CLEC5A

Chr 7

C-type lectin domain containing 5A

Also known as: CLECSF5, MDL-1, MDL1

NCBI Gene: 23601ENSG00000258227UniProt: Q9NY25

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 signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type II transmembrane protein interacts with dnax-activation protein 12 and may play a role in cell activation. Alternative splice variants have been described but their full-length sequence has not been determined. [provided by RefSeq, Jul 2008]

74
ClinVar variants
46
Pathogenic / LP
0.13
pLI score
0
Active trials
Clinical Summary— CLEC5A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 28 VUS of 74 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.126
Z-score 1.99
OE 0.31 (0.14–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.24Z-score
OE missense 0.93 (0.79–1.11)
94 obs / 100.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.14–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.79–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 3 / 9.7Missense obs/exp: 94 / 100.7Syn Z: 0.19

ClinVar Variant Classifications

74 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic1
VUS28
45
Pathogenic
1
Likely Pathogenic
28
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
45
0
45
Likely Pathogenic
0
0
1
0
1
VUS
0
25
3
0
28
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total02549074

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

View in ClinVar →

Protein Context — Lollipop Plot

CLEC5A · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The influence of CLEC5A on early macrophage-mediated inflammation in COPD progression.
Li Q et al.·Cell Mol Life Sci
2024
CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections.
Sung PS et al.·Front Immunol
2019Review
Six potential biomarkers in septic shock: a deep bioinformatics and prospective observational study.
Kong C et al.·Front Immunol
2023
A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery.
Crouchet E et al.·Nat Commun
2021Functional
Epigenetic upregulation of CLEC5A contributes to monocyte/macrophage dysfunction in coronary artery disease.
Qi D et al.·Int J Biol Macromol
2025
[Overexpression of CLEC5A inhibits cell proliferation and metastasis and reverses epithelial-mesenchymal transition in hepatocellular carcinoma].
Lin J et al.·Nan Fang Yi Ke Da Xue Xue Bao
2023
CD163L1 and CLEC5A discriminate subsets of human resident and inflammatory macrophages in vivo.
González-Domínguez É et al.·J Leukoc Biol
2015
Current and emerging biomarkers for ulcerative colitis.
Nowak JK et al.·Expert Rev Mol Diagn
2023Review
Genetic association analysis of CLEC5A and CLEC7A gene single-nucleotide polymorphisms and Crohn's disease.
Elleisy N et al.·World J Gastroenterol
2020
CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis.
Huang YL et al.·J Mol Med (Berl)
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Causal inference of CLEC5A and ISG20 in atherosclerosis: integrating Mendelian randomization and eQTL evidence.
Zhang Y et al.·Front Immunol
2025🔓 Open Access
CLEC5A Knockdown Reduces Oxidative Stress and Inflammation Caused by Lipopolysaccharide in Renal Tubular Epithelial Cells via the NF-κB/NLRP3 Signaling Pathway.
Chen Z et al.·Arch Immunol Ther Exp (Warsz)
2026
Correction: Galuzo et al. CLEC5A Activation in Inflammatory Monocytes: A Mechanism for Enhanced Adaptive Immunity Following COVID-19 mRNA Vaccination in a Preclinical Study. Viruses 2025, 17, 1233.
Galuzo R et al.·Viruses
2025🔓 Open AccessFunctional
CLEC5A Activation in Inflammatory Monocytes: A Mechanism for Enhanced Adaptive Immunity Following COVID-19 mRNA Vaccination in a Preclinical Study.
Galuzo R et al.·Viruses
2025🔓 Open AccessFunctional
Dendritic Cells Induce Clec5a-mediated Immune Modulation in MPTP-induced Parkinson's Disease Mouse Model.
Choi SY et al.·Front Biosci (Landmark Ed)
2025Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools