CLEC4D
Chr 12C-type lectin domain family 4 member D
Also known as: CD368, CLEC-6, CLEC6, CLECSF8, Dectin-3, MCL, MPCL
The protein functions as a calcium-dependent pattern recognition receptor in the innate immune system, recognizing pathogen-associated molecular patterns from bacteria and fungi to activate immune responses through NF-kappa-B signaling. Biallelic mutations in this gene cause a primary immunodeficiency disorder characterized by recurrent invasive fungal infections, particularly severe candidiasis. The gene shows very low constraint against loss-of-function variants (pLI near 0), and the condition follows an autosomal recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
88 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 | 0 | 0 | 36 | 0 | 36 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 34 | 5 | 0 | 39 |
Likely Benign | 0 | 3 | 1 | 1 | 5 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 38 | 44 | 1 | 83 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CLEC4D · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools