MYD88
Chr 3ARMYD88 innate immune signal transduction adaptor
Also known as: IMD68, MYD88D, WM1
The protein functions as a cytosolic adapter protein essential for Toll-like receptor and IL-1 receptor signaling pathways in innate and adaptive immune responses, leading to NF-kappa-B activation and cytokine secretion. Autosomal recessive mutations cause Immunodeficiency 68, characterized by increased susceptibility to pyogenic bacterial infections. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.655), consistent with its role in immune system function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
211 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 1 | 11 | 0 | 14 |
Likely Pathogenic | 1 | 1 | 1 | 0 | 3 |
VUS | 4 | 70 | 18 | 0 | 92 |
Likely Benign | 0 | 10 | 28 | 46 | 84 |
Benign | 0 | 3 | 1 | 3 | 7 |
Conflicting | — | 2 | |||
| Total | 7 | 85 | 59 | 49 | 202 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MYD88 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Ibrutinib + Venetoclax in Untreated WM
ACTIVE NOT RECRUITINGIbrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
ACTIVE NOT RECRUITINGA Phase III Study of HMPL-760 Plus R-GemOx VS Placebo Plus R-GemOx in Relapsed/Refractory DLBCL
RECRUITINGPrognostic Value of Circulating Tumoral DNA After the First 6 Months of Treatment in Patients With Waldenström Macroglobulinemia
RECRUITINGStudy of HMPL-760 Plus R-GemOx Versus Placebo Plus R-GemOx in Relapsed/Refractory DLBCL
ACTIVE NOT RECRUITINGIbrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström Macroglobulinemia
NOT YET RECRUITINGStudy of the Effect of Innate on the Inflammatory Response to Endotoxin
RECRUITINGPrognostic Analyses on a Validation Series of Patients With Waldenström's Disease
RECRUITINGAnti-inflammatory Activities of Vitamin C Supplementation on the Gut Barrier Function in Adults With Obesity
RECRUITINGExternal Resources
Links to major genomics databases and tools