Genetics: SUDS3

Hutan

Hutan

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DecodeMe Candidate Gene
In DecodeME, we attempted to link GWAS variants to target genes. Here we discuss the top two tiers of predicted linked genes that we are most confident about –‘Tier 1’ and ’Tier 2’.

We defined genes as Tier 1 genes if: (i) they are protein-coding genes, (ii) they have GTEx-v10 expression quantitative trait loci (eQTLs) lying within one of the FUMA-defined ME/CFS-associated intervals, and (iii) their expression and ME/CFS risk are predicted to share a single causal variant with a posterior probability for colocalisation (H4) of at least 75%. For this definition, we disregarded the histone genes in the chr6p22.2 HIST1 cluster, as their sequences and functions are highly redundant (1). This prioritisation step yielded 29 Tier 1 genes. For the intervals without Tier 1 genes, three Tier 2 genes were defined as the closest protein-coding genes without eQTL association: FBXL4 (chr6q16.1), OLFM4 (chr13q14.3), and CCPG1 (chr15q21.3).
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CHROMOSOME 12 (GWAS-2)
Chr12 contained three Tier 1 genes.

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SUDS3 (Tier 1)

• Protein: SIN3A corepressor complex component, also known as SDS3. UniProt. GeneCards.
The allele that increases the risk of ME/CFS is associated with increased SUDS3 expression.7

• Molecular function: Regulatory protein that represses transcription and augments histone deacetylase activity of HDAC1 (UniProt). SUDS3 alters expression of the upstream kinase, ASK1, in the p38 MAPK pathway cascade (44).

• Cellular function: Chromatin remodeling and transcriptional regulation. Depletion of mouse Suds3 reveals an essential role in early lineage specification (45).

• Link to disease: Proposed to contribute to the microglial inflammatory response (44).

• Potential relevance to ME/CFS: Unclear, but potentially to neuroinflammation.

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References
7. Johnson BS, Farkas D, El-Mergawy R, Adair JA, Elhance A, Eltobgy M, et al. Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses. Nat Commun. 2024 Dec 1;15(1).

44. Shen J, Lai W, Li Z, Zhu W, Bai X, Yang Z, et al. SDS3 regulates microglial inflammation by modulating the expression of the upstream kinase ASK1 in the p38 MAPK signaling pathway. Inflamm Res. 2024 Sep;73(9):1547–64.
(note SDS3 is an earlier name for SUDS3)

45. Zhang K, Dai X, Wallingford MC, Mager J. Depletion of Suds3 reveals an essential role in early lineage specification. Dev Biol. 2013 Jan 15;373(2):359–72.
 
No mentions of SUDS3 or SDS3 on the forum as yet, however

Other mentions of HDAC1 on the forum

Increased HDAC1 Expression Increases Mitochondrial Dysfunction in Endothelial Cells, 2022, Jones et al

Abstract Endothelial dysfunction is a critical determinant of many chronic diseases including cardiovascular and kidney disease. Endothelial dysfunction is defined by a loss of NO bioavailability and increased reactive oxygen species (ROS). Previous reports show that mitochondrial-derived ROS...
s4me.info s4me.info

SNT Gatchaman

Preprint Thread 'Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis, 2025, Zhang+'

Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis
Sai Zhang; Fereshteh Jahanbani; Varuna Chander; Martin Kjellberg; Menghui Liu; Katherine Glass; David Iu; Faraz Ahmed; Han Li; Rajan Douglas Maynard; Tristan Chou; Johnathan Cooper-Knock; Martin Jinye Zhang; Durga Thota; Michael Zeineh; Jennifer Grenier; Andrew Grimson; Maureen Hanson; Michael Snyder

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogeneous, and systemic disease defined by a suite of symptoms, including...
  • SNT Gatchaman
  • b cells cd4+ genetics hanson hla machine learning neuroligin proteasome t cells ubiquitin
  • Replies: 449
  • Forum: ME/CFS research
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forestglip

Preprint Thread 'Integrative Multi-Omics Framework for Causal Gene Discovery in Long COVID, 2025, Le et al'

Integrative Multi-Omics Framework for Causal Gene Discovery in Long COVID

Thuc Duy Le, Sindy Licette Pinero, Xiaomei Li, Lin Liu, Jiuyong Li, Sang Hong Lee, Marnie Winter, Thin Nguyen, Junpeng Zhang

Background
Long COVID, or Post–Acute Sequelae of COVID–19 (PASC), involves persistent, multisystemic symptoms in about 10–20% of COVID-19 patients. Although age, sex, ethnicity, and comorbidities are recognized as risk factors, identifying genetic contributors is essential for developing targeted therapies.

Methods
We developed a multi–omics framework using...
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Sly Saint

Open Thread 'Epigenetics of Post-exertional Malaise in Patients With ME/CFS: Oct 2020 [This trial is not yet open for recruitment]'

Sponsor Vrije Universiteit Brussel
Overall contact Andrea Polli, MSc
Summary
Exploring epigenetic mechanisms of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is crucial to understand the mechanisms underlying its pathophysiology. Three potential candidates have been selected (BDNF, COMT, and HDAC genes). DNA methylation in the promoter regions of those genes will be explored.

The investigators designed a randomised controlled trial with cross-over design and will enrol 80 patients with ME/CFS and 25 age-, sex-, and BMI-matched healthy controls. Both groups...
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HDAC1 was a significant hit in the Zhang study, no?

[Edit: ah sorry that was already mentioned above. I think it's interesting to see a few hits between studies on general epigenetic regulation, which might provide hints for findings in cultured cells, which are more likely to be reflective of epigenetic changes that persist in culture]
 
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