RAET1L

Summary

RAET1L (retinoic acid early transcript 1L, HGNC:16798) is a protein-coding gene on chromosome 6q25.1, encoding UL16-binding protein 6 (Q5VY80). Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity.

RAET1L belongs to the RAET1 family of major histocompatibility complex (MHC) class I-related genes, which are located within a 180-kb cluster on chromosome 6q24.2-q25.3. The REAT1 genes encode glycoproteins that contain extracellular alpha-1 and alpha-2 domains, but they lack the membrane proximal Ig-like alpha-3 domain. Most RAET1 glycoproteins are anchored to the membrane via glycosylphosphatidylinositol (GPI) linkage (Radosavljevic et al., 2002 [PubMed 11827464]).

Source: NCBI Gene 154064 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 59 total
• Druggable target: yes
• MANE Select transcript: NM_130900

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16798
Approved symbol	RAET1L
Name	retinoic acid early transcript 1L
Location	6q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000155918
Ensembl biotype	protein_coding
OMIM	611047
Entrez	154064

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000286380, ENST00000367341

RefSeq mRNA: 1 — MANE Select: NM_130900 NM_130900

CCDS: CCDS5224

Canonical transcript exons

ENST00000367341 — 5 exons

Exon	Start	End
ENSE00001444263	150018334	150018855
ENSE00002477274	150021980	150022243
ENSE00002493067	150020905	150021186
ENSE00002497182	150025387	150025532
ENSE00002503069	150020108	150020239

Expression profiles

Bgee: expression breadth broad, 63 present calls, max score 91.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4427 / max 77.1484, expressed in 120 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76163	0.4268	119
76164	0.0159	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	91.83	gold quality
esophagus mucosa	UBERON:0002469	90.16	gold quality
vagina	UBERON:0000996	69.99	gold quality
skin of leg	UBERON:0001511	67.55	gold quality
zone of skin	UBERON:0000014	67.13	gold quality
skin of abdomen	UBERON:0001416	66.65	gold quality
esophagus	UBERON:0001043	61.68	gold quality
minor salivary gland	UBERON:0001830	60.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	59.86	gold quality
saliva-secreting gland	UBERON:0001044	58.67	gold quality
islet of Langerhans	UBERON:0000006	53.13	gold quality
tonsil	UBERON:0002372	51.80	gold quality
ectocervix	UBERON:0012249	45.41	gold quality
uterine cervix	UBERON:0000002	44.35	gold quality
stromal cell of endometrium	CL:0002255	42.01	silver quality
smooth muscle tissue	UBERON:0001135	41.75	gold quality
pancreas	UBERON:0001264	40.74	gold quality
right coronary artery	UBERON:0001625	39.94	silver quality
ventricular zone	UBERON:0003053	39.82	gold quality
left adrenal gland cortex	UBERON:0035825	39.60	gold quality
bone marrow cell	CL:0002092	38.75	gold quality
muscle tissue	UBERON:0002385	38.12	silver quality
ganglionic eminence	UBERON:0004023	37.86	gold quality
left adrenal gland	UBERON:0001234	37.58	gold quality
rectum	UBERON:0001052	37.50	silver quality
skeletal muscle tissue	UBERON:0001134	37.39	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
metanephros cortex	UBERON:0010533	37.20	gold quality
urinary bladder	UBERON:0001255	36.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	36.54	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.87

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• Here, we show that a sixth gene, ULBP6/RAET1L, is a polymorphic locus that expresses a functional transcript (PMID:19658097)
• genetic polymorphism among the ethnic groups (PMID:20219610)
• RAET1L may have an important influence on regulating the strength of the alloreactive immune response in hematologic maliganacies treated with allogeneic stem cell transplantation. (PMID:23025544)
• Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells. (PMID:25212604)
• ULBP6 polymorphisms affect the strength of human lymphocyte responses to cellular stress signals and is increased in abundance in hematopoietic tumors. (PMID:28559451)
• From genomic variation to protein aberration: Mutational analysis of single nucleotide polymorphism present in ULBP6 gene and implication in immune response. (PMID:31302457)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	mhc1laa	ENSDARG00000016056
danio_rerio	mhc1lba	ENSDARG00000016227
danio_rerio	mhc1lda	ENSDARG00000023203
danio_rerio		ENSDARG00000051710
danio_rerio		ENSDARG00000051711
danio_rerio	mhc1lfa	ENSDARG00000051712
danio_rerio	mhc1lga	ENSDARG00000051713
danio_rerio	mhc1lca	ENSDARG00000055813
danio_rerio	mhc1lja	ENSDARG00000096830
danio_rerio	si:dkey-52p2.5	ENSDARG00000096940
danio_rerio	mhc1lla	ENSDARG00000096977
mus_musculus	Ulbp1	ENSMUSG00000079685

Paralogs (22): HFE (ENSG00000010704), FCGRT (ENSG00000104870), ULBP1 (ENSG00000111981), ULBP2 (ENSG00000131015), ULBP3 (ENSG00000131019), MR1 (ENSG00000153029), CD1D (ENSG00000158473), CD1A (ENSG00000158477), CD1C (ENSG00000158481), CD1B (ENSG00000158485), CD1E (ENSG00000158488), AZGP1 (ENSG00000160862), RAET1E (ENSG00000164520), RAET1G (ENSG00000203722), MICB (ENSG00000204516), MICA (ENSG00000204520), HLA-C (ENSG00000204525), HLA-E (ENSG00000204592), HLA-G (ENSG00000204632), HLA-F (ENSG00000204642), HLA-A (ENSG00000206503), HLA-B (ENSG00000234745)

Protein

Protein identifiers

UL16-binding protein 6 — Q5VY80 (reviewed: Q5VY80)

Alternative names: Retinoic acid early transcript 1L protein

All UniProt accessions (1): Q5VY80

UniProt curated annotations — full annotation on UniProt →

Function. Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity.

Subunit / interactions. Interacts with KLRK1/NKG2D. (Microbial infection) In CMV-infected cells, interacts with the viral glycoprotein UL16; this interaction causes relocalization from the cell surface to the cytoplasm and prevents binding to and activation of KLRK1/NKG2D, providing CMV with an immune evasion mechanism.

Subcellular location. Cell membrane. Endoplasmic reticulum.

Tissue specificity. Widely expressed. Expressed in trachea. Constitutively expressed in peripheral blood mononuclear cells, including B-cells and natural killer cells, as well as CD4+ and CD8+ T-cells and monocytes. Tends to be up-regulated in various lymphoid malignancies, including chronic lymphocytic leukemia.

Polymorphism. 4 alleles have been identified in 32 Caucasian individuals: ULBP601 (frequency 0.483), ULBP602 (frequency 0.424), ULBP603 (frequency 0.069) and ULBP604 (frequency 0.024). The sequence shown is that of ULBP603. Allele ULBP602 has a much higher affinity for KLRK1/NKG2D than allele ULBP6*01, but elicits less-efficient cytotoxicity. This high binding affinity and limited functional potency may depend upon the presence of the Leu residue at position 106.

Miscellaneous. UL16-binding proteins (ULBPs) are unusual members of the extended MHC class I superfamily. They do not contain the alpha 3 domain and lack a transmembrane domain.

Similarity. Belongs to the MHC class I family.

RefSeq proteins (1): NP_570970* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011161	MHC_I-like_Ag-recog	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR037055	MHC_I-like_Ag-recog_sf	Homologous_superfamily
IPR050208	MHC_class-I_related	Family

Pfam: PF00129

UniProt features (34 total): strand 11, helix 6, sequence variant 4, turn 3, region of interest 2, glycosylation site 2, disulfide bond 2, signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8RWB	X-RAY DIFFRACTION	2.31
4S0U	X-RAY DIFFRACTION	2.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VY80-F1	83.12	0.65

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

Functional residue map

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

Post-translational modifications (1): 218

Disulfide bonds (2): 50–66, 127–190

Glycosylation sites (2): 68, 82

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 55 (showing top): GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_VIA_MHC_CLASS_IB, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_POSITIVE_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY, chr6q25, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, GOBP_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN_VIA_MHC_CLASS_I

GO Biological Process (5): positive regulation of T cell mediated cytotoxicity (GO:0001916), antigen processing and presentation of endogenous peptide antigen via MHC class Ib (GO:0002476), antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent (GO:0002486), immune response (GO:0006955), immune system process (GO:0002376)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
positive regulation of T cell mediated immunity	1
antigen processing and presentation of peptide antigen via MHC class Ib	1
antigen processing and presentation of endogenous peptide antigen	1
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway	1
immune system process	1
response to stimulus	1
biological_process	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAET1L	KLRK1	P26718	960
RAET1L	MICB	P79525	697
RAET1L	HCST	Q9UBK5	513
RAET1L	KLRF1	Q9NZS2	493
RAET1L	MICA	P79506	470
RAET1L	NCR1	O76036	408
RAET1L	KLRG1	Q96E93	385
RAET1L	A2M	P01023	353
RAET1L	FCGRT	P55899	351
RAET1L	PIGT	Q969N2	347
RAET1L	ITPKB	P27987	340
RAET1L	MYO18A	O95411	339
RAET1L	SHC1	P29353	338
RAET1L	RFPL2	O75678	324
RAET1L	ESYT3	A0FGR9	323

IntAct

15 interactions, top by confidence:

A	B	Type	Score
KLRK1	RAET1L	psi-mi:“MI:0407”(direct interaction)	0.680
KLRK1	RAET1L	psi-mi:“MI:0915”(physical association)	0.680
MFF	RAET1L	psi-mi:“MI:0915”(physical association)	0.560
YIPF6	RAET1L	psi-mi:“MI:0915”(physical association)	0.560
RAET1L	MFF	psi-mi:“MI:0915”(physical association)	0.560
RAET1L	YIPF6	psi-mi:“MI:0915”(physical association)	0.560
RAET1L	UL16	psi-mi:“MI:0915”(physical association)	0.460
RAET1L	UL16	psi-mi:“MI:0403”(colocalization)	0.460
PRPH2	TOR1A	psi-mi:“MI:0914”(association)	0.350
RAET1L	ENDOD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): MFF (Two-hybrid), YIPF6 (Two-hybrid), GP5 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), RAET1L (Affinity Capture-MS), GPC3 (Affinity Capture-MS), SRA1 (Affinity Capture-MS), NEK7 (Affinity Capture-MS), PCDHA7 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), SRC (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K7V7, A7TZG3, A7UHZ5, A7XV14, B1B212, B1B213, B2KG20, O08602, O08603, O08604, O77812, P01574, P01575, P01576, P01577, P01578, P01590, P05012, P21581, P21583, P26717, P70499, Q01965, Q07444, Q29980, Q29983, Q504P2, Q5DT36, Q5DT37, Q5DT39, Q5UKY4, Q5VY80, Q60I18, Q6H3X3, Q6XZW6, Q7TSL0, Q80ZF2, Q86WN2, Q8HWE5, Q8HWE7

Diamond homologs: Q5VY80, Q6H3X3, Q8TD07, Q9BZM4, Q9BZM5, Q9BZM6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

788 predictions. Top by Δscore:

Variant	Effect	Δscore
6:150020906:T:TA	donor_gain	0.9900
6:150025386:CCGT:C	donor_gain	0.9900
6:150021978:AC:A	donor_gain	0.9800
6:150021979:CC:C	donor_gain	0.9800
6:150022037:C:CT	donor_gain	0.9800
6:150025381:GCTCA:G	donor_loss	0.9800
6:150025382:CTCA:C	donor_loss	0.9800
6:150025383:TCAC:T	donor_loss	0.9800
6:150025384:CACCG:C	donor_loss	0.9800
6:150025385:A:AC	donor_gain	0.9800
6:150025385:ACC:A	donor_loss	0.9800
6:150025386:C:CC	donor_gain	0.9800
6:150018643:C:CT	acceptor_gain	0.9700
6:150018869:CCAAA:C	acceptor_gain	0.9700
6:150020127:T:A	donor_gain	0.9700
6:150022038:C:CT	donor_gain	0.9700
6:150022240:GGGT:G	acceptor_gain	0.9700
6:150022244:C:CC	acceptor_gain	0.9700
6:150025308:C:A	donor_gain	0.9700
6:150020240:C:CC	acceptor_gain	0.9600
6:150020903:ACCT:A	donor_gain	0.9600
6:150020904:CCTC:C	donor_gain	0.9600
6:150021973:AACTT:A	donor_loss	0.9600
6:150021975:CTT:C	donor_loss	0.9600
6:150021976:TTA:T	donor_loss	0.9600
6:150021977:T:TA	donor_loss	0.9600
6:150021978:A:AG	donor_loss	0.9600
6:150021979:C:CG	donor_loss	0.9600
6:150022243:TCT:T	acceptor_loss	0.9600
6:150022244:C:T	acceptor_loss	0.9600

AlphaMissense

1614 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:150022146:A:C	F61L	0.962
6:150022146:A:T	F61L	0.962
6:150022148:A:G	F61L	0.962
6:150021113:G:C	F141L	0.951
6:150021113:G:T	F141L	0.951
6:150021115:A:G	F141L	0.951
6:150021114:A:G	F141S	0.950
6:150021020:C:A	W172C	0.935
6:150021020:C:G	W172C	0.935
6:150021092:G:C	F148L	0.933
6:150021092:G:T	F148L	0.933
6:150021094:A:G	F148L	0.933
6:150021062:C:A	W158C	0.926
6:150021062:C:G	W158C	0.926
6:150021121:A:G	W139R	0.921
6:150021121:A:T	W139R	0.921
6:150021064:A:G	W158R	0.920
6:150021064:A:T	W158R	0.920
6:150021083:A:C	F151L	0.919
6:150021083:A:T	F151L	0.919
6:150021085:A:G	F151L	0.919
6:150021022:A:G	W172R	0.915
6:150021022:A:T	W172R	0.915
6:150020945:G:C	F197L	0.910
6:150020945:G:T	F197L	0.910
6:150020947:A:G	F197L	0.910
6:150020966:G:C	C190W	0.906
6:150022068:C:A	W87C	0.902
6:150022068:C:G	W87C	0.902
6:150022147:A:G	F61S	0.890

dbSNP variants (sampled 300 via entrez): RS1000955922 (6:150024586 T>G), RS1001053898 (6:150018373 C>G,T), RS1001111754 (6:150018540 A>T), RS1001237655 (6:150024191 G>T), RS1001295515 (6:150027020 C>T), RS1001690368 (6:150024446 C>A,T), RS1002106417 (6:150019273 A>C,G), RS1002288320 (6:150025312 C>G,T), RS1003060633 (6:150020709 G>A), RS1004073651 (6:150021881 C>G,T), RS1004301632 (6:150027383 G>A), RS1004655449 (6:150027242 T>C,G), RS1004948269 (6:150018333 GT>G), RS1005076067 (6:150023842 G>T), RS1005305684 (6:150018118 G>A)

Disease associations

OMIM: gene MIM:611047 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004866_2	Alopecia areata	6.000000e-24

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5483006 (PROTEIN COMPLEX)

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

ChEMBL bioactivities

30 potent at pChembl≥5 of 30 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	CHEMBL5438591
6.70	IC50	200	nM	CHEMBL5400409
6.52	IC50	300	nM	CHEMBL5400078
6.40	IC50	400	nM	CHEMBL5405635
6.40	IC50	400	nM	CHEMBL5397883
6.40	IC50	400	nM	CHEMBL5406023
6.30	IC50	500	nM	CHEMBL5420013
6.22	IC50	600	nM	CHEMBL5428731
6.16	IC50	700	nM	CHEMBL5421826
6.16	IC50	700	nM	CHEMBL5418204
6.10	IC50	800	nM	CHEMBL5408363
5.96	IC50	1100	nM	CHEMBL5401653
5.85	IC50	1400	nM	CHEMBL5434369
5.82	IC50	1500	nM	CHEMBL5406354
5.82	IC50	1500	nM	CHEMBL5426771
5.77	IC50	1700	nM	CHEMBL5435052
5.62	IC50	2400	nM	CHEMBL5406012
5.57	IC50	2700	nM	CHEMBL5416566
5.55	IC50	2800	nM	CHEMBL5399509
5.51	IC50	3100	nM	CHEMBL5412456
5.51	IC50	3100	nM	CHEMBL5405730
5.47	IC50	3400	nM	CHEMBL5430627
5.42	IC50	3800	nM	CHEMBL5411788
5.38	IC50	4200	nM	CHEMBL5419966
5.32	IC50	4800	nM	CHEMBL5407256
5.30	IC50	5000	nM	CHEMBL5433799
5.29	IC50	5100	nM	CHEMBL5413007
5.24	IC50	5800	nM	CHEMBL5438606
5.09	IC50	8200	nM	CHEMBL5421112
5.06	IC50	8700	nM	CHEMBL5393727

PubChem BioAssay actives

30 with measured affinity, of 46 total; 29 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
N-[(1S)-1-[3,4-dichloro-5-(trifluoromethyl)phenyl]-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.2000	uM
N-[(1S)-1-[3-chloro-5-(trifluoromethyl)phenyl]-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.2000	uM
N-[(1S)-1-[4-chloro-3-(trifluoromethyl)phenyl]-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.3000	uM
N-[(1S)-2-(dimethylamino)-1-[3-methyl-5-(trifluoromethyl)phenyl]-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.4000	uM
N-[(1S)-2-(dimethylamino)-1-[4-fluoro-3-(trifluoromethyl)phenyl]-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.4000	uM
N-[(1S)-1-(3,4-dichlorophenyl)-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.4000	uM
N-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.5000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-(3,5-dimethyl-1H-pyrazol-4-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.6000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-(2-methylpyrazol-3-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.7000	uM
N-[(1S)-2-(dimethylamino)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.7000	uM
N-[(1S)-2-(dimethylamino)-1-[4-methyl-3-(trifluoromethyl)phenyl]-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.8000	uM
N-[2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-[2-(oxetan-3-yl)pyrazol-3-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.1000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.4000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-(2H-tetrazol-5-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.5000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-4-[4-(trifluoromethyl)phenyl]pyridazine-3-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.5000	uM
3-N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-1-N-methylsulfonyl-4-[4-(trifluoromethyl)phenyl]benzene-1,3-dicarboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.7000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-(1-methyltetrazol-5-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	2.4000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	2.7000	uM
N-[2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-(5-methyl-1H-pyrazol-4-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	2.8000	uM
N-[(1S)-2-[(1S,5R)-6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexan-3-yl]-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	3.1000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-[3-(2,2,2-trifluoroethyl)azetidin-1-yl]phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	3.4000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-3-[4-(trifluoromethyl)phenyl]pyridine-2-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	3.8000	uM
N-[(1S)-1-(3-cyclopropylphenyl)-2-(dimethylamino)-2-oxoethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	4.2000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-3-[4-(trifluoromethyl)phenyl]pyridine-4-carboxamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	4.8000	uM
N-[2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	5.0000	uM
N-[2-oxo-2-pyrrolidin-1-yl-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	5.1000	uM
N-[(1S)-1-(4-chlorophenyl)-2-(dimethylamino)-2-oxoethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	5.8000	uM
N-[2-(azetidin-1-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	8.2000	uM
N-[2-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036563: Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	8.7000	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, affects binding	2
sodium arsenate	decreases expression, increases abundance	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
CGP 52608	affects binding, increases reaction	1
clothianidin	increases expression	1
abrine	increases expression	1
NSC668394	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	affects methylation, increases abundance	1
Arsenic	increases abundance, decreases expression	1
Benzo(a)pyrene	increases expression	1
Ivermectin	decreases expression	1
Ozone	affects methylation, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Thiram	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5390951	Binding	Inhibition of NKG2D (unknown origin)/ULBP6 (unknown origin) protein-protein interaction by cell-based TR-FRET assay	Development of small molecule inhibitors of natural killer group 2D receptor (NKG2D). — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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