CD69

Summary

CD69 (CD69 molecule, HGNC:1694) is a protein-coding gene on chromosome 12p13.31, encoding Early activation antigen CD69 (Q07108). Transmembrane protein expressed mainly on T-cells resident in mucosa that plays an essential role in immune cell homeostasis.

This gene encodes a member of the calcium dependent lectin superfamily of type II transmembrane receptors. Expression of the encoded protein is induced upon activation of T lymphocytes, and may play a role in proliferation. Furthermore, the protein may act to transmit signals in natural killer cells and platelets.

Source: NCBI Gene 969 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 21 total
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001781

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1694
Approved symbol	CD69
Name	CD69 molecule
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	CLEC2C
Ensembl gene	ENSG00000110848
Ensembl biotype	protein_coding
OMIM	107273
Entrez	969

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 retained_intron

ENST00000228434, ENST00000416624, ENST00000536709, ENST00000543147

RefSeq mRNA: 1 — MANE Select: NM_001781 NM_001781

CCDS: CCDS8604

Canonical transcript exons

ENST00000228434 — 5 exons

Exon	Start	End
ENSE00000718659	9754587	9754690
ENSE00000718665	9755062	9755261
ENSE00000821822	9752486	9753589
ENSE00003529080	9760757	9760901
ENSE00003640877	9756297	9756419

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 95.53.

FANTOM5 (CAGE): breadth broad, TPM avg 54.5363 / max 4160.0768, expressed in 509 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129431	54.4267	508
129432	0.1096	34

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	95.53	gold quality
vermiform appendix	UBERON:0001154	95.45	gold quality
spleen	UBERON:0002106	93.09	gold quality
gall bladder	UBERON:0002110	92.57	gold quality
rectum	UBERON:0001052	90.75	gold quality
bone marrow cell	CL:0002092	90.59	gold quality
granulocyte	CL:0000094	90.03	gold quality
caecum	UBERON:0001153	90.00	gold quality
epithelium of nasopharynx	UBERON:0001951	89.23	gold quality
nasopharynx	UBERON:0001728	89.21	gold quality
right lung	UBERON:0002167	88.33	gold quality
bone marrow	UBERON:0002371	87.95	gold quality
colonic epithelium	UBERON:0000397	87.90	gold quality
upper lobe of left lung	UBERON:0008952	87.43	gold quality
tonsil	UBERON:0002372	86.37	gold quality
upper lobe of lung	UBERON:0008948	86.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.93	gold quality
omental fat pad	UBERON:0010414	85.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.49	gold quality
peritoneum	UBERON:0002358	85.45	gold quality
amniotic fluid	UBERON:0000173	84.71	gold quality
leukocyte	CL:0000738	84.22	gold quality
upper leg skin	UBERON:0004262	83.81	gold quality
mononuclear cell	CL:0000842	83.80	gold quality
left uterine tube	UBERON:0001303	83.58	gold quality
monocyte	CL:0000576	83.44	gold quality
lung	UBERON:0002048	83.31	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.27	gold quality
smooth muscle tissue	UBERON:0001135	82.53	gold quality
small intestine	UBERON:0002108	82.21	gold quality

Single-cell (SCXA)

Detected in 41 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-GEOD-70580	yes	12685.29
E-CURD-126	yes	8543.91
E-MTAB-6308	yes	5737.80
E-CURD-46	yes	5680.35
E-HCAD-1	yes	3926.71
E-GEOD-130148	yes	3891.20
E-MTAB-9543	yes	3540.58
E-MTAB-6701	yes	3311.33
E-MTAB-9221	yes	3196.14
E-MTAB-10553	yes	3109.75
E-HCAD-15	yes	3061.81
E-CURD-114	yes	2946.62
E-CURD-79	yes	2800.17
E-MTAB-6678	yes	2550.21
E-MTAB-9467	yes	2539.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CREB1, FOS, JUN, NFKB1, NFKB, NFKBID, PPARG, RELA, RUNX1, SLA2, STAT1, STAT5A

miRNA regulators (miRDB)

101 targeting CD69, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6809-3P	99.91	71.45	3814

Literature-anchored findings (GeneRIF, showing 40)

• CD69 engagement initiates protein tyrosine kinase-dependent signaling pathways in IL-2-activated NK cells by inducing selective activation of Syk, but not ZAP70, kinase. (PMID:12077230)
• CD69 transduces a Bcl-2-dependent death signal when ligated by a specific antibody. As the function of CD69 appears to be restricted to activated eosinophils, making an ideal target for therapeutic intervention in asthma. (PMID:12234263)
• a higher CD69 expression when atopic neutrophils were incubated with GM-CSF compared to non-atopic neutrophils (PMID:12540017)
• GM-CSF, IFN-gamma or IFN-alpha significantly induced CD69 expression on neutrophils. We demonstrated the capacity of CD69 to act as a costimulus for TNF-alpha production by neutrophils. (PMID:12718936)
• expression of CD69 on CD3+ and CD8+ peripheral blood T cells correlates closely with the presence of acute graft rejection in renal allograft recipients (PMID:12865808)
• Increased CD69 of T lymphocytes, along with abnormally elevated immunologically active molecules play an important role in immune pathogenesis of patients with myelodysplastic syndrome(MDS). (PMID:14728878)
• Our study has identified, by immunoprecipitation and direct protein sequencing (LC/MS/MS), binding of CD69 to an N-terminal protein fragment of calreticulin expressed on the cell surface of human PBMCs. (PMID:15893733)
• The expression of CD69 in T lymphocytes from nasal polyps was abnormally high. (PMID:15952571)
• The expression of CD69 and CD154 molecules depend partially on the prolactine. (PMID:16396693)
• CD69 forms a complex with and negatively regulates S1P1 and that it functions downstream of IFN-alpha/beta, and possibly other activating stimuli, to promote lymphocyte retention in lymphoid organs (PMID:16525420)
• Plasmodium falciparum histidine-rich protein II reduces CD69 expression in T cells. (PMID:16788832)
• data suggest unidentified natural ligands for CD69 and/or CD69 autoantibodies possibly affect joint-composing cell types through increased production of S100A9 in neutrophils, providing insight into functions of CD69 on neutrophils in rheumatoid arthritis (PMID:17237603)
• IL-3 is a central inducer of CD69 expression. Upregulated CD69 expression on locally accumulated basophils in bronchial asthma may be partly due to a combination of local cytokines, especially IL-3, plus IgE-cross-linking allergens. (PMID:17541278)
• Since induction of CD69 surface expression is dependent on the activation of the protein kinase C (PKC) activation pathway, it is suggested that in chronic fatigue syndrome there is a disorder in the early activation of the immune system involving PKC. (PMID:17693977)
• results do not support a major role for the CD69 gene polymorphisms in RA genetic predisposition in our population. (PMID:18627570)
• the physical, biochemical and in vivo characteristics of a highly stable soluble form of CD69 obtained by bacterial expression of an appropriate extracellular segment of this protein. (PMID:18959746)
• Expression of CD69 and IL8 is upregulated upon Bcr-Abl expression (PMID:19383348)
• soluble factors in SSc plasma inhibit Treg function specifically that is associated with altered Treg CD69 and TGFbeta expression (PMID:19543397)
• analysis of CD69 molecules on human CD4+ T cell membrane (PMID:19670272)
• structure refined to 1.37 A resolution provides further details of the overall structure and the asymmetric interface between the monomers in the native dimer (PMID:20054122)
• Caffeine does not appear to depress Natural killer cell CD69 expression. (PMID:21152932)
• Studies provide a mechanistic link between CD69 and the regulation of T(H)17 responses. (PMID:21427408)
• Increased CD4(+) CD69(+) CD25(-) T cells exert a critical role in hepatocellular carcinoma progression and might represent a clinically aggressive tumor phenotype. (PMID:21557772)
• Results suggest that H. pylori induces CD69 expression through the activation of NF-kappaB, and that cagPAI might be relevant in the induction of CD69 expression in T cells. CD69 in T cells may play a role in H. pylori-induced gastritis. (PMID:21990950)
• CD69 is significantly correlated with poor clinical and biological prognostic factors and is confirmed to be an independent disease prognosticator in chronic lymphocytic leukemia. (PMID:21993667)
• T cells isolated from the hepatocellular carcinoma tissues expressed significantly more CD69 molecules than did those on paired circulating and nontumor-infiltrating T cells; these tumor-derived CD69(+) T cells could induce considerable IDO in monocytes (PMID:22184722)
• Intron I acts as an important regulatory element of CD69 expression. (PMID:22456278)
• Priming with apoptotic debris prevented DCs from establishing cytotoxicity toward live human tumor cells by inducing a Treg-cell population, defined by coexpression of CD39 and CD69 (PMID:22678911)
• In patients with allergic rhinitis CD69 antigen is overexpressed on human peripheral blood natural killer cells reflecting their activation status. (PMID:23454781)
• CD69 overexpression is associated with the human T-cell leukemia virus type 1 infection and adult T-cell leukemia. (PMID:23507197)
• This is the first report of the regulation of CD69 expression by LMP-1, and this novel finding may, thus, represent an important link between the EBV oncoprotein LMP-1 and its critical role in the development of EBV-associated diseases. (PMID:23546309)
• CD69 is induced by integrin alpha4beta1 outside-in signalling and T-cell receptor signalling. (PMID:23758320)
• REVIEW: CD69 exerts a complex immunoregulatory role in humans, and that it could be considered as a target molecule for the therapy of immune-mediated diseases (PMID:23954168)
• Following coculture with GTKO/CD46 pig mesenchymal stromal cells, it is possible that upregulation of CD69 on human T cells initiates signaling events that would regulate CD4+ and CD8+ T cell activation and differentiation. (PMID:24044963)
• Human tumor-infiltrating CD4+CD69+ T cells suppress T cell proliferation via membarene -bound TGF-beta1. (PMID:24668348)
• these findings identify CD69 and galectin-1 to be a novel regulatory receptor-ligand pair that modulates Th17 effector cell differentiation and function. (PMID:24752896)
• Elevated expression of CD69 and CD161 on NK cells can be considered as immunological risk markers in RSA and IVF failure. (PMID:24975965)
• In vitro functional assays showed that CD69(+) Treg cells exerted an important suppressive effect on the activation of T effector cells (PMID:26100786)
• results demonstrate the functional and mechanistic interplays between CD69 and S100A8/S100A9 in supporting Treg-cell differentiation (PMID:26296369)
• Higher CD69 expression were less sensitive to bendamustine and is associated with chronic lymphocytic leukemia. (PMID:26701728)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-193e13.5	ENSDARG00000052656
danio_rerio		ENSDARG00000074732
danio_rerio	si:dkey-26c10.5	ENSDARG00000088023
danio_rerio	si:ch211-170d8.8	ENSDARG00000090945
mus_musculus	Cd69	ENSMUSG00000030156
rattus_norvegicus	Cd69	ENSRNOG00000056783
drosophila_melanogaster	rgn	FBGN0261258
caenorhabditis_elegans		WBGENE00009156
caenorhabditis_elegans		WBGENE00013008

Paralogs (23): CLEC2D (ENSG00000069493), CLEC2B (ENSG00000110852), KLRB1 (ENSG00000111796), KLRD1 (ENSG00000134539), KLRC1 (ENSG00000134545), KLRG1 (ENSG00000139187), KLRF1 (ENSG00000150045), CLEC1A (ENSG00000150048), CLEC1B (ENSG00000165682), CLEC7A (ENSG00000172243), CLEC12A (ENSG00000172322), OLR1 (ENSG00000173391), KLRC4 (ENSG00000183542), CLEC2A (ENSG00000188393), KLRG2 (ENSG00000188883), CLEC9A (ENSG00000197992), KLRC2 (ENSG00000205809), KLRC3 (ENSG00000205810), KLRK1 (ENSG00000213809), CLEC2L (ENSG00000236279), CLEC12B (ENSG00000256660), KLRF2 (ENSG00000256797), CLEC5A (ENSG00000258227)

Protein

Protein identifiers

Early activation antigen CD69 — Q07108 (reviewed: Q07108)

Alternative names: Activation inducer molecule, BL-AC/P26, C-type lectin domain family 2 member C, EA1, Early T-cell activation antigen p60, GP32/28, Leukocyte surface antigen Leu-23, MLR-3

All UniProt accessions (3): Q07108, B4E009, Q53ZX0

UniProt curated annotations — full annotation on UniProt →

Function. 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. Negatively regulates Th17 cell differentiation through its carbohydrate dependent interaction with galectin-1/LGALS1 present on immature dendritic cells. Association of CD69 cytoplasmic tail with the JAK3/STAT5 signaling pathway regulates the transcription of RORgamma/RORC and, consequently, differentiation toward the Th17 lineage. 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. 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. 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. In eosinophils, induces IL-10 production through the ERK1/2 pathway. 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.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with S100A8 and S100A9. Interacts with galactin-1/LGALS1. Interacts with S1PR1; this interaction mediates S1PR1 degradation.

Subcellular location. Cell membrane.

Tissue specificity. Expressed on the surface of activated T-cells, B-cells, natural killer cells, neutrophils, eosinophils, epidermal Langerhans cells and platelets.

Post-translational modifications. Constitutive Ser/Thr phosphorylation in both mature thymocytes and activated T-lymphocytes.

Induction. By antigens, mitogens or activators of PKC on the surface of T and B-lymphocytes. By interaction of IL-2 with the p75 IL-2R on the surface of NK cells.

RefSeq proteins (1): NP_001772* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR033992	NKR-like_CTLD	Domain
IPR050828	C-type_lectin/matrix_domain	Family

Pfam: PF00059

UniProt features (22 total): strand 8, disulfide bond 4, topological domain 2, helix 2, chain 1, turn 1, transmembrane region 1, domain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3HUP	X-RAY DIFFRACTION	1.37
1E87	X-RAY DIFFRACTION	1.5
3CCK	X-RAY DIFFRACTION	1.8
1E8I	X-RAY DIFFRACTION	1.95
1FM5	X-RAY DIFFRACTION	2.27
8G94	ELECTRON MICROSCOPY	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07108-F1	82.84	0.66

Antibody-complex structures (SAbDab): 1 — 8G94

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (4): 173–186, 68, 85–96, 113–194

Glycosylation sites (1): 166

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 487 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, CREL_01, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, LU_IL4_SIGNALING, GOBP_INFLAMMATORY_RESPONSE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MODULE_64, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION

GO Biological Process (6): negative regulation of inflammatory response (GO:0050728), cellular response to xenobiotic stimulus (GO:0071466), negative regulation of T-helper 17 cell lineage commitment (GO:2000329), negative regulation of T cell migration (GO:2000405), sphingosine-1-phosphate receptor signaling pathway (GO:0003376), T cell migration (GO:0072678)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), carbohydrate binding (GO:0030246), identical protein binding (GO:0042802), molecular sequestering activity (GO:0140313), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), protein-containing complex (GO:0032991), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
response to xenobiotic stimulus	1
cellular response to chemical stimulus	1
negative regulation of cell fate commitment	1
T-helper 17 cell lineage commitment	1
negative regulation of T-helper 17 cell differentiation	1
regulation of T-helper 17 cell lineage commitment	1
T cell migration	1
negative regulation of lymphocyte migration	1
regulation of T cell migration	1
G protein-coupled receptor signaling pathway	1
sphingolipid mediated signaling pathway	1
lymphocyte migration	1
signaling receptor activity	1
protein binding	1
molecular_function	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular_component	1

Protein interactions and networks

STRING

2672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD69	S1PR1	P21453	993
CD69	CD4	P01730	941
CD69	CD8A	P01732	927
CD69	KLRB1	Q12918	905
CD69	IL2	P01585	904
CD69	CD80	P33681	895
CD69	IFNG	P01579	890
CD69	CD44	P16070	886
CD69	SELL	P14151	881
CD69	CCR7	P32248	877
CD69	IL7R	P16871	852
CD69	CD2	P06729	848
CD69	CD27	P26842	847
CD69	CD19	P15391	834
CD69	CD28	P10747	831

IntAct

51 interactions, top by confidence:

A	B	Type	Score
TMEM190	CD69	psi-mi:“MI:0915”(physical association)	0.720
CD69	TMEM190	psi-mi:“MI:0915”(physical association)	0.720
CD69	NINJ2	psi-mi:“MI:0915”(physical association)	0.600
UPK1B	CD69	psi-mi:“MI:0915”(physical association)	0.560
CD69	BRICD5	psi-mi:“MI:0915”(physical association)	0.560
CD69	SLC35B2	psi-mi:“MI:0915”(physical association)	0.560
CLDN1	CD69	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	CD69	psi-mi:“MI:0915”(physical association)	0.560
CD69	RPRM	psi-mi:“MI:0915”(physical association)	0.560
CD69	TSPO2	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0C	CD69	psi-mi:“MI:0915”(physical association)	0.560
CD69	EBP	psi-mi:“MI:0915”(physical association)	0.560
MAL	CD69	psi-mi:“MI:0915”(physical association)	0.560
PMP22	CD69	psi-mi:“MI:0915”(physical association)	0.560
CD69	PALM3	psi-mi:“MI:0914”(association)	0.530
CD69	S1PR1	psi-mi:“MI:0915”(physical association)	0.520
CD69	DDAH1	psi-mi:“MI:0915”(physical association)	0.400
CD69	SMARCB1	psi-mi:“MI:0915”(physical association)	0.370
TMEM190	CD69	psi-mi:“MI:0915”(physical association)	0.000
UPK1B	CD69	psi-mi:“MI:0915”(physical association)	0.000
NINJ2	CD69	psi-mi:“MI:0915”(physical association)	0.000
MAL	CD69	psi-mi:“MI:0915”(physical association)	0.000
BRICD5	CD69	psi-mi:“MI:0915”(physical association)	0.000
SLC35B2	CD69	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): TMEM190 (Two-hybrid), PALM3 (Affinity Capture-MS), ERICH5 (Affinity Capture-MS), PYGB (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), CADM4 (Affinity Capture-MS), CD69 (Two-hybrid), CD69 (Two-hybrid), TSPO2 (Two-hybrid), UPK1B (Two-hybrid), EBP (Two-hybrid), SLC35B2 (Two-hybrid), TMEM190 (Two-hybrid), CLDN1 (Two-hybrid), NINJ2 (Two-hybrid)

ESM2 similar proteins: A4KWA1, D3W0D1, D4AD02, O54709, O70215, O88713, P20937, P26715, P27471, P27811, P27812, P27814, Q07108, Q0ZUP0, Q0ZUP1, Q12918, Q149M0, Q2HXU8, Q2NL33, Q5NKN2, Q5NKN4, Q5QGZ9, Q60652, Q60654, Q63378, Q64335, Q67EQ0, Q6QLQ4, Q6UXN8, Q80XD9, Q80ZC8, Q8BRU4, Q8BWY2, Q8C1T8, Q8CJC7, Q8MI05, Q8NC01, Q8VD98, Q8VI21, Q95MI5

Diamond homologs: A4KWA5, A4KWA6, A4KWA8, O70156, O89335, P06734, P08290, P0C7M9, P14370, P37217, P49259, P79391, Q07108, Q0H8B9, Q5M9I1, Q5QGZ9, Q60660, Q6QLQ4, Q6UVW9, Q6UXN8, Q80XD9, Q8BWY2, Q8C1T8, Q8N1N0, Q8VI21, Q91V08, Q92478, Q925N7, Q9D676, Q9UBG0, Q9UHP7, Q9WVF9, Q9XTA8, A4KWA1, P02706, P0C7M8, P14371, P24721, P26715, P26717

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STAG2	up-regulates	CD69

Disease & clinical

Clinical variants and AI predictions

ClinVar

21 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

338 predictions. Top by Δscore:

Variant	Effect	Δscore
12:9755257:GCCCA:G	acceptor_gain	1.0000
12:9755258:CCCA:C	acceptor_gain	1.0000
12:9755258:CCCAC:C	acceptor_gain	1.0000
12:9755259:CCA:C	acceptor_gain	1.0000
12:9755259:CCAC:C	acceptor_gain	1.0000
12:9755260:CA:C	acceptor_gain	1.0000
12:9755260:CAC:C	acceptor_gain	1.0000
12:9755261:ACT:A	acceptor_loss	1.0000
12:9755262:C:CC	acceptor_gain	1.0000
12:9755262:C:T	acceptor_loss	1.0000
12:9755263:T:A	acceptor_loss	1.0000
12:9756416:TCAT:T	acceptor_gain	1.0000
12:9756417:CATC:C	acceptor_gain	1.0000
12:9756419:TCTG:T	acceptor_loss	1.0000
12:9756420:C:CC	acceptor_gain	1.0000
12:9756420:CTGG:C	acceptor_loss	1.0000
12:9756421:T:A	acceptor_loss	1.0000
12:9760755:A:AC	donor_gain	1.0000
12:9760756:C:CT	donor_gain	1.0000
12:9760756:CTTT:C	donor_gain	1.0000
12:9753588:ACCT:A	acceptor_loss	0.9900
12:9753590:CT:C	acceptor_loss	0.9900
12:9754692:T:C	acceptor_gain	0.9900
12:9755056:TCTTA:T	donor_loss	0.9900
12:9755057:CTTA:C	donor_loss	0.9900
12:9755058:TTAC:T	donor_loss	0.9900
12:9755059:T:TG	donor_loss	0.9900
12:9755060:A:AC	donor_gain	0.9900
12:9755061:C:CA	donor_loss	0.9900
12:9755061:C:CC	donor_gain	0.9900

AlphaMissense

1325 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:9754652:C:A	W142C	0.991
12:9754652:C:G	W142C	0.991
12:9755131:C:A	W106C	0.988
12:9755131:C:G	W106C	0.988
12:9754613:C:A	W155C	0.987
12:9754613:C:G	W155C	0.987
12:9753500:C:G	C194S	0.985
12:9753501:A:T	C194S	0.985
12:9755110:A:C	C113W	0.985
12:9755111:C:T	C113Y	0.982
12:9755111:C:G	C113S	0.981
12:9755112:A:T	C113S	0.981
12:9753500:C:T	C194Y	0.980
12:9755182:C:A	W89C	0.979
12:9755182:C:G	W89C	0.979
12:9753499:A:C	C194W	0.977
12:9755097:C:G	A118P	0.976
12:9754654:A:G	W142R	0.973
12:9754654:A:T	W142R	0.973
12:9754615:A:G	W155R	0.972
12:9754615:A:T	W155R	0.972
12:9754685:A:C	F131L	0.972
12:9754685:A:T	F131L	0.972
12:9754687:A:G	F131L	0.972
12:9755112:A:G	C113R	0.971
12:9753501:A:G	C194R	0.969
12:9755123:G:T	A109D	0.969
12:9755124:C:G	A109P	0.969
12:9755160:A:C	Y97D	0.969
12:9754683:A:G	L132P	0.967

dbSNP variants (sampled 300 via entrez): RS1000137412 (12:9754455 G>A,T), RS1000682406 (12:9758910 C>G), RS1000882261 (12:9752053 C>G), RS1001010428 (12:9758581 G>A,T), RS1001799834 (12:9759074 C>A,T), RS1001914193 (12:9759143 A>G), RS1001942059 (12:9753331 A>G), RS1002059569 (12:9752370 C>A), RS1002410995 (12:9752413 A>C), RS1002546141 (12:9752796 C>T), RS1002578587 (12:9762175 C>A,T), RS1002731744 (12:9756112 A>G), RS1003025714 (12:9755748 T>C), RS1003587219 (12:9760701 A>T), RS1003624265 (12:9753709 G>A,C)

Disease associations

OMIM: gene MIM:107273 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000392_11	Type 1 diabetes	2.000000e-11
GCST004627_25	Lymphocyte count	2.000000e-75
GCST004632_30	Lymphocyte percentage of white cells	3.000000e-42
GCST004632_31	Lymphocyte percentage of white cells	9.000000e-50
GCST004633_23	Neutrophil percentage of white cells	5.000000e-27
GCST005531_56	Multiple sclerosis	6.000000e-13
GCST005536_26	Type 1 diabetes	2.000000e-07
GCST005997_1	Lymphocyte count	6.000000e-11
GCST007932_31	Medication use (thyroid preparations)	1.000000e-27
GCST90002388_419	Lymphocyte count	1.000000e-55
GCST90002388_420	Lymphocyte count	8.000000e-17
GCST90002388_421	Lymphocyte count	1.000000e-82
GCST90002389_381	Lymphocyte percentage of white cells	4.000000e-30
GCST90002389_382	Lymphocyte percentage of white cells	3.000000e-13
GCST90002399_329	Neutrophil percentage of white cells	3.000000e-23
GCST90002407_276	White blood cell count	4.000000e-19

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0009933	Thyroid preparation use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3308911 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 5,806 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4072833	EVOBRUTINIB	3	960
CHEMBL4650323	TOLEBRUTINIB	3	371
CHEMBL3301625	SPEBRUTINIB	2	2,965
CHEMBL3900554	BMS-986142	2	66
CHEMBL4163691	POSELTINIB	2	1,341
CHEMBL4209441	SOFNOBRUTINIB	2	17
CHEMBL5083772	BIIB-091	2	86

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11052877	Efficacy	3	tocilizumab	Rheumatoid arthritis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11052877	CD69	3	2.75	1	tocilizumab

ChEMBL bioactivities

52 potent at pChembl≥5 of 55 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.49	Kd	0.32	nM	CHEMBL591694
9.30	IC50	0.5012	nM	CHEMBL601098
9.19	IC50	0.65	nM	CHEMBL591694
9.15	IC50	0.71	nM	CHEMBL591694
8.95	Kd	1.12	nM	CHEMBL1222111
8.52	Kd	3	nM	CHEMBL601099
8.49	Kd	3.2	nM	CHEMBL1222111
8.47	Kd	3.4	nM	CHEMBL1222111
8.43	IC50	3.7	nM	CHEMBL601099
8.37	IC50	4.3	nM	CHEMBL601099
8.00	IC50	10	nM	CHEMBL5080861
7.90	IC50	12.59	nM	CHEMBL591694
7.85	IC50	14	nM	CHEMBL601100
7.82	IC50	15	nM	CHEMBL591694
7.68	IC50	21	nM	CHEMBL601100
7.60	IC50	25.12	nM	CHEMBL601099
7.41	Kd	39	nM	CHEMBL601100
7.40	IC50	40	nM	CHEMBL4066176
7.40	IC50	40	nM	CHEMBL5088454
7.30	IC50	50.12	nM	CHEMBL601100
7.23	IC50	59	nM	CHEMBL5076817
7.20	IC50	63.1	nM	CHEMBL591636
7.16	IC50	70	nM	BIIB-091
7.15	IC50	71	nM	BIIB-091
7.10	IC50	79.43	nM	CHEMBL596977
7.05	IC50	90	nM	CHEMBL5206309
7.00	IC50	100	nM	CHEMBL5085192
6.98	IC50	104	nM	CHEMBL5085931
6.89	IC50	130	nM	CHEMBL5083323
6.82	IC50	150	nM	CHEMBL601099
6.70	IC50	200	nM	TOLEBRUTINIB
6.70	IC50	200	nM	CHEMBL5094998
6.66	IC50	220	nM	CHEMBL5084997
6.48	IC50	330	nM	CHEMBL5089327
6.41	IC50	390	nM	CHEMBL5090589
6.40	IC50	400	nM	CHEMBL5090290
6.40	IC50	400	nM	CHEMBL5081318
6.20	IC50	630	nM	CHEMBL5169765
6.16	IC50	700	nM	CHEMBL5073995
6.10	IC50	800	nM	CHEMBL5093189
6.07	IC50	860	nM	CHEMBL5087011
6.01	IC50	980	nM	POSELTINIB
5.96	IC50	1100	nM	EVOBRUTINIB
5.92	IC50	1200	nM	CHEMBL5069979
5.92	IC50	1200	nM	SOFNOBRUTINIB
5.92	IC50	1200	nM	CHEMBL5207862
5.89	IC50	1300	nM	BMS-986142
5.89	IC50	1300	nM	CHEMBL601100
5.80	IC50	1600	nM	CHEMBL5075191
5.52	IC50	3000	nM	CHEMBL4744041

PubChem BioAssay actives

52 with measured affinity, of 107 total; 37 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[[26,27,28-tris(carboxymethoxy)-2,8,14,20-tetrathiapentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3(28),4,6,9(27),10,12,15,17,19(26),21,23-dodecaen-25-yl]oxy]acetic acid	459222: Inhibition of human recombinant soluble CD69 receptor by direct binding assay	kd	0.0003	uM
N-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-[[11,17,23-tris[[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]carbamothioylamino]-25,26,27,28-tetrapropoxy-5-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaenyl]carbamothioylamino]oxan-3-yl]acetamide	459221: Inhibition of human rhodamine-labelled soluble CD69 by standard plate inhibition assay	ic50	0.0005	uM
N-[(2R,3R,4R,5S,6R)-2-[[(2R,3S,4R,5R,6R)-5-acetamido-3,4-bis[[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy]-6-hydroxyoxan-2-yl]methoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide	501258: Binding affinity to human monomeric CD69 receptor expressed in Escherichia coli by equilibrium dialysis	kd	0.0011	uM
2-[[5,11,17,23-tetratert-butyl-26,27,28-tris(carboxymethoxy)-25-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaenyl]oxy]acetic acid	459222: Inhibition of human recombinant soluble CD69 receptor by direct binding assay	kd	0.0030	uM
5-tert-butyl-N-[(5R)-2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]-1,2,4-oxadiazole-3-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.0100	uM
2-[[17,25,27-tris(carboxymethoxy)-5-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3(28),4,6,9(27),10,12,15,17,19(26),21,23-dodecaenyl]oxy]acetic acid	459224: Inhibition of SiaTnTRI2-induced activation of CD69 high in human lymphocytes assessed as InsP2 production	ic50	0.0140	uM
(3S)-3-tert-butyl-N-[2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]pyrrolidine-1-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.0400	uM
10-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2R)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridinyl]amino]-6-oxo-3-pyridinyl]-2-pyridinyl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.0400	uM
3-tert-butyl-N-[(5R)-2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]-1,2,4-oxadiazole-5-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.0590	uM
4-[[11,17,23-tris[(4-carboxyphenyl)diazenyl]-25,26,27,28-tetrahydroxy-5-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaenyl]diazenyl]benzoic acid	459221: Inhibition of human rhodamine-labelled soluble CD69 by standard plate inhibition assay	ic50	0.0631	uM
1-tert-butyl-N-[(5R)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(oxetan-3-yl)-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.0700	uM
2-[[27-(carboxymethoxy)-26,28-dihydroxy-2,8,14,20-tetrathiapentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3(28),4,6,9(27),10,12,15,17,19(26),21,23-dodecaen-25-yl]oxy]acetic acid	459221: Inhibition of human rhodamine-labelled soluble CD69 by standard plate inhibition assay	ic50	0.0794	uM
(3R)-3-(3-chloro-5-fluoroanilino)-1-[(3R)-1-(1H-pyrazolo[5,4-d]pyrimidin-4-yl)piperidin-3-yl]piperidin-2-one	1847391: Inhibition of CD69 (unknown origin) in PBMC preincubated for 30 mins followed by IL-4 stimulation for 3 days by cell titer glo assay	ic50	0.0900	uM
1-tert-butyl-N-[(5R)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.1000	uM
1-tert-butyl-N-[(5R)-2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]triazole-4-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.1040	uM
5-tert-butyl-N-[2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]-1,2,4-oxadiazole-3-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.1300	uM
4-amino-3-(4-phenoxyphenyl)-1-[(3R)-1-prop-2-enoylpiperidin-3-yl]imidazo[4,5-c]pyridin-2-one	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.2000	uM
1-tert-butyl-N-[(5R)-2-methyl-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.2000	uM
3-tert-butyl-N-[2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]-1,2,4-oxadiazole-5-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.2200	uM
5-tert-butyl-N-[(5R)-2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]-1,3,4-oxadiazole-2-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.3300	uM
5-tert-butyl-N-[2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]-1,3,4-oxadiazole-2-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.3900	uM
N-[(5R)-2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]-3-propan-2-yloxyazetidine-1-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.4000	uM
1-tert-butyl-N-[(5S)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2,3,4,5-tetrahydro-1H-3-benzazepin-5-yl]triazole-4-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.4000	uM
(3R)-3-(3-chloro-5-fluoroanilino)-1-[(3R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl]piperidin-2-one	1847391: Inhibition of CD69 (unknown origin) in PBMC preincubated for 30 mins followed by IL-4 stimulation for 3 days by cell titer glo assay	ic50	0.6300	uM
1-tert-butyl-N-[(5S)-3-methyl-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-1,2,4,5-tetrahydro-3-benzazepin-5-yl]triazole-4-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.7000	uM
1-tert-butyl-N-[(5R)-2-(2-methoxyethyl)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.8000	uM
1-tert-butyl-N-[2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]triazole-4-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.8600	uM
N-[3-[2-[4-(4-methylpiperazin-1-yl)anilino]furo[3,2-d]pyrimidin-4-yl]oxyphenyl]prop-2-enamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	0.9800	uM
1-[4-[[[6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl]amino]methyl]piperidin-1-yl]prop-2-en-1-one	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	1.1000	uM
N-[3-[6-[4-(1,4-dimethyl-6-oxopiperazin-2-yl)anilino]-4-methyl-5-oxopyrazin-2-yl]-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	1.2000	uM
(2R)-2-cyclopropyl-2-(3,5-dichloroanilino)-N-[(3R)-1-(1H-pyrazolo[5,4-d]pyrimidin-4-yl)piperidin-3-yl]acetamide	1847391: Inhibition of CD69 (unknown origin) in PBMC preincubated for 30 mins followed by IL-4 stimulation for 3 days by cell titer glo assay	ic50	1.2000	uM
2-[3-[4-amino-6-[(1-methylpyrazol-4-yl)amino]-1,3,5-triazin-2-yl]-2-(hydroxymethyl)phenyl]-6-cyclopropyl-8-fluoroisoquinolin-1-one	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	1.2000	uM
(7S)-3-fluoro-4-[3-(8-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-6,7,8,9-tetrahydro-5H-carbazole-1-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	1.3000	uM
1-tert-butyl-N-[(5R)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2,3,4,5-tetrahydro-1H-2-benzazepin-5-yl]triazole-4-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	1.6000	uM
N-[[2-methyl-4-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]phenyl]methyl]-3-propan-2-yloxyazetidine-1-carboxamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	3.0000	uM
N-[3-[[5-fluoro-2-[4-(2-methoxyethoxy)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide	1820502: Inhibition of CD69 in human whole blood preincubated for 30 mins followed by anti-human IgD stimulation and measured after 18 to 22 hrs by flow cytometry	ic50	3.1000	uM
[(2R,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-(triazol-1-yl)oxan-3-yl] acetate	489739: Binding affinity to rhodamine-labeled human CD69 receptor after 2 hrs by fluorescence assay	ic50	3.9811	uM

CTD chemical–gene interactions

78 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression	6
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	3
Tetrachlorodibenzodioxin	decreases reaction, increases expression, increases reaction, decreases expression	3
Ionomycin	increases expression, affects cotreatment	3
bis(tri-n-butyltin)oxide	increases expression	2
deoxynivalenol	increases expression	2
Calcimycin	increases expression, affects cotreatment, decreases reaction	2
Arsenic	affects expression, decreases expression	2
Benzene	decreases expression, increases expression	2
Dacarbazine	affects reaction, increases expression, affects cotreatment	2
Nickel	increases expression	2
Silicon Dioxide	decreases reaction, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
OTX015	decreases reaction, increases expression	1
fenebrutinib	decreases expression	1
evobrutinib	decreases expression	1
remibrutinib	decreases expression	1
orelabrutinib	decreases expression	1
rilzabrutinib	decreases expression	1
titanium dioxide	increases expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	increases expression	1
ochratoxin A	decreases expression	1
zomepirac glucuronide	increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
tolmetin glucuronide	increases expression	1

ChEMBL screening assays

22 unique, capped per target: 22 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1068004	Binding	Inhibition of human rhodamine-labelled soluble CD69 by standard plate inhibition assay	Carboxylated calixarenes bind strongly to CD69 and protect CD69(+) killer cells from suicidal cell death induced by tumor cell surface ligands. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8D5	Abcam HCT 116 CD69 KO	Cancer cell line	Male
CVCL_B9FC	Abcam A-549 CD69 KO	Cancer cell line	Male
CVCL_D2EA	Abcam MCF-7 CD69 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.