MYD88

Chr 3AR

MYD88 innate immune signal transduction adaptor

Also known as: IMD68, MYD88D, WM1

NCBI Gene: 4615 ENSG00000172936 UniProt: Q99836 OMIM: 602170

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 68MIM #612260

Macroglobulinemia, Waldenstrom, somaticMIM #153600

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Immunodeficiency 68; Macroglobulinemia, Waldenstrom, somatic; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

2151

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

GOF

Mechanism· predicted

📖

GeneReview available — MYD88

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.124

Z-score 2.47

OE 0.29 (0.14–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.11Z-score

OE missense 0.77 (0.67–0.89)

143 obs / 185.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.14–0.66)

0≤0.351.4

Missense OE?0.77 (0.67–0.89)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 4 / 14.0Missense obs/exp: 143 / 185.7Syn Z: -0.56

Background carrier burden — how many people carry a rare variant somewhere in MYD88?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

351 rare PASS variants

Rare truncating (LoF)

1 in 4,300

54 rare PASS variants

Rare synonymous (reference)

1 in 230

156 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MYD88. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 280	1 in 3,800
South Asian	~43k	1 in 210	1 in 4,800
Remaining (unassigned)	~30k	1 in 220	1 in 1,000
European (Finnish)	~27k	1 in 650	≈ 1 in 8,800
Admixed American	~22k	1 in 200	≈ 1 in 22,000
African / African American	~21k	1 in 150	≈ 1 in 9,200
East Asian	~20k	1 in 210	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 970	none seen
Middle Eastern	~2,884	≈ 1 in 720	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓