CD69

Chr 12

CD69 molecule

Transmembrane protein expressed mainly on T-cells resident in mucosa that plays an essential role in immune cell homeostasis. Rapidly expressed on the surface of platelets, T-lymphocytes and NK cells upon activation by various stimuli, such as antigen recognition or cytokine signaling, stimulates different signaling pathways in different cell types (PubMed:24752896, PubMed:26296369, PubMed:35930205). Negatively regulates Th17 cell differentiation through its carbohydrate dependent interaction with galectin-1/LGALS1 present on immature dendritic cells (PubMed:24752896). Association of CD69 cytoplasmic tail with the JAK3/STAT5 signaling pathway regulates the transcription of RORgamma/RORC and, consequently, differentiation toward the Th17 lineage (By similarity). Also acts via the S100A8/S100A9 complex present on peripheral blood mononuclear cells to promote the conversion of naive CD4 T-cells into regulatory T-cells (PubMed:26296369). Acts as an oxidized low-density lipoprotein (oxLDL) receptor in CD4 T-lymphocytes and negatively regulates the inflammatory response by inducing the expression of PDCD1 through the activation of NFAT (PubMed:35930205). Participates in adipose tissue-derived mesenchymal stem cells (ASCs)-mediated protection against P.aeruginosa infection. Mechanistically, specifically recognizes P.aeruginosa to promote ERK1 activation, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) and other inflammatory cytokines secretion (PubMed:34841721). In eosinophils, induces IL-10 production through the ERK1/2 pathway (By similarity). Negatively regulates the chemotactic responses of effector lymphocytes and dendritic cells (DCs) to sphingosine 1 phosphate/S1P by acting as a S1PR1 receptor agonist and facilitating the internalization and degradation of the receptor (PubMed:37039481)

ResearchGenerating clinical summary…
10
Active trials
562
Pubs (1 yr)
P/LP submissions
P/LP missense
0.92
LOEUF
Multiple*
Mechanism· predicted
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.92LOEUF
pLI 0.030
Z-score 1.75
OE 0.40 (0.200.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.26Z-score
OE missense 1.07 (0.921.25)
112 obs / 104.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.40 (0.200.92)
00.351.4
Missense OE?1.07 (0.921.25)
00.61.4
Synonymous OE?0.78
01.21.6
LoF obs/exp: 4 / 10.0Missense obs/exp: 112 / 104.5Syn Z: 1.05

ClinVar

No ClinVar data available.

Protein Context — Lollipop Plot

CD69 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

EndometriosisAdenomyosis

Pain in Endometriosis And the Relation to Lifestyle

RECRUITING
NCT06332560Phase NARadboud University Medical CenterStarted 2024-10-04
Anti-inflammatory diet (DI)Cognitive behavioral therapy (CBT)
Meningiomas

An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma

ACTIVE NOT RECRUITING
NCT02648997Phase PHASE2Dana-Farber Cancer InstituteStarted 2016-03
Nivolumab - 240 mgIpilimumab - 1 mg/kgNivolumab - 480 mg
Borderline Resectable/Unresectable Pancreatic CancerNon Metastatic Pancreatic Cancer

Intratumoral MMR Vaccine Injection in Borderline Resectable/Unresectable Pancreatic Cancer

RECRUITING
NCT07539155Phase PHASE1, PHASE2University of ArkansasStarted 2026-06-26
Intratumoral MMR Injection
Type1diabetes

Crosstalk Between Mucosal-Associated Invariant T (MAIT) Cells and the Gut Microbiota and Mucosa in the Development of Type 1 Diabetes in Children

RECRUITING
NCT05054361Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2022-01-01
MAIT cells analysisMAIT cytokines production analysisLactulose/Mannitol Test
Malignant Glioma of BrainAstrocytomaMalignant Astrocytoma

Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

RECRUITING
NCT05686798Phase PHASE1Henry Ford Health SystemStarted 2022-11-29
Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)
Psoriasis VulgarisPsoriasisSkin Diseases

Residual Disease MEMory in PSOriasis Skin During EnstiLAR® and Narrow-band Ultraviolet B Therapy: The MEMPSOLAR Study

ACTIVE NOT RECRUITING
NCT05185258Phase PHASE4Aarhus University HospitalStarted 2022-02-16
EnstilarPlacebo-vehicle
Advanced Pancreatic CancerDuctal Adenocarcinoma of Pancreas

A Phase I/IIa Study of GKL-006 Injection in Patients With Advanced Pancreatic Cancer

ACTIVE NOT RECRUITING
NCT07777211Phase PHASE1, PHASE2Beijing Gene Key Life Technology Co., LtdStarted 2025-08-14
GKL-006 injectionNab-paclitaxel and Gemcitabine
Circadian Rhythm

CIRCA-MED WP1 & WP3 - Circadian Rhythms in ICU Patients

ACTIVE NOT RECRUITING
NCT07811492Charite University, Berlin, GermanyStarted 2025-10-01
Exposure to routine clinical parametersExposure to ICU clinical factors and treatmentsExposure to critical illness-related conditions
Vascular Complications

Prospective Exploration of Vascular Complications Associated With the Use of Immune Checkpoint Inhibitors

NOT YET RECRUITING
NCT07535944University Hospital, RouenStarted 2026-06-01
Evaluation of the vascular impact of ICIs (Immune Checkpoint Inhibitors)
Rectal Cancer PatientsObesity &Amp; OverweightLocally Advanced Rectal Cancer (LARC)

Evaluating the Impact of GLP-1 Receptor Agonists With Total Neoadjuvant Therapy in Rectal Cancer

NOT YET RECRUITING
NCT07314528Phase PHASE2St. James's Hospital, IrelandStarted 2026-04
GLP-1 receptor agonistTotal neoadjuvant therapy (TNT)