BTN3A1

Summary

BTN3A1 (butyrophilin subfamily 3 member A1, HGNC:1138) is a protein-coding gene on chromosome 6p22.2, encoding Butyrophilin subfamily 3 member A1 (O00481). Plays a role in T-cell activation and in the adaptive immune response.

The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A1) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]).

Source: NCBI Gene 11119 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 85 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007048

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1138
Approved symbol	BTN3A1
Name	butyrophilin subfamily 3 member A1
Location	6p22.2
Locus type	gene with protein product
Status	Approved
Aliases	BT3.1, BTF5, CD277, BTN3.1
Ensembl gene	ENSG00000026950
Ensembl biotype	protein_coding
OMIM	613593
Entrez	11119

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 4 retained_intron

ENST00000082468, ENST00000289361, ENST00000414912, ENST00000425234, ENST00000427334, ENST00000450085, ENST00000465690, ENST00000476549, ENST00000502361, ENST00000506698, ENST00000513047, ENST00000850859, ENST00000865808, ENST00000865809, ENST00000865810, ENST00000865811, ENST00000865812

RefSeq mRNA: 4 — MANE Select: NM_007048 NM_001145008, NM_001145009, NM_007048, NM_194441

CCDS: CCDS4608, CCDS4609, CCDS47388, CCDS47389

Canonical transcript exons

ENST00000289361 — 10 exons

Exon	Start	End
ENSE00000848315	26410006	26410032
ENSE00000848317	26409894	26409914
ENSE00001360548	26413169	26415208
ENSE00002070967	26402275	26402412
ENSE00003515188	26411555	26411581
ENSE00003535860	26411109	26411135
ENSE00003537968	26405372	26405648
ENSE00003538349	26407671	26407952
ENSE00003618383	26405909	26406256
ENSE00003665286	26409533	26409733

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7333 / max 259.8376, expressed in 1559 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66520	8.8235	1478
66521	2.0789	925
66522	0.6812	399
66523	0.1498	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.93	gold quality
spleen	UBERON:0002106	96.49	gold quality
pancreatic ductal cell	CL:0002079	96.36	silver quality
lymph node	UBERON:0000029	96.08	gold quality
leukocyte	CL:0000738	95.76	gold quality
monocyte	CL:0000576	95.64	gold quality
mononuclear cell	CL:0000842	95.58	gold quality
blood	UBERON:0000178	95.50	gold quality
rectum	UBERON:0001052	94.69	gold quality
gall bladder	UBERON:0002110	94.61	gold quality
vermiform appendix	UBERON:0001154	94.36	gold quality
colonic epithelium	UBERON:0000397	93.35	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.04	gold quality
right uterine tube	UBERON:0001302	91.97	gold quality
small intestine	UBERON:0002108	91.94	gold quality
caecum	UBERON:0001153	91.87	gold quality
right lung	UBERON:0002167	91.53	gold quality
upper lobe of left lung	UBERON:0008952	91.34	gold quality
endocervix	UBERON:0000458	91.33	gold quality
bone marrow cell	CL:0002092	90.98	gold quality
adrenal tissue	UBERON:0018303	90.90	gold quality
tonsil	UBERON:0002372	90.76	gold quality
right adrenal gland	UBERON:0001233	90.50	gold quality
upper lobe of lung	UBERON:0008948	90.44	gold quality
smooth muscle tissue	UBERON:0001135	90.23	gold quality
body of uterus	UBERON:0009853	90.23	gold quality
left adrenal gland	UBERON:0001234	90.19	gold quality
stromal cell of endometrium	CL:0002255	90.17	gold quality
apex of heart	UBERON:0002098	90.02	gold quality
left adrenal gland cortex	UBERON:0035825	89.96	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.86
E-CURD-112	no	3.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting BTN3A1, 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-4455	100.00	65.48	1587
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
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-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-217-5P	99.49	69.93	1419

Literature-anchored findings (GeneRIF, showing 31)

• Results point to a role for CD277 up-regulated by microenvironmental signals in the acquisition of a regulatory phenotype by ovarian tumor-associated myeloid cells. (PMID:21113407)
• CD277 triggering is not involved in CD16- or NKp46-induced NK cell activation. (PMID:21918970)
• investigation of role of CD277 in activation/inactivation of T-lymphocytes: Data indicate that modulation of CD277 interaction (with agonists or blocking antibodies) with T-cell antigen receptor can modulate activation/inactivation of T-lymphocytes. (PMID:22767497)
• BTN3A1 is necessary for Vgamma9Vdelta2 activation and begin to unravel the extracellular events that occur during stimulation through the Vgamma9Vdelta2 T cell receptor. (PMID:22846996)
• BTN3A1 represents an antigen-presenting molecule required for the activation of Vgamma9Vdelta2 T cells. (PMID:23872678)
• These studies demonstrate that internal sensing of changes in pAg metabolite concentrations by BTN3A1 molecules is a critical step in Vgamma9Vdelta2 T cell detection of infection and tumorigenesis. (PMID:24703779)
• evidence that gene(s) on Chr6 in addition to BTN3A1 are mandatory for PAg-mediated activation of Vgamma9Vdelta2 T cells. (PMID:24890657)
• Ligand binding to the BTN3A1 B30.2 domain affects residues in the juxtamembrane region, suggesting ligand-induced conformational change. (PMID:25065532)
• Human gamma-delta T cells are activated by cytosolic interactions of BTN3A1 with soluble phosphoantigens and the cytoskeletal adaptor periplakin. (PMID:25637025)
• These findings support intracellular sensing of prenyl pyrophosphates by BTN3A1 rather than extracellular presentation. (PMID:26475929)
• Microtubule-associated protein 4 (MAP4) controls the dynein-dependent transport of BTN3A1 in response to nucleic acid stimulation, thereby identifying MAP4 as an upstream regulator of BTN3A1. Thus, the depletion of either MAP4 or BTN3A1 impairs cytosolic DNA- or RNA-mediated type I IFN responses. (PMID:27911820)
• findings show that changes in the juxtamembrane domain of BTN3A1, but not its transmembrane domain, induce a markedly enhanced or reduced gammadelta T cell reactivity (PMID:28461569)
• results show that ligand binding to BTN3A1 induces a conformational change within the intracellular domain that involves the JM region and is required for full activation. (PMID:28705810)
• this paper describes regulation of human gammadelta T cells by BTN3A1 protein stability and ATP-binding cassette transporters (PMID:29670629)
• Crystal structures of intracellular butyrophilin 3A proteins alone or in complex with the potent microbial phosphoantigen HMBPP or a synthetic analog revealed key features of phosphoantigens and butyrophilins required for gammadelta T cell activation. HMBPP binding to butyrophilin doubled the binding force between a gammadelta T cell and a target cell during “outside” signaling, as measured by single-cell force microsc… (PMID:30902636)
• We identified four Type 1 diabetes (T1D) risk loci reaching genome-wide significance in the Chinese Han population, including two novel loci: rs4320356 near BTN3A1, rs3802604 in GATA3, and two previously reported loci: rs1770 in MHC and rs705699 in SUOX. A higher genetic risk score were associated with an earlier age of T1D diagnosis and lower fasting C-peptide levels in individuals newly diagnosed with T1D. (PMID:31152121)
• Despite maintaining surface expression, BTN3A1 mutagenesis either abrogated or decreased stimulation by (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate demonstrating that the coiled-coil domains of BTN3A1 play critical roles for its function. (PMID:31227581)
• this study identified butyrophilin 2A1 (BTN2A1) as a key ligand that binds to the Vgamma9(+) TCR gamma chain (PMID:31919129)
• BTN3A1 governs antitumor responses by coordinating alphabeta and gammadelta T cells. (PMID:32820120)
• Comprehensive analysis of BTN3A1 in cancers: mining of omics data and validation in patient samples and cellular models. (PMID:34293829)
• Elevated Expressions of BTN3A1 and RhoB in Psoriasis Vulgaris Lesions by an Immunohistochemical Study. (PMID:34545848)
• Expression level of BTN3A1 on the surface of CD14(+) monocytes is a potential predictor of gammadelta T cell expansion efficiency. (PMID:34952469)
• The intracellular domain of BTN2A1 binds to the intracellular domain of BTN3A1 only in the presence of phosphoantigen. (PMID:35081362)
• Up-regulation of BTN3A1 on CD14(+) cells promotes Vgamma9Vdelta2 T cell activation in psoriasis. (PMID:36288286)
• BTN3A: A Promising Immune Checkpoint for Cancer Prognosis and Treatment. (PMID:36362212)
• BTN3A1 promotes tumor progression and radiation resistance in esophageal squamous cell carcinoma by regulating ULK1-mediated autophagy. (PMID:36418890)
• Mutations to the BTN2A1 Linker Region Impact Its Homodimerization and Its Cytoplasmic Interaction with Phospho-Antigen-Bound BTN3A1. (PMID:37171180)
• Phosphoantigens glue butyrophilin 3A1 and 2A1 to activate Vgamma9Vdelta2 T cells. (PMID:37674084)
• Synergistic effects of BTN3A1, SHP2, CD274, and STAT3 gene polymorphisms on the risk of systemic lupus erythematosus: a multifactorial dimensional reduction analysis. (PMID:37688767)
• Association of BTN3A1 gene polymorphisms with systemic lupus erythematosus in a Chinese Han population. (PMID:38450995)
• BTN3A1 expressed in cervical cancer cells promotes Vgamma9Vdelta2 T cells exhaustion through upregulating transcription factors NR4A2/3 downstream of TCR signaling. (PMID:39342337)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Btnl12	ENSMUSG00000108763
rattus_norvegicus	Btnl12	ENSRNOG00000068993

Paralogs (15): CD276 (ENSG00000103855), BTN3A3 (ENSG00000111801), BTN2A1 (ENSG00000112763), BTNL8 (ENSG00000113303), HHLA2 (ENSG00000114455), BTN2A2 (ENSG00000124508), BTN1A1 (ENSG00000124557), VTCN1 (ENSG00000134258), ICOSLG (ENSG00000160223), ERMAP (ENSG00000164010), BTNL9 (ENSG00000165810), BTNL3 (ENSG00000168903), BTN3A2 (ENSG00000186470), BTNL2 (ENSG00000204290), MOG (ENSG00000204655)

Protein

Protein identifiers

Butyrophilin subfamily 3 member A1 — O00481 (reviewed: O00481)

All UniProt accessions (4): A6PVC0, E7EPR2, E9PFB8, O00481

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in T-cell activation and in the adaptive immune response. Regulates the proliferation of activated T-cells. Regulates the release of cytokines and IFNG by activated T-cells. Mediates the response of T-cells toward infected and transformed cells that are characterized by high levels of phosphorylated metabolites, such as isopentenyl pyrophosphate.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Tissue specificity. Detected on T-cells, natural killer cells, dendritic cells and macrophages (at protein level). Ubiquitous. Highly expressed in heart, pancreas and lung, Moderately expressed in placenta, liver and muscle.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the immunoglobulin superfamily. BTN/MOG family.

Isoforms (4)

UniProt ID	Names	Canonical?
O00481-1	1	yes
O00481-2	2
O00481-3	3
O00481-4	4

RefSeq proteins (4): NP_001138480, NP_001138481, NP_008979, NP_919423 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001870	B30.2/SPRY	Domain
IPR003599	Ig_sub	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037954	SPRY_PRY_BTN3	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050504	IgSF_BTN/MOG-like	Family
IPR053896	BTN3A2-like_Ig-C	Domain

Pfam: PF00622, PF07686, PF13765, PF22705

UniProt features (76 total): strand 32, sequence conflict 10, helix 8, turn 7, splice variant 4, sequence variant 4, domain 3, disulfide bond 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

44 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6ITA	X-RAY DIFFRACTION	1.2
6ISM	X-RAY DIFFRACTION	1.25
8IZE	X-RAY DIFFRACTION	1.4
4N7I	X-RAY DIFFRACTION	1.4
4N7U	X-RAY DIFFRACTION	1.46
5LYG	X-RAY DIFFRACTION	1.6
8IZG	X-RAY DIFFRACTION	1.6
5LYK	X-RAY DIFFRACTION	1.7
8IXV	X-RAY DIFFRACTION	1.72
4K55	X-RAY DIFFRACTION	1.91
5HM7	X-RAY DIFFRACTION	1.93
4F80	X-RAY DIFFRACTION	1.94
5ZXK	X-RAY DIFFRACTION	1.96
4JKW	X-RAY DIFFRACTION	2.01
4V1P	X-RAY DIFFRACTION	2.04
8JYE	X-RAY DIFFRACTION	2.18
8JYC	X-RAY DIFFRACTION	2.29
6J06	X-RAY DIFFRACTION	2.65
6XLQ	X-RAY DIFFRACTION	3
8ZHR	ELECTRON MICROSCOPY	3
9JQR	ELECTRON MICROSCOPY	3
4F9L	X-RAY DIFFRACTION	3.14
9IRD	ELECTRON MICROSCOPY	3.2
9JQQ	ELECTRON MICROSCOPY	3.26
9II6	ELECTRON MICROSCOPY	3.27
9JQP	ELECTRON MICROSCOPY	3.34
8ZJX	ELECTRON MICROSCOPY	3.35
8ZK0	ELECTRON MICROSCOPY	3.4
8ZAA	ELECTRON MICROSCOPY	3.46
4F9P	X-RAY DIFFRACTION	3.52

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00481-F1	89.66	0.68

Antibody-complex structures (SAbDab): 7 — 4F9L, 4F9P, 6XLQ, 9JQP, 9KWE, 9KWZ, 9L1Q

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 (2): 166–220, 52–126

Glycosylation sites (1): 115

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8851680	Butyrophilin (BTN) family interactions
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 182 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, JI_RESPONSE_TO_FSH_UP, GNF2_CASP8, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_LEUKOCYTE_PROLIFERATION, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, GOBP_CYTOKINE_PRODUCTION, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOBP_T_CELL_RECEPTOR_SIGNALING_PATHWAY, DOUGLAS_BMI1_TARGETS_DN, WANG_CISPLATIN_RESPONSE_AND_XPC_DN

GO Biological Process (7): regulation of cytokine production (GO:0001817), positive regulation of cytokine production (GO:0001819), adaptive immune response (GO:0002250), positive regulation of type II interferon production (GO:0032729), activated T cell proliferation (GO:0050798), T cell receptor signaling pathway (GO:0050852), immune system process (GO:0002376)

GO Molecular Function (2): signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytokine production	2
regulation of gene expression	1
regulation of multicellular organismal process	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
immune response	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
T cell proliferation	1
antigen receptor-mediated signaling pathway	1
biological_process	1
protein binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

832 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTN3A1	XDH	P47989	966
BTN3A1	PLIN2	Q99541	910
BTN3A1	KPNA7	A9QM74	777
BTN3A1	MFGE8	Q08431	765
BTN3A1	IL1F10	Q8WWZ1	760
BTN3A1	PPL	O60437	643
BTN3A1	KPNA6	O60684	599
BTN3A1	MUC1	P13931	582
BTN3A1	FDPS	P14324	578
BTN3A1	LTF	P02788	557
BTN3A1	FOXP1	Q9H334	545
BTN3A1	GOT2	P00505	524
BTN3A1	RHOB	P01121	511
BTN3A1	MUC3A	Q02505	510
BTN3A1	KLRK1	P26718	507

IntAct

28 interactions, top by confidence:

A	B	Type	Score
BTN3A1	PPL	psi-mi:“MI:0915”(physical association)	0.630
BTN3A2	BTN3A1	psi-mi:“MI:0915”(physical association)	0.600
BTN3A2	BTN3A1	psi-mi:“MI:0403”(colocalization)	0.600
BTN3A2	BTN3A1	psi-mi:“MI:0914”(association)	0.600
BTN3A3	BTN3A1	psi-mi:“MI:0915”(physical association)	0.560
BTN3A1	DMWD	psi-mi:“MI:0915”(physical association)	0.560
BTN3A3	BTN3A1	psi-mi:“MI:0914”(association)	0.560
TFF1	BTN3A1	psi-mi:“MI:0915”(physical association)	0.540
TFF1	BTN3A1	psi-mi:“MI:0407”(direct interaction)	0.540
BTN3A1	TFF1	psi-mi:“MI:0407”(direct interaction)	0.540
BTN3A2	BTN3A3	psi-mi:“MI:0914”(association)	0.530
	BTN3A1	psi-mi:“MI:0407”(direct interaction)	0.440
BTN3A1	LILRA3	psi-mi:“MI:0915”(physical association)	0.400
BTN3A1	PIK3CA	psi-mi:“MI:0914”(association)	0.350
BTN3A1	LRPAP1	psi-mi:“MI:0914”(association)	0.350
SLC39A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
BTN3A1	folC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): BTN3A1 (Affinity Capture-MS), BTN3A1 (Affinity Capture-MS), BTN3A1 (Affinity Capture-MS), BTN3A1 (Affinity Capture-MS), BTN3A1 (Affinity Capture-RNA), TAOK3 (Affinity Capture-MS), CHAC2 (Affinity Capture-MS), TAOK1 (Affinity Capture-MS), BTN3A1 (Affinity Capture-MS), BTN3A1 (Affinity Capture-MS), PIK3CA (Affinity Capture-MS), PIK3CB (Affinity Capture-MS), BTN3A1 (Affinity Capture-MS), VEZT (Affinity Capture-MS), RABGEF1 (Affinity Capture-MS)

ESM2 similar proteins: A0JN74, A6NCK2, A6NGJ6, A6NI03, B1H278, K7N6K2, O00478, O00481, P14373, P19474, Q13410, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q1XHU0, Q2YEM8, Q2YEM9, Q3ZEE5, Q587N6, Q5C8T6, Q5C8T8, Q5C8U1, Q5D7I9, Q5D7J0, Q5D7J1, Q5NCC9, Q5R996, Q62158, Q6MFZ5, Q7YR33, Q7YRV4, Q80V85, Q8BGE7, Q8NG06, Q923T7, Q96BQ3, Q96F44, Q99PP6, Q99PQ2

Diamond homologs: A0A0E4BZH1, A4QPC6, A7TZE6, A7TZF0, A7TZF3, A7TZG1, A7TZG3, A7XUX6, A7XUY5, A7XUZ6, A7XV04, A7XV07, A7XV14, A8MVZ5, O00478, O00481, O70355, P18892, P55803, P78410, Q13410, Q16653, Q29ZQ1, Q5R7W8, Q5R960, Q5R996, Q61885, Q62556, Q63345, Q6MG97, Q6UX41, Q6UXE8, Q6UXG8, Q7KYR7, Q7TST0, Q8BJE2, Q8WVV5, Q96KV6, Q96PL5, Q9BGS7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1632 predictions. Top by Δscore:

Variant	Effect	Δscore
6:26405908:GCTCA:G	acceptor_gain	1.0000
6:26410033:G:GG	donor_gain	1.0000
6:26402411:AGGT:A	donor_loss	0.9900
6:26402412:GGTG:G	donor_loss	0.9900
6:26402413:G:GA	donor_loss	0.9900
6:26402414:T:A	donor_loss	0.9900
6:26409892:A:AG	acceptor_gain	0.9900
6:26409893:G:GA	acceptor_gain	0.9900
6:26409893:GT:G	acceptor_gain	0.9900
6:26409893:GTGAA:G	acceptor_gain	0.9900
6:26410031:TCGT:T	donor_loss	0.9900
6:26410032:CG:C	donor_loss	0.9900
6:26410033:GTAA:G	donor_loss	0.9900
6:26410034:T:A	donor_loss	0.9900
6:26410035:AA:A	donor_loss	0.9900
6:26411468:A:T	donor_gain	0.9900
6:26411550:TTCAG:T	acceptor_loss	0.9900
6:26411551:TCAGA:T	acceptor_loss	0.9900
6:26411552:CA:C	acceptor_loss	0.9900
6:26411553:A:AC	acceptor_loss	0.9900
6:26411553:A:AG	acceptor_gain	0.9900
6:26411553:AGAAT:A	acceptor_gain	0.9900
6:26411554:G:GC	acceptor_gain	0.9900
6:26411554:GA:G	acceptor_gain	0.9900
6:26411554:GAATG:G	acceptor_gain	0.9900
6:26411579:CTGGT:C	donor_loss	0.9900
6:26411582:GT:G	donor_loss	0.9900
6:26411583:T:TC	donor_loss	0.9900
6:26411584:G:GG	donor_loss	0.9900
6:26402410:GAG:G	donor_gain	0.9800

AlphaMissense

3355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:26413369:T:A	W407R	0.997
6:26413369:T:C	W407R	0.997
6:26413282:T:C	F378L	0.994
6:26413284:T:A	F378L	0.994
6:26413284:T:G	F378L	0.994
6:26413339:T:A	W397R	0.991
6:26413339:T:C	W397R	0.991
6:26413341:G:C	W397C	0.991
6:26413341:G:T	W397C	0.991
6:26413371:G:C	W407C	0.991
6:26413371:G:T	W407C	0.991
6:26413379:G:A	G410E	0.988
6:26413438:T:C	F430L	0.987
6:26413440:C:A	F430L	0.987
6:26413440:C:G	F430L	0.987
6:26413567:T:C	F473L	0.987
6:26413569:C:A	F473L	0.987
6:26413569:C:G	F473L	0.987
6:26413283:T:C	F378S	0.986
6:26413378:G:T	G410W	0.986
6:26413370:G:C	W407S	0.982
6:26413301:T:A	V384D	0.981
6:26413568:T:C	F473S	0.981
6:26413200:C:A	N350K	0.979
6:26413200:C:G	N350K	0.979
6:26413340:G:C	W397S	0.979
6:26413643:T:C	F498S	0.979
6:26413208:T:C	L353P	0.978
6:26406024:G:C	W67C	0.977
6:26406024:G:T	W67C	0.977

dbSNP variants (sampled 300 via entrez): RS1000508885 (6:26410854 T>A,C), RS1000573713 (6:26414921 T>C), RS1000981828 (6:26402447 A>C,G), RS1001110201 (6:26409263 T>C), RS1001601096 (6:26405504 C>T), RS1001613556 (6:26406918 A>G), RS1001901395 (6:26412447 G>A,C), RS1002006751 (6:26405683 A>G,T), RS1002210106 (6:26408340 A>G), RS1002339491 (6:26402145 A>G), RS1002744369 (6:26414639 T>G), RS1003218019 (6:26409791 C>A,T), RS1003243430 (6:26406901 C>A,T), RS1003352696 (6:26403536 C>A), RS1003492377 (6:26403135 G>A)

Disease associations

OMIM: gene MIM:613593 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000433_1	Schizophrenia	1.000000e-08
GCST004521_113	Autism spectrum disorder or schizophrenia	3.000000e-19
GCST004521_208	Autism spectrum disorder or schizophrenia	5.000000e-17
GCST004521_234	Autism spectrum disorder or schizophrenia	4.000000e-10
GCST004521_299	Autism spectrum disorder or schizophrenia	6.000000e-13
GCST004521_301	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST004521_69	Autism spectrum disorder or schizophrenia	8.000000e-24
GCST004746_35	Small cell lung carcinoma	1.000000e-06
GCST004748_57	Lung cancer	4.000000e-09
GCST005316_553	Intelligence (MTAG)	4.000000e-10
GCST005316_554	Intelligence (MTAG)	4.000000e-08
GCST006269_322	General cognitive ability	2.000000e-11
GCST008377_2	Type 1 diabetes	3.000000e-08
GCST009735_4	Urinary metabolite modules (eigenmetabolites) in chronic kidney disease	9.000000e-11
GCST010002_50	Refractive error	4.000000e-34
GCST010083_313	Hemoglobin levels	4.000000e-52
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010142_74	Fish- and plant-related diet	9.000000e-09
GCST010142_82	Fish- and plant-related diet	3.000000e-08
GCST010173_102	Triglyceride levels	2.000000e-10
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16
GCST012231_235	A body shape index	9.000000e-10
GCST90020028_821	Hip circumference adjusted for BMI	3.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0005116	urinary metabolite measurement
EFO:0004509	hemoglobin measurement
EFO:0008111	diet measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105758 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 23,242 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4303669	ZOLEDRONIC ACID	4	523
CHEMBL923	RISEDRONIC ACID	4	22,719

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Butyrophilin and butyrophilin-like proteins

ChEMBL bioactivities

102 potent at pChembl≥5 of 120 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	EC50	0.06	nM	CHEMBL145233
9.84	EC50	0.145	nM	CHEMBL145233
9.47	EC50	0.34	nM	CHEMBL4203452
9.44	EC50	0.36	nM	CHEMBL4204044
9.44	EC50	0.36	nM	CHEMBL4215122
9.36	EC50	0.44	nM	CHEMBL4216254
9.35	EC50	0.45	nM	CHEMBL4126016
9.29	EC50	0.51	nM	CHEMBL145233
9.29	EC50	0.519	nM	CHEMBL4746113
9.28	EC50	0.53	nM	CHEMBL4215653
9.24	EC50	0.58	nM	CHEMBL4210700
9.21	EC50	0.617	nM	CHEMBL4743632
9.14	EC50	0.728	nM	CHEMBL4764764
9.12	EC50	0.759	nM	CHEMBL4788989
9.10	EC50	0.79	nM	CHEMBL4160740
9.09	EC50	0.82	nM	CHEMBL4207267
8.96	EC50	1.1	nM	CHEMBL4204584
8.86	EC50	1.38	nM	CHEMBL4126163
8.82	EC50	1.5	nM	CHEMBL4208921
8.80	EC50	1.6	nM	CHEMBL145233
8.70	EC50	2	nM	CHEMBL4302450
8.38	EC50	4.2	nM	CHEMBL145233
8.34	EC50	4.6	nM	CHEMBL4746099
8.27	EC50	5.4	nM	CHEMBL4088948
8.27	EC50	5.4	nM	CHEMBL4161808
8.10	EC50	8	nM	CHEMBL4744593
8.05	EC50	8.92	nM	CHEMBL4127261
8.05	EC50	9	nM	CHEMBL4160740
7.97	EC50	10.62	nM	CHEMBL4127400
7.92	EC50	12	nM	CHEMBL4745129
7.85	EC50	14	nM	CHEMBL4174454
7.82	EC50	15	nM	CHEMBL4088948
7.70	EC50	20	nM	CHEMBL4739889
7.68	EC50	21	nM	CHEMBL4561436
7.62	EC50	24	nM	CHEMBL4161808
7.59	EC50	25.8	nM	CHEMBL4793602
7.39	EC50	41	nM	CHEMBL4061531
7.37	EC50	43	nM	CHEMBL4475541
7.33	EC50	47	nM	CHEMBL4743999
7.33	EC50	47	nM	CHEMBL4776906
7.31	EC50	49	nM	CHEMBL4780556
7.29	EC50	51	nM	CHEMBL4204044
7.21	EC50	62	nM	CHEMBL4215122
7.13	EC50	73.4	nM	CHEMBL4790695
7.10	EC50	79	nM	CHEMBL4561436
7.10	EC50	80	nM	RISEDRONIC ACID
7.07	EC50	86	nM	CHEMBL4302450
7.03	EC50	93	nM	CHEMBL4215653
6.92	EC50	120	nM	CHEMBL4210700
6.89	EC50	130	nM	CHEMBL4216254

PubChem BioAssay actives

104 with measured affinity, of 309 total; 50 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
benzyl (2S)-2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1676481: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as increase in CD69/CD25 level incubated for overnight by flow cytometric analysis	ec50	<0.0001	uM
benzyl (2S)-2-[[[(E)-1,1-difluoro-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1676481: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as increase in CD69/CD25 level incubated for overnight by flow cytometric analysis	ec50	<0.0001	uM
[(E)-4-hydroxy-3-methylbut-2-enyl] phosphono hydrogen phosphate	1494447: Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cells by upregulation of CD69 and CD25 after 18 hrs	ec50	0.0001	uM
propan-2-yl 2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-naphthalen-1-yloxyphosphoryl]amino]acetate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0003	uM
benzyl (2S)-2-[[[(E)-4-[tert-butyl(dimethyl)silyl]oxy-3-methylbut-2-enoxy]-phenoxyphosphoryl]amino]propanoate	1494447: Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cells by upregulation of CD69 and CD25 after 18 hrs	ec50	0.0004	uM
ethyl 2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]acetate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0004	uM
ethyl 2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-naphthalen-1-yloxyphosphoryl]amino]acetate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0004	uM
methyl 2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-naphthalen-1-yloxyphosphoryl]amino]acetate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0004	uM
ethyl 2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-naphthalen-2-yloxyphosphoryl]amino]acetate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0005	uM
propan-2-yl (2S)-2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1676481: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as increase in CD69/CD25 level incubated for overnight by flow cytometric analysis	ec50	0.0005	uM
methyl 2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-naphthalen-2-yloxyphosphoryl]amino]acetate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0006	uM
methyl (2S)-2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1676481: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as increase in CD69/CD25 level incubated for overnight by flow cytometric analysis	ec50	0.0006	uM
methyl (2S)-2-[[[(E)-1,1-difluoro-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1676481: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as increase in CD69/CD25 level incubated for overnight by flow cytometric analysis	ec50	0.0007	uM
propan-2-yl 2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-naphthalen-2-yloxyphosphoryl]amino]acetate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0008	uM
[[(E)-5-hydroxy-4-methylpent-3-enyl]-naphthalen-1-yloxyphosphoryl]methyl 2,2-dimethylpropanoate	1502332: Activation of BTN3A1 in human PBMC-derived Vgamma9Vdelta2 T cells assessed as induction of interleukin 2 stimulated cell proliferation by measuring increase in CD3 positive cells incubated for 3 days followed by 11 days incubation post compound wash out with subsequent stimulation with IL-2 every 3 days measured after 14 days by flow cytometry	ec50	0.0008	uM
propan-2-yl (2S)-2-[[[(E)-1,1-difluoro-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1676481: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as increase in CD69/CD25 level incubated for overnight by flow cytometric analysis	ec50	0.0008	uM
propan-2-yl 2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]acetate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0011	uM
methyl (2S)-2-[[[(E)-4-[tert-butyl(dimethyl)silyl]oxy-3-methylbut-2-enoxy]-phenoxyphosphoryl]amino]propanoate	1494447: Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cells by upregulation of CD69 and CD25 after 18 hrs	ec50	0.0014	uM
methyl 2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]acetate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0015	uM
[(E)-5-hydroxy-4-methylpent-3-enyl]-phosphonooxyphosphinic acid	1569591: Activation of BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of IL2-stimulated IFNgamma production measured after 48 hrs by ELISA	ec50	0.0020	uM
[[(E)-4-methyl-5-oxopent-3-enyl]-naphthalen-2-yloxyphosphoryl]oxymethyl 2,2-dimethylpropanoate	1685089: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of Vgamma9Vdelta2 T cells proliferation incubated for 3 days by gamma delta TCR/PE-CD3+ antibody staining based FACS analysis	ec50	0.0046	uM
[2,2-dimethylpropanoyloxymethyl-[(E)-5-hydroxy-4-methylpent-3-enyl]phosphoryl]oxymethyl 2,2-dimethylpropanoate	1502332: Activation of BTN3A1 in human PBMC-derived Vgamma9Vdelta2 T cells assessed as induction of interleukin 2 stimulated cell proliferation by measuring increase in CD3 positive cells incubated for 3 days followed by 11 days incubation post compound wash out with subsequent stimulation with IL-2 every 3 days measured after 14 days by flow cytometry	ec50	0.0054	uM
[2,2-dimethylpropanoyloxymethoxy-[(E)-5-hydroxy-4-methylpent-3-enyl]phosphoryl]oxymethyl 2,2-dimethylpropanoate	1386821: Binding affinity to BTN3A1 in human PBMC assessed as stimulation of Vgamma9 Vdelta2 T cells incubated for 3 days and measured after 11 days post compound removal by flow cytometry	ec50	0.0054	uM
[[(E)-5-hydroxy-4-methylpent-3-enyl]-(2-oxochromen-7-yl)oxyphosphoryl]oxymethyl 2,2-dimethylpropanoate	1685089: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of Vgamma9Vdelta2 T cells proliferation incubated for 3 days by gamma delta TCR/PE-CD3+ antibody staining based FACS analysis	ec50	0.0080	uM
tert-butyl (2S)-2-[[[(E)-4-[tert-butyl(dimethyl)silyl]oxy-3-methylbut-2-enoxy]-phenoxyphosphoryl]amino]propanoate	1494447: Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cells by upregulation of CD69 and CD25 after 18 hrs	ec50	0.0089	uM
propan-2-yl (2S)-2-[[[(E)-4-[tert-butyl(dimethyl)silyl]oxy-3-methylbut-2-enoxy]-phenoxyphosphoryl]amino]propanoate	1494447: Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cells by upregulation of CD69 and CD25 after 18 hrs	ec50	0.0106	uM
[[(E)-4-methyl-5-oxopent-3-enyl]-(2-oxochromen-7-yl)oxyphosphoryl]oxymethyl 2,2-dimethylpropanoate	1685089: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of Vgamma9Vdelta2 T cells proliferation incubated for 3 days by gamma delta TCR/PE-CD3+ antibody staining based FACS analysis	ec50	0.0120	uM
[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]methyl 2,2-dimethylpropanoate	1502332: Activation of BTN3A1 in human PBMC-derived Vgamma9Vdelta2 T cells assessed as induction of interleukin 2 stimulated cell proliferation by measuring increase in CD3 positive cells incubated for 3 days followed by 11 days incubation post compound wash out with subsequent stimulation with IL-2 every 3 days measured after 14 days by flow cytometry	ec50	0.0140	uM
ethyl 2-[[[(E)-4-methyl-5-oxopent-3-enyl]-phenoxyphosphoryl]amino]acetate	1685089: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of Vgamma9Vdelta2 T cells proliferation incubated for 3 days by gamma delta TCR/PE-CD3+ antibody staining based FACS analysis	ec50	0.0200	uM
ethyl (2S)-2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1511948: Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 240 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA	ec50	0.0210	uM
tert-butyl (2S)-2-[[[(E)-1,1-difluoro-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1676481: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as increase in CD69/CD25 level incubated for overnight by flow cytometric analysis	ec50	0.0258	uM
[bis(2,2-dimethylpropanoyloxymethoxy)phosphorylmethyl-[(E)-5-hydroxy-4-methylpent-3-enyl]phosphoryl]oxymethyl 2,2-dimethylpropanoate	1441713: Activation of BTN3A1 in human Vgamma9Vdelta2 T cells assessed as induction of interleukin 2 stimulated cell proliferation treated for 72 hrs measured on day 11 post last treatment by flow cytometry	ec50	0.0410	uM
ethyl (2S)-2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1511948: Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 240 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA	ec50	0.0430	uM
methyl 2-[[[(E)-4-methyl-5-oxopent-3-enyl]-phenoxyphosphoryl]amino]acetate	1685089: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of Vgamma9Vdelta2 T cells proliferation incubated for 3 days by gamma delta TCR/PE-CD3+ antibody staining based FACS analysis	ec50	0.0470	uM
[2,2-dimethylpropanoyloxymethoxy-[(E)-4-methyl-5-oxopent-3-enyl]phosphoryl]oxymethyl 2,2-dimethylpropanoate	1685089: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of Vgamma9Vdelta2 T cells proliferation incubated for 3 days by gamma delta TCR/PE-CD3+ antibody staining based FACS analysis	ec50	0.0470	uM
propan-2-yl 2-[[[(E)-4-methyl-5-oxopent-3-enyl]-phenoxyphosphoryl]amino]acetate	1685089: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of Vgamma9Vdelta2 T cells proliferation incubated for 3 days by gamma delta TCR/PE-CD3+ antibody staining based FACS analysis	ec50	0.0490	uM
tert-butyl (2S)-2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1676481: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as increase in CD69/CD25 level incubated for overnight by flow cytometric analysis	ec50	0.0734	uM
risedronic acid	1676487: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells	ec50	0.0800	uM
trisodium;[(E)-5-hydroxy-4-methylpent-3-enyl]-phosphonatooxyphosphinate	1511948: Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 240 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA	ec50	0.2800	uM
ethyl (2R)-2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1511948: Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 240 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA	ec50	0.4300	uM
(1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid;hydrate	1494447: Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cells by upregulation of CD69 and CD25 after 18 hrs	ec50	0.4866	uM
ethyl (2R)-2-[[[(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]propanoate	1511948: Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 240 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA	ec50	0.5200	uM
sodium [(E)-5-hydroxy-4-methylpent-3-enyl]-naphthalen-1-yloxyphosphinate	1502332: Activation of BTN3A1 in human PBMC-derived Vgamma9Vdelta2 T cells assessed as induction of interleukin 2 stimulated cell proliferation by measuring increase in CD3 positive cells incubated for 3 days followed by 11 days incubation post compound wash out with subsequent stimulation with IL-2 every 3 days measured after 14 days by flow cytometry	ec50	0.6100	uM
ethyl 2-[[[(E,5E)-5-hydroxyimino-4-methylpent-3-enyl]-phenoxyphosphoryl]amino]acetate	1685089: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of Vgamma9Vdelta2 T cells proliferation incubated for 3 days by gamma delta TCR/PE-CD3+ antibody staining based FACS analysis	ec50	0.7900	uM
sodium [(E)-5-hydroxy-4-methylpent-3-enyl]-phenoxyphosphinate	1502332: Activation of BTN3A1 in human PBMC-derived Vgamma9Vdelta2 T cells assessed as induction of interleukin 2 stimulated cell proliferation by measuring increase in CD3 positive cells incubated for 3 days followed by 11 days incubation post compound wash out with subsequent stimulation with IL-2 every 3 days measured after 14 days by flow cytometry	ec50	0.8700	uM
3-methylbut-3-enyl phosphono hydrogen phosphate	1676487: Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells	ec50	1.0000	uM
3-methylbut-2-enyl phosphono hydrogen phosphate	1569591: Activation of BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of IL2-stimulated IFNgamma production measured after 48 hrs by ELISA	ec50	1.5000	uM
[(E)-3-(hydroxymethyl)-4-(4-methylphenyl)but-2-enyl] phosphono hydrogen phosphate	2125524: Binding affinity to butyrophilin 3A1 (unknown origin) intracellular domain assessed as dissociation constant by ITC analysis	kd	2.9200	uM
[(E)-3-[(4-chlorophenyl)methyl]-4-hydroxybut-2-enyl] phosphono hydrogen phosphate	2125524: Binding affinity to butyrophilin 3A1 (unknown origin) intracellular domain assessed as dissociation constant by ITC analysis	kd	3.1000	uM
[(E)-5-hydroxy-4-methylpent-3-enyl]phosphonic acid	1569591: Activation of BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as induction of IL2-stimulated IFNgamma production measured after 48 hrs by ELISA	ec50	3.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	4
Valproic Acid	decreases expression, decreases methylation, increases expression	3
Air Pollutants	increases abundance, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
nutlin 3	increases expression, affects cotreatment	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1

ChEMBL screening assays

75 unique, capped per target: 75 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4009307	Binding	Activation of BTN3A1 in human Vgamma9Vdelta2 T cells assessed as induction of interleukin 2 stimulated cell proliferation by measuring increase in CD3 positive cells at 0.1 uM treated for 72 hrs measured on day 11 post last treatment by flo	Phosphinophosphonates and Their Tris-pivaloyloxymethyl Prodrugs Reveal a Negatively Cooperative Butyrophilin Activation Mechanism. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E6TC	Genomeditech HEK-293 H_BTN3A1	Transformed cell line	Female

Clinical trials (associated diseases)

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