KLRK1

Summary

KLRK1 (killer cell lectin like receptor K1, HGNC:18788) is a protein-coding gene on chromosome 12p13.2, encoding NKG2-D type II integral membrane protein (P26718). Functions as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells.

Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. The NKG2 gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed in NK cells. This gene encodes a member of the NKG2 family. The encoded transmembrane protein is characterized by a type II membrane orientation (has an extracellular C terminus) and the presence of a C-type lectin domain. It binds to a diverse family of ligands that include MHC class I chain-related A and B proteins and UL-16 binding proteins, where ligand-receptor interactions can result in the activation of NK and T cells. The surface expression of these ligands is important for the recognition of stressed cells by the immune system, and thus this protein and its ligands are therapeutic targets for the treatment of immune diseases and cancers. Read-through transcription exists between this gene and the upstream KLRC4 (killer cell lectin-like receptor subfamily C, member 4) family member in the same cluster.

Source: NCBI Gene 22914 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 2 total
• Druggable target: yes
• MANE Select transcript: NM_007360

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18788
Approved symbol	KLRK1
Name	killer cell lectin like receptor K1
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	NKG2D, KLR, NKG2-D, CD314
Ensembl gene	ENSG00000213809
Ensembl biotype	protein_coding
OMIM	611817
Entrez	22914

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000240618, ENST00000396451, ENST00000540267, ENST00000540818, ENST00000544449

RefSeq mRNA: 2 — MANE Select: NM_007360 NM_001199805, NM_007360

Canonical transcript exons

ENST00000240618 — 8 exons

Exon	Start	End
ENSE00002316009	10389943	10390041
ENSE00003492587	10378132	10378235
ENSE00003493458	10372353	10373231
ENSE00003505795	10378554	10378705
ENSE00003509697	10379700	10379792
ENSE00003640305	10388771	10388875
ENSE00003684754	10386903	10387010
ENSE00003691748	10379447	10379482

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 98.87.

FANTOM5 (CAGE): breadth broad, TPM avg 6.8736 / max 1059.7507, expressed in 207 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129517	5.5708	191
129518	0.9886	73
129516	0.2433	3
206587	0.0494	25
206588	0.0216	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.87	gold quality
spleen	UBERON:0002106	93.09	gold quality
lymph node	UBERON:0000029	93.00	gold quality
blood	UBERON:0000178	88.87	gold quality
vermiform appendix	UBERON:0001154	87.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.15	gold quality
gall bladder	UBERON:0002110	81.80	gold quality
small intestine	UBERON:0002108	80.75	gold quality
upper lobe of left lung	UBERON:0008952	80.11	gold quality
mucosa of transverse colon	UBERON:0004991	79.93	gold quality
bone marrow	UBERON:0002371	79.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.48	gold quality
endometrium	UBERON:0001295	77.74	gold quality
duodenum	UBERON:0002114	77.38	gold quality
lung	UBERON:0002048	77.32	gold quality
omental fat pad	UBERON:0010414	77.26	gold quality
right lung	UBERON:0002167	76.92	gold quality
right lobe of liver	UBERON:0001114	76.45	gold quality
rectum	UBERON:0001052	76.29	gold quality
leukocyte	CL:0000738	76.10	gold quality
right uterine tube	UBERON:0001302	75.99	gold quality
tonsil	UBERON:0002372	74.88	gold quality
right coronary artery	UBERON:0001625	74.03	gold quality
monocyte	CL:0000576	74.00	gold quality
body of stomach	UBERON:0001161	73.47	gold quality
bone marrow cell	CL:0002092	73.43	gold quality
adipose tissue	UBERON:0001013	73.43	gold quality
liver	UBERON:0002107	72.33	gold quality
smooth muscle tissue	UBERON:0001135	71.53	gold quality
stomach	UBERON:0000945	71.23	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	898.66
E-CURD-46	yes	320.43
E-MTAB-9067	yes	247.30
E-HCAD-1	yes	141.06
E-HCAD-4	yes	115.51
E-MTAB-6701	yes	106.45
E-MTAB-8142	yes	66.28
E-MTAB-10553	yes	48.25
E-CURD-122	yes	47.23
E-HCAD-8	yes	40.97
E-CURD-88	yes	40.82
E-MTAB-9467	yes	38.90
E-MTAB-8410	yes	33.15
E-HCAD-10	yes	31.32
E-MTAB-6678	yes	30.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATM, HMBOX1, KAT7, STAT3

miRNA regulators (miRDB)

40 targeting KLRK1, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-6516-5P	98.42	70.19	1551

Literature-anchored findings (GeneRIF, showing 40)

• NKG2D is the receptor for UL16-binding proteins expressed on primary natural killer cells. (PMID:11777960)
• binding of MICA and MICB induces endocytosis and downregulation of NKG2D, and in turn severe impairment of the responsiveness of tumour-antigen-specific effector T cells (PMID:12384702)
• Selective intracellular retention of virally induced NKG2D ligands by the human cytomegalovirus UL16 glycoprotein. (PMID:12594848)
• Expression of this receptor, inhibited by TGF-beta1, affects NK-mediated killing of dendritic cells (PMID:12646700)
• Results suggest that ligands appear to utilize different strategies to interact with structurally conserved elements of the consensus NKG2D binding site. (PMID:12679019)
• ULBP4 is a novel ligand for NKG2D (ULBP4) (PMID:12732206)
• In the thymus NKG2D may be a signal allowing newly matured CD8+ T cells to emigrate to the periphery; in thymomas there is a decreased percentage of NKG2D-positive thymocytes, which express a less mature phenotype than in normal thymus. (PMID:12902493)
• NKG2D signalling enhances innate and adaptive immune responses (review) (PMID:14523385)
• Cell surface organization of stress-inducible proteins ULBP and MICA that stimulate human NK cells and T cells via NKG2D. (PMID:15051759)
• NKG2D structure, ligands, function, and tissue distribution (review) (PMID:15065764)
• NKG2D triggering accounts for the majority of major histocompatibility complex (MHC)-unrestricted cytotoxicity of activated and expanded CD8+ T cells, likely through DAP10-mediated signaling. (PMID:15070686)
• incubation of NK cells and LAK cells with TGF-beta1 resulted in dramatic reduction of surface NKG2D expression associated with impaired NK cytotoxicity (PMID:15187109)
• natural cytotoxicity receptor (NCR) and NK receptor member D of the lectin-like receptor family (NKG2D) were the key NK activating receptors for bone marrow-derived myeloma cell recognition (PMID:15328155)
• analysis of functional sites in NKG2D-MICA interaction in mouse and human (PMID:15652646)
• NKG2D, NKp30, NKp44, and NKp46 acitvation affected by ligand-negative phenotype in bone marrow-derived progenitor cells, acquisition of cell-surface ligands during myeloid differentiation, defective expression of ligands on malignant transformation (PMID:15657183)
• NKG2D engagement by ligand or monoclonal antibody is not sufficient to costimulate naive or effector CD8+ T cell responses in conventional T cell populations. (PMID:15699119)
• Polymorphic MICA in HLA Class I interacts with non-polymorphic NKG2d receptor on NK cells. (PMID:15699512)
• NKG2D serves as a costimulatory receptor for TCR induced Ca2+ mobilization and proliferation in naive CD8+ T cells (PMID:15814668)
• tumor exosome-phenotype showed positive expression of several NKG2D ligands, important in driving the reduction in the proportion of NKG2D-positive effector cells (PMID:15885603)
• Remarkable similarities in NKG2D function in natural killer (NK) and Vgamma9 Vdelta2 T cells may open new perspectives for Vgamma9 Vdelta2 T cell-based immunotherapy (PMID:16081780)
• expression increased by Il-15 in NK cells (PMID:16136475)
• Freshly isolated natural killer (NK) cells lyse porcine endothelial cells exclusively in an NKG2D-dependent fashion; lysis of porcine endothelial cells mediated by activated human NK cells depends on both NKp44 and NKG2D (PMID:16210654)
• acute myeloid leukemia cells expressed the NKG2D receptor and its signal-transducing adaptator DAP 10, which were functional as confirmed by redirected lysis experiments (PMID:16239914)
• NKG2D/MHC-I-related stress-inducible molecule A and/or NKG2D/UL-16 binding protein 3 engagement is responsible for the delivery of a lethal hit (PMID:16272287)
• The role of TLR3 in the immunobiology of muscle is reported; its implications for the understanding of the pathogenesis of inflammatory myopathies or therapeutic interventions are included. (PMID:16293707)
• soluble MHC class I chain-related molecules in pregnancy serum were able to interact with NKG2D and down-regulate the receptor on PBMC from healthy donors, with the consequent inhibition of the NKG2D-dependent cytotoxic response (PMID:16517727)
• Engagement of MIC by NKG2D promotes spontaneous HAM/TSP T cell proliferation and, apparently, CTL activities against HTLV-1-infected T cells. (PMID:16568261)
• down-regulation of NKG2D by soluble ULBP provides a potential mechanism by which gastric cancer cells escape NKG2D-mediated attack by the immune cells (PMID:16630603)
• defect in cytotoxic effector function is associated with a reduced surface expression of activating NK receptors (NKp30, NKp46, and NKG2D) on CD56(dim) NK cells compared with uninfected newborns. (PMID:16690951)
• Observations with normal peripheral blood NKG2D(+)CD8(+) T cells demonstrated unrecognized NKG2D-mediated immune functions, whereby FasL release promotes tumor cell death and NKG2D costimulation prolongs T cell survival. (PMID:16732291)
• NKG2D and MICB in the cytotoxic NK cell immune synapse have roles in NK cell cytotoxic function (PMID:16849432)
• NKG2D mediates xenogeneic human anti-pig endothelial cell NK cell cytotoxicity by binding to the surface of porcine endothelial cells and to porcine UL16-binding protein 1 (pULBP1). (PMID:16887974)
• ULBP1 is a human ligand of the NKG2D receptor (PMID:16901903)
• Recent insights into the regulation of NKG2D function, the control over NKG2D ligand expression and the role of NKG2D in tumor immunity. (PMID:16914326)
• To be fully sensitive to triggering, optimal natural killer (NK) cell reactivity requires a threshold of NKG2D expression above that of receptor levels in resting NK cells. (PMID:17043026)
• Functions as a prototypic costimulatory receptor in a subset of human cytomegalovirus-specific CD4+ T lymphocytes. (PMID:17109473)
• Significant elevated levels of NKG2D mRNA could be further detected in urine sediment prior to acute rejection, suggesting this receptor as a new candidate marker for the diagnosis of acute and chronic allograft rejection. (PMID:17173658)
• reveal distinct modes of activation of the genes for the MHC class I-related chain ligands of NKG2D and provide a molecular framework for analyses of gene regulation under different cellular insult conditions (PMID:17202358)
• NKG2D expression may have a role in immune evasion by tumors in gastric cancer (PMID:17255258)
• NKG2D-NKG2D ligand interactions can potentially contribute to cytotoxic responses mediated by activated immune effector cells in the inflamed central nervous system, as observed in multiple sclerosis. (PMID:17267578)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klrk1	ENSMUSG00000030149
rattus_norvegicus	Klrk1	ENSRNOG00000061739
caenorhabditis_elegans		WBGENE00009156

Paralogs (23): CLEC2D (ENSG00000069493), CD69 (ENSG00000110848), 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), CLEC2L (ENSG00000236279), CLEC12B (ENSG00000256660), KLRF2 (ENSG00000256797), CLEC5A (ENSG00000258227)

Protein

Protein identifiers

NKG2-D type II integral membrane protein — P26718 (reviewed: P26718)

Alternative names: Killer cell lectin-like receptor subfamily K member 1, NK cell receptor D, NKG2-D-activating NK receptor

All UniProt accessions (2): P26718, Q8WZ67

UniProt curated annotations — full annotation on UniProt →

Function. Functions as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF. Participates in NK cell-mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4.

Subunit / interactions. Homodimer; disulfide-linked. Heterohexamer composed of two subunits of KLRK1 and four subunits of HCST/DAP10. Interacts (via transmembrane domain) with HCST/DAP10 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface and induces NK cell-mediated cytotoxicity. Does not interact with TYROBP. Interacts with CEACAM1; recruits PTPN6 that dephosphorylates VAV1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in natural killer (NK) cells, CD8(+) alpha-beta and gamma-delta T-cells. Expressed on essentially all CD56+CD3- NK cells from freshly isolated PBMC. Expressed in interferon-producing killer dendritic cells (IKDCs).

Induction. Up-regulated by interleukin IL15 in primary NK cells.

Miscellaneous. Is not capable of signal transduction by itself, but operates through the adapter protein HCST. Some families of ligands for human and mouse KLRK1 receptors have been characterized being very similar in structure and highly likely to be orthologs. In humans, an additional distinct subfamily of ligands (MICA and MICB) differs structurally, having an extra MHC alpha 3-like domain.

Isoforms (1)

UniProt ID	Names	Canonical?
P26718-1	1	yes

RefSeq proteins (2): NP_001186734, NP_031386* (*=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
IPR042169	NKG2D	Family

Pfam: PF00059

UniProt features (33 total): strand 11, disulfide bond 4, turn 4, glycosylation site 3, topological domain 2, sequence variant 2, helix 2, chain 1, mutagenesis site 1, sequence conflict 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
8EA7	X-RAY DIFFRACTION	1.28
8SE6	X-RAY DIFFRACTION	1.36
8SE5	X-RAY DIFFRACTION	1.43
8EAB	X-RAY DIFFRACTION	1.44
8EAA	X-RAY DIFFRACTION	1.57
8EA9	X-RAY DIFFRACTION	1.58
8EA5	X-RAY DIFFRACTION	1.63
8EA6	X-RAY DIFFRACTION	1.73
8EA8	X-RAY DIFFRACTION	1.77
4PDC	X-RAY DIFFRACTION	1.99
7FI9	X-RAY DIFFRACTION	2.16
4S0U	X-RAY DIFFRACTION	2.35
7FI5	X-RAY DIFFRACTION	2.39
1MPU	X-RAY DIFFRACTION	2.5
1KCG	X-RAY DIFFRACTION	2.6
1HYR	X-RAY DIFFRACTION	2.7
7FI7	X-RAY DIFFRACTION	2.78
7FI8	X-RAY DIFFRACTION	2.8
8TM2	X-RAY DIFFRACTION	2.85
7FI6	X-RAY DIFFRACTION	2.9
9DH2	X-RAY DIFFRACTION	2.98
8TM0	X-RAY DIFFRACTION	3.83

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26718-F1	78.49	0.60

Antibody-complex structures (SAbDab): 1 — 9DH2

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): 127–211, 189–203, 96–105, 99–110

Glycosylation sites (3): 131, 163, 202

Mutagenesis-validated functional residues (1):

Position	Phenotype
66	inhibits association with the hcst signaling dimer.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2172127	DAP12 interactions
R-HSA-2424491	DAP12 signaling

MSigDB gene sets: 374 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INNATE_IMMUNE_SYSTEM, MODULE_169, GOBP_CELL_CHEMOTAXIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, FISCHER_G1_S_CELL_CYCLE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_45, MODULE_64, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_LYMPHOCYTE_COSTIMULATION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOCC_CELL_SURFACE

GO Biological Process (19): stimulatory C-type lectin receptor signaling pathway (GO:0002223), adaptive immune response (GO:0002250), nitric oxide biosynthetic process (GO:0006809), signal transduction (GO:0007165), natural killer cell activation (GO:0030101), cell differentiation (GO:0030154), T cell costimulation (GO:0031295), positive regulation of type II interferon production (GO:0032729), negative regulation of GTPase activity (GO:0034260), natural killer cell mediated cytotoxicity (GO:0042267), positive regulation of nitric oxide biosynthetic process (GO:0045429), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), defense response to Gram-positive bacterium (GO:0050830), cellular response to lipopolysaccharide (GO:0071222), negative regulation of natural killer cell chemotaxis (GO:2000502), immune system process (GO:0002376), innate immune response (GO:0045087), positive regulation of multicellular organismal process (GO:0051240), defense response to other organism (GO:0098542)

GO Molecular Function (6): carbohydrate binding (GO:0030246), MHC class Ib receptor activity (GO:0032394), signaling receptor activity (GO:0038023), MHC class I protein binding (GO:0042288), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Adaptive Immune System	1
Innate Immune System	1
DAP12 interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	2
binding	2
cellular anatomical structure	2
innate immune response activating cell surface receptor signaling pathway	1
cellular response to lectin	1
biosynthetic process	1
nitric oxide metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
lymphocyte activation	1
cellular developmental process	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
GTPase activity	1
regulation of GTPase activity	1
negative regulation of biological process	1
negative regulation of hydrolase activity	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
nitric oxide biosynthetic process	1
positive regulation of biosynthetic process	1
regulation of nitric oxide biosynthetic process	1
positive regulation of leukocyte mediated cytotoxicity	1
positive regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
defense response to bacterium	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
natural killer cell chemotaxis	1
negative regulation of lymphocyte chemotaxis	1
regulation of natural killer cell chemotaxis	1

Protein interactions and networks

STRING

2234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLRK1	ULBP1	Q9BZM6	999
KLRK1	MICB	P79525	999
KLRK1	ULBP3	Q9BZM4	999
KLRK1	ULBP2	Q9BZM5	999
KLRK1	HCST	Q9UBK5	999
KLRK1	RAET1E	Q8TD07	998
KLRK1	TYROBP	O43914	996
KLRK1	HLA-E	P13747	996
KLRK1	MICA	P79506	996
KLRK1	RAET1G	Q6H3X3	995
KLRK1	NCR1	O76036	983
KLRK1	NECTIN2	Q92692	980
KLRK1	NCR3	O14931	970
KLRK1	NCR2	O95944	963
KLRK1	RAET1L	Q5VY80	960

IntAct

46 interactions, top by confidence:

A	B	Type	Score
ULBP3	KLRK1	psi-mi:“MI:0407”(direct interaction)	0.800
KLRK1	ULBP3	psi-mi:“MI:0407”(direct interaction)	0.800
ULBP3	KLRK1	psi-mi:“MI:0915”(physical association)	0.800
RAET1E	KLRK1	psi-mi:“MI:0407”(direct interaction)	0.710
KLRK1	RAET1E	psi-mi:“MI:0915”(physical association)	0.710
RAET1G	KLRK1	psi-mi:“MI:0915”(physical association)	0.700
KLRK1	RAET1G	psi-mi:“MI:0915”(physical association)	0.700
KLRK1	RAET1L	psi-mi:“MI:0407”(direct interaction)	0.680
KLRK1	RAET1L	psi-mi:“MI:0915”(physical association)	0.680
KLRK1	MICA	psi-mi:“MI:0407”(direct interaction)	0.620
KLRK1	ULBP2	psi-mi:“MI:0407”(direct interaction)	0.610
KLRK1	ULBP2	psi-mi:“MI:0915”(physical association)	0.610
ULBP2	KLRK1	psi-mi:“MI:0915”(physical association)	0.610
KLRK1	PDE4C	psi-mi:“MI:0915”(physical association)	0.560
KLRK1	KLRK1	psi-mi:“MI:0407”(direct interaction)	0.440
KLRK1	ULBP1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (24): KLRK1 (Two-hybrid), RAE1 (Reconstituted Complex), DUPD1 (Affinity Capture-MS), REEP4 (Affinity Capture-MS), SEC11A (Affinity Capture-MS), VPS52 (Affinity Capture-MS), ABCB8 (Affinity Capture-MS), KLRK1 (Affinity Capture-Western), PRKDC (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), ACSL1 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), PIGB (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), ATP5G1 (Affinity Capture-MS)

ESM2 similar proteins: A4KWA5, A4KWA6, A4KWA8, B2KG20, D4AD02, O54709, O70215, P26717, P26718, P27471, P27811, P27814, P37217, P61252, Q07108, Q07444, Q0H8B9, Q149M0, Q504P2, Q5DT36, Q5DT37, Q5DT39, Q5M9I1, Q5RFR2, Q60652, Q60654, Q68D85, Q6QLQ4, Q6UXN8, Q80XD9, Q80ZC8, Q8C1T8, Q8MI05, Q8MJH1, Q8VBX4, Q8VI21, Q8WXI8, Q91V08, Q925N7, Q95MI4

Diamond homologs: B2KG20, B4XSZ4, D4AD02, O54709, O70215, P0DL30, P26718, P61252, Q149M0, Q2HXU8, Q2NL33, Q38HS3, Q49BZ4, Q4TU93, Q5DT36, Q5DT39, Q64449, Q67EQ0, Q6QLQ4, Q6UXN8, Q80ZC8, Q8BRU4, Q8MJH1, Q9MZ37, Q9MZJ7, Q9UBG0, A3FM55, B4XSY4, B4XSZ2, B4XSZ3, B4XSZ5, B4XSZ6, B4XSZ7, B4XSZ9, O35778, O54707, O70156, P07897, P08290, P10716

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ULBP2	up-regulates	KLRK1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 10 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of T cell mediated cytotoxicity	6	306.4×	7e-14
natural killer cell mediated cytotoxicity	7	302.5×	3e-16
immune response	7	33.0×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1226 predictions. Top by Δscore:

Variant	Effect	Δscore
12:10378130:A:AC	donor_gain	1.0000
12:10378131:C:CC	donor_gain	1.0000
12:10378131:CAGG:C	donor_gain	1.0000
12:10378702:CTTT:C	acceptor_gain	1.0000
12:10379698:A:AC	donor_gain	1.0000
12:10379699:C:CC	donor_gain	1.0000
12:10379791:TG:T	acceptor_gain	1.0000
12:10379793:C:CC	acceptor_gain	1.0000
12:10387006:CATCT:C	acceptor_gain	1.0000
12:10387011:C:CC	acceptor_gain	1.0000
12:10378125:GACT:G	donor_loss	0.9900
12:10378126:ACTTA:A	donor_loss	0.9900
12:10378127:CTTAC:C	donor_loss	0.9900
12:10378128:T:TC	donor_loss	0.9900
12:10378128:TTAC:T	donor_loss	0.9900
12:10378129:T:TC	donor_loss	0.9900
12:10378130:A:AT	donor_loss	0.9900
12:10378130:AC:A	donor_loss	0.9900
12:10378131:C:T	donor_loss	0.9900
12:10378131:CA:C	donor_gain	0.9900
12:10378131:CAG:C	donor_gain	0.9900
12:10378131:CAGGT:C	donor_gain	0.9900
12:10378234:TC:T	acceptor_gain	0.9900
12:10378235:CC:C	acceptor_gain	0.9900
12:10378236:C:A	acceptor_loss	0.9900
12:10378236:C:CC	acceptor_gain	0.9900
12:10378237:T:A	acceptor_loss	0.9900
12:10378240:T:C	acceptor_gain	0.9900
12:10378551:AAC:A	donor_gain	0.9900
12:10378552:A:C	donor_gain	0.9900

AlphaMissense

1451 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:10378161:C:A	W168C	0.995
12:10378161:C:G	W168C	0.995
12:10378203:C:A	W154C	0.990
12:10378203:C:G	W154C	0.990
12:10378674:C:A	W103C	0.987
12:10378674:C:G	W103C	0.987
12:10378614:G:C	S123R	0.986
12:10378614:G:T	S123R	0.986
12:10378616:T:G	S123R	0.986
12:10378623:C:A	W120C	0.985
12:10378623:C:G	W120C	0.985
12:10378163:A:G	W168R	0.984
12:10378163:A:T	W168R	0.984
12:10373133:C:G	C211S	0.979
12:10373134:A:T	C211S	0.979
12:10373199:C:G	C189S	0.979
12:10373200:A:T	C189S	0.979
12:10378603:C:G	C127S	0.979
12:10378604:A:T	C127S	0.979
12:10378652:A:C	Y111D	0.977
12:10373198:A:C	C189W	0.976
12:10373132:G:C	C211W	0.975
12:10378602:A:C	C127W	0.974
12:10378205:A:G	W154R	0.970
12:10378205:A:T	W154R	0.970
12:10373157:C:G	C203S	0.968
12:10373158:A:T	C203S	0.968
12:10378195:A:G	L157P	0.968
12:10378603:C:T	C127Y	0.964
12:10373133:C:T	C211Y	0.962

dbSNP variants (sampled 300 via entrez): RS1000147161 (12:10381503 G>C), RS1000194817 (12:10375794 T>C), RS1000446964 (12:10389733 A>G), RS1000455309 (12:10379061 G>A,T), RS1000657951 (12:10385579 T>C,G), RS1000706439 (12:10372418 C>A,T), RS1000751081 (12:10375444 T>C), RS1000928506 (12:10385953 A>T), RS1000974249 (12:10389356 C>T), RS1001096292 (12:10382835 A>G), RS1001181698 (12:10386117 T>C), RS1001210881 (12:10375173 G>A), RS1001337093 (12:10389882 T>C), RS1001419706 (12:10372622 C>G,T), RS1001431554 (12:10389569 G>A)

Disease associations

OMIM: gene MIM:611817 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_534	Obesity-related traits	6.000000e-06
GCST004346_53	Psoriasis	4.000000e-09
GCST006104_1	Interleukin-1-receptor antagonist levels	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004887	maximal oxygen uptake measurement
EFO:0004754	interleukin 1 receptor antagonist measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5483005 (PROTEIN COMPLEX), CHEMBL5483006 (PROTEIN COMPLEX)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1049174	KLRK1		0.00	0

ChEMBL bioactivities

61 potent at pChembl≥5 of 63 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.00	IC50	100	nM	CHEMBL5405635
7.00	IC50	100	nM	CHEMBL5438591
7.00	IC50	100	nM	CHEMBL5400078
7.00	IC50	100	nM	CHEMBL5400409
6.70	IC50	200	nM	CHEMBL5420013
6.70	IC50	200	nM	CHEMBL5418204
6.70	IC50	200	nM	CHEMBL5397883
6.70	IC50	200	nM	CHEMBL5406023
6.70	IC50	200	nM	CHEMBL5438591
6.70	IC50	200	nM	CHEMBL5400409
6.52	IC50	300	nM	CHEMBL5421826
6.52	IC50	300	nM	CHEMBL5408363
6.52	IC50	300	nM	CHEMBL5400078
6.40	IC50	400	nM	CHEMBL5428731
6.40	IC50	400	nM	CHEMBL5434369
6.40	IC50	400	nM	CHEMBL5426771
6.40	IC50	400	nM	CHEMBL5405635
6.40	IC50	400	nM	CHEMBL5397883
6.40	IC50	400	nM	CHEMBL5406023
6.30	IC50	500	nM	CHEMBL5401653
6.30	IC50	500	nM	CHEMBL5406354
6.30	IC50	500	nM	CHEMBL5404943
6.30	IC50	500	nM	CHEMBL5420013
6.22	IC50	600	nM	CHEMBL5428731
6.16	IC50	700	nM	CHEMBL5435052
6.16	IC50	700	nM	CHEMBL5421826
6.16	IC50	700	nM	CHEMBL5418204
6.10	IC50	800	nM	CHEMBL5408363
6.05	IC50	900	nM	CHEMBL5399509
6.05	IC50	900	nM	CHEMBL5406012
6.00	IC50	1000	nM	CHEMBL5411788
5.96	IC50	1100	nM	CHEMBL5412456
5.96	IC50	1100	nM	CHEMBL5401653
5.92	IC50	1200	nM	CHEMBL5416566
5.85	IC50	1400	nM	CHEMBL5434369
5.82	IC50	1500	nM	CHEMBL5406354
5.82	IC50	1500	nM	CHEMBL5426771
5.80	IC50	1600	nM	CHEMBL5405730
5.80	IC50	1600	nM	CHEMBL5407256
5.80	IC50	1600	nM	CHEMBL5430627
5.77	IC50	1700	nM	CHEMBL5435052
5.75	IC50	1800	nM	CHEMBL5419966
5.66	IC50	2200	nM	CHEMBL5433799
5.62	IC50	2400	nM	CHEMBL5406012
5.60	IC50	2500	nM	CHEMBL5413007
5.57	IC50	2700	nM	CHEMBL5416566
5.55	IC50	2800	nM	CHEMBL5399509
5.51	IC50	3100	nM	CHEMBL5412456
5.51	IC50	3100	nM	CHEMBL5405730
5.48	IC50	3300	nM	CHEMBL5438606

PubChem BioAssay actives

122 with measured affinity, of 184 total; 30 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)-2-(dimethylamino)-1-[3-methyl-5-(trifluoromethyl)phenyl]-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.1000	uM
N-[(1S)-1-[3,4-dichloro-5-(trifluoromethyl)phenyl]-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.1000	uM
N-[(1S)-1-[4-chloro-3-(trifluoromethyl)phenyl]-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.1000	uM
N-[(1S)-1-[3-chloro-5-(trifluoromethyl)phenyl]-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.1000	uM
N-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.2000	uM
N-[(1S)-2-(dimethylamino)-1-[4-fluoro-3-(trifluoromethyl)phenyl]-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.2000	uM
N-[(1S)-1-(3,4-dichlorophenyl)-2-(dimethylamino)-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.2000	uM
N-[(1S)-2-(dimethylamino)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.2000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-(2-methylpyrazol-3-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.3000	uM
N-[(1S)-2-(dimethylamino)-1-[4-methyl-3-(trifluoromethyl)phenyl]-2-oxoethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.3000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-4-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.4000	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	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.4000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-4-[4-(trifluoromethyl)phenyl]pyridazine-3-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.4000	uM
N-[2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-[2-(oxetan-3-yl)pyrazol-3-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.5000	uM
N-[(1S)-1-[4-chloro-3-(trifluoromethyl)phenyl]-2-(dimethylamino)-2-oxoethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (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-(2H-tetrazol-5-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.5000	uM
3-N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-1-N-methylsulfonyl-4-[4-(trifluoromethyl)phenyl]benzene-1,3-dicarboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.7000	uM
N-[2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-(5-methyl-1H-pyrazol-4-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.9000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-5-(1-methyltetrazol-5-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	0.9000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-3-[4-(trifluoromethyl)phenyl]pyridine-2-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.0000	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	2036562: Inhibition of NKG2D (unknown origin)/MICA (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]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.2000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-[3-(2,2,2-trifluoroethyl)azetidin-1-yl]phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.6000	uM
N-[(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-3-[4-(trifluoromethyl)phenyl]pyridine-4-carboxamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.6000	uM
N-[(1S)-1-(3-cyclopropylphenyl)-2-(dimethylamino)-2-oxoethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	1.8000	uM
N-[2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	2.2000	uM
N-[2-oxo-2-pyrrolidin-1-yl-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	2.5000	uM
N-[(1S)-1-(4-chlorophenyl)-2-(dimethylamino)-2-oxoethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	3.3000	uM
N-[2-(azetidin-1-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	3.4000	uM
N-[2-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide	2036562: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay	ic50	4.0000	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cadmium sulfate	decreases expression	2
Resveratrol	increases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression, increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
mirdametinib	increases expression, decreases reaction	1
Bortezomib	decreases expression	1
Arsenic Trioxide	increases response to substance	1
Arsenic	affects expression	1
Benzo(a)pyrene	increases methylation	1
Toxic Actions	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Mycophenolic Acid	decreases expression	1
Nickel	increases expression	1
Tamoxifen	affects cotreatment, decreases expression	1
Dronabinol	increases expression	1
Asbestos, Serpentine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Raloxifene Hydrochloride	affects cotreatment, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5390950	Binding	Inhibition of NKG2D (unknown origin)/MICA (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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8NW	Ubigene HCT 116 KLRK1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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