroxidase activity (GO:0004601), thioredoxin peroxidase activity (GO:0008379), identical protein binding (GO:0042802), cadherin binding (GO:0045296), 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 (6): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), melanosome (GO:0042470), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Binding and Uptake of Ligands by Scavenger Receptors	1
Cellular response to chemical stress	1
Transcriptional Regulation by TP53	1
Neurodegenerative Diseases	1
Nuclear events mediated by NFE2L2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular oxidant detoxification	2
cellular anatomical structure	2
system development	1
response to stress	1
intracellular signaling cassette	1
cellular process	1
superoxide metabolic process	1
cellular response to superoxide	1
lymphocyte activation	1
regulation of MAPK cascade	1
stress-activated MAPK cascade	1
regulation of stress-activated protein kinase signaling cascade	1
myeloid cell homeostasis	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
catabolic process	1
hydrogen peroxide metabolic process	1
cell activation	1
immune system process	1
cellular homeostasis	1
cell population proliferation	1
non-canonical NF-kappaB signal transduction	1
regulation of intracellular signal transduction	1
response to oxidative stress	1
response to oxygen-containing compound	1
cellular detoxification	1
nucleic acid binding	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
thioredoxin-dependent peroxiredoxin activity	1
protein binding	1
cell adhesion molecule binding	1
binding	1
molecular_function	1
catalytic activity	1
peroxidase activity	1
peroxiredoxin activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

237 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
MED11	MED19	psi-mi:“MI:0914”(association)	0.840
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
MED25	MED24	psi-mi:“MI:0914”(association)	0.740
PPP2R1B	STRN	psi-mi:“MI:0914”(association)	0.730
TPT1	XRCC6	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
STK4	PRDX1	psi-mi:“MI:0217”(phosphorylation reaction)	0.660
PRDX1	STK4	psi-mi:“MI:0217”(phosphorylation reaction)	0.660
PRDX1	STK4	psi-mi:“MI:0407”(direct interaction)	0.660
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
SRXN1	PRDX1	psi-mi:“MI:0407”(direct interaction)	0.620
TPT1	PRDX1	psi-mi:“MI:0915”(physical association)	0.570
PRDX1	PRDX4	psi-mi:“MI:0915”(physical association)	0.570
PRDX4	PRDX1	psi-mi:“MI:0915”(physical association)	0.570
PRDX1	DPP9	psi-mi:“MI:0915”(physical association)	0.560
MAGEB6	PRDX1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (561): PRDX1 (Affinity Capture-MS), PRDX1 (Affinity Capture-MS), PRDX1 (Affinity Capture-MS), PRDX1 (Affinity Capture-MS), PRDX1 (Affinity Capture-MS), PRDX1 (Two-hybrid), PRDX1 (Affinity Capture-MS), PRDX1 (Affinity Capture-MS), PRDX1 (Affinity Capture-MS), ASS1 (Co-fractionation), MSH6 (Co-fractionation), PRDX1 (Co-fractionation), PRDX1 (Co-fractionation), PRDX1 (Co-fractionation), PRDX1 (Co-fractionation)

ESM2 similar proteins: A0A0K3AUJ9, A0A2Z5VKM8, K0J4Q8, O04005, O74887, P0A0B5, P0A0B6, P0A0B7, P0CB50, P0CU34, P21762, P23161, P32119, P34760, P35700, P35704, P51272, P52574, P56876, P80239, P80602, P91883, P99074, Q04120, Q06830, Q17172, Q1XDL4, Q26695, Q2FJN4, Q2PFZ3, Q2YVK2, Q55624, Q5E947, Q5HIR5, Q5HRY1, Q5RC63, Q61171, Q63716, Q6B4U9, Q6DV14

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

10 interactions.

A	Effect	B	Mechanism
PBK	up-regulates	PRDX1	phosphorylation
CDK1	down-regulates	PRDX1	phosphorylation
CDK2	down-regulates	PRDX1	phosphorylation
CDK4	down-regulates	PRDX1	phosphorylation
CDK6	down-regulates	PRDX1	phosphorylation
LCK	“down-regulates activity”	PRDX1	phosphorylation
ABL1	“down-regulates activity”	PRDX1	phosphorylation
STK4	“down-regulates activity”	PRDX1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 215 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
Aggrephagy	6	9.4×	3e-03
Negative regulation of the PI3K/AKT network	5	8.8×	8e-03
Selective autophagy	5	8.8×	8e-03
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	7	8.5×	2e-03
Transcriptional Regulation by VENTX	5	8.3×	9e-03
Respiratory Syncytial Virus Infection Pathway	6	7.4×	7e-03
Degradation of beta-catenin by the destruction complex	6	6.5×	9e-03
MAPK family signaling cascades	9	5.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
amyloid fibril formation	5	16.2×	3e-03
autophagosome maturation	7	13.2×	5e-04
positive regulation of transcription initiation by RNA polymerase II	8	11.7×	3e-04
intrinsic apoptotic signaling pathway	6	11.6×	3e-03
positive regulation of transcription elongation by RNA polymerase II	7	11.3×	1e-03
mitophagy	6	10.3×	5e-03
JNK cascade	6	8.8×	7e-03
G1/S transition of mitotic cell cycle	8	8.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	32
Likely benign	21
Benign	11

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1179112	GRCh37/hg19 1p34.1(chr1:45965972-45979054)	Pathogenic
495209	NM_181697.3(PRDX1):c.515-1G>T	Pathogenic

SpliceAI

931 predictions. Top by Δscore:

Variant	Effect	Δscore
1:45511411:CACA:C	acceptor_gain	1.0000
1:45511412:ACA:A	acceptor_gain	1.0000
1:45511413:CA:C	acceptor_gain	1.0000
1:45511413:CAC:C	acceptor_gain	1.0000
1:45511414:ACT:A	acceptor_loss	1.0000
1:45511415:C:CC	acceptor_gain	1.0000
1:45514503:TTACC:T	donor_loss	1.0000
1:45514504:TA:T	donor_loss	1.0000
1:45514505:ACCTT:A	donor_gain	1.0000
1:45514506:C:CT	donor_loss	1.0000
1:45514506:CCTTC:C	donor_gain	1.0000
1:45514635:CCC:C	acceptor_gain	1.0000
1:45514636:CC:C	acceptor_gain	1.0000
1:45514636:CCC:C	acceptor_gain	1.0000
1:45514637:CC:C	acceptor_gain	1.0000
1:45514638:C:CC	acceptor_gain	1.0000
1:45514639:T:C	acceptor_loss	1.0000
1:45514871:A:AG	donor_loss	1.0000
1:45514872:C:CT	donor_loss	1.0000
1:45514991:TGACC:T	acceptor_gain	1.0000
1:45514993:ACCC:A	acceptor_loss	1.0000
1:45514994:CC:C	acceptor_gain	1.0000
1:45514995:CCTA:C	acceptor_gain	1.0000
1:45514996:C:CC	acceptor_gain	1.0000
1:45514996:C:CG	acceptor_loss	1.0000
1:45514996:C:T	acceptor_gain	1.0000
1:45514998:A:C	acceptor_gain	1.0000
1:45519050:ATCAG:A	acceptor_gain	1.0000
1:45519051:TCAG:T	acceptor_gain	1.0000
1:45519052:CAG:C	acceptor_gain	1.0000

AlphaMissense

1324 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:45511400:A:G	W177R	0.999
1:45511400:A:T	W177R	0.999
1:45514873:C:A	R128M	0.999
1:45515655:A:G	W87R	0.999
1:45515655:A:T	W87R	0.999
1:45515764:A:C	F50L	0.999
1:45515764:A:T	F50L	0.999
1:45515766:A:G	F50L	0.999
1:45515770:G:C	F48L	0.999
1:45515770:G:T	F48L	0.999
1:45515772:A:G	F48L	0.999
1:45511398:C:A	W177C	0.998
1:45511398:C:G	W177C	0.998
1:45514542:A:T	V160D	0.998
1:45514570:G:T	R151S	0.998
1:45514575:A:T	V149D	0.998
1:45514602:C:G	R140P	0.998
1:45514873:C:G	R128T	0.998
1:45515664:G:C	H84D	0.998
1:45515750:T:A	E55V	0.998
1:45515758:G:C	C52W	0.998
1:45515759:C:T	C52Y	0.998
1:45515760:A:G	C52R	0.998
1:45511410:G:C	C173W	0.997
1:45514545:A:G	L159P	0.997
1:45514586:A:C	N145K	0.997
1:45514586:A:T	N145K	0.997
1:45514995:C:A	W87C	0.997
1:45514995:C:G	W87C	0.997
1:45515678:T:A	D79V	0.997

dbSNP variants (sampled 300 via entrez): RS1000059673 (1:45523363 G>A), RS1000240833 (1:45523657 C>T), RS1000355237 (1:45510918 T>C), RS1000410685 (1:45510632 C>A), RS1000415407 (1:45524086 GA>G), RS1000688178 (1:45512743 C>G,T), RS1000883257 (1:45517165 G>A), RS1001006749 (1:45522339 C>A,T), RS1001170788 (1:45513345 G>A), RS1001194334 (1:45512301 G>A,C), RS1001253222 (1:45517391 T>C), RS1001296065 (1:45519345 A>G), RS1001325601 (1:45519044 C>A,T), RS1001390514 (1:45517677 G>A), RS1001498262 (1:45524588 C>T)

Disease associations

OMIM: gene MIM:176763 | disease phenotypes: MIM:277400

GenCC curated gene-disease

Disease	Classification	Inheritance
methylmalonic aciduria and homocystinuria type cblC	Strong	Autosomal recessive

Mondo (1): methylmalonic aciduria and homocystinuria type cblC (MONDO:0010184)

Orphanet (2): Methylmalonic acidemia with homocystinuria (Orphanet:26), Methylmalonic acidemia with homocystinuria, type cblC (Orphanet:79282)

HPO phenotypes

65 total (30 of 65 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000112	Nephropathy
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000319	Smooth philtrum
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000505	Visual impairment
HP:0000580	Pigmentary retinopathy
HP:0000639	Nystagmus
HP:0000726	Dementia
HP:0000790	Hematuria
HP:0000980	Pallor
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001289	Confusion
HP:0001290	Generalized hypotonia
HP:0001337	Tremor
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001649	Tachycardia
HP:0001662	Bradycardia
HP:0001695	Cardiac arrest

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005951_37	Body mass index	8.000000e-10
GCST90002384_537	Hemoglobin	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5315 (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)

ChEMBL bioactivities

43 potent at pChembl≥5 of 44 total, top 43 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.34	Kd	45.85	nM	CHEMBL3752910
7.34	ED50	45.85	nM	CHEMBL3752910
6.79	IC50	164	nM	CHEMBL5647448
6.78	IC50	165	nM	CHEMBL5647239
6.62	IC50	239	nM	CHEMBL5639299
6.54	IC50	285	nM	CHEMBL5647369
6.51	IC50	310	nM	CHEMBL5569469
6.48	IC50	330	nM	CHEMBL5569818
6.47	IC50	340	nM	CHEMBL5572018
6.46	IC50	350	nM	CHEMBL5565154
6.44	IC50	360	nM	CHEMBL5569995
6.44	IC50	360	nM	CHEMBL5571353
6.43	IC50	370	nM	CHEMBL5594961
6.43	Kd	370	nM	CHEMBL5565154
6.42	IC50	380	nM	CHEMBL5572187
6.40	IC50	400	nM	CHEMBL5591790
6.39	IC50	410	nM	CHEMBL5570187
6.38	IC50	420	nM	CHEMBL5573037
6.35	IC50	450	nM	CHEMBL5566003
6.34	IC50	460	nM	CHEMBL5575303
6.34	IC50	460	nM	CHEMBL5564537
6.33	IC50	470	nM	CHEMBL5572492
6.33	IC50	470	nM	CHEMBL5566476
6.32	IC50	481	nM	CHEMBL5646554
6.31	IC50	490	nM	CHEMBL5532404
6.31	IC50	490	nM	CHEMBL5572158
6.30	IC50	500	nM	CELASTROL
6.30	IC50	500	nM	CHEMBL5575142
6.28	IC50	530	nM	CHEMBL5571140
6.28	IC50	525	nM	CHEMBL5639325
6.27	IC50	540	nM	CHEMBL5572484
6.19	IC50	640	nM	CHEMBL5574572
6.02	IC50	950	nM	CHEMBL574646
6.01	IC50	979	nM	CHEMBL5647003
5.83	IC50	1472	nM	CHEMBL5647534
5.81	IC50	1534	nM	CHEMBL5646385
5.79	IC50	1622	nM	CELASTROL
5.74	Kd	1830	nM	CHEMBL4092369
5.60	IC50	2488	nM	CHEMBL5647082
5.58	Kd	2610	nM	PIERICIDIN A
5.01	Kd	9723	nM	CHEMBL5653589
5.01	ED50	9723	nM	CHEMBL5653589
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

41 with measured affinity, of 81 total; 39 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	2149061: Binding affinity to human PRDX1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0459	uM
[(6aS,6bS,8aS,11R,12aR,14aR)-4,6a,6b,8a,11,14a-hexamethyl-2-oxo-11-[(3,5,6-trimethylpyrazin-2-yl)methylcarbamoyl]-7,8,9,10,12,12a,13,14-octahydropicen-3-yl] (E)-3-phenylprop-2-enoate	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	0.1640	uM
(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-N-[(3,5,6-trimethylpyrazin-2-yl)methyl]-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxamide	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	0.1650	uM
[(6aS,6bS,8aS,11R,12aR,14aR)-4,6a,6b,8a,11,14a-hexamethyl-2-oxo-11-[(3,5,6-trimethylpyrazin-2-yl)methylcarbamoyl]-7,8,9,10,12,12a,13,14-octahydropicen-3-yl] cyclopropanecarboxylate	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	0.2390	uM
[(6aS,6bS,8aS,11R,12aR,14aR)-4,6a,6b,8a,11,14a-hexamethyl-2-oxo-11-[(3,5,6-trimethylpyrazin-2-yl)methylcarbamoyl]-7,8,9,10,12,12a,13,14-octahydropicen-3-yl] butanoate	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	0.2850	uM
(2S)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]propanamide	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.3100	uM
1-[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]-3-[(3S)-2-oxooxolan-3-yl]urea	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.3300	uM
methyl (2S)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]-3-(1H-indol-3-yl)propanoate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.3400	uM
methyl 1-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]cyclobutane-1-carboxylate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.3500	uM
ethyl 1-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]cyclopropane-1-carboxylate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.3600	uM
methyl (2S,4R)-1-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoyl]-4-hydroxypyrrolidine-2-carboxylate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.3600	uM
dimethyl (2S)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]pentanedioate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.3700	uM
methyl 3-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]oxetane-3-carboxylate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.3800	uM
methyl (2S)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4000	uM
1-[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]-3-[2-(2-hydroxyethoxy)ethyl]urea	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4100	uM
methyl (2S)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]-3-(4-hydroxyphenyl)propanoate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4200	uM
1-[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]-3-(1,3-dihydroxypropan-2-yl)urea	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4500	uM
methyl (2S)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]-3-methylbutanoate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4600	uM
1-[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]-3-[(1S,3R,4R)-3-hydroxy-4-(hydroxymethyl)cyclopentyl]urea	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4600	uM
methyl (2S)-1-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoyl]pyrrolidine-2-carboxylate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4700	uM
methyl (2S)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]-3-hydroxypropanoate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4700	uM
(3,5,6-trimethylpyrazin-2-yl)methyl (2R,4aS,6aR,6aS,14aS,14bR)-10-acetyloxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	0.4810	uM
methyl (2S)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]propanoate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4900	uM
methyl (2S,3R)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]-3-hydroxybutanoate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.4900	uM
(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.5000	uM
1-[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]-3-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]urea	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.5000	uM
(3,5,6-trimethylpyrazin-2-yl)methyl (2R,4aS,6aR,6aS,14aS,14bR)-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-10-[(E)-3-phenylprop-2-enoyl]oxy-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	0.5250	uM
1-[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]-3-[(2R)-1-hydroxypropan-2-yl]urea	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.5300	uM
methyl (2S)-2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]-4-methylsulfanylbutanoate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.5400	uM
methyl 2-[[(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicen-2-yl]carbamoylamino]acetate	2106298: Inhibition of recombinant PRDX1 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay	ic50	0.6400	uM
(3E,5E)-3,5-bis(pyridin-2-ylmethylidene)piperidin-4-one	1527554: Inhibition of PRDX1 in human PMA-differentiated LPS-stimulated THP1 cells assessed as reduction in NLRP3 inflammasome activation preincubated for 1 hr followed by addition of ATP and mesured after 1 hr by ELISA	ic50	0.9500	uM
[(6aS,6bS,8aS,11R,12aR,14aR)-4,6a,6b,8a,11,14a-hexamethyl-2-oxo-11-[(3,5,6-trimethylpyrazin-2-yl)methylcarbamoyl]-7,8,9,10,12,12a,13,14-octahydropicen-3-yl] propanoate	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	0.9790	uM
[(6aS,6bS,8aS,11R,12aR,14aR)-4,6a,6b,8a,11,14a-hexamethyl-2-oxo-11-[(3,5,6-trimethylpyrazin-2-yl)methylcarbamoyl]-7,8,9,10,12,12a,13,14-octahydropicen-3-yl] acetate	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	1.4720	uM
[(6aS,6bS,8aS,11R,12aR,14aR)-4,6a,6b,8a,11,14a-hexamethyl-2-oxo-11-[(3,5,6-trimethylpyrazin-2-yl)methylcarbamoyl]-7,8,9,10,12,12a,13,14-octahydropicen-3-yl] oxane-4-carboxylate	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	1.5340	uM
2,3-dimethoxy-5-methyl-6-[(2E,5E,7E,9R,10R,11E)-3,7,9,11-tetramethyl-10-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxytrideca-2,5,7,11-tetraenyl]-1H-pyridin-4-one	1516530: Binding affinity to full-length human PRDX1 by surface plasmon resonance analysis	kd	1.8300	uM
(3,5,6-trimethylpyrazin-2-yl)methyl (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate	2140191: Inhibition of PRDX1 (unknown origin) in presence of cofactor A/cofactor B/NADPH incubated for 25 mins	ic50	2.4880	uM
2-[(2E,5E,7E,9R,10R,11E)-10-hydroxy-3,7,9,11-tetramethyltrideca-2,5,7,11-tetraenyl]-5,6-dimethoxy-3-methyl-1H-pyridin-4-one	1516530: Binding affinity to full-length human PRDX1 by surface plasmon resonance analysis	kd	2.6100	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149061: Binding affinity to human PRDX1 incubated for 45 mins by Kinobead based pull down assay	kd	9.7229	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	2178523: Inhibition of PRDX1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects reaction, affects response to substance, affects cotreatment, increases methylation, decreases expression (+6 more)	9
Tobacco Smoke Pollution	increases metabolic processing, affects expression, decreases expression, increases expression	9
Arsenic	affects methylation, increases expression, affects cotreatment, increases abundance	6
Cadmium Chloride	increases abundance, increases expression	6
Benzo(a)pyrene	affects cotreatment, decreases oxidation, increases abundance, increases expression, increases methylation (+1 more)	5
Hydrogen Peroxide	decreases activity, increases abundance, affects expression, decreases expression, increases expression (+2 more)	5
Cadmium	increases abundance, increases expression	4
Tretinoin	decreases expression	4
Acetylcysteine	increases expression, decreases activity, increases abundance, decreases expression, decreases reaction	3
Aerosols	increases expression	3
Vehicle Emissions	increases expression, decreases expression, decreases reaction	3
Paraquat	increases oxidation, affects cotreatment, increases expression	3
Particulate Matter	decreases expression, decreases reaction, increases expression	3
arsenite	increases abundance, increases expression, affects binding, increases reaction	2
indole-3-carbinol	decreases expression, decreases reaction	2
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Vorinostat	increases expression	2
Acetaminophen	affects cotreatment, increases expression	2
Air Pollutants	decreases oxidation, increases abundance, increases expression, affects cotreatment	2
Atrazine	decreases expression, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Copper	affects binding	2
Dinitrochlorobenzene	affects oxidation, affects binding	2
Glucose	increases expression, affects response to substance, affects uptake	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Potassium Dichromate	increases expression	2
Quercetin	affects cotreatment, increases expression, decreases reaction	2
Smoke	decreases expression	2
Valproic Acid	increases expression	2

ChEMBL screening assays

35 unique, capped per target: 35 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1025712	Binding	Binding affinity to sulfenic acid modified peroxiredoxin human HeLa cells at 10 mM by Western blot	Facile synthesis and biological evaluation of a cell-permeable probe to detect redox-regulated proteins. — Bioorg Med Chem Lett

Cellosaurus cell lines

11 cell lines: 9 cancer cell line, 1 transformed cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4GN	U2OS PRDX1 KO	Cancer cell line	Female
CVCL_B3ER	Abcam HEK293T PRDX1 KO	Transformed cell line	Female
CVCL_B4K5	WG3838	Finite cell line	Female
CVCL_KT95	HeLa SilenciX PRDX1	Cancer cell line	Female
CVCL_TG37	HAP1 PRDX1 (-) 1	Cancer cell line	Male
CVCL_TG38	HAP1 PRDX1 (-) 2	Cancer cell line	Male
CVCL_TG39	HAP1 PRDX1 (-) 3	Cancer cell line	Male
CVCL_TG40	HAP1 PRDX1 (-) 4	Cancer cell line	Male
CVCL_TG41	HAP1 PRDX1 (-) 5	Cancer cell line	Male
CVCL_TG42	HAP1 PRDX1 (-) 6	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns