MICA

Summary

MICA (MHC class I polypeptide-related sequence A, HGNC:7090) is a protein-coding gene on chromosome 6p21.33, encoding MHC class I polypeptide-related sequence A (Q29983). Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8 alphabeta T-cells.

This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 100507436 — RefSeq curated summary.

At a glance

• GWAS associations: 108
• Clinical variants (ClinVar): 67 total
• Druggable target: yes
• MANE Select transcript: NM_001177519

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7090
Approved symbol	MICA
Name	MHC class I polypeptide-related sequence A
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	PERB11.1
Ensembl gene	ENSG00000204520
Ensembl biotype	protein_coding
OMIM	600169
Entrez	100507436

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000421350, ENST00000449934, ENST00000616296, ENST00000667609, ENST00000673647, ENST00000673996, ENST00000674069, ENST00000674131, ENST00000892120, ENST00000934208

RefSeq mRNA: 4 — MANE Select: NM_001177519 NM_001177519, NM_001289152, NM_001289153, NM_001289154

CCDS: CCDS56412, CCDS75421, CCDS93880

Canonical transcript exons

ENST00000418465 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.5712 / max 159.3539, expressed in 1775 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66883	19.3447	1654
66882	3.2266	1388

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	94.74	gold quality
left ovary	UBERON:0002119	94.30	gold quality
popliteal artery	UBERON:0002250	94.17	gold quality
tibial artery	UBERON:0007610	94.15	gold quality
body of uterus	UBERON:0009853	94.08	gold quality
thoracic aorta	UBERON:0001515	94.02	gold quality
ascending aorta	UBERON:0001496	94.01	gold quality
right uterine tube	UBERON:0001302	93.87	gold quality
stromal cell of endometrium	CL:0002255	93.82	gold quality
left coronary artery	UBERON:0001626	93.77	gold quality
ovary	UBERON:0000992	93.57	gold quality
right ovary	UBERON:0002118	93.48	gold quality
myometrium	UBERON:0001296	93.37	gold quality
endocervix	UBERON:0000458	93.31	gold quality
mucosa of transverse colon	UBERON:0004991	93.31	gold quality
left adrenal gland cortex	UBERON:0035825	93.26	gold quality
vagina	UBERON:0000996	93.07	gold quality
ectocervix	UBERON:0012249	93.07	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.03	gold quality
right adrenal gland	UBERON:0001233	93.00	gold quality
apex of heart	UBERON:0002098	92.98	gold quality
upper lobe of left lung	UBERON:0008952	92.95	gold quality
left adrenal gland	UBERON:0001234	92.93	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.87	gold quality
lower esophagus	UBERON:0013473	92.85	gold quality
right adrenal gland cortex	UBERON:0035827	92.81	gold quality
metanephros cortex	UBERON:0010533	92.76	gold quality
uterine cervix	UBERON:0000002	92.75	gold quality
tibial nerve	UBERON:0001323	92.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA2, HDAC1, HIF1A, HSF1, NFKB1, NFKB, NFKBID, PITX2, RELA, SP1, STAT3

miRNA regulators (miRDB)

35 targeting MICA, 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-4673	100.00	66.64	1490
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-4763-3P	99.10	67.83	2649

Literature-anchored findings (GeneRIF, showing 40)

• 11 new alleles are described, some associated with particular HLA-B alleles (PMID:11841487)
• We observed a high degree of linkage disequilibrium between certain alleles of MICA and of HLA-B in the South American Indian populations (PMID:11862390)
• MICA genetic polymorphisms in African-Americans (PMID:11862403)
• From pairwise associations in the random panel and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well-known Caucasoid (PMID:11881819)
• MICA is a target for complement-dependent cytotoxicity with mouse monoclonal antibodies and human alloantibodies. (PMID:11916168)
• analysis of MICA microsatellite polymorphisms in genetic susceptibility to juvenile idiopathic arthritis (PMID:11975986)
• Contribution of MIC-A polymorphism to type 1 diabetes mellitus in Basques (PMID:12021133)
• MHC class I chain-related gene a alleles distinguish malnutrition-modulated diabetes, insulin-dependent diabetes, and non-insulin- dependent diabetes mellitus patients from eastern India. (PMID:12021138)
• MICA is associated with susceptibility to psoriatic arthritis. (PMID:12022360)
• A strong linkage disequilibrium was observed between the MICA*A6 and HLA-B51 in both the patients with Behcet’s disease (PMID:12068141)
• Celiac disease (CD) is characterized by a striking expansion of gamma delta T cells in the intestine. These cells interact with MICA, a cell surface protein encoded by a major histocompatibility complex gene. (PMID:12074713)
• 1)MICA expressed in the M8 melanoma cell line triggered NK cell tumor lysis and 2)HLA-G1 coexpression mediated the inhibition of NK cytotoxicity by mitigating the MICA activating signal (PMID:12115588)
• allele A6 might confer the risk of oral squamous cell carcinoma (PMID:12190814)
• high frequency of the MIC null haplotype, HLA-B48-MICA-del-MICB*0107 N, in the Angaite Amerindian community in Paraguay (PMID:12242594)
• MICA is released as a soluble form from the cell surface of tumor cells and can be detected at high levels in sera of patients with gastrointestinal malignancies. (PMID:12370336)
• The study of MICA gene polymorphisms disclosed an independent association with genetic risk for juvenile Behcet disease. (PMID:12373294)
• 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)
• Intra-MHC sequences including MHC class I chain-related genes (MICAs), D6S273 and D6S2223 are associated with autoimmune diseases in addition to HLA class II (PMID:12392510)
• Involvement of NKG2D in natural killer cell-mediated cytotoxicity strictly correlates with the expression and the surface density of MICA and ULBP on target cell tumors of different histotypes. (PMID:12414645)
• Alternatively spliced forms of MICA and MICB lacking exon 3 in a human cell line and evidence of presence of similar RNA in human peripheral blood mononuclear cells (PMID:12466900)
• MICA is induced on dendritic cells upon IFN-alpha stimulation and is capable of activating NK cells by a mechanism that is impaired in hepatitis C virus infection. (PMID:12538683)
• novel allele in the transmembrane region of the MICA gene consisting of seven GCT repeats found in a family based study of MICA polymorphism in celiac disease. (PMID:12542746)
• MICA, overexpressed on a subset of human HCCs, may play an important role in their susceptibility to NK cells. (PMID:12569559)
• Determination of sMICA and sMICB levels may be implemented as a prognostic parameter in patients with hematopoietic malignancies. (PMID:12714493)
• MICA alleles studied bear no relation to cholelithiasis. (PMID:12854159)
• results indicate MICA-A5.1 allele seems to be protective against extensive forms of ulcerative colitis, and MICA-A5 may condition a worse progression of the disease. (PMID:12878361)
• Invasive rectal tumors tend to up-regulate MICA whereas MICA mRNA levels were lower in early tumors. (PMID:12894536)
• MICA expression is observed in epithelial cells and Hassal’s corpuscles of the normal thymic medulla; in thymomas, an overexpression of MICA in cortical and medullar epithelial cells is associated with a decreased percentage of NKG2D-positive T cells. (PMID:12902493)
• association with Behcet’s disease (PMID:12918694)
• polymorphism in Tunisian Behcet’s disease patients (PMID:12918695)
• MICA alanine repeat is not a disease-associated factor in POHS (presumed ocular histoplasmosis syndrome). (PMID:12963865)
• Overexpression of MICA in the gut of transgenic mice results in a clonal expansion of double-positive intraepithelial lymphocytes exhibiting a bias to the Vbeta8.2 T cell receptor motif in the small bowel. (PMID:14530335)
• MICA showed a high degree of variation and linkage disequilibrium. (PMID:14551603)
• Genetic variations of MHC class I polypeptide-related sequence A (MICA) are associated with susceptibility to rheumatoid arthritis (PMID:14630402)
• Circulating soluble MICA in cancer patients deactivates natural killer (NK) cell-mediated NK immunity by down-modulating important activating and chemokine receptors in vitro and in vivo. (PMID:14662896)
• MICA was strongly induced in the aortic tissue and that at least part of the infiltrating cells expressed NKG2D receptors in Takayasu’s arteritis (PMID:14752253)
• data provide little support for the hypothesis that MICA alleles substantially affect recovery from HCV and HBV infections. (PMID:15029237)
• ULBPs and MICA are expressed in lipid rafts at the cell surface of NK and T cells. (PMID:15051759)
• Among Indonesians,frequency of MICA-A9 allele,reported as negatively associated with Behcet’s disease, was significantly higher; MICA-A6 allele frequency, reported as positively associated with Behcet’s disease, was significantly lower among Japanese. (PMID:15272769)
• The polymorphisms and haplotype distributions of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population have their own distinct genetic characteristics (PMID:15304009)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mill2	ENSMUSG00000040987
mus_musculus	Mill1	ENSMUSG00000054005
rattus_norvegicus	Mill1	ENSRNOG00000017699
rattus_norvegicus	Micb	ENSRNOG00000057645

Paralogs (22): HFE (ENSG00000010704), FCGRT (ENSG00000104870), ULBP1 (ENSG00000111981), ULBP2 (ENSG00000131015), ULBP3 (ENSG00000131019), MR1 (ENSG00000153029), RAET1L (ENSG00000155918), CD1D (ENSG00000158473), CD1A (ENSG00000158477), CD1C (ENSG00000158481), CD1B (ENSG00000158485), CD1E (ENSG00000158488), AZGP1 (ENSG00000160862), RAET1E (ENSG00000164520), RAET1G (ENSG00000203722), MICB (ENSG00000204516), HLA-C (ENSG00000204525), HLA-E (ENSG00000204592), HLA-G (ENSG00000204632), HLA-F (ENSG00000204642), HLA-A (ENSG00000206503), HLA-B (ENSG00000234745)

Protein

Protein identifiers

MHC class I polypeptide-related sequence A — Q29983 (reviewed: Q29983)

All UniProt accessions (6): A0A024RCL3, A0A0G2JJ55, A0A669KAV5, A0A669KAV8, H0Y615, Q96QC4

UniProt curated annotations — full annotation on UniProt →

Function. Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8 alphabeta T-cells. Up-regulated in stressed conditions, such as viral and bacterial infections or DNA damage response, serves as signal of cellular stress, and engagement of KLRK1/NKG2D by MICA triggers NK-cells resulting in a range of immune effector functions, such as cytotoxicity and cytokine production.

Subunit / interactions. Unlike classical MHC class I molecules, does not form a heterodimer with beta-2-microglobulin. Binds as a monomer to a KLRK1/NKG2D homodimer. KLRK1 forms a complex with HCST/DAP10 in which KLRK1 binds MICA while HCST acts as an adapter molecule which enables signal transduction. Interacts with PDIA6 on the surface of tumor cells, leading to disulfide bond reduction which is required for release of MICA from tumor cells. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL142.

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Widely expressed with the exception of the central nervous system where it is absent. Expressed predominantly in gastric epithelium and also in monocytes, keratinocytes, endothelial cells, fibroblasts and in the outer layer of Hassal’s corpuscles within the medulla of normal thymus. In skin, expressed mainly in the keratin layers, basal cells, ducts and follicles. Also expressed in many, but not all, epithelial tumors of lung, breast, kidney, ovary, prostate and colon. In thyomas, overexpressed in cortical and medullar epithelial cells. Tumors expressing MICA display increased levels of gamma delta T-cells.

Post-translational modifications. N-glycosylated. Glycosylation is not essential for interaction with KLRK1/NKG2D but enhances complex formation. Proteolytically cleaved and released from the cell surface of tumor cells which impairs KLRK1/NKG2D expression and T-cell activation. Palmitoylated on cysteine residues in the cytoplasmic tail leading to its association with membrane microdomains enriched in cholesterol. N-glycosylation is necessary for cell surface expression. (Microbial infection) Ubiquitinated by human herpesvirus 8 protein K5, leading to degradation.

Disease relevance. Anti-MICA antibodies and ligand shedding are involved in the progression of monoclonal gammopathy of undetermined significance (MGUS)to multiple myeloma. Psoriasis 1 (PSORS1) [MIM:177900] A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Psoriatic arthritis (PSORAS) [MIM:607507] An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). Disease susceptibility is associated with variants affecting the gene represented in this entry.

Induction. By heat shock, by infection with human cytomegalovirus (HCMV), human adenovirus 5, M.tuberculosis and diarrheagenic E.coli, and by exposure to DNA damaging conditions such as high doses of ionizing radiation, chromatin-modifying treatments and inhibitors of DNA replication. The HCMV UL142 protein causes down-regulation of the full-length protein but not of the truncated MICA*008 allele.

Polymorphism. The following alleles of MICA are known: MICA001, MICA002, MICA004, MICA005, MICA006, MICA007, MICA008, MICA009, MICA010, MICA011, MICA012, MICA013, MICA014, MICA015, MICA016, MICA017, MICA018, MICA019, MICA020, MICA022, MICA023, MICA024, MICA025, MICA026, MICA027, MICA028, MICA029, MICA030, MICA031, MICA032, MICA033, MICA034, MICA035, MICA036, MICA037, MICA038, MICA039, MICA040, MICA041, MICA042, MICA043, MICA044, MICA045, MICA046, MICA047, MICA048, MICA049, MICA050, MICA051, MICA052, MICA053, MICA054, MICA055 and MICA056. The sequence shown is that of MICA*001.

Miscellaneous. Recognized by antibodies in the sera of some organ transplant recipients and may be a target molecule in allograft rejection. Found in about 10% of examined clones.

Similarity. Belongs to the MHC class I family. MIC subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q29983-1	1, MICA1	yes
Q29983-2	2, MICA2

RefSeq proteins (4): NP_001170990, NP_001276081, NP_001276082, NP_001276083 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003597	Ig_C1-set	Domain
IPR007110	Ig-like_dom	Domain
IPR011161	MHC_I-like_Ag-recog	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037055	MHC_I-like_Ag-recog_sf	Homologous_superfamily
IPR050208	MHC_class-I_related	Family

Pfam: PF00129, PF07654

UniProt features (92 total): sequence variant 44, strand 17, helix 8, glycosylation site 5, disulfide bond 3, mutagenesis site 3, turn 3, topological domain 2, lipid moiety-binding region 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
7FI9	X-RAY DIFFRACTION	2.16
7FI5	X-RAY DIFFRACTION	2.39
1HYR	X-RAY DIFFRACTION	2.7
8TLZ	X-RAY DIFFRACTION	2.75
7FI7	X-RAY DIFFRACTION	2.78
7FI8	X-RAY DIFFRACTION	2.8
8TM2	X-RAY DIFFRACTION	2.85
7FI6	X-RAY DIFFRACTION	2.9
1B3J	X-RAY DIFFRACTION	3
8TM0	X-RAY DIFFRACTION	3.83

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q29983-F1	82.52	0.60

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 (2): 330, 331

Disulfide bonds (3): 59–64, 119–187, 225–282

Glycosylation sites (5): 210, 220, 261, 31, 79

Mutagenesis-validated functional residues (3):

Position	Phenotype
47	completely restores cell surface expression of a non n-glycosylated mica.
330	complete loss of localization in cholesterol and sphingolipid-enriched microdomains; when associated with s-331.
331	complete loss of localization in cholesterol and sphingolipid-enriched microdomains; when associated with s-330.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

MSigDB gene sets: 154 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_NEGATIVE_REGULATION_OF_NATURAL_KILLER_CELL_MEDIATED_IMMUNITY, CHANDRAN_METASTASIS_DN, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, CHEOK_RESPONSE_TO_MERCAPTOPURINE_DN, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY

GO Biological Process (14): T cell mediated cytotoxicity (GO:0001913), immune response to tumor cell (GO:0002418), immune response (GO:0006955), DNA damage response (GO:0006974), response to heat (GO:0009408), killing of cells of another organism (GO:0031640), negative regulation of natural killer cell activation (GO:0032815), natural killer cell mediated cytotoxicity (GO:0042267), defense response to bacterium (GO:0042742), negative regulation of natural killer cell mediated cytotoxicity (GO:0045953), gamma-delta T cell activation (GO:0046629), defense response to virus (GO:0051607), negative regulation of defense response (GO:0031348), regulation of immune response (GO:0050776)

GO Molecular Function (3): natural killer cell lectin-like receptor binding (GO:0046703), receptor ligand activity (GO:0048018), metal ion binding (GO:0046872)

GO Cellular Component (6): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), 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-1 pathways:

Category	Pathways
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	3
cellular anatomical structure	3
leukocyte mediated cytotoxicity	2
immune response	2
signaling receptor binding	2
T cell mediated immunity	1
response to tumor cell	1
immune system process	1
response to stimulus	1
cellular response to stress	1
response to stress	1
response to temperature stimulus	1
cell killing	1
disruption of cell in another organism	1
natural killer cell activation	1
regulation of natural killer cell activation	1
negative regulation of lymphocyte activation	1
natural killer cell mediated immunity	1
response to bacterium	1
negative regulation of leukocyte mediated cytotoxicity	1
negative regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
T cell activation	1
response to virus	1
regulation of defense response	1
negative regulation of response to stimulus	1
regulation of immune system process	1
regulation of response to stimulus	1
signal transduction	1
signaling receptor activator activity	1
cation binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

78 interactions, top by confidence:

A	B	Type	Score
KLRK1	MICA	psi-mi:“MI:0407”(direct interaction)	0.620
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
SPINK4	PLXNA2	psi-mi:“MI:0914”(association)	0.530
AAR2	SNRNP200	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
ELSPBP1	PFDN1	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
DLK1	SCAMP3	psi-mi:“MI:0914”(association)	0.530
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
LGALS3	MICA	psi-mi:“MI:0915”(physical association)	0.520
MICA	LGALS3	psi-mi:“MI:0915”(physical association)	0.520
MICA		psi-mi:“MI:0915”(physical association)	0.400
MICA	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
WFDC3	MICA	psi-mi:“MI:0915”(physical association)	0.400
MICA	LTF	psi-mi:“MI:0915”(physical association)	0.400
MICA	HAPLN1	psi-mi:“MI:0915”(physical association)	0.400
MICA	ICAM5	psi-mi:“MI:0915”(physical association)	0.400
LRRTM2	MICA	psi-mi:“MI:0915”(physical association)	0.400
MICA	PRTG	psi-mi:“MI:0915”(physical association)	0.400
POT1	MICA	psi-mi:“MI:0915”(physical association)	0.370
TAFA3	FUOM	psi-mi:“MI:0914”(association)	0.350
AVP	B4GALT5	psi-mi:“MI:0914”(association)	0.350
PTPRK	MANBA	psi-mi:“MI:0914”(association)	0.350
EPHA7	AGAP1	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (136): MICA (Affinity Capture-MS), MICA (Affinity Capture-MS), MICA (Affinity Capture-MS), VAC14 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), TNPO2 (Affinity Capture-MS), SCAMP1 (Affinity Capture-MS), RYK (Affinity Capture-MS), ADAP2 (Affinity Capture-MS), TNPO3 (Affinity Capture-MS), NCR3LG1 (Affinity Capture-MS), ERLEC1 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), PGRMC2 (Affinity Capture-MS), TNFRSF10B (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K7V7, C1ITJ8, O08602, O08603, O08604, O19477, O35799, P01901, P01902, P06339, P13599, P14427, P14432, P16391, P25311, P26151, P30383, P55899, P60018, P70387, Q01965, Q29980, Q29983, Q2KN22, Q30201, Q3B8P2, Q5RD09, Q60I18, Q61559, Q63678, Q64726, Q6H3X3, Q8HWB0, Q8HWE5, Q8HWE7, Q8SPV9, Q8VD31, Q920A9, Q95460, Q9BCU3

Diamond homologs: A0A0G2K7V7, O19477, O35799, P01896, P01899, P01900, P01901, P10321, P13752, P15979, P16391, P30377, P30379, P30380, P30381, P30386, P30388, P30511, P30516, P60018, P70387, Q29980, Q29983, Q30201, Q60I18, Q8HWE5, Q8HWE7, Q9GKZ0, Q9GL41, Q9GL42, Q9GL43, C1ITJ8, P01888, P01889, P01893, P01894, P01895, P01897, P01898, P01902

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Defensins	5	15.9×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
antibacterial humoral response	5	17.6×	2e-03
killing of cells of another organism	6	17.4×	8e-04
defense response to Gram-positive bacterium	7	9.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

722 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31403699:GCTG:G	donor_gain	1.0000
6:31403700:CTGG:C	donor_loss	1.0000
6:31403701:TGG:T	donor_loss	1.0000
6:31403703:G:A	donor_loss	1.0000
6:31403703:G:GG	donor_gain	1.0000
6:31403704:T:A	donor_loss	1.0000
6:31403705:GA:G	donor_loss	0.9900
6:31411945:A:AG	acceptor_gain	0.9900
6:31411946:G:GA	acceptor_gain	0.9900
6:31411946:GT:G	acceptor_gain	0.9900
6:31412223:CTGGT:C	donor_loss	0.9900
6:31412224:TGGT:T	donor_loss	0.9900
6:31412226:G:GG	donor_gain	0.9900
6:31412226:GTG:G	donor_loss	0.9900
6:31412227:T:A	donor_loss	0.9900
6:31412228:GA:G	donor_loss	0.9900
6:31411944:CA:C	acceptor_loss	0.9800
6:31411945:A:AC	acceptor_loss	0.9800
6:31411946:GTGC:G	acceptor_gain	0.9800
6:31411946:GTGCC:G	acceptor_gain	0.9800
6:31412197:G:T	donor_gain	0.9800
6:31415007:TCCA:T	acceptor_loss	0.9800
6:31415010:A:AC	acceptor_loss	0.9800
6:31415010:A:AG	acceptor_gain	0.9800
6:31415011:G:GG	acceptor_gain	0.9800
6:31415011:GA:G	acceptor_gain	0.9800
6:31411945:AGT:A	acceptor_gain	0.9700
6:31411946:GTG:G	acceptor_gain	0.9700
6:31412197:G:GT	donor_gain	0.9700
6:31412323:AG:A	acceptor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000359507 (6:31399954 A>G), RS1001009814 (6:31410580 C>A,T), RS1001126437 (6:31403706 A>G), RS1001227426 (6:31415728 C>T), RS1001494227 (6:31403890 C>T), RS1002293103 (6:31403341 G>A), RS1002478073 (6:31410036 A>C,G), RS1002569948 (6:31408643 A>G), RS1002597414 (6:31402519 T>A), RS1002630625 (6:31414809 G>A), RS1002631569 (6:31402112 AT>A,ATT), RS1002702742 (6:31414502 C>T), RS1005049725 (6:31404530 T>C), RS1005490748 (6:31404250 G>A), RS1005546896 (6:31409944 C>G)

Disease associations

OMIM: gene MIM:600169 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

108 associations (top):

Study	Trait	p-value
GCST000817_192	Height	8.000000e-29
GCST000817_23	Height	2.000000e-07
GCST000863_1	HIV-1 control	1.000000e-34
GCST001041_1	Hepatocellular carcinoma	4.000000e-13
GCST001768_6	Behcet’s disease	2.000000e-10
GCST001863_11	Beta-2 microglubulin plasma levels	2.000000e-12
GCST001876_9	Pubertal anthropometrics	4.000000e-06
GCST001900_3	Cervical cancer	4.000000e-18
GCST002083_20	Self-reported allergy	3.000000e-12
GCST002084_12	Allergic sensitization	4.000000e-08
GCST002357_1	Rheumatoid arthritis (ACPA-negative)	9.000000e-09
GCST002595_4	Clozapine-induced agranulocytosis	2.000000e-07
GCST002737_4	Atopic dermatitis	3.000000e-07
GCST002876_3	Type 1 diabetes and autoimmune thyroid diseases	1.000000e-22
GCST002884_5	Cutaneous lupus erythematosus	3.000000e-14
GCST003046_1	Trichloroethylene-induced hypersensitivity syndrome	1.000000e-37
GCST003046_2	Trichloroethylene-induced hypersensitivity syndrome	9.000000e-35
GCST003450_2	Clozapine-induced agranulocytosis/granulocytopenia in treatment-resistant schizophrenia	3.000000e-09
GCST003526_4	Non-chemotherapy drug induced agranulocytosis	2.000000e-15
GCST003987_8	Asthma	1.000000e-16
GCST003995_4	Tonsillectomy	5.000000e-21
GCST004067_110	Hip circumference adjusted for BMI	8.000000e-08
GCST004067_148	Hip circumference adjusted for BMI	2.000000e-08
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_127	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_141	Autism spectrum disorder or schizophrenia	2.000000e-09

EFO canonical traits (29, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0005197	beta-2 microglobulin measurement
EFO:0001382	puberty
EFO:0005298	allergic sensitization measurement
EFO:0007685	trichloroethylene-induced hypersensitivity
EFO:0007924	tonsillectomy risk measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007984	platelet component distribution width
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007992	basophil percentage of leukocytes
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008380	perceived unattractiveness to mosquitos measurement
EFO:0008402	susceptibility to cold sores measurement
EFO:0008403	susceptibility to mononucleosis measurement
EFO:0008410	susceptibility to pneumonia measurement
EFO:0009180	rosacea severity measurement
EFO:0004842	eosinophil count
EFO:0007796	parental longevity
EFO:0009270	heel bone mineral density
EFO:1002011	adult onset asthma
EFO:0004338	body weight
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5483005 (PROTEIN COMPLEX)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1051792	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Rheumatoid arthritis

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2848716	MICA		0.00	0
rs1051792	MICA	3	6.00	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors

ChEMBL bioactivities

31 potent at pChembl≥5 of 33 total, top 31 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
6.52	IC50	300	nM	CHEMBL5421826
6.52	IC50	300	nM	CHEMBL5408363
6.40	IC50	400	nM	CHEMBL5428731
6.40	IC50	400	nM	CHEMBL5434369
6.40	IC50	400	nM	CHEMBL5426771
6.30	IC50	500	nM	CHEMBL5401653
6.30	IC50	500	nM	CHEMBL5406354
6.30	IC50	500	nM	CHEMBL5404943
6.16	IC50	700	nM	CHEMBL5435052
6.05	IC50	900	nM	CHEMBL5399509
6.05	IC50	900	nM	CHEMBL5406012
6.00	IC50	1000	nM	CHEMBL5411788
5.96	IC50	1100	nM	CHEMBL5412456
5.92	IC50	1200	nM	CHEMBL5416566
5.80	IC50	1600	nM	CHEMBL5405730
5.80	IC50	1600	nM	CHEMBL5407256
5.80	IC50	1600	nM	CHEMBL5430627
5.75	IC50	1800	nM	CHEMBL5419966
5.66	IC50	2200	nM	CHEMBL5433799
5.60	IC50	2500	nM	CHEMBL5413007
5.48	IC50	3300	nM	CHEMBL5438606
5.47	IC50	3400	nM	CHEMBL5421112
5.40	IC50	4000	nM	CHEMBL5393727

PubChem BioAssay actives

31 with measured affinity, of 46 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
sodium arsenite	decreases expression	2
Resveratrol	decreases reaction, increases expression	2
Arsenic Trioxide	increases expression	2
Acetaminophen	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction, affects cotreatment	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
avobenzone	increases expression	1
entinostat	increases expression	1
nickel acetate	decreases reaction, increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
MRK 003	decreases expression	1
Gefitinib	increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Lycopene	increases expression	1
Vorinostat	increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	affects expression, increases reaction	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases reaction, increases expression	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	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
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

5 cell lines: 3 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8KG	Abcam HCT 116 MICA KO	Cancer cell line	Male
CVCL_B9MQ	Abcam A-549 MICA KO	Cancer cell line	Male
CVCL_D2GD	Abcam MCF-7 MICA KO	Cancer cell line	Female
CVCL_E6R7	Genomeditech CHO-K1 H_MICA	Spontaneously immortalized cell line	Female
CVCL_E6UK	Genomeditech HEK-293 H_MICA	Transformed cell line	Female

Clinical trials (associated diseases)

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