MYD88 Gene: Innate Immune Signaling Adaptor and Oncogene
Comprehensive guide to MYD88 (MYD88 innate immune signal transduction adaptor): genomic context, protein function, associated diseases, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | MYD88 |
|---|---|
| Full Name | MYD88 innate immune signal transduction adaptor |
| Gene Type | protein coding |
| Chromosomal Location | 3p22.2 |
| NCBI Gene ID | 4615 ncbi.nlm.nih.gov/gene/4615 |
| Ensembl ID | ENSG00000172936 |
| UniProt ID | Q99836 |
| OMIM ID | 602170 |
| HGNC ID | 7562 |
| Aliases | MYD88D; MYD88; FLJ40386; MGC104326 |
Description
The MYD88 gene encodes a cytosolic adapter protein that plays a central role in the innate immune response. It mediates signal transduction from Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs) via the NF-κB pathway, leading to the production of inflammatory cytokines. MYD88 is essential for the activation of innate immune cells in response to pathogens. Somatic mutations, particularly the L265P variant, are recurrent in B-cell malignancies and lead to constitutive NF-κB activation, promoting cell survival and proliferation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Waldenström macroglobulinemia | Somatic MYD88 L265P mutation leads to constitutive NF-κB activation via IRAK1/IRAK4, promoting malignant B-cell survival. | High frequency (90-95%) in WM; COSMIC and ClinVar entries. |
| Diffuse large B-cell lymphoma (activated B-cell subtype) | L265P mutation activates NF-κB and JAK/STAT3 signaling, contributing to tumorigenesis. | Present in ~30% of ABC-DLBCL; COSMIC and ClinVar. |
| Primary central nervous system lymphoma | MYD88 L265P is a frequent driver mutation, activating NF-κB and promoting tumor growth. | Found in ~70-80% of PCNSL; ClinVar and literature. |
| Primary cutaneous marginal zone lymphoma | MYD88 L265P is recurrent, suggesting a role in lymphomagenesis. | Reported in a subset; COSMIC. |
| MyD88 deficiency (immunodeficiency) | Biallelic loss-of-function mutations impair TLR/IL-1R signaling, leading to recurrent pyogenic infections. | Rare; OMIM 612260. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | High (e.g., 50-100 nTPM) | High expression in immune tissues. |
| Bone Marrow | High (e.g., 50-100 nTPM) | High expression in hematopoietic cells. |
| Lymph Node | High (e.g., 50-100 nTPM) | High expression in lymphoid tissue. |
| Blood | Moderate (e.g., 20-50 nTPM) | Expressed in leukocytes. |
| Liver | Low (e.g., <10 nTPM) | Low expression. |
| Brain | Low (e.g., <10 nTPM) | Low expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 | Moderate (e.g., 30 nTPM) | Chronic myeloid leukemia cell line. |
| HeLa | Low (e.g., 5 nTPM) | Cervical carcinoma cell line. |
| HUVEC | Low (e.g., 3 nTPM) | Endothelial cells. |
| A549 | Low (e.g., 2 nTPM) | Lung carcinoma cell line. |
| GM12878 | High (e.g., 60 nTPM) | B-lymphoblastoid cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| L265P | Missense (SNV) | ~90% in WM, ~30% in ABC-DLBCL, ~70% in PCNSL | Gain-of-function: constitutive NF-κB activation. |
| S222R | Missense | Rare | Gain-of-function: activates NF-κB. |
| M232T | Missense | Rare | Gain-of-function: activates NF-κB. |
| V217F | Missense | Rare | Gain-of-function: activates NF-κB. |
| T294P | Missense | Rare | Gain-of-function: activates NF-κB. |
| Loss-of-function (e.g., R196C, frameshift) | Various | Rare in germline | Loss-of-function: impaired TLR signaling. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., R196C, truncations) impair TLR/IL-1R signaling, leading to immunodeficiency (OMIM 612260).
Gain of Function (GOF)
Gain-of-function mutations (e.g., L265P) cause constitutive activation of NF-κB and JAK/STAT3 pathways, promoting B-cell survival and oncogenesis.
Dominant Negative (DN)
Some MYD88 mutations may act as dominant-negative by disrupting signaling complexes, but this is less characterized; L265P is not dominant-negative but rather a gain-of-function.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 protein binding | • GO:0007165 signal transduction |
| • GO:0007254 JNK cascade | • GO:0007249 I-kappaB kinase/NF-kappaB signaling |
| • GO:0002755 MyD88-dependent toll-like receptor signaling pathway | • GO:0002224 toll-like receptor signaling pathway |
| • GO:0002230 positive regulation of defense response to virus by host | • GO:0006954 inflammatory response |
| • GO:0009615 response to virus | • GO:0034134 toll-like receptor 2 signaling pathway |
| • GO:0034138 toll-like receptor 3 signaling pathway | • GO:0034141 toll-like receptor 5 signaling pathway |
| • GO:0034146 toll-like receptor 9 signaling pathway | • GO:0034162 toll-like receptor 4 signaling pathway |
| • GO:0034166 toll-like receptor 10 signaling pathway | • GO:0035666 TRIF-dependent toll-like receptor signaling pathway |
| • GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling | • GO:0045087 innate immune response |
| • GO:0051092 positive regulation of NF-kappaB transcription factor activity | • GO:0070498 interleukin-1-mediated signaling pathway |
Pathways
• Toll-like receptor signaling pathway (KEGG hsa04620)
• NF-kappa B signaling pathway (KEGG hsa04064)
• Interleukin-1 signaling pathway (Reactome R-HSA-446652)
• MyD88 cascade (Reactome R-HSA-166058)
• Innate Immune System (Reactome R-HSA-168249)
• TRAF6-mediated NF-κB activation (Reactome R-HSA-933713)
Protein Summary
MYD88 is a 296-amino acid cytosolic adapter protein with an N-terminal death domain (DD) and a C-terminal Toll/interleukin-1 receptor (TIR) domain. It functions as a key signal transducer for TLRs and IL-1Rs. Upon ligand binding, MYD88 recruits IRAK kinases via DD interactions, leading to IRAK4-mediated phosphorylation, TRAF6 activation, and downstream NF-κB and MAPK signaling. The oncogenic L265P mutation in the TIR domain promotes spontaneous aggregation and constitutive signaling, driving B-cell malignancies. MYD88 also interacts with other proteins like TIRAP/MAL and is involved in both innate and adaptive immunity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MYD88 Knockout HEK293 Cell Line | EDJ-KQ578 | Human | 4615 | Details Get a Quote |
| MYD88 Knockout A-549 Cell Line | EDJ-KQ18982 | Human | 4615 | Details Get a Quote |
| MYD88 Knockout HCT 116 Cell Line | EDJ-KQ18983 | Human | 4615 | Details Get a Quote |
| MYD88 Knockout HeLa Cell Line | EDJ-KQ18984 | Human | 4615 | Details Get a Quote |
| Myd88 Knockout RAW 264.7 Cell Line | EDJ-KZ354 | Mouse | 17874 | Details Get a Quote |
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