MYD88 Gene

Last updated on: 29.04.2022

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Definition
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The MYD88 gene (MYD88 stands for "Innate Immune Signal Transduction Adaptor") is a protein coding gene located at chromosome 3p22.2. Alternative splicing results in multiple transcript variants.

The MYD88 gene encodes a cytosolic adaptor protein that plays a central role in innate and adaptive immune responses . The encoded protein consists of an N-terminal death domain and a C-terminal Toll interleukin-1 receptor domain. It functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate the activation of numerous proinflammatory genes.

General information
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Specifically, the adapter protein acts through IRAK1, IRAK2, IRF7, and TRAF6, leading to NF-kappa-B activation, cytokine secretion, and inflammatory response. It increases IL-8 transcription and participates in IL-18-mediated signaling.

Furthermore, the protein activates IRF1, leading to its rapid migration into the nucleus to cause efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. Upon TLR8 activation by GU-rich single-stranded RNA (GU-rich RNA) derived from viruses such as SARS-CoV-2, SARS-CoV, and HIV-1, it induces the release of IL1B by activating the NLRP3 inflammasome. MyD88-mediated signaling in intestinal epithelial cells is critical for maintaining intestinal homeostasis and controls the expression of the antimicrobial lectin REG3G in the small intestine.

Clinical picture
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Patients with defects in the MYD88 gene have an increased susceptibility to pyogenic bacterial infections.

Diseases associated with MYD88 include:

  • Immunodeficiency 68
  • Macroglobulinemia, Waldenström 1 (Familial Waldenström's disease).

Literature
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  1. Braggio E et al (2009) Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappa-B signaling pathways in Waldenstrom's macroglobulinemia. Cancer Res 69: 3579-3588.
  2. Conway DH et al (2010) Myeloid differentiation primary response gene 88 (MyD88) deficiency in a large kindred. (Letter) J Allergy Clin Immun 126: 172-175.
  3. Kyle RA et al (2003) Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood 102: 3759-3764.
  4. McMaster ML et al (2006) Genomewide linkage screen for Waldenstrom macroglobulinemia susceptibility loci in high-risk families. Am J Hum Genet 79: 695-701.
  5. Picard C et al (2010) Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine 89: 403-425.
  6. Platt CD et al (2019) A novel truncating mutation in MYD88 in a patient with BCG adenitis, neutropenia and delayed umbilical cord separation. Clin Immun 207: 40-42.

Incoming links (2)

Immunodeficiency 68; PID;

Last updated on: 29.04.2022