PRDX6

Summary

PRDX6 (peroxiredoxin 6, HGNC:16753) is a protein-coding gene on chromosome 1q25.1, encoding Peroxiredoxin-6 (P30041). Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.

The protein encoded by this gene is a member of the thiol-specific antioxidant protein family. This protein is a bifunctional enzyme with two distinct active sites. It is involved in redox regulation of the cell; it can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. It may play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury.

Source: NCBI Gene 9588 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease type 4 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,489 total — 51 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• MANE Select transcript: NM_004905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16753
Approved symbol	PRDX6
Name	peroxiredoxin 6
Location	1q25.1
Locus type	gene with protein product
Status	Approved
Aliases	AOP2, KIAA0106, 1-Cys, NSGPx, PRX, aiPLA2, MGC46173, p29
Ensembl gene	ENSG00000117592
Ensembl biotype	protein_coding
OMIM	602316
Entrez	9588

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000340385, ENST00000460950, ENST00000470017, ENST00000867927, ENST00000867928, ENST00000922551, ENST00000922552, ENST00000922553, ENST00000922554, ENST00000922555

RefSeq mRNA: 1 — MANE Select: NM_004905 NM_004905

CCDS: CCDS1307

Canonical transcript exons

ENST00000340385 — 5 exons

Exon	Start	End
ENSE00000814648	173481326	173481482
ENSE00001161142	173487735	173488815
ENSE00001887950	173477335	173477492
ENSE00003615087	173485361	173485507
ENSE00003682006	173486255	173486401

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 408.6727 / max 1919.1845, expressed in 1827 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6723	296.6759	1827
6725	51.1588	1815
6722	45.9806	1818
6724	11.7842	1780
6728	0.7891	405
6726	0.7848	435
6721	0.6267	132
6729	0.5753	308
6730	0.2975	138

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.53	gold quality
gastrocnemius	UBERON:0001388	99.49	gold quality
mucosa of stomach	UBERON:0001199	99.47	gold quality
amniotic fluid	UBERON:0000173	99.42	gold quality
right atrium auricular region	UBERON:0006631	99.39	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.39	gold quality
peritoneum	UBERON:0002358	99.38	gold quality
omental fat pad	UBERON:0010414	99.38	gold quality
mucosa of transverse colon	UBERON:0004991	99.36	gold quality
germinal epithelium of ovary	UBERON:0001304	99.35	gold quality
cardiac atrium	UBERON:0002081	99.35	gold quality
muscle of leg	UBERON:0001383	99.34	gold quality
colonic mucosa	UBERON:0000317	99.33	gold quality
adipose tissue	UBERON:0001013	99.32	gold quality
rectum	UBERON:0001052	99.32	gold quality
left uterine tube	UBERON:0001303	99.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.29	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.29	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.28	gold quality
lower esophagus	UBERON:0013473	99.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.27	gold quality
caput epididymis	UBERON:0004358	99.26	gold quality
connective tissue	UBERON:0002384	99.25	gold quality
oral cavity	UBERON:0000167	99.24	gold quality
right lobe of liver	UBERON:0001114	99.24	gold quality
right adrenal gland	UBERON:0001233	99.23	gold quality
muscle organ	UBERON:0001630	99.23	gold quality
deltoid	UBERON:0001476	99.21	gold quality
pericardium	UBERON:0002407	99.20	gold quality
right adrenal gland cortex	UBERON:0035827	99.20	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	2113.96
E-HCAD-4	yes	63.71
E-HCAD-5	yes	42.28
E-MTAB-10553	yes	33.93
E-GEOD-125970	yes	31.69
E-HCAD-10	yes	31.21
E-GEOD-137537	yes	31.09
E-CURD-88	yes	24.24
E-MTAB-7316	yes	23.21
E-CURD-122	yes	19.66
E-MTAB-8142	yes	16.29
E-MTAB-8410	yes	14.31
E-GEOD-93593	yes	14.26
E-MTAB-10042	yes	8.38
E-MTAB-9801	yes	6.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFE2L2, NFE2L3, NFKB, PAX5, POU1F1, SP1, SPI1, TP53

miRNA regulators (miRDB)

78 targeting PRDX6, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 40)

• Data show that p29 is a novel protein that associates with p67, has peroxiredoxin activity, and has a potential role in protecting the NADPH oxidase by inactivating H(2)O(2) or altering signaling pathways affected by H(2)O(2) [neutrophil protein p29 ] (PMID:12121978)
• overexpression protects cells against phospholipid peroxidation-mediated membrane damage [1-cys peroxiredoxin] (PMID:12193653)
• The significant increase in peroxiredoxin 6 level in frontal cortex of patients with Pick’s disease is useful in discriminating it from Down syndrome/Alzheimer’s disease. (PMID:12650976)
• AOP2 protects hyperglycemia-induced lens epithelial cell apoptosis; this molecule may have the potential to prevent hyperglycemia-mediated complications in diabetes (PMID:14751239)
• Prdx6 is an important antioxidant enzyme and has a major role in lung phospholipid metabolism [review] (PMID:15890616)
• Protects HeLa cells from H(2)O(2)-induced cell death. (PMID:15941719)
• Saitohin interacts with peroxiredoxin 6, a unique member of that family that is bifunctional and the levels of which increase in Pick disease. (PMID:16186110)
• SP-A and Prdx6 directly interact, which provides a mechanism for regulation of the PLA(2) activity of Prdx6 by SP-A (PMID:16330552)
• overexpression of peroxiredoxin 6 is associated with oligodendroglioma (PMID:17653765)
• Overexpression of peroxiredoxin 6 leads to a more invasive phenotype and metastatic potential in human breast cancer, at least in part, through regulation of the levels of uPAR, Ets-1, MMP-9, RhoC and TIMP-2 expression. (PMID:17980029)
• PRDX6 is required for blood vessel integrity in wounded skin. (PMID:18025307)
• In brain tissue of patients with Alzheimer’s disease , many blood vessels exhibited peroxiredoxin 6 staining that appeared to be due to the astrocytic foot processes. (PMID:18386021)
• two potential interaction partners of Prx6: the calcium-activated cysteine endopeptidase calpain and the p50RhoGAP protein of the family of Sec14-like proteins. (PMID:18619034)
• H2O2-mediated hyperoxidation of Prdx6 induces cell cycle arrest at the G2/M transition through up-regulation of iPLA2 activity. (PMID:18826942)
• expression is upregulated during response to oxidative stress (PMID:18973804)
• The MAPKs can mediate phosphorylation of Prdx6 at Thr-177 with a consequent marked increase in its aiPLA(2) activity. (PMID:19140803)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Prdx6 binds to reduced phospholipid at acidic pH but at cytosolic pH binds only phospholipid that is oxidized compatible with a role for Prdx6 in the repair of peroxidized cell membranes (PMID:19236840)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• Overexpression of peroxiredoxin I and is associated with breast carcinoma. (PMID:19566940)
• PRDX6 attenuates oxidative stress- and TGFbeta-induced abnormalities of human trabecular meshwork cells. (PMID:19572226)
• The localization of Prdx6 in acidic organelles and consequent PLA2 activity depend on a novel 10-aa peptide located at positions 31-40 of the protein. (PMID:19700648)
• Extrinsic PRDX6 prevents UV-triggered cell death and abnormal protein expression in PRDX6-deficient lens epitheial cells. (PMID:19889963)
• promotes lung cancer cell invasion by inducing urokinase-type plasminogen activator via p38 kinase, phosphoinositide 3-kinase, and Ak (PMID:19937138)
• This study is the first to define the functions of the enzymatic activities of PRDX6 in metastasis and to show the involvement of arachidonic acid in PRDX6 action in intact cells. (PMID:20354123)
• It could be detected that PRDX6 is associated with tumorigenesis in tonge squamous cell carcinoma. (PMID:20796224)
• Prx6 modulates TRAIL signaling as a negative regulator of caspase-8 and caspase-10 in death-inducing signaling complex formation of TRAIL-resistant metastatic cancer cells. (PMID:20829884)
• The antioxidant Prdx 6 protects ovarian cancer cells against cisplatin-induced apoptosis via inactivation of the caspase signaling pathway. (PMID:21166495)
• Results suggest that ERK and p38 MAPK regulate subcellular localization of Prdx6 by activation of 14-3-3epsilon as a chaperone protein, resulting in its translocation to acidic organelles. (PMID:21346153)
• Results provide new insights into the distinct roles of bifunctional Prdx6 with peroxidase and PLA(2) activities in oxidative stress-induced and TNF-induced apoptosis, respectively. (PMID:21415860)
• Study revealed novel SNPs within the PRDX6 gene and its 5’ and 3’ flanking regions via direct sequencing. (PMID:21627785)
• Data suggest that Prdx6 serves an additional biochemical or structural role in supporting optimal NADPH oxidase activity. (PMID:22178385)
• Data suggest that SNPs of peroxiredoxin 1, 2 and 6 are not associated with esophageal cancer. (PMID:22215146)
• expression and function of Prdx1 and Prdx6 in MCF-7 and noncancerous MCF-10A cell lines; found elevated Prdx1 expression in MCF-7 cells and comparable expression of Prdx6; data suggest synergistic role for Prdx1 and Prdx6 in MCF-10A cells (PMID:22236188)
• decreased levels, combined with higher thiol oxidation (and probable inhibition) of PRDXs (particularly PRDX6), are noted when human sperm function is altered. (PMID:22492841)
• a change in the conformation of Prdx6 upon its phosphorylation is the basis for enhancement of PLA(2) enzymatic activity (PMID:22663767)
• (2) activity of Prdx6-PLA(2) in intact cells mediates its ability to enhance phox activity in response to fMLF (PMID:22678913)
• The protein and mRNA expressions of Prx1 and Prx6 increased significantly in the order of normal brain tissue, grade II astrocytoma, grade III astrocytoma and grade IV astrocytoma. (PMID:22985558)
• Drug resistance formation was accompanied by a significant increase in the expression of PRDX1, PRDX2, PRDX3, PRDX6 genes in all cancer cell strains, which confirms the importance of redox-dependent mechanisms into development of cisplatin resistance. (PMID:23113308)
• The level of Prx6 protein is lower in gastric cancer tissues than in normal para-cancer tissue. Prx6 expression is significantly correlated with the differentiation degree of GC. (PMID:23158669)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prdx6	ENSMUSG00000026701
mus_musculus	Prdx6b	ENSMUSG00000050114
rattus_norvegicus	Prdx6	ENSRNOG00000081976
drosophila_melanogaster	Prx6c	FBGN0033518
drosophila_melanogaster	Prx6b	FBGN0033520
drosophila_melanogaster	CG12896	FBGN0033521

Paralogs (4): PRDX1 (ENSG00000117450), PRDX4 (ENSG00000123131), PRDX3 (ENSG00000165672), PRDX2 (ENSG00000167815)

Protein

Protein identifiers

Peroxiredoxin-6 — P30041 (reviewed: P30041)

Alternative names: 1-Cys peroxiredoxin, 24 kDa protein, Acidic calcium-independent phospholipase A2, Antioxidant protein 2, Glutathione-dependent peroxiredoxin, Liver 2D page spot 40, Lysophosphatidylcholine acyltransferase 5, Non-selenium glutathione peroxidase, Red blood cells page spot 12

All UniProt accessions (2): P30041, V9HWC7

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. Can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides. Also has phospholipase activity, can therefore either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity). These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH. Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis. Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC). Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate.

Subunit / interactions. Homodimer. Interacts with GSTP1; mediates PRDX6 glutathionylation and regeneration. Interacts with APEX1. Interacts with STH. May interact with FAM168B. May interact with HTR2A.

Subcellular location. Cytoplasm. Lysosome.

Post-translational modifications. Irreversibly inactivated by overoxidation of Cys-47 to sulfinic acid (Cys-SO(2)H) and sulfonic acid (Cys-SO(3)H) forms upon oxidative stress. Phosphorylation at Thr-177 by MAP kinases increases the phospholipase activity of the enzyme. The phosphorylated form exhibits a greater lysophosphatidylcholine acyltransferase activity compared to the non-phosphorylated form.

Activity regulation. MJ33 or lithium;[(2R)-1-hexadecoxy-3-(2,2,2-trifluoroethoxy)propan-2-yl] methyl phosphate inhibits its phospholipase A2 activity. CI-976 or 2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide inhibits its lysophosphatidylcholine acyltransferase activity.

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 1-Cys peroxiredoxin, no C(R) is present and C(P) instead forms a disulfide with a cysteine from another protein or with a small thiol molecule. C(P) is reactivated by glutathionylation mediated by glutathione S-transferase Pi, followed by spontaneous reduction of the enzyme with glutathione.

Similarity. Belongs to the peroxiredoxin family. Prx6 subfamily.

RefSeq proteins (1): NP_004896* (*=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
IPR045020	PRX_1cys	Family

Pfam: PF00578, PF10417

Enzyme classification (BRENDA):

• EC 1.11.1.27 — glutathione-dependent peroxiredoxin (BRENDA: 12 organisms, 26 substrates, 4 inhibitors, 9 Km, 0 kcat entries)
• EC 2.3.1.23 — 1-acylglycerophosphocholine O-acyltransferase (BRENDA: 25 organisms, 283 substrates, 101 inhibitors, 64 Km, 2 kcat entries)
• EC 3.1.1.4 — phospholipase A2 (BRENDA: 129 organisms, 452 substrates, 710 inhibitors, 90 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

83 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
OLEOYL-COA	0.0004–0.152	15
PHOSPHATIDYLCHOLINE	0.05–17	12
1-ACYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.0017–0.107	9
1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.94–13.85	7
ARACHIDONOYL-COA	0.0032–0.7156	6
PHOSPHATIDYLETHANOLAMINE	0.02–10.5	5
PALMITOYL-COA	0.0027–0.0413	4
STEAROYL-COA	0.0021–0.232	4
1-PALMITOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.0018–0.0081	3
1,2-DIHEPTANOYL-SN-GLYCERO-3-PHOPHORYLCHOLINE	1.12–5.13	3
1,2-DIHEPTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	3–3.92	3
1,2-DIOCTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.12–3.2	3
H2O2	0.0023–0.18	2
TERT-BUTYL HYDROPEROXIDE	0.142–0.2088	2
1-PALMITOYL-LYSOPHOSPHATIDYLCHOLINE	0.0023–0.7219	2

Catalyzed reactions (Rhea), 5 shown:

• a 1-acyl-sn-glycero-3-phosphocholine + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphocholine + CoA (RHEA:12937)
• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:15801)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoyl-CoA = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + CoA (RHEA:35983)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:41223)
• a hydroperoxide + 2 glutathione = an alcohol + glutathione disulfide + H2O (RHEA:62632)

UniProt features (36 total): strand 14, modified residue 6, helix 6, mutagenesis site 2, active site 2, initiator methionine 1, chain 1, domain 1, turn 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1PRX	X-RAY DIFFRACTION	2
5B6M	X-RAY DIFFRACTION	2.5
5B6N	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30041-F1	96.75	0.99

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 (3): 47 (cysteine sulfenic acid (-soh) intermediate; for peroxidase activity); 140 (for phospholipase activity); 32 (important for phospholipase activity)

Post-translational modifications (6): 177, 209, 209, 44, 63, 89

Mutagenesis-validated functional residues (2):

Position	Phenotype
32	loss of phospholipase activity, but no effect on peroxidase activity.
47	loss of peroxidase activity, but no effect on phospholipase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3299685	Detoxification of Reactive Oxygen Species
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 537 (showing top): MODULE_172, RNGTGGGC_UNKNOWN, MODULE_93, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, MODY_HIPPOCAMPUS_POSTNATAL, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, MODULE_151, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_GLIAL_CELL_DEVELOPMENT, HSIAO_HOUSEKEEPING_GENES, GOBP_NEUROGENESIS

GO Biological Process (8): response to oxidative stress (GO:0006979), hydrogen peroxide catabolic process (GO:0042744), cell redox homeostasis (GO:0045454), glycerophospholipid catabolic process (GO:0046475), positive regulation of mRNA splicing, via spliceosome (GO:0048026), cellular oxidant detoxification (GO:0098869), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042)

GO Molecular Function (15): peroxidase activity (GO:0004601), glutathione peroxidase activity (GO:0004602), A2-type glycerophospholipase activity (GO:0004623), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), cadherin binding (GO:0045296), 1-acylglycerophosphocholine O-acyltransferase activity (GO:0047184), obsolete calcium-independent phospholipase A2 activity (GO:0047499), peroxiredoxin activity (GO:0051920), catalytic activity (GO:0003824), protein binding (GO:0005515), antioxidant activity (GO:0016209), oxidoreductase activity (GO:0016491), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), azurophil granule lumen (GO:0035578), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), lysosome (GO:0005764)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cellular response to chemical stress	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
catalytic activity	3
catabolic process	2
peroxidase activity	2
molecular_function	2
cytoplasm	2
response to stress	1
hydrogen peroxide metabolic process	1
cellular homeostasis	1
glycerophospholipid metabolic process	1
phospholipid catabolic process	1
glycerolipid catabolic process	1
mRNA splicing, via spliceosome	1
positive regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
positive regulation of mRNA processing	1
cellular detoxification	1
primary metabolic process	1
lipid metabolic process	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
ubiquitin-like protein ligase binding	1
protein binding	1
cell adhesion molecule binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
binding	1
cellular oxidant detoxification	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
extracellular vesicle	1
lytic vacuole	1

Protein interactions and networks

STRING

3631 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDX6	TXN	P10599	753
PRDX6	GPX7	Q96SL4	685
PRDX6	GPX8	Q8TED1	682
PRDX6	PRDX5	P30044	679
PRDX6	GPX2	P18283	652
PRDX6	STH	Q8IWL8	652
PRDX6	GPX3	P22352	651
PRDX6	GPX5	O75715	648
PRDX6	ENO1	P06733	648
PRDX6	GPX6	P59796	645
PRDX6	GAPDH	P00354	633
PRDX6	PGK1	P00558	582
PRDX6	GPX4	P36969	579
PRDX6	HSPE1	P61604	577
PRDX6	GSR	P00390	564

IntAct

142 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PRDX6	PCNA	psi-mi:“MI:0915”(physical association)	0.570
PRDX6	PSMD8	psi-mi:“MI:0915”(physical association)	0.560
PRDX6	ARFGAP3	psi-mi:“MI:0915”(physical association)	0.560
NME1	NME2P1	psi-mi:“MI:0914”(association)	0.530
E6	CASK	psi-mi:“MI:0914”(association)	0.520
TERF1	PRDX6	psi-mi:“MI:0915”(physical association)	0.510
COX15	PRDX6	psi-mi:“MI:0915”(physical association)	0.500
VDAC1	PRDX6	psi-mi:“MI:0915”(physical association)	0.500
DLD	PRDX6	psi-mi:“MI:0915”(physical association)	0.500
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
Ncf2	PRDX6	psi-mi:“MI:0407”(direct interaction)	0.440
	Ncf2	psi-mi:“MI:1146”(phospholipase reaction)	0.440
	PRDX6	psi-mi:“MI:1146”(phospholipase reaction)	0.440
DNM1L	PRDX6	psi-mi:“MI:0403”(colocalization)	0.430
	TK2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (333): PRDX6 (Affinity Capture-MS), PRDX6 (Reconstituted Complex), PRDX6 (Affinity Capture-Western), CASP10 (Reconstituted Complex), CASP8 (Reconstituted Complex), CASP10 (Affinity Capture-Western), CASP8 (Affinity Capture-Western), PRDX6 (Two-hybrid), PRDX6 (Affinity Capture-Western), CASP10 (PCA), CASP8 (PCA), PRDX6 (Affinity Capture-MS), AKR1B1 (Co-fractionation), ASS1 (Co-fractionation), CD2AP (Co-fractionation)

ESM2 similar proteins: A9PCL4, G0S1P8, O08709, O14313, O22711, O35244, O43099, O69777, O77834, P0A251, P0A252, P0A862, P0A863, P0A864, P0A865, P0A866, P0AE08, P0AE09, P0AE10, P0AE11, P30041, P30044, P32119, P35704, P44758, P52572, P57668, P57880, P73728, P99029, Q2KJE4, Q2PFL9, Q5ASN8, Q5R7E0, Q61171, Q6W8Q2, Q8K3U7, Q8KED5, Q8XVP0, Q8Z7A8

Diamond homologs: A0A0K3AUJ9, A0A2Z5VKM8, A2BJD9, A2SZW8, A3DKL1, A4FWZ9, A5IIX7, A6UPH7, A8A9P0, O04005, O08709, O08807, O17433, O24364, O26262, O29969, O33665, O35244, O58966, O67024, O77834, P0C5C8, P0C5C9, P0C5D0, P0C5D1, P0CB50, P19476, P20108, P23161, P30041, P30048, P32119, P34227, P35700, P35704, P48822, P51272, P52570, P52571, P52572

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAPK1	up-regulates	PRDX6	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1489 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	51
Likely pathogenic	21
Uncertain significance	848
Likely benign	408
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075484	NM_181882.3(PRX):c.1171del (p.Leu391fs)	Pathogenic
1075829	NM_181882.3(PRX):c.205C>T (p.Arg69Ter)	Pathogenic
1323502	NM_181882.3(PRX):c.2602del (p.Gln868fs)	Pathogenic
1324966	NM_181882.3(PRX):c.2581del (p.Leu861fs)	Pathogenic
1385857	NM_181882.3(PRX):c.2815_2816del (p.Ser939fs)	Pathogenic
1392880	NM_181882.3(PRX):c.3099_3100del (p.Glu1034fs)	Pathogenic
1423233	NM_181882.3(PRX):c.2050C>T (p.Gln684Ter)	Pathogenic
1686102	NM_181882.3(PRX):c.1552_1558del (p.Pro518fs)	Pathogenic
1908695	NM_181882.3(PRX):c.3054del (p.Arg1020fs)	Pathogenic
2703425	NM_181882.3(PRX):c.2362A>T (p.Lys788Ter)	Pathogenic
2777990	NM_181882.3(PRX):c.2180_2181del (p.Ile727fs)	Pathogenic
2787432	NM_181882.3(PRX):c.1552_1562delinsT (p.Pro518fs)	Pathogenic
2803049	NM_181882.3(PRX):c.3275del (p.Val1092fs)	Pathogenic
2806966	NM_181882.3(PRX):c.1657del (p.Glu553fs)	Pathogenic
2823989	NM_181882.3(PRX):c.3371C>G (p.Ser1124Ter)	Pathogenic
2851365	NM_181882.3(PRX):c.2301del (p.Leu768fs)	Pathogenic
2851657	NM_181882.3(PRX):c.1999del (p.Leu667fs)	Pathogenic
3018157	NM_181882.3(PRX):c.1001_1022del (p.Gly334fs)	Pathogenic
3248510	NC_000019.9:g.(?40913793)(40913839_?)del	Pathogenic
3611669	NM_181882.3(PRX):c.667del (p.Val223fs)	Pathogenic
3655356	NM_181882.3(PRX):c.2252C>G (p.Ser751Ter)	Pathogenic
3663633	NM_181882.3(PRX):c.3157del (p.Asp1053fs)	Pathogenic
3687942	NM_181882.3(PRX):c.1782_1783insTTCCTGAGATGAAA (p.Leu595delinsPheLeuArgTer)	Pathogenic
3690156	NM_181882.3(PRX):c.2447C>G (p.Ser816Ter)	Pathogenic
433553	NM_181882.3(PRX):c.1012del (p.Ala338fs)	Pathogenic
448140	NM_181882.3(PRX):c.3611del (p.Leu1204fs)	Pathogenic
4725896	NM_181882.3(PRX):c.1572_1650del (p.Val525fs)	Pathogenic
4787	NM_181882.3(PRX):c.2857C>T (p.Arg953Ter)	Pathogenic
4791	NM_181882.3(PRX):c.586C>T (p.Arg196Ter)	Pathogenic
549686	NM_181882.3(PRX):c.3703G>T (p.Glu1235Ter)	Pathogenic

SpliceAI

984 predictions. Top by Δscore:

Variant	Effect	Δscore
1:173477488:GACTC:G	donor_gain	1.0000
1:173477489:ACTC:A	donor_gain	1.0000
1:173477489:ACTCG:A	donor_loss	1.0000
1:173477490:CTC:C	donor_gain	1.0000
1:173477491:TC:T	donor_gain	1.0000
1:173477491:TCG:T	donor_loss	1.0000
1:173477492:CGTA:C	donor_loss	1.0000
1:173477493:G:GG	donor_gain	1.0000
1:173477493:G:T	donor_loss	1.0000
1:173477494:T:TC	donor_loss	1.0000
1:173477495:AA:A	donor_loss	1.0000
1:173481322:TCAG:T	acceptor_loss	1.0000
1:173481324:A:AG	acceptor_gain	1.0000
1:173481324:AG:A	acceptor_loss	1.0000
1:173481324:AGAT:A	acceptor_gain	1.0000
1:173481324:AGATG:A	acceptor_gain	1.0000
1:173481325:G:A	acceptor_loss	1.0000
1:173481325:G:GA	acceptor_gain	1.0000
1:173481325:GAT:G	acceptor_gain	1.0000
1:173481325:GATG:G	acceptor_gain	1.0000
1:173481325:GATGG:G	acceptor_gain	1.0000
1:173481427:T:G	donor_gain	1.0000
1:173481480:AAGG:A	donor_loss	1.0000
1:173481483:G:GC	donor_loss	1.0000
1:173485355:TTTCA:T	acceptor_loss	1.0000
1:173485357:TCA:T	acceptor_loss	1.0000
1:173485359:A:AG	acceptor_gain	1.0000
1:173485359:AG:A	acceptor_gain	1.0000
1:173485360:G:GT	acceptor_gain	1.0000
1:173485360:GG:G	acceptor_gain	1.0000

AlphaMissense

1469 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:173481345:C:G	H39D	0.999
1:173481357:T:C	F43L	0.999
1:173481359:T:A	F43L	0.999
1:173481359:T:G	F43L	0.999
1:173481371:C:G	C47W	0.999
1:173481474:T:A	W82R	0.999
1:173481474:T:C	W82R	0.999
1:173486316:G:A	G154D	0.999
1:173486319:G:C	R155T	0.999
1:173486319:G:T	R155M	0.999
1:173486320:G:C	R155S	0.999
1:173486320:G:T	R155S	0.999
1:173486340:G:T	R162M	0.999
1:173481327:T:A	W33R	0.998
1:173481327:T:C	W33R	0.998
1:173481347:C:A	H39Q	0.998
1:173481347:C:G	H39Q	0.998
1:173481369:T:C	C47R	0.998
1:173481370:G:A	C47Y	0.998
1:173486289:T:C	L145P	0.998
1:173486331:A:T	E159V	0.998
1:173486340:G:C	R162T	0.998
1:173486379:T:A	V175D	0.998
1:173486396:T:A	W181R	0.998
1:173486396:T:C	W181R	0.998
1:173487754:T:A	V189D	0.998
1:173481346:A:G	H39R	0.997
1:173481354:G:C	D42H	0.997
1:173481379:A:T	E50V	0.997
1:173481380:G:C	E50D	0.997

dbSNP variants (sampled 300 via entrez): RS1000196271 (1:173482322 C>T), RS1000227542 (1:173481971 C>G,T), RS1000324588 (1:173476576 TAACA>T), RS1000541494 (1:173488966 T>C), RS1000544094 (1:173488584 A>G), RS1000666657 (1:173482247 T>C), RS1000696671 (1:173488947 A>G), RS1000710417 (1:173476233 T>C), RS1000785546 (1:173483903 C>A), RS1001606137 (1:173483843 C>T), RS1001675497 (1:173477488 G>T), RS1001717781 (1:173481132 A>G), RS1001947205 (1:173484141 GATATATATATTTATAT>G), RS1002010848 (1:173476156 T>C), RS1002023796 (1:173483273 G>T)

Disease associations

OMIM: gene MIM:602316 | disease phenotypes: MIM:614895, MIM:145900, MIM:118220, MIM:600361, MIM:617770

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 4	Definitive	Autosomal recessive
Charcot-Marie-Tooth disease type 4F	Strong	Autosomal recessive
Charcot-Marie-Tooth disease type 3	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 4	Definitive	AR

Mondo (10): Charcot-Marie-Tooth disease type 4 (MONDO:0018995), Charcot-Marie-Tooth disease type 4F (MONDO:0013959), Charcot-Marie-Tooth disease type 3 (MONDO:0007790), Charcot-Marie-Tooth disease (MONDO:0015626), Charcot-Marie-Tooth disease type 5 (MONDO:0010877), Charcot-Marie-Tooth disease type 1 (MONDO:0019011), spinocerebellar ataxia 46 (MONDO:0033481), peripheral neuropathy (MONDO:0005244), distal hereditary motor neuropathy (MONDO:0018894), Gaucher disease (MONDO:0018150)

Orphanet (9): Charcot-Marie-Tooth disease type 4 (Orphanet:64749), Charcot-Marie-Tooth disease type 4F (Orphanet:99952), Dejerine-Sottas syndrome (Orphanet:64748), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Spinocerebellar ataxia type 46 (Orphanet:589522), Hereditary motor and sensory neuropathy type 5 (Orphanet:64751), Charcot-Marie-Tooth disease type 1 (Orphanet:65753), Distal hereditary motor neuropathy (Orphanet:53739), Gaucher disease (Orphanet:355)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000639	Nystagmus
HP:0001171	Split hand
HP:0001178	Ulnar claw
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001308	Tongue fasciculations
HP:0001604	Vocal cord paresis
HP:0001761	Pes cavus
HP:0001763	Pes planus
HP:0001765	Hammertoe
HP:0002066	Gait ataxia
HP:0002136	Broad-based gait
HP:0002280	Enlarged cisterna magna
HP:0002460	Distal muscle weakness
HP:0002505	Loss of ambulation
HP:0002650	Scoliosis
HP:0002751	Kyphoscoliosis
HP:0002922	Increased CSF protein concentration
HP:0002936	Distal sensory impairment
HP:0003202	Skeletal muscle atrophy
HP:0003376	Steppage gait
HP:0003380	Decreased number of peripheral myelinated nerve fibers
HP:0003382	Hypertrophic nerve changes
HP:0003383	Onion bulb formation
HP:0003387	Decreased number of large peripheral myelinated nerve fibers

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003827_4	Otitis media	2.000000e-07
GCST003828_1	Otitis media (chronic)	3.000000e-08
GCST003829_4	Otitis media (recurrent)	1.000000e-07

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D005776	Gaucher Disease	C10.228.140.163.100.435.825.400; C16.320.565.189.435.825.400; C16.320.565.398.641.803.441; C16.320.565.595.554.825.400; C18.452.132.100.435.825.400; C18.452.584.563.641.803.441; C18.452.648.189.435.825.400; C18.452.648.398.641.803.441; C18.452.648.595.554.825.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295741 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.21	Kd	61.12	nM	CHEMBL5653589
7.21	ED50	61.12	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 18 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149066: Binding affinity to human PRDX6 incubated for 45 mins by Kinobead based pull down assay	kd	0.0611	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, decreases methylation	3
Cadmium Chloride	increases expression, decreases reaction, increases abundance, increases palmitoylation	3
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
Arsenic	increases expression, affects cotreatment, increases abundance	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Hydrogen Peroxide	increases expression, decreases response to substance	2
tert-Butylhydroperoxide	decreases response to substance, increases expression	2
Nanotubes, Carbon	affects expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
bisphenol F	increases expression	1
bismuth tripotassium dicitrate	increases expression	1
triphenyl phosphate	affects expression	1
chlorophyllin	decreases expression	1
cumene hydroperoxide	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	decreases reaction, decreases expression, increases reaction	1
cupric oxide	increases expression	1
1,2-naphthoquinone	affects binding, decreases activity	1
glycidamide	increases expression	1
CGP 52608	affects binding, increases reaction	1
1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine	decreases expression, increases reaction	1
gambierol	decreases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
obeticholic acid	decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118669	Binding	Binding affinity to PRDX6 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7AS	HeLa PRDX6 KO	Cancer cell line	Female
CVCL_C7DF	Abcam A-549 PRDX6 KO	Cancer cell line	Male
CVCL_C7E5	Abcam HCT 116 PRDX6 KO	Cancer cell line	Male
CVCL_D1YJ	Abcam THP-1 PRDX6 KO	Cancer cell line	Male
CVCL_TG55	HAP1 PRDX6 (-) 1	Cancer cell line	Male
CVCL_XR82	HAP1 PRDX6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00058071	PHASE3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	PHASE3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	PHASE3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	PHASE3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	PHASE3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	PHASE3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	PHASE3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	PHASE3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	PHASE3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	PHASE3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	PHASE3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	PHASE3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	PHASE3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	PHASE3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	PHASE3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	PHASE3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	PHASE3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	PHASE3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	PHASE3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	PHASE3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	PHASE3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	PHASE3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	PHASE3	COMPLETED	Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
NCT06071936	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06072573	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy