CLEC12A

Chr 12

C-type lectin domain family 12 member A

Also known as: CD371, CLL-1, CLL1, DCAL-2, MICL, hKLRL1

NCBI Gene: 160364 ENSG00000172322 UniProt: Q5QGZ9

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The protein encoded by this gene is a negative regulator of granulocyte and monocyte function. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. This gene is closely linked to other CTL/CTLD superfamily members in the natural killer gene complex region on chromosome 12p13. [provided by RefSeq, May 2011]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.43

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score 0.44

OE 0.87 (0.54–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.22Z-score

OE missense 1.05 (0.92–1.21)

141 obs / 133.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.87 (0.54–1.43)

0≤0.351.4

Missense OE?1.05 (0.92–1.21)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 11 / 12.7Missense obs/exp: 141 / 133.9Syn Z: -0.23

ClinVar Variant Classifications

0 submitted variants in ClinVar

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

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Acute Myeloid LeukemiaChimeric Antigen Receptor T-cellUniversal CLL1 CAR-T

Clinical Study on the Safety, Efficacy and Pharmacokinetics of Universal CLL1 Chimeric Antigen Receptor T-Cell in Relapsed/Refractory Acute Myeloid Leukemia

NOT YET RECRUITING

NCT07432100Phase PHASE1Mingfeng ZhaoStarted 2026-02

universal CLL1 CAR-T cells

Refractory Acute Myeloid LeukemiaRelapsed Acute Myeloid LeukemiaAcute Myeloid Leukemia

A Study of CD371-YSNVZIL-18 CAR T Cells in People With Acute Myeloid Leukemia

RECRUITING

NCT06017258Phase PHASE1Memorial Sloan Kettering Cancer CenterStarted 2023-09-01

CD371-specific/YSNVz/I-18 CAR T cells

Relapsed/Refractory B-cell Acute Lymphoblastic LeukemiaRelapsed/Refractory B-cell Non-Hodgkin Lymphoma or CLL/SLLRelapsed/Refractory Multiple Myeloma or Plasma Cell Leukemia

Adaptive Dual-Target CAR-T Cells for Relapsed or Refractory Hematologic Malignancies

RECRUITING

NCT07523555Phase PHASE1, PHASE2Beijing BiotechStarted 2026-03-02