MYD88

Chr 3AR

MYD88 innate immune signal transduction adaptor

Also known as: IMD68, MYD88D, WM1

This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal Toll-interleukin1 receptor domain. Patients with defects in this gene have an increased susceptibility to pyogenic bacterial infections. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

GeneReviewsOMIMResearchGenerating clinical summary…
GOFmechanismARLOEUF 0.662 OMIM phenotypes
Clinical SummaryMYD88
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
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ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 84 VUS of 193 total submissions
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Clinical Trials
9 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — MYD88
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.66LOEUF
pLI 0.124
Z-score 2.47
OE 0.29 (0.140.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.11Z-score
OE missense 0.77 (0.670.89)
143 obs / 185.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.29 (0.140.66)
00.351.4
Missense OE?0.77 (0.670.89)
00.61.4
Synonymous OE?1.08
01.21.6
LoF obs/exp: 4 / 14.0Missense obs/exp: 143 / 185.7Syn Z: -0.56

This gene — mechanism propensity

DN
0.6163th %ile
GOF
0.77top 25%
LOF
0.2774th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

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

193 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS84
Likely Benign84
Benign7
Conflicting2
4
Pathogenic
3
Likely Pathogenic
84
VUS
84
Likely Benign
7
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
1
0
4
Likely Pathogenic
2
1
0
0
3
VUS
4
70
10
0
84
Likely Benign
0
10
28
46
84
Benign
0
3
1
3
7
Conflicting
2
Total8854049184

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

11 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap MYD88 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MYD88 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell TypeRefractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type

Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

ACTIVE NOT RECRUITING
NCT02443077Phase PHASE3National Cancer Institute (NCI)Started 2016-10-12
Autologous Bone Marrow TransplantationAutologous Hematopoietic Stem Cell TransplantationCarmustine
AsthmaAtherosclerosisMetabolic Syndrome

Study of the Effect of Innate on the Inflammatory Response to Endotoxin

RECRUITING
NCT01143480National Institute of Environmental Health Sciences (NIEHS)Started 2012-07-30
Waldenstrom's DiseasePrognostic Index

Prognostic Analyses on a Validation Series of Patients With Waldenström's Disease

RECRUITING
NCT05911802French Innovative Leukemia OrganisationStarted 2023-08-11
Waldenström Macroglobulinemia (WM)

Ibrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström Macroglobulinemia

NOT YET RECRUITING
NCT07169565Phase PHASE1Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2025-09-01
IbrutinibBendamustineRituximab
Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Study of HMPL-760 Plus R-GemOx Versus Placebo Plus R-GemOx in Relapsed/Refractory DLBCL

ACTIVE NOT RECRUITING
NCT06601504Phase PHASE2HutchmedStarted 2024-11-05
HMPL-760 planned dose 1R-GemOxHMPL-760 placebo planned dose 1
Adequate Vitamin C StatusInadequate Vitamin C Status

Anti-inflammatory Activities of Vitamin C Supplementation on the Gut Barrier Function in Adults With Obesity

RECRUITING
NCT07151105Phase NAOhio State UniversityStarted 2025-10-01
Vitamin C Supplement + Low Vitamin C DietPlacebo + Low Vitamin C Diet
Waldenstrom MacroglobulinemiaMYD88 Gene Mutation

Ibrutinib + Venetoclax in Untreated WM

ACTIVE NOT RECRUITING
NCT04273139Phase PHASE2Dana-Farber Cancer InstituteStarted 2020-07-09
IBRUTINIBVenetoclax
Relapsed/Refractory Diffuse Large B-Cell Lymphoma

A Phase III Study of HMPL-760 Plus R-GemOx VS Placebo Plus R-GemOx in Relapsed/Refractory DLBCL

RECRUITING
NCT07409428Phase PHASE3HutchmedStarted 2026-03-20
HMPL-760HMPL-760 PlaceboR-GemOx
Waldenstrom's DiseaseWaldenstrom Macroglobulinemia

Prognostic Value of Circulating Tumoral DNA After the First 6 Months of Treatment in Patients With Waldenström Macroglobulinemia

RECRUITING
NCT04893564Phase NACentre Hospitalier Universitaire, AmiensStarted 2022-05-16
bone marrow sampleblood sample