CD86

Summary

CD86 (CD86 molecule, HGNC:1705) is a protein-coding gene on chromosome 3q13.33, encoding T-lymphocyte activation antigen CD86 (P42081). Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation.

This gene encodes a type I membrane protein that is a member of the immunoglobulin superfamily. This protein is expressed by antigen-presenting cells, and it is the ligand for two proteins at the cell surface of T cells, CD28 antigen and cytotoxic T-lymphocyte-associated protein 4. Binding of this protein with CD28 antigen is a costimulatory signal for activation of the T-cell. Binding of this protein with cytotoxic T-lymphocyte-associated protein 4 negatively regulates T-cell activation and diminishes the immune response. Alternative splicing results in several transcript variants encoding different isoforms.

Source: NCBI Gene 942 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 70 total
• Druggable target: yes
• MANE Select transcript: NM_175862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1705
Approved symbol	CD86
Name	CD86 molecule
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	B7.2, B7-2
Ensembl gene	ENSG00000114013
Ensembl biotype	protein_coding
OMIM	601020
Entrez	942

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264468, ENST00000330540, ENST00000393627, ENST00000469710, ENST00000478390, ENST00000478741, ENST00000482356, ENST00000483949, ENST00000493101

RefSeq mRNA: 5 — MANE Select: NM_175862 NM_001206924, NM_001206925, NM_006889, NM_175862, NM_176892

CCDS: CCDS3009, CCDS43138, CCDS56272, CCDS56273, CCDS74991

Canonical transcript exons

ENST00000330540 — 7 exons

Exon	Start	End
ENSE00000776449	122106198	122106500
ENSE00000823725	122109265	122109408
ENSE00001049938	122118048	122118093
ENSE00001926989	122119438	122121136
ENSE00002302983	122055362	122055503
ENSE00003547043	122091601	122091650
ENSE00003590773	122103512	122103847

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 97.27.

FANTOM5 (CAGE): breadth broad, TPM avg 17.7612 / max 969.7959, expressed in 514 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38212	13.3481	463
38221	2.1576	258
38213	0.8227	190
38217	0.6000	67
38219	0.5271	61
38220	0.1684	66
38218	0.0971	33
38216	0.0402	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.27	gold quality
mononuclear cell	CL:0000842	96.85	gold quality
leukocyte	CL:0000738	96.72	gold quality
granulocyte	CL:0000094	93.50	gold quality
vermiform appendix	UBERON:0001154	87.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.44	gold quality
blood	UBERON:0000178	86.63	gold quality
lymph node	UBERON:0000029	84.54	gold quality
gall bladder	UBERON:0002110	84.49	gold quality
caecum	UBERON:0001153	81.64	gold quality
spleen	UBERON:0002106	81.33	gold quality
right lung	UBERON:0002167	80.13	gold quality
rectum	UBERON:0001052	79.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.75	gold quality
bone marrow	UBERON:0002371	77.36	gold quality
upper lobe of left lung	UBERON:0008952	77.23	gold quality
descending thoracic aorta	UBERON:0002345	76.62	gold quality
upper lobe of lung	UBERON:0008948	76.35	gold quality
colonic epithelium	UBERON:0000397	76.25	gold quality
spinal cord	UBERON:0002240	76.25	gold quality
bone marrow cell	CL:0002092	75.46	gold quality
right coronary artery	UBERON:0001625	75.24	gold quality
smooth muscle tissue	UBERON:0001135	74.70	gold quality
lung	UBERON:0002048	74.38	gold quality
thoracic aorta	UBERON:0001515	73.28	gold quality
left coronary artery	UBERON:0001626	73.13	gold quality
epithelium of nasopharynx	UBERON:0001951	72.94	silver quality
nasopharynx	UBERON:0001728	72.93	silver quality
ascending aorta	UBERON:0001496	72.88	gold quality
omental fat pad	UBERON:0010414	72.36	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	72.50
E-HCAD-1	yes	49.55
E-GEOD-84465	yes	36.66
E-MTAB-10553	yes	33.15
E-CURD-122	yes	22.09
E-CURD-46	yes	17.24
E-CURD-112	yes	15.42
E-MTAB-8410	yes	13.28
E-MTAB-9067	yes	10.15
E-MTAB-9801	yes	7.63
E-MTAB-5061	no	215.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLEC7A, CREB1, CREBZF, CREM, ESR1, GATA1, IL33, IRF6, KLF4, MYB, NFE2L2, NFIL3, NFKB1, NFKB, NR5A1, PPARG, PTPN22, RELA, RELB, SPI1, STAT1, STAT6, TRERF1, TYROBP

miRNA regulators (miRDB)

58 targeting CD86, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613

Literature-anchored findings (GeneRIF, showing 40)

• Structure in complex with CTLA-4; may represent a distinct signalling mechanism available to dimeric cell-surface receptors. (PMID:11279501)
• Thus, this study is the first demonstration of a distinct signaling event induced by CD80 and CD86 molecules in B cell lymphoma. (PMID:11726649)
• In AML, CD86 is a marker of monocytic/dendritic lineage (PMID:11823047)
• The B7-CD28/CTLA-4 costimulatory pathway has a dominant role in regulating T-cell activation. Antagonists enable graft survival and suppress autoimmunity. (PMID:11826754)
• a soluble form of CD86 encoded by an alternatively spliced transcript is present at elevated levels in blood in some leukaemia patients (PMID:11986949)
• CD80 and CD86 molecules can substitute for each other in the initial activation of resting CD4(+) T cells and in the maintenance of their proliferative response (PMID:12015893)
• expression, refolding, purification, characterization, and crystallization of the receptor-binding domain of human B7-2 is described; glycosylation is not important for proper folding of the receptor-binding domain of B7-2 nor for its binding to CTLA-4 (PMID:12071705)
• Leishmania major infection of macrophages cocultured with neutrophils results in a neutrophil-macrophage interaction via CD86 leading to IFN-gamma secretion and restriction of Leishmania growth. (PMID:12097397)
• Impaired up-regulation of CD70 and CD86 in naive B cells from patients with CVID suggests an intrinsic signalling or expression defect at the level of naive B cells in type I CVID. (PMID:12100033)
• polymorphisms have no association with type I diabetes among Finnish subjects (PMID:12187923)
• Intense expression is an unfavorable prognostic indicator for differentiated thyroid carcinoma of children and adolescents (PMID:12213904)
• After B7-1 and B7-2 induction, proximal tubular epithelial cells costimulate CD28 on T lymphocytes resulting in cytokine production. (PMID:12372936)
• Data show that interaction between iC3b-opsonized apoptotic cells and immature dendritic cells down-regulated the expression of CD86 and up-regulated expression of CC chemokine receptor 7. (PMID:12486098)
• The identical effects of B7-1 and B7-2 on regulation of human IL-2 gene transcription factors NF-kappa B and AP-1. (PMID:12513711)
• c-MIR induced specific down-regulation of B7-2 surface expression through ubiquitination, rapid endocytosis, and lysosomal degradation (PMID:12582153)
• B7-2 dimer observed in the B7-2/CTLA-4 complex displays a very hydrophilic dimer interface which provides a mechanism for preventing the formation of B7-1/B7-2 heterodimers (PMID:12606712)
• A key mechanism in the pathogenesis of MS is the increased expression of CD86 and CD40L and the increased production of IL12 during disease progression. (PMID:12672403)
• expression profiles and relative contribution in the porcine-human xenogeneic response (PMID:12829914)
• results demonstrate that herpes simplex virus-2 infection effects the expression of B7 isoforms (B7-1 and B7-2) on monocytes in two ways with opposing outcomes (PMID:12878356)
• Immature dendritic cells engulfed apoptotic and necrotic neutrophils, resulting in up-regulation of CD83 and class II major histocompatibility complex molecules, but down-regulation of CD40, CD80, and CD86 (PMID:12905492)
• results confirm that both the CD80 and CD86 molecules play an important role in the maintenance and amplification of the inflammatory process (PMID:14692664)
• Decreased expression of CD86 antigen is associated with melanoma (PMID:14727087)
• CD80 and CD86 activate T cells in IgA nephropathy, CD80/CD86 expressions correlated with renal function at the time of renal biopsy, and monocyte/macrophages and tubular epithelial cells act as antigen presenting cells (PMID:14871408)
• CD86 and CD80 have opposite roles in the functioning of human regulatory T cells via CTLA-4 and CD28, an observation that has significant implications for manipulation of immune responses and tolerance in vivo. (PMID:14978077)
• PIII also promoted a significant increase in the percentage of cells expressing CD86 (PMID:15019278)
• Engagement of B7-1/B7-2 molecules on human indoleamine 2,3-dioxygenase (IDO)-positive dendritic cells delivers a signal that is obligately required for the triggering of IDO activity during antigen presentation. (PMID:15034022)
• CTLA-4 gene polymorphism may not play a role in the development of rheumatoid arthritis in Chinese. (PMID:15045639)
• CD86 may play an important role in asthma pathogenesis. (PMID:15059478)
• utilized as cellular attachment receptor by Adenovirus serotype 3 and thus may achieve both goals of cellular entry and evasion of the immune system (PMID:15110532)
• insertion of CD80 and CD86 antigens into HIV-1 virions increases virus infectivity by facilitating the attachment and entry process due to interactions with their two natural ligands, CD28 and CTLA-4 (PMID:15163715)
• kK5 proteins of Kaposi’s sarcoma associated herepsvirus does not affect class I expression but does downregulate human B7.2 molecules in a TAP/tapasin-independent manner (PMID:15280476)
• CD86 was found to be concentrated within the cytoplasmic vesicles of macrophages and dendritic cells. (PMID:15623548)
• Upregulation in the colonic mucosa of patients with ulcerative colitis. (PMID:15628695)
• NF-kappaB signal plays a key role in LIGHT-mediated upregulation of CD86 expression. (PMID:15895390)
• There was no relationship between the B7 gene polymorphisms studied and disease susceptibility or BAL fluid cell profiles in Japanese sarcoidosis patients. (PMID:15942292)
• B7.1/B7.2 binding ultimately determines the formation of dimer-dependent CTLA-4 lattices that may be necessary for triggering B7-dependent T cell inactivation. (PMID:16002699)
• Results indicate the expression of functional B7.2 molecule may facilitate progression of acute myeloid leukemia. (PMID:16115907)
• CD86 AA genotype at +1057 position could be involved in liver transplant acceptance, given that its presence is related to a decrease of acute rejection frequency and to a graft survival increase. (PMID:16223675)
• in human T4 cells in the absence of TCR ligation, CD28/CD86 interaction induced lipid raft polarization, activation of Vav1, increase in intracellular calcium, and nuclear translocation of NFKBp65, but not T cell proliferation or cytokine production (PMID:16339520)
• While purified CD123+ plasmacytoid dendritic cells from adults up-regulated co-stimulatory molecules CD80 and CD86 with IL-3 alone those from neonates required the addition of CpG-DNA to reach adult levels. (PMID:16690948)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd86	ENSMUSG00000022901
rattus_norvegicus	Cd86	ENSRNOG00000038835

Paralogs (12): CD274 (ENSG00000120217), CD80 (ENSG00000121594), RFPL1 (ENSG00000128250), RFPL2 (ENSG00000128253), RFPL3 (ENSG00000128276), SPRYD4 (ENSG00000176422), RNF152 (ENSG00000176641), RNF135 (ENSG00000181481), PDCD1LG2 (ENSG00000197646), RFPL4A (ENSG00000223638), RFPL4AL1 (ENSG00000229292), RFPL4B (ENSG00000251258)

Protein

Protein identifiers

T-lymphocyte activation antigen CD86 — P42081 (reviewed: P42081)

Alternative names: Activation B7-2 antigen, B70, BU63, CTLA-4 counter-receptor B7.2, FUN-1

All UniProt accessions (3): P42081, C9JXS1, H7C4F8

UniProt curated annotations — full annotation on UniProt →

Function. Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation. Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor which is constitutively expressed on the cell surface of T-cells. May play a critical role in the early events of T-cell activation and costimulation of naive T-cells, such as deciding between immunity and anergy that is made by T-cells within 24 hours after activation. Also involved in the regulation of B cells function, plays a role in regulating the level of IgG(1) produced. Upon CD40 engagement, activates NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation. Also acts as an inhibitor of T-cell activation by acting as a ligand for CTLA4, a decoy receptor, thereby blocking CD28-mediated T-cell priming. Interferes with the formation of CD86 clusters, and thus acts as a negative regulator of T-cell activation. (Microbial infection) Acts as a receptor for adenovirus subgroup B.

Subunit / interactions. Homodimer. Interacts with MARCH8. Interacts (via cytoplasmic domain) with PHB1 and PHB2; the interactions increases after priming with CD40. (Microbial infection) Interacts with adenovirus subgroup b fiber protein. (Microbial infection) Interacts with Orthopoxvirus OPG038/M2 protein, inhibiting the interaction with CTLA4 and CD28.

Subcellular location. Cell membrane.

Tissue specificity. Expressed on the surfaces of antigen-presenting cells.

Post-translational modifications. Polyubiquitinated; which is promoted by MARCH8 and results in endocytosis and lysosomal degradation.

Isoforms (6)

UniProt ID	Names	Canonical?
P42081-1	1	yes
P42081-3	2
P42081-2	3, CD86 deltaEC
P42081-4	4, CD86 deltaTM
P42081-5	5
P42081-6	6

RefSeq proteins (5): NP_001193853, NP_001193854, NP_008820, NP_787058, NP_795711 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037677	CD86_IgV	Domain
IPR051713	T-cell_Activation_Regulation	Family

Pfam: PF07686

UniProt features (43 total): strand 10, glycosylation site 8, splice variant 5, sequence variant 4, helix 3, disulfide bond 2, topological domain 2, domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5YXK	X-RAY DIFFRACTION	1.9
1NCN	X-RAY DIFFRACTION	2.7
8HXB	ELECTRON MICROSCOPY	2.7
8HXC	ELECTRON MICROSCOPY	3.12
1I85	X-RAY DIFFRACTION	3.2
8FXX	ELECTRON MICROSCOPY	3.26
8FXY	ELECTRON MICROSCOPY	3.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42081-F1	80.10	0.57

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): 40–110, 157–218

Glycosylation sites (8): 47, 135, 146, 154, 177, 192, 213, 33

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-389356	Co-stimulation by CD28
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-389359	CD28 dependent Vav1 pathway
R-HSA-389513	Co-inhibition by CTLA4
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-199418	Negative regulation of the PI3K/AKT network
R-HSA-2219528	PI3K/AKT Signaling in Cancer
R-HSA-388841	Regulation of T cell activation by CD28 family
R-HSA-449147	Signaling by Interleukins
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-9006925	Intracellular signaling by second messengers

MSigDB gene sets: 561 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, CREL_01, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, MODULE_169, LU_IL4_SIGNALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (24): adaptive immune response (GO:0002250), positive regulation of immunoglobulin production (GO:0002639), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), positive regulation of cell population proliferation (GO:0008284), T cell costimulation (GO:0031295), positive regulation of interleukin-2 production (GO:0032743), positive regulation of interleukin-4 production (GO:0032753), positive regulation of lymphotoxin A production (GO:0032761), positive regulation of T cell proliferation (GO:0042102), T cell activation (GO:0042110), B cell activation (GO:0042113), negative regulation of T cell proliferation (GO:0042130), positive regulation of T-helper 2 cell differentiation (GO:0045630), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of T cell receptor signaling pathway (GO:0050860), positive regulation of T cell receptor signaling pathway (GO:0050862), negative regulation of T cell activation (GO:0050868), cellular response to lipopolysaccharide (GO:0071222), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), immune system process (GO:0002376), signal transduction (GO:0007165), lymphocyte activation (GO:0046649), symbiont entry into host cell (GO:0046718)

GO Molecular Function (5): virus receptor activity (GO:0001618), coreceptor activity (GO:0015026), signaling receptor activity (GO:0038023), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), centriolar satellite (GO:0034451), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Regulation of T cell activation by CD28 family	2
Co-stimulation by CD28	2
Immune System	2
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Signaling by Interleukins	1
Negative regulation of the PI3K/AKT network	1
PIP3 activates AKT signaling	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Adaptive Immune System	1
Cytokine Signaling in Immune system	1
Disease	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
positive regulation of T cell activation	2
positive regulation of cytokine production	2
T cell proliferation	2
regulation of T cell proliferation	2
lymphocyte activation	2
T cell receptor signaling pathway	2
regulation of T cell receptor signaling pathway	2
immune response	1
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
immune system process	1
response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
lymphocyte costimulation	1
interleukin-2 production	1
regulation of interleukin-2 production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
lymphotoxin A production	1
regulation of lymphotoxin A production	1
positive regulation of protein metabolic process	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
positive regulation of lymphocyte proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
positive regulation of immune effector process	1
positive regulation of type 2 immune response	1
T-helper 2 cell differentiation	1
positive regulation of T-helper cell differentiation	1
regulation of T-helper 2 cell differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
negative regulation of antigen receptor-mediated signaling pathway	1
positive regulation of antigen receptor-mediated signaling pathway	1

Protein interactions and networks

STRING

3644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD86	CD28	P10747	999
CD86	CTLA4	P16410	999
CD86	CD40LG	P29965	998
CD86	ICOS	Q9Y6W8	996
CD86	PDCD1	Q15116	996
CD86	CD27	P26842	992
CD86	CD80	P33681	990
CD86	TNFRSF4	P43489	990
CD86	CD276	Q5ZPR3	988
CD86	CD40	P25942	986
CD86	LAG3	P18627	979
CD86	ICAM1	P05362	974
CD86	PDCD1LG2	Q9BQ51	970
CD86	CD274	Q9NZQ7	969
CD86	HAVCR2	Q8TDQ0	965

IntAct

13 interactions, top by confidence:

A	B	Type	Score
CD86	CTLA4	psi-mi:“MI:0407”(direct interaction)	0.840
CD86	CTLA4	psi-mi:“MI:0915”(physical association)	0.840
CTLA4	CD86	psi-mi:“MI:0915”(physical association)	0.840
CD86	CTLA4	psi-mi:“MI:2364”(proximity)	0.840
CD28	CD86	psi-mi:“MI:0915”(physical association)	0.610
CD28	CD86	psi-mi:“MI:0407”(direct interaction)	0.610
FSTL5	CD86	psi-mi:“MI:0915”(physical association)	0.400
CD86	PARP1	psi-mi:“MI:0915”(physical association)	0.370
CD86	ECE2	psi-mi:“MI:0915”(physical association)	0.370
CD86	CD80	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (15): CTLA4 (Co-localization), CD80 (Co-localization), CD86 (Co-crystal Structure), CD86 (Affinity Capture-RNA), CD86 (Affinity Capture-Western), ATR (Affinity Capture-Western), MARCH1 (Affinity Capture-Western), CD86 (Reconstituted Complex), CD86 (Reconstituted Complex), CD86 (Affinity Capture-Western), CD86 (Affinity Capture-Western), MARCH1 (Affinity Capture-Western), CD86 (Reconstituted Complex), PARP1 (Two-hybrid), ECE2 (Two-hybrid)

ESM2 similar proteins: A0A0E4BZH1, A7TZE6, A7TZF0, A7TZF3, A7TZG1, A7TZG3, A7XUX6, A7XV04, A7XV07, A7XV14, O54709, O70215, O95727, P0C1X9, P0DTI4, P26718, P42081, P61252, P83556, Q00609, Q29ZQ1, Q2YHT7, Q5RFR2, Q5UKY4, Q60651, Q60652, Q60654, Q60660, Q61885, Q63203, Q64329, Q68D85, Q6Q8B3, Q6XJV4, Q7Z6M3, Q8BG84, Q8BTP3, Q8MJH1, Q8TD46, Q921W8

Diamond homologs: P42071, P42081, P42082, Q9D780, Q00609, O00478, O00481, P78410, Q5R996, P33681, P42070, Q92823

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NfKb-p65/p50	“up-regulates quantity by expression”	CD86	“transcriptional regulation”
sirolimus	“down-regulates quantity by repression”	CD86
MARCHF1	“down-regulates quantity by destabilization”	CD86	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

969 predictions. Top by Δscore:

Variant	Effect	Δscore
3:122079815:G:T	donor_gain	0.9800
3:122103804:A:T	donor_gain	0.9800
3:122105397:G:GG	donor_gain	0.9800
3:122109362:AT:A	acceptor_gain	0.9800
3:122119436:A:AG	acceptor_gain	0.9800
3:122119437:G:GG	acceptor_gain	0.9800
3:122055501:GTG:G	donor_gain	0.9700
3:122079815:G:GT	donor_gain	0.9700
3:122103506:TTTTA:T	acceptor_loss	0.9700
3:122103507:TTTAG:T	acceptor_loss	0.9700
3:122103508:TTA:T	acceptor_loss	0.9700
3:122103509:TAGGT:T	acceptor_loss	0.9700
3:122103510:AGGTG:A	acceptor_loss	0.9700
3:122103608:T:TA	donor_gain	0.9700
3:122103609:A:AA	donor_gain	0.9700
3:122103803:G:GT	donor_gain	0.9700
3:122106280:C:CA	acceptor_gain	0.9700
3:122119437:G:C	acceptor_gain	0.9700
3:122119437:GA:G	acceptor_gain	0.9700
3:122055500:AGTGG:A	donor_loss	0.9600
3:122055501:GTGGT:G	donor_loss	0.9600
3:122055504:G:GG	donor_gain	0.9600
3:122055504:GTG:G	donor_loss	0.9600
3:122055505:T:A	donor_loss	0.9600
3:122106196:A:AG	acceptor_gain	0.9600
3:122106197:G:GG	acceptor_gain	0.9600
3:122106380:GAACT:G	donor_gain	0.9600
3:122109363:T:G	acceptor_gain	0.9600
3:122109363:T:TA	acceptor_gain	0.9600
3:122119521:A:AG	donor_gain	0.9600

AlphaMissense

2203 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:122103701:G:C	R85P	0.995
3:122103775:T:A	C110S	0.994
3:122103776:G:C	C110S	0.994
3:122106266:T:C	C157R	0.992
3:122103620:A:C	Q58P	0.991
3:122103775:T:C	C110R	0.991
3:122106203:T:C	F136L	0.991
3:122106205:C:A	F136L	0.991
3:122106205:C:G	F136L	0.991
3:122103777:T:G	C110W	0.990
3:122106266:T:A	C157S	0.990
3:122106267:G:C	C157S	0.990
3:122106449:T:C	C218R	0.990
3:122103565:T:A	C40S	0.989
3:122103566:G:C	C40S	0.989
3:122103616:T:A	W57R	0.989
3:122103616:T:C	W57R	0.989
3:122106213:C:A	P139H	0.989
3:122106272:T:C	S159P	0.989
3:122103769:T:G	Y108D	0.988
3:122103560:T:C	L38P	0.986
3:122103613:T:C	F56L	0.986
3:122103615:T:A	F56L	0.986
3:122103615:T:G	F56L	0.986
3:122103618:G:C	W57C	0.986
3:122103618:G:T	W57C	0.986
3:122106204:T:G	F136C	0.986
3:122106282:G:A	G162D	0.986
3:122106450:G:A	C218Y	0.986
3:122106451:T:G	C218W	0.986

dbSNP variants (sampled 300 via entrez): RS1000050127 (3:122118948 C>T), RS1000050980 (3:122071952 T>C,G), RS1000162711 (3:122091831 G>A), RS1000219103 (3:122057809 T>G), RS1000231377 (3:122061269 T>C), RS1000320171 (3:122107510 G>A), RS1000378085 (3:122078508 T>C), RS1000453825 (3:122101158 A>T), RS1000499977 (3:122059190 G>A), RS1000539830 (3:122083236 G>T), RS1000560913 (3:122111251 T>C), RS1000658798 (3:122106271 A>G,T), RS1000804579 (3:122068038 A>G), RS1000812203 (3:122085491 C>A,G), RS1000926975 (3:122082793 A>G)

Disease associations

OMIM: gene MIM:601020 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001198_10	Multiple sclerosis	1.000000e-11
GCST001198_78	Multiple sclerosis	2.000000e-08
GCST001198_79	Multiple sclerosis	6.000000e-08
GCST001341_9	Multiple sclerosis	2.000000e-07
GCST002636_8	Diffuse large B cell lymphoma	8.000000e-08
GCST002643_8	Follicular lymphoma	2.000000e-07
GCST003566_10	Multiple sclerosis	1.000000e-09
GCST003814_4	Selective IgA deficiency	2.000000e-07
GCST003854_45	Gut microbiota (functional units)	2.000000e-06
GCST004867_29	Systemic lupus erythematosus	6.000000e-06
GCST005531_112	Multiple sclerosis	1.000000e-24
GCST007847_108	Type 2 diabetes	5.000000e-09
GCST009597_324	Multiple sclerosis	8.000000e-10
GCST010571_22	Autoimmune thyroid disease	3.000000e-08
GCST90002381_183	Eosinophil count	4.000000e-13
GCST90002382_578	Eosinophil percentage of white cells	7.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364156 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — CD molecules

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
abatacept	Inhibition	7.92	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases expression, affects response to substance, affects expression, affects reaction, affects cotreatment (+2 more)	20
Dinitrochlorobenzene	increases expression, affects expression, affects reaction, decreases reaction	15
nickel sulfate	decreases reaction, increases expression, affects expression	11
4-phenylenediamine	increases expression, decreases reaction	6
cinnamaldehyde	increases expression	5
Bandrowski’s base	affects expression, increases expression, affects reaction	5
Acetylcysteine	decreases reaction, increases expression, affects expression, affects reaction	5
Eugenol	decreases activity, decreases reaction, increases expression	5
Particulate Matter	increases expression, increases reaction, decreases reaction, decreases expression, affects reaction	5
Vehicle Emissions	affects reaction, increases expression, increases reaction, decreases reaction, decreases expression	4
Nickel	increases expression	4
Poly I-C	decreases reaction, increases expression, affects cotreatment, increases secretion	4
nickel chloride	increases expression	3
Ribomunyl	affects cotreatment, increases secretion, increases expression, increases reaction	3
lipopolysaccharide, E coli O55-B5	increases expression	3
Arsenic Trioxide	decreases reaction, increases expression, decreases expression, affects cotreatment	3
Calcitriol	decreases expression, increases expression, affects cotreatment	3
Silicon Dioxide	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, decreases reaction, increases expression, increases reaction	3
Thimerosal	decreases reaction, increases expression	3
methylmercuric chloride	increases expression	2
diethyl phthalate	affects expression, affects cotreatment, decreases expression, decreases reaction	2
diethyl maleate	decreases reaction, increases expression, affects cotreatment	2
tetrachloroplatinate	increases expression	2
hexyl cinnamic aldehyde	affects cotreatment, increases expression, affects reaction	2
SB 203580	decreases reaction, increases expression	2
6-formylindolo(3,2-b)carbazole	affects reaction, decreases expression, affects cotreatment, affects expression	2
lipopolysaccharide, Escherichia coli O111 B4	increases expression, decreases reaction	2
Aluminum Hydroxide	increases expression, increases reaction	2
Benzo(a)pyrene	decreases reaction, increases expression, increases methylation	2

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 2 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1BP	Abcam Raji CD86 KO	Cancer cell line	Male
CVCL_B8DA	Abcam HCT 116 CD86 KO	Cancer cell line	Male
CVCL_B8TT	Abcam MCF-7 CD86 KO	Cancer cell line	Female
CVCL_B9FH	Abcam A-549 CD86 KO	Cancer cell line	Male
CVCL_C1IJ	CMT-12HuB7-2C10	Cancer cell line	Female
CVCL_C4TR	L14-hCD86(13)	Transformed cell line	Male
CVCL_D9BK	Ubigene HEK293 CD86 KO	Transformed cell line	Female
CVCL_KA36	CHO-K1/CD86	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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