Genetics: PRDX6

Hoopoe

Hoopoe

Senior Member (Voting Rights)
One of the candidate genes in the DecodeME preprint.
PRDX6 (Tier 1)
• Protein: Peroxiredoxin 6. UniProt. GeneCards. The allele that increases the risk of ME/CFS is
associated with decreasing PRDX6 gene expression.
• Molecular function: Thiol-specific peroxidase that catalyses the reduction of hydrogen
peroxide and organic hydroperoxides. PRDX6 also has phospholipase A2 activity (18) and acts
in antioxidant defence by facilitating repair of damaged cell membranes via reduction of
peroxidised phospholipids (19).
• Cellular function: PRDX6 protects against oxidative stress (20). Cytoplasmic enzyme involved
in phosphatidylcholine synthesis and repair of membrane lipid peroxidation. PRDX6 is not
peroxisomal.
• Link to disease: No genetic diseases known.
• Potential relevance to ME/CFS: Phosphatidylcholine has been reported to be depleted in a
group of people with ME/CFS (21). One study showed increased plasma peroxides in ME/CFS
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Curcumin increases PRDX6 expression.
 
Peroxiredoxin 6 (Prdx6), a unique 1-Cys member of the peroxiredoxin family, exhibits peroxidase activity, phospholipase activity, and lysophosphatidylcholine acyltransferase (LPCAT) activity. Prdx6 has been known to be an important enzyme for the maintenance of lipid peroxidation repair, cellular metabolism, inflammatory signaling, and antioxidant damage. Growing research has demonstrated that the altered activity of this enzyme is linked with various pathological processes including central nervous system (CNS) disorders. This review discusses the distinctive structure, enzyme activity, and function of Prdx6 in different CNS disorders, as well as emphasizing the significance of Prdx6 in neurological disorders.
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Downregulated in LC here:

SNT Gatchaman said:
Molecular Insights into Long COVID: Plasma Proteomics Reveals Oxidative Stress, Coagulation Cascade Activation, and Glycolytic Imbalance
Sheela Ramanathan; Mohammad Mobarak Hussain Chowdhury; Akouavi Julite Irmin Quenum; Christine Rioux-Perreault; Jean-Francois Lucier; Subburaj Ilangumaran; Hugues Allard-Chamard; Alain Piche

Persistent symptoms following SARS-CoV-2 infection are the hallmark of post-COVID condition (PCC), also referred to as long COVID. However, our knowledge is limited on the underlying molecular mechanisms.

In this study, we performed data-independent acquisition mass spectrometry plasma proteomics (DIA-MS) to identify molecular alterations associated with PCC. DIA-MS proteomic analysis revealed a few proteins linked to oxidative stress that had altered expression.

Notably, PCC samples exhibited downregulation of the antioxidant protein peroxiredoxin 6 (PRDX6) and upregulation of oxidative stress-associated proteins particularly vanin-1 (VNN1) and paraoxonase-3 (PON3). Additionally, the PCC group showed significantly higher levels of six proteins (PCSK9, CST3, C1Q, CPB2, KNG1 GAPDH), which were linked to pathways involving glycolysis, complement and coagulation cascades, and inflammation.

Oxidative stress analysis confirmed that PCC samples had significantly higher levels of DNA damage (8-OHdG) than the convalescent group, whereas antioxidant markers, such as reduced and oxidized glutathione (GSH and GSSG), were significantly lower in PCC samples than in uninfected controls. Our observations point towards ongoing oxidative and inflammatory processes in PCC and suggest potential targets for biomarker development and therapeutic intervention.

Web | PDF | Preprint:
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Strangely higher 15 mins after exercise in this small Hanson study:

hotblack said:
Genecards links for easy perusal, sorry I lost the nice colour coding and not all have directly associated genes, I haven’t checked them all individually yet, just generated the URLs

Baseline
Lower:
ANXA3
VIM
RAP1A
PRKAR2A
SCRN1
PCSK6
PPP1R14A
SYNCRIP
DARS1
MPST
DAPP1
PAFAH1B1
PGD
TXNDC5
FKBP3
ADH5
HNRNPK
RDX
KPNB1
CMPK1
RAB7A
AKR1A1
CNPY2
PTGES3
PSMA5

Higher:
BLMH
TBCA
GGCT
NSF
CD84
ACTN3

15 mins after exercise
Lower:
DSG1
RAP1A
SERPIN89
PRKAR2A
SCP2
GAB
DARS1
TXNDC5
PTPN11
ADH5
PDCD6IP
CRLF3
HNRNPK
TAOK3
GSTP1
PGK1
ERP44
P1L4 (no genecard, see RPL4, thanks @Hutan)
IPO07 (no genecard, possibly IPO7 ?)
VBP1
FKBP3
UBE2L3
PSMA4
USO1
INPP4B
P4HB
YWHAE
CLTA
HYOU1
TPM3
PDIA4
RDX
RAB8B
PTGES3
CALR

Higher:
BLMH
PRDX6
ADD1
TFRC

24 hours after exercise
Lower:
VIM
SYNCRIP
PRKAR2A
ANXA3
ARCN1
DARS1
VBP1
TPT1

Higher:
GGCT
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Last edited:
Very happy to see that the potential importance of Phospholipids emerged via PRDX6 and AI suggests a central role in the pathology :

Phospholipids — especially phosphatidylcholine (PC) — emerged as a key player mainly because of PRDX6 in the Tier 1 DecodeME genes:


  • PRDX6 isn’t just an antioxidant enzyme; it also has phospholipase A₂ activity and directly repairs peroxidised phospholipids in cell membranes.
  • The DecodeME write-up notes that PRDX6 is involved in phosphatidylcholine synthesis and repair, and it explicitly links this to ME/CFS by pointing out PC depletion in a patient group and elevated plasma peroxides.
  • Phospholipids here are not just structural — they are dynamic participants in membrane integrity, signalling, and vesicle trafficking. If they are damaged by oxidative stress and not repaired efficiently, it can:
    • Destabilise ion channels and receptors in neurons and muscle cells.
    • Disrupt mitochondrial and ER membranes, affecting energy and protein processing.
    • Alter immune cell signalling, since lipid rafts are PC-rich domains.

In your dataset, this made phospholipid integrity a central mechanistic hub because:


  • PRDX6 sits at the crossroads of redox biology and lipid homeostasis.
  • Membrane phospholipid damage can link oxidative stress, mitochondrial dysfunction, immune dysregulation, and neurological symptoms — all of which recur in ME/CFS models.
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Good to see that we have convergence to specific research targets.

First, the theory of @TamaraRC regarding Phosphatidylcholine and the importance of cell membrane integrity :


https://www.s4me.info/threads/a-sys...euron-dysregulation-2025-tamara-carnac.43423/

Below a Network Analysis graph (2015) identified Choline Deficiency (annotated with a square ) as a potential topic of interest along with other topics related to Oxidation, Bile acids , Peroxisomes, etc

network_clean_choline.png
 
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