CLEC12A
Chr 12C-type lectin domain family 12 member A
Also known as: CD371, CLL-1, CLL1, DCAL-2, MICL, hKLRL1
The protein functions as a myeloid inhibitory C-type lectin receptor that negatively regulates immune cell activation by recognizing various ligands including neutrophil extracellular traps, urate crystals, and pathogen-associated molecules. Mutations in CLEC12A cause autosomal recessive autoinflammatory disease with immunodeficiency, typically presenting in infancy with recurrent infections and inflammatory manifestations. The gene shows low constraint against loss-of-function variants (LOEUF 1.43), consistent with recessive inheritance requiring biallelic mutations for disease manifestation.
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
142 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 | 34 | 0 | 34 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 81 | 5 | 0 | 86 |
Likely Benign | 0 | 11 | 0 | 0 | 11 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 92 | 41 | 0 | 133 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CLEC12A · 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
Clinical Study on the Safety, Efficacy and Pharmacokinetics of Universal CLL1 Chimeric Antigen Receptor T-Cell in Relapsed/Refractory Acute Myeloid Leukemia
NOT YET RECRUITINGA Study of CD371-YSNVZIL-18 CAR T Cells in People With Acute Myeloid Leukemia
RECRUITINGExternal Resources
Links to major genomics databases and tools