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): 80 total — 2 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 34 tissues, sQTL in 7 (q < 0.05)
• Phenotypes (HPO): 65
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.32 (unconstrained)
• 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: 56 — 48 protein_coding, 8 nonsense_mediated_decay

MANE Select: ENST00000319248

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 1, TSL 5: 2

ENST00000319248, ENST00000262746, 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, ENST00001000986, ENST00001000987, ENST00001069649, ENST00001069656, ENST00001069659, ENST00001069678, ENST00001069681, ENST00001069686, ENST00001069692, ENST00001069696, ENST00001069698, ENST00001069704, ENST00001092121, ENST00001092122, ENST00001092123, ENST00001092124, ENST00001092125, ENST00001092126, ENST00001092127, ENST00001092128, ENST00001092129, ENST00001092130, ENST00001111580, ENST00001130807, ENST00001144593

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.

Highest expression (Bgee): lobe of thyroid gland, nasal cavity epithelium, olfactory segment of nasal mucosa, palpebral conjunctiva, esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRDX1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 34 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 41 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.8e-48	-0.31	1:45500626:A:G
Artery Tibial	eqtl	5.7e-48	-0.45	1:45521902:C:A
Lung	sqtl	8.0e-34	-0.74	1:45513566:G:T
Adipose Subcutaneous	eqtl	1.6e-27	-0.43	1:45521902:C:A
Cells Cultured fibroblasts	eqtl	9.7e-25	-0.22	1:45521902:C:A
Nerve Tibial	eqtl	7.9e-23	-0.30	1:45521902:C:A
Liver	sqtl	3.9e-16	+0.89	1:45480964:G:T
Skin Sun Exposed Lower leg	eqtl	8.1e-16	-0.28	1:45521902:C:A
Artery Aorta	eqtl	3.7e-14	-0.34	1:45521902:C:A
Adipose Visceral Omentum	eqtl	1.3e-13	-0.27	1:45521902:C:A
Esophagus Gastroesophageal Junction	eqtl	7.5e-13	-0.26	1:45521902:C:A
Skin Not Sun Exposed Suprapubic	eqtl	7.2e-12	-0.27	1:45521902:C:A
Heart Left Ventricle	eqtl	7.3e-12	-0.26	1:45521902:C:A
Esophagus Muscularis	eqtl	2.9e-11	-0.21	1:45521902:C:A
Lung	eqtl	1.7e-10	-0.27	1:45521902:C:A
Breast Mammary Tissue	eqtl	1.0e-09	-0.23	1:45521902:C:A
Whole Blood	eqtl	1.5e-09	-0.13	1:45527446:C:T
Testis	eqtl	5.9e-08	-0.12	1:45336998:A:C
Artery Coronary	eqtl	1.6e-06	-0.28	1:45521902:C:A
Brain Putamen basal ganglia	eqtl	4.8e-06	+0.26	1:45454734:G:A

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

showing 100 of 295 tissues 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
hypothalamus	UBERON:0001898	99.39	gold quality
ileal mucosa	UBERON:0000331	99.38	gold quality
smooth muscle tissue	UBERON:0001135	99.38	gold quality
left adrenal gland cortex	UBERON:0035825	99.38	gold quality
bronchial epithelial cell	CL:0002328	99.37	gold quality
gall bladder	UBERON:0002110	99.37	gold quality
corpus callosum	UBERON:0002336	99.37	gold quality
descending thoracic aorta	UBERON:0002345	99.37	gold quality
right uterine tube	UBERON:0001302	99.36	gold quality
epithelium of bronchus	UBERON:0002031	99.36	gold quality
substantia nigra	UBERON:0002038	99.36	gold quality
bronchus	UBERON:0002185	99.36	gold quality
left coronary artery	UBERON:0001626	99.34	gold quality
mucosa of transverse colon	UBERON:0004991	99.34	gold quality
lower esophagus	UBERON:0013473	99.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.34	gold quality
body of stomach	UBERON:0001161	99.33	gold quality
mucosa of stomach	UBERON:0001199	99.33	gold quality
thoracic aorta	UBERON:0001515	99.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.33	gold quality
ascending aorta	UBERON:0001496	99.32	gold quality
midbrain	UBERON:0001891	99.32	gold quality
adrenal tissue	UBERON:0018303	99.32	gold quality
amygdala	UBERON:0001876	99.31	gold quality
right frontal lobe	UBERON:0002810	99.30	gold quality
adult mammalian kidney	UBERON:0000082	99.29	gold quality
mouth mucosa	UBERON:0003729	99.29	gold quality
upper lobe of left lung	UBERON:0008952	99.29	gold quality
ectocervix	UBERON:0012249	99.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.28	gold quality
cingulate cortex	UBERON:0003027	99.27	gold quality
anterior cingulate cortex	UBERON:0009835	99.27	gold quality
minor salivary gland	UBERON:0001830	99.26	gold quality
vagina	UBERON:0000996	99.25	gold quality
rectum	UBERON:0001052	99.25	gold quality
adrenal cortex	UBERON:0001235	99.25	gold quality
right coronary artery	UBERON:0001625	99.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.25	gold quality
skin of leg	UBERON:0001511	99.24	gold quality
adrenal gland	UBERON:0002369	99.24	gold quality
coronary artery	UBERON:0001621	99.23	gold quality
calcaneal tendon	UBERON:0003701	99.23	gold quality
upper lobe of lung	UBERON:0008948	99.23	gold quality
endocervix	UBERON:0000458	99.22	gold quality
aorta	UBERON:0000947	99.22	gold quality
duodenum	UBERON:0002114	99.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.22	gold quality
left uterine tube	UBERON:0001303	99.21	gold quality
gastrocnemius	UBERON:0001388	99.21	gold quality
caudate nucleus	UBERON:0001873	99.21	gold quality
pons	UBERON:0000988	99.20	gold quality
right lobe of liver	UBERON:0001114	99.20	gold quality
transverse colon	UBERON:0001157	99.20	gold quality
skin of abdomen	UBERON:0001416	99.20	gold quality
nucleus accumbens	UBERON:0001882	99.19	gold quality
small intestine	UBERON:0002108	99.19	gold quality
adenohypophysis	UBERON:0002196	99.19	gold quality
ventricular zone	UBERON:0003053	99.19	gold quality
muscle of leg	UBERON:0001383	99.16	gold quality
popliteal artery	UBERON:0002250	99.16	gold quality
tibial artery	UBERON:0007610	99.16	gold quality
tonsil	UBERON:0002372	99.15	gold quality
adult organism	UBERON:0007023	99.15	gold quality
putamen	UBERON:0001874	99.14	gold quality
right ovary	UBERON:0002118	99.14	gold quality
superior vestibular nucleus	UBERON:0007227	99.13	gold quality
body of uterus	UBERON:0009853	99.13	gold quality
zone of skin	UBERON:0000014	99.12	gold quality
stromal cell of endometrium	CL:0002255	99.11	gold quality
apex of heart	UBERON:0002098	99.09	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	785.5	low
Thyroid gland	tissue	751.7	high
Kidney	tissue	731.9	medium
Tonsil	tissue	564.7	medium
Esophagus	tissue	553.2	medium
Duodenum	tissue	471.5	medium
Tongue	tissue	445.2
Heart muscle	tissue	435.9	not detected
Epididymis	tissue	433.8	medium
Breast	tissue	426.1	medium
Vagina	tissue	396.2	not detected
Locus coeruleus	tissue	393.4
Skeletal muscle	tissue	390.0	low
Caudate putamen	tissue	385.2
Small intestine	tissue	378.6	medium
Urinary bladder	tissue	367.0	medium
Lymph node	tissue	347.2	medium
Placenta	tissue	331.8	medium
Retina	tissue	321.7
Stomach 1	tissue	321.5	medium
Lung	tissue	320.4	medium
Smooth muscle	tissue	307.4	low
Rectum	tissue	307.0	medium
Colon	tissue	306.1	medium
Frontal cortex	tissue	294.1
Seminal vesicle	tissue	289.3	medium
Fallopian tube	tissue	288.0	medium
Gallbladder	tissue	279.1	medium
Ovary	tissue	274.5	low
Appendix	tissue	273.8	medium
Choroid plexus	tissue	272.2
Skin 1	tissue	271.3	low
Cervix	tissue	259.7	low
Adrenal gland	tissue	253.1	low
Thymus	tissue	244.8
Spinal cord	tissue	242.4
Adipose tissue	tissue	240.1	not detected
Prostate	tissue	239.9	medium
Nucleus accumbens	tissue	236.8
Hippocampus	tissue	234.2	medium
Spleen	tissue	224.2	high
Pituitary gland	tissue	218.5
Endometrium 1	tissue	208.2	medium
Parathyroid gland	tissue	201.8	low
Salivary gland	tissue	196.7	low
Postcentral gyrus	tissue	177.7
Medulla oblongata	tissue	167.9
Substantia nigra	tissue	137.8
Testis	tissue	134.3	medium
Pons	tissue	128.2
Cerebellum	tissue	126.3	medium
Midbrain	tissue	123.6
Corpus callosum	tissue	110.0
Superior colliculi	tissue	108.2
Putamen	tissue	103.1
Periaqueductal gray	tissue	97.2
Hypothalamus	tissue	96.7
Thalamus	tissue	96.6
Hippocampal formation	tissue	94.5
Pancreas	tissue	90.2	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Lateral funiculus (white matter) (567.3), Dorsal funiculus (white matter) (546.5), Anterior funiculus (white matter) (487.2), Cerebellar white matter (467.8), Nucleus raphe pallidus (463.1).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting PRDX1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

14 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 9.98e-07, LOEUF 1.32, missense Z 0.521 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000319248 — one region, missense o/e 0.94.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99523) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 47 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal erythrocyte morphology	2
decreased hematocrit	1
extramedullary hematopoiesis	1
decreased cell proliferation	1
abnormal spleen morphology	1
enlarged spleen	1
thin skin	1
hemolytic anemia	1
increased mammary adenocarcinoma incidence	1
increased malignant tumor incidence	1
increased tumor incidence	1
increased B cell derived lymphoma incidence	1
increased T cell derived lymphoma incidence	1
increased lung adenocarcinoma incidence	1
increased sarcoma incidence	1
increased carcinoma incidence	1
premature death	1
abnormal lymphocyte morphology	1
reticulocytosis	1
anisocytosis	1
poikilocytosis	1
microcytosis	1
decreased hemoglobin content	1
abnormal cell cycle	1
abnormal redox activity	1

+22 more (showing top 25).

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
Oryza sativa Indica Group	P0C5D4	100.0%	Diamond
Oryza sativa Japonica Group	P0C5D5	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	P9WIE2	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WIE3	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

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
AKR1A1	protein-coding	10327
CCDC163	protein-coding	126661
MMACHC	protein-coding	25974
NASP	protein-coding	4678
CCDC17	protein-coding	149483
TOE1	protein-coding	114034
MUTYH	protein-coding	4595
HPDL	protein-coding	84842
TESK2	protein-coding	10420

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)

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

UniProt features (51 total): helix 12, modified residue 10, strand 8, 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)

20 structures by resolution:

PDB	Title	Method	Resolution (Å)
8Z54	Crystal structure of human SIRT5 in complex with succinylated Prx1 fragment	X-RAY DIFFRACTION	1.45
9VQ5	Crystal structure of Peroxiredoxin I in complex with SAC	X-RAY DIFFRACTION	1.5
8X71	Crystal structure of Peroxiredoxin I in complex with compound 19-064	X-RAY DIFFRACTION	1.58
8X73	Crystal structure of Peroxiredoxin I in complex with compound 19-069	X-RAY DIFFRACTION	1.61
9LNH	Crystal structure of Peroxiredoxin I in complex with compound LC-PDin20	X-RAY DIFFRACTION	1.63
9B7A	Crystal structure of peroxiredoxin 1 with RA	X-RAY DIFFRACTION	1.71
7WET	Crystal structure of Peroxiredoxin I in complex with the inhibitor Cela	X-RAY DIFFRACTION	1.76
9VGT	Crystal structure of Peroxiredoxin I in complex with compound 19-150	X-RAY DIFFRACTION	1.79
9VE2	Crystal Structure of Human Peroxiredoxin I in Complex with Fluvastatin	X-RAY DIFFRACTION	1.8
8Z56	Crystal structure of human Q140L-SIRT5 in complex with succinylated Prx1 fragment	X-RAY DIFFRACTION	1.81
7WEU	Crystal structure of Peroxiredoxin I in complex with compound 19-048	X-RAY DIFFRACTION	1.81
9LG0	Crystal Structure of Human Peroxiredoxin I in Complex with SAB	X-RAY DIFFRACTION	1.81
8Z55	Crystal structure of human SIRT5 in complex with succPrx1 and ADP ribose	X-RAY DIFFRACTION	1.83
8Z57	Crystal structure of human Q140L-SIRT5 in complex with succinylated Prx1 fragment and ADP …	X-RAY DIFFRACTION	1.96
3HY2	Crystal Structure of Sulfiredoxin in Complex with Peroxiredoxin I and ATP:Mg2+	X-RAY DIFFRACTION	2.1
4XCS	Human peroxiredoxin-1 C83S mutant	X-RAY DIFFRACTION	2.1
9DEX	Crystal structure of human peroxiredoxin 1 in complex with inhibitor WF-097	X-RAY DIFFRACTION	2.3
8Z58	Crystal structure of human N141V-SIRT5 in complex with succinylated Prx1 fragment	X-RAY DIFFRACTION	2.4
2RII	Crystal Structure of Human Peroxiredoxin I in complex with Sulfiredoxin	X-RAY DIFFRACTION	2.6
7LJ1	Human Prx1-Srx Decameric Complex	X-RAY DIFFRACTION	2.97

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of amino acid metabolism, Congenital disorders of cofactor/vitamin metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH approved · IF approved

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
52	cysteine sulfenic acid (-soh) intermediate

Post-translational modifications (13)

Type	Positions
Phosphoserine	32
N6-acetyllysine	35, 136, 197, 7, 16, 27
N6-succinyllysine	35
Phosphothreonine	90
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	7, 120
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	185
N-acetylserine	2

Disulfide bonds (2)

Type	Positions
Interchain (with c-173)	52
Interchain (with c-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

4 curated (TAS) of 18; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

18 pathways:

ID	Pathway	Evidence
R-HSA-3299685	Detoxification of Reactive Oxygen Species	curated
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes	curated
R-HSA-3000471	Scavenging by Class B Receptors	curated
R-HSA-5628897	TP53 Regulates Metabolic Genes	curated
R-HSA-9734009	Defective Intrinsic Pathway for Apoptosis ⚕	—
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models ⚕	electronic
R-HSA-1643685	Disease ⚕	—
R-HSA-9645723	Diseases of programmed cell death ⚕	—
R-HSA-8863678	Neurodegenerative Diseases ⚕	—
R-HSA-9711123	Cellular response to chemical stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9755511	KEAP1-NFE2L2 pathway	—
R-HSA-9759194	Nuclear events mediated by NFE2L2	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

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 (9): skeletal system development (GO:0001501), response to oxidative stress (GO:0006979), cell population proliferation (GO:0008283), removal of superoxide radicals (GO:0019430), natural killer cell activation (GO:0030101), hydrogen peroxide catabolic process (GO:0042744), leukocyte activation (GO:0045321), cell redox homeostasis (GO:0045454), 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 (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), melanosome (GO:0042470), extracellular exosome (GO:0070062)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Cellular response to chemical stress	2
Binding and Uptake of Ligands by Scavenger Receptors	1
Transcriptional Regulation by TP53	1
Neurodegenerative Diseases	1
Nuclear events mediated by NFE2L2	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Generic Transcription Pathway	1
Gene expression (Transcription)	1
Defective Intrinsic Pathway for Apoptosis	1
Disease	1
Cellular responses to stress	1
Diseases of programmed cell death	1
KEAP1-NFE2L2 pathway	1

GO top-level categories

31 GO namespaces:

Category	Terms
cellular oxidant detoxification	2
cellular anatomical structure	2
system development	1
animal gross anatomical part developmental process	1
response to stress	1
cellular process	1
superoxide metabolic process	1
cellular response to superoxide	1
lymphocyte activation	1
catabolic process	1
hydrogen peroxide metabolic process	1
cell activation	1
immune system process	1
cellular homeostasis	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
pigment granule	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
hydrogen peroxide catabolic process	BP	direct assay
natural killer cell activation	BP	direct assay
cytoplasm	CC	direct assay
extracellular exosome	CC	high-throughput assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay
cadherin binding	MF	high-throughput assay
peroxidase activity	MF	direct assay
thioredoxin peroxidase activity	MF	direct assay

Protein interactions and networks

IntAct

Human interaction partners of PRDX1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 33 partners by confidence:

Partner	Interaction type	MIscore	Records
STK4	phosphorylation reaction	0.660	9
PTEN	physical association	0.630	7
SRXN1	direct interaction	0.620	3
PRDX4	physical association	0.570	2
TPT1	physical association	0.570	2
DPP9	physical association	0.560	3
MAGEB6	physical association	0.560	3
EGFR	physical association	0.550	2
AR	physical association	0.540	3
TERF1	physical association	0.510	2
PRNP	physical association	0.500	2
ADRM1	physical association	0.400	1
CDC20	physical association	0.400	1
GDPD5	physical association	0.400	1
STK3	physical association	0.400	1
TXN	physical association	0.400	1
YWHAZ	physical association	0.400	1
ABL1	physical association	0.370	1
ADH5	physical association	0.370	1
ADRB2	physical association	0.370	1
AXIN2	physical association	0.370	1
BTRC	physical association	0.370	1
CCR4	physical association	0.370	1
IRF3	physical association	0.370	1
LUC7L	physical association	0.370	1
MYC	physical association	0.370	1
MYD88	physical association	0.370	1
PTGER4	physical association	0.370	1
SH2D1B	physical association	0.370	1
SMARCD1	physical association	0.370	1

BioGRID (596 interactions; top human partners by supporting records): PRDX2 (Co-fractionation; 21 records), PRDX4 (Two-hybrid; 11 records), GAPDH (Co-fractionation; 4 records), IRAK1 (Affinity Capture-MS; 4 records), MYC (Affinity Capture-MS; 4 records), PARK2 (Affinity Capture-MS; 4 records), TXN (Co-fractionation; 4 records), UCHL5 (Affinity Capture-Western; 4 records), AGR2 (Affinity Capture-MS; 3 records), EGFR (PCA; 3 records), ISG15 (Affinity Capture-MS; 3 records), LRP6 (Affinity Capture-MS; 3 records), PRDX5 (Co-fractionation; 3 records), UBE3A (Affinity Capture-Western; 3 records), YAP1 (Proximity Label-MS; 3 records)

SIGNOR signaling

showing 8 of 10 signaling 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

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Sulphiredoxin-peroxiredoxin complex	2	PRDX1, SRXN1
PI4K2A-PRDX1 complex	2	PI4K2A, PRDX1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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
Nuclear events mediated by NFE2L2	5	57.9×	9e-06
Deubiquitination	6	25.7×	2e-05
Cellular response to chemical stress	5	24.6×	2e-04
KEAP1-NFE2L2 pathway	5	20.7×	4e-04
Ub-specific processing proteases	7	12.8×	1e-04
Cellular responses to stress	6	7.6×	5e-03
Cellular responses to stimuli	7	7.6×	2e-03
Cell Cycle	6	7.5×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of apoptotic process	6	6.3×	9e-03

Disease & clinical

Genetic variants

Variant evidence for PRDX1: 80 ClinVar records (3 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	32
Likely benign	21
Benign	11

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
495209	NM_181697.3(PRDX1):c.515-1G>T	Pathogenic	criteria provided, multiple submitters, no conflicts	5
4886570	NM_181697.3(PRDX1):c.144_148del (p.Thr49fs)	Likely pathogenic	criteria provided, single submitter	1
1179112	GRCh37/hg19 1p34.1(chr1:45965972-45979054)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PRDX1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 438):

Position(s)	Effect	Δscore	Sites
1:45511415–45511416	acceptor_loss	1.0000	4
1:45514505–45514506	donor_loss	1.0000	5
1:45514638–45514639	acceptor_loss	1.0000	6
1:45514871–45514872	donor_loss	1.0000	4
1:45514996–45514998	acceptor_gain	1.0000	2
1:45514996–45514997	acceptor_loss	1.0000	5
1:45518936–45518937	donor_loss	1.0000	4
1:45519055–45519056	acceptor_loss	1.0000	6
1:45519061	acceptor_gain	1.0000
1:45519066	acceptor_gain	1.0000

AlphaMissense

685 missense substitutions predicted likely pathogenic (of 1,324 scored), across 153 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
D79	8	0.993	0.997
D47	8	0.987	0.996
H84	8	0.985	0.998
D107	8	0.976	0.986
F50	8	0.971	0.999
F48	8	0.965	0.999
D146	8	0.959	0.981
F195	8	0.957	0.992
F66	8	0.940	0.996
D134	8	0.933	0.994
F15	8	0.915	0.988
F43	8	0.886	0.984
F26	8	0.837	0.975
D167	8	0.756	0.938
W177	7	0.995	0.999
W87	7	0.994	0.999
E55	7	0.992	0.998
C52	7	0.991	0.998
R128	7	0.990	0.999
C173	7	0.988	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	3.64e-07
Bladder Urothelial Carcinoma (TCGA)	unfavorable	0.000102
Breast Invasive Carcinoma (TCGA)	unfavorable	0.000103

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
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

showing 60 of 65 phenotypes (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
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001889	Megaloblastic anemia
HP:0001907	Thromboembolism
HP:0001919	Acute kidney injury
HP:0001942	Metabolic acidosis
HP:0002013	Vomiting
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002092	Pulmonary arterial hypertension
HP:0002120	Cerebral cortical atrophy
HP:0002156	Homocystinuria
HP:0002160	Hyperhomocystinemia
HP:0002240	Hepatomegaly
HP:0002615	Hypotension
HP:0002912	Methylmalonic acidemia
HP:0003145	Decreased circulating adenosylcobalamin concentration
HP:0003153	Cystathioninuria
HP:0003210	Decreased methylmalonyl-CoA mutase activity
HP:0003223	Decreased circulating methylcobalamin concentration
HP:0003286	Cystathioninemia
HP:0003524	Decreased methionine synthase activity
HP:0003593	Infantile onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0003658	Hypomethioninemia
HP:0004341	Abnormal vitamin B12 concentration
HP:0005575	Hemolytic-uremic syndrome
HP:0007663	Reduced visual acuity
HP:0008872	Feeding difficulties in infancy

GWAS associations

2 associations:

Study	Trait	p-value
GCST005951_47	Body mass index	8e-10
GCST90002384_213	Hemoglobin	1e-9

EFO canonical traits (from GWAS)

2 canonical traits:

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

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)

Binding affinities (BindingDB)

36 measured of 37 human assays (41 total across all organisms); most potent 36 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5647448	IC50	164 nM
CHEMBL5647239	IC50	165 nM
CHEMBL5639299	IC50	239 nM
CHEMBL5647369	IC50	285 nM
CHEMBL5569469	IC50	310 nM
CHEMBL5569818	IC50	330 nM
CHEMBL5572018	IC50	340 nM
CHEMBL5565154	IC50	350 nM
CHEMBL5569995	IC50	360 nM
CHEMBL5571353	IC50	360 nM
CHEMBL5594961	IC50	370 nM
CHEMBL5572187	IC50	380 nM
CHEMBL5591790	IC50	400 nM
CHEMBL5570187	IC50	410 nM
CHEMBL5573037	IC50	420 nM
CHEMBL5566003	IC50	450 nM
CHEMBL5575303	IC50	460 nM
CHEMBL5564537	IC50	460 nM
CHEMBL5572492	IC50	470 nM
CHEMBL5566476	IC50	470 nM
CHEMBL5646554	IC50	481 nM
CHEMBL5532404	IC50	490 nM
CHEMBL5572158	IC50	490 nM
CHEMBL5575142	IC50	500 nM
CHEMBL5639325	IC50	525 nM
CHEMBL5571140	IC50	530 nM
CHEMBL5572484	IC50	540 nM
CHEMBL5574572	IC50	640 nM
CHEMBL5647003	IC50	979 nM
CHEMBL5653589	KD	1440 nM
CHEMBL5647534	IC50	1470 nM
CHEMBL574646	IC50	1500 nM
CHEMBL5646385	IC50	1530 nM
CHEMBL5647082	IC50	2490 nM
CHEMBL4860684	IC50	14800 nM
CHEMBL4092369	KD	3.49e+09 nM

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 response to substance, affects localization, affects cotreatment, decreases expression, decreases reaction (+6 more)	9
Tobacco Smoke Pollution	increases expression, increases metabolic processing, affects expression, decreases expression	9
Arsenic	affects methylation, increases expression, affects cotreatment, increases abundance	6
Cadmium Chloride	increases expression, increases abundance	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
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	4
Acetylcysteine	increases abundance, decreases expression, decreases reaction, increases expression, decreases activity	3
Aerosols	increases expression	3
Air Pollutants	decreases oxidation, increases abundance, decreases expression, increases expression, affects cotreatment	3
Vehicle Emissions	decreases expression, decreases reaction, increases expression	3
Paraquat	increases expression, increases oxidation, affects cotreatment	3
arsenite	affects binding, increases reaction, increases abundance, increases expression	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	increases expression, affects cotreatment, decreases expression	2
Vorinostat	increases expression	2
Acetaminophen	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)

Via MONDO — disease-level, not drug-specific.

1 trials:

NCT	Phase	Status	Title
NCT03655223	Not specified	ACTIVE_NOT_RECRUITING	Early Check: Expanded Screening in Newborns

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRDX1 across ~30M SureChEMBL compounds — explore on Sugi Predict.