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
• GTEx eGene: eQTL in 11 tissues, sQTL in 2 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs
• Approved drugs (ChEMBL mechanism of action): 2 — Abatacept, Belatacept
• Constraint (gnomAD): pLI 0.93 (loss-of-function intolerant), LOEUF 0.56 (moderately constrained)
• MANE Select transcript: NM_175862
• Interaction hub: 3,560 STRING partners (top 1% of genes corpus-wide)
• Notable: 70 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 12 — 9 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000330540

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 4: 2, TSL 5: 2

ENST00000330540, ENST00000264468, ENST00000393627, ENST00000469710, ENST00000478390, ENST00000478741, ENST00000482356, ENST00000483949, ENST00000493101, ENST00001099115, ENST00001126990, ENST00001144752

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.

Highest expression (Bgee): monocyte, mononuclear cell, leukocyte, granulocyte, vermiform appendix.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CD86 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	9.8e-15	+0.50	3:122102296:T:G
Cells EBV-transformed lymphocytes	sqtl	8.0e-09	-0.97	3:122077242:G:A
Nerve Tibial	eqtl	2.7e-04	-0.16	3:122174777:A:G
Whole Blood	eqtl	5.5e-03	+0.16	3:121995172:T:C
Heart Atrial Appendage	eqtl	8.2e-03	-0.12	3:121892967:G:A
Esophagus Mucosa	eqtl	1.8e-02	+0.40	3:122964663:G:A
Uterus	eqtl	2.1e-02	-1.49	3:122964663:G:A
Colon Transverse	eqtl	2.7e-02	+0.19	3:121906076:T:C
Lung	eqtl	3.1e-02	-0.10	3:122011616:T:C
Esophagus Muscularis	eqtl	3.2e-02	+0.16	3:121995172:T:C
Brain Cerebellar Hemisphere	eqtl	4.6e-02	-0.47	3:122935935:C:A
Artery Coronary	sqtl	4.7e-02	+0.66	3:122976381:C:T
Thyroid	eqtl	4.8e-02	-0.21	3:121658727:A:G

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

showing 100 of 285 tissues 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
peritoneum	UBERON:0002358	72.31	gold quality
coronary artery	UBERON:0001621	72.18	gold quality
adipose tissue of abdominal region	UBERON:0007808	71.91	gold quality
right adrenal gland cortex	UBERON:0035827	71.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	71.32	gold quality
superficial temporal artery	UBERON:0001614	71.21	silver quality
calcaneal tendon	UBERON:0003701	71.07	gold quality
tonsil	UBERON:0002372	70.87	gold quality
left adrenal gland cortex	UBERON:0035825	70.53	gold quality
left adrenal gland	UBERON:0001234	70.50	gold quality
right adrenal gland	UBERON:0001233	70.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.25	gold quality
aorta	UBERON:0000947	69.70	gold quality
parotid gland	UBERON:0001831	69.67	silver quality
adrenal cortex	UBERON:0001235	69.56	gold quality
adrenal gland	UBERON:0002369	69.53	gold quality
pancreatic ductal cell	CL:0002079	69.51	silver quality
tibial nerve	UBERON:0001323	69.42	gold quality
small intestine	UBERON:0002108	69.13	gold quality
placenta	UBERON:0001987	68.93	gold quality
cranial nerve II	UBERON:0000941	68.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	68.72	gold quality
lower lobe of lung	UBERON:0008949	68.67	silver quality
colonic mucosa	UBERON:0000317	68.24	gold quality
layer of synovial tissue	UBERON:0007616	68.20	gold quality
intestine	UBERON:0000160	68.07	gold quality
adipose tissue	UBERON:0001013	67.83	gold quality
transverse colon	UBERON:0001157	67.80	gold quality
large intestine	UBERON:0000059	67.79	gold quality
amniotic fluid	UBERON:0000173	67.72	gold quality
colon	UBERON:0001155	67.46	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	67.37	silver quality
connective tissue	UBERON:0002384	67.31	gold quality
tibial artery	UBERON:0007610	67.20	gold quality
inferior olivary complex	UBERON:0002127	67.19	silver quality
popliteal artery	UBERON:0002250	67.16	gold quality
mucosa of stomach	UBERON:0001199	67.04	gold quality
ileal mucosa	UBERON:0000331	66.93	silver quality
urinary bladder	UBERON:0001255	66.90	gold quality
parietal pleura	UBERON:0002400	66.68	gold quality
pleura	UBERON:0000977	66.64	gold quality
substantia nigra	UBERON:0002038	66.34	gold quality
sigmoid colon	UBERON:0001159	66.04	gold quality
epithelial cell of pancreas	CL:0000083	65.88	silver quality
mucosa of transverse colon	UBERON:0004991	65.85	gold quality
right atrium auricular region	UBERON:0006631	65.70	gold quality
gluteal muscle	UBERON:0002000	65.35	silver quality
triceps brachii	UBERON:0001509	65.25	gold quality
palpebral conjunctiva	UBERON:0001812	65.06	gold quality
visceral pleura	UBERON:0002401	65.06	gold quality
midbrain	UBERON:0001891	65.00	gold quality
islet of Langerhans	UBERON:0000006	64.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	64.92	gold quality
saliva-secreting gland	UBERON:0001044	64.84	gold quality
upper leg skin	UBERON:0004262	64.77	gold quality
cardiac atrium	UBERON:0002081	64.63	gold quality
left uterine tube	UBERON:0001303	64.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.45	gold quality
minor salivary gland	UBERON:0001830	64.34	gold quality
CA1 field of hippocampus	UBERON:0003881	64.19	gold quality
liver	UBERON:0002107	63.96	gold quality
jejunal mucosa	UBERON:0000399	63.95	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	63.90	gold quality
skin of hip	UBERON:0001554	63.68	gold quality
anatomical system	UBERON:0000467	63.67	gold quality
trabecular bone tissue	UBERON:0002483	63.65	gold quality
multicellular organism	UBERON:0000468	63.63	gold quality
material anatomical entity	UBERON:0000465	63.62	gold quality
duodenum	UBERON:0002114	63.53	gold quality
prefrontal cortex	UBERON:0000451	63.52	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Appendix	tissue	32.5
Lymph node	tissue	27.0	high
Spleen	tissue	22.0	medium
Olfactory bulb	tissue	21.2
Tonsil	tissue	20.6	medium
Cerebellum	tissue	18.7	medium
Amygdala	tissue	18.2
Lung	tissue	17.6	medium
Cerebral cortex	tissue	17.2	medium
Corpus callosum	tissue	17.2
Periaqueductal gray	tissue	17.2
Insular cortex	tissue	17.2
Retrosplenial cortex	tissue	16.7
Retrosplenial and cingulate cortex	tissue	16.5
Septum	tissue	16.5
Basal ganglia	tissue	16.3	low
Hypothalamus	tissue	16.3
Ventral forebrain	tissue	15.9
Temporal cortex	tissue	15.7
Hippocampal formation	tissue	15.6
Entorhinal cortex	tissue	15.6
Prefrontal cortex	tissue	15.4
Substantia nigra	tissue	14.6
Spinal cord	tissue	14.6
Putamen	tissue	14.5
Occipital cortex	tissue	14.4
Placenta	tissue	14.0	medium
Urinary bladder	tissue	13.9	medium
Motor cortex	tissue	13.9
Gallbladder	tissue	13.4	not detected
Midbrain	tissue	13.3
Medulla oblongata	tissue	13.0
Somatosensory cortex	tissue	12.9
Pons	tissue	12.5
Thalamus	tissue	11.3
Liver	tissue	10.5	not detected
Superior colliculi	tissue	10.3
Thymus	tissue	9.9
Bone marrow	tissue	9.7	low
Choroid plexus	tissue	7.5
Adipose tissue	tissue	7.3	not detected
Rectum	tissue	7.2	medium
Smooth muscle	tissue	6.9	not detected
Small intestine	tissue	6.4	medium
Colon	tissue	5.9	medium
Adrenal gland	tissue	5.0	not detected
Stomach 1	tissue	4.9	medium
Locus coeruleus	tissue	4.6
Breast	tissue	4.1	medium
Esophagus	tissue	3.8	low
Hippocampus	tissue	3.8	medium
Duodenum	tissue	3.5	medium
Cervix	tissue	3.3	not detected
Testis	tissue	2.9	low
Parathyroid gland	tissue	2.7	not detected
Frontal cortex	tissue	2.7
Nucleus accumbens	tissue	2.7
Caudate putamen	tissue	2.6
Heart muscle	tissue	2.5	not detected
Pancreas	tissue	2.4	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Lateral funiculus (white matter) (18.8), White matter (17.2), Subiculum (15.1), Dorsal spinal cord (14.6), Ventral hippocampus (14.4).

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)

Targeting CD86 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 58 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.926, LOEUF 0.555, missense Z 1.11 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000330540 — one region, missense o/e 0.90.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:101773) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 35 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased B cell number	3
decreased T cell proliferation	2
abnormal nerve conduction	2
increased CD8-positive, alpha-beta T cell number	2
increased interferon-gamma secretion	2
lymphoid hyperplasia	1
spleen hyperplasia	1
paresis	1
hindlimb paralysis	1
demyelination	1
abnormal dorsal root ganglion morphology	1
abnormal humoral immune response	1
decreased IgG level	1
abnormal inflammatory response	1
abnormal B cell differentiation	1
muscular atrophy	1
abnormal nervous system morphology	1
increased autoantibody level	1
abnormal myelin sheath morphology	1
abnormal ventral spinal root morphology	1
abnormal dorsal spinal root morphology	1
increased susceptibility to autoimmune diabetes	1
decreased susceptibility to autoimmune diabetes	1
decreased regulatory T cell number	1
increased T cell number	1

+10 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryctolagus cuniculus	P42071	57.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIX23	protein-coding	131076
CSTA	protein-coding	1475
ILDR1	protein-coding	286676
CASR	protein-coding	846
EAF2	protein-coding	55840
SLC15A2	protein-coding	6565
IQCB1	protein-coding	9657

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 by resolution:

PDB	Title	Method	Resolution (Å)
5YXK	High resolution crystal structure of Human B7-2 IgV domain in P21 space group	X-RAY DIFFRACTION	1.9
1NCN	the receptor-binding domain of human B7-2	X-RAY DIFFRACTION	2.7
8HXB	Cryo-EM structure of MPXV M2 hexamer in complex with human B7.2	ELECTRON MICROSCOPY	2.7
8HXC	Cryo-EM structure of MPXV M2 heptamer in complex with human B7.2	ELECTRON MICROSCOPY	3.12
1I85	CRYSTAL STRUCTURE OF THE CTLA-4/B7-2 COMPLEX	X-RAY DIFFRACTION	3.2
8FXX	Cryo-EM structure of cowpox virus M2 in complex with human B7.2 (heptameric ring)	ELECTRON MICROSCOPY	3.26
8FXY	Cryo-EM structure of cowpox virus M2 in complex with human B7.2 (hexameric ring)	ELECTRON MICROSCOPY	3.34

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins, FDA approved drug targets, Biotech drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; centriolar satellite

Antibody reliability (HPA): IH approved · IF supported

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)

Type	Positions
Disulfide bond	40–110, 157–218

Glycosylation sites (8)

Type	Positions
N-linked (glcnac…) asparagine	47, 135, 146, 154, 177, 192, 213, 33

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 20; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

20 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-389357	CD28 dependent PI3K/Akt signaling	curated
R-HSA-389359	CD28 dependent Vav1 pathway	curated
R-HSA-389513	Co-inhibition by CTLA4	curated
R-HSA-389356	Co-stimulation by CD28	curated
R-HSA-9968734	Differentiation of Circulating Monocytes	curated
R-HSA-6783783	Interleukin-10 signaling	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-1280218	Adaptive Immune System	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-168256	Immune System	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-199418	Negative regulation of the PI3K/AKT network	—
R-HSA-388841	Regulation of T cell activation by CD28 family	—
R-HSA-162582	Signal Transduction	—
R-HSA-449147	Signaling by Interleukins	—

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 (22): 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), positive regulation of T cell receptor signaling pathway (GO:0050862), 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 (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), extracellular exosome (GO:0070062)

Reactome top-level categories

14 top-level categories:

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
Developmental Cell Lineages	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

showing 60 of 65 GO namespaces:

Category	Terms
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
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
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
positive regulation of antigen receptor-mediated signaling pathway	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
biological_process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
symbiont entry into host cell	1
exogenous protein binding	1
signaling receptor activity	1
molecular transducer activity	1
signaling receptor binding	1
signaling receptor activator activity	1
binding	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
T cell activation	BP	direct assay
positive regulation of T cell receptor signaling pathway	BP	direct assay
cell surface	CC	high-throughput assay
extracellular exosome	CC	direct assay
plasma membrane	CC	direct assay
receptor ligand activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,560 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD86	CD40	P25942	962
CD86	CTLA4	P16410	954
CD86	CD4	P01730	953
CD86	CD28	P10747	945
CD86	IL10	P22301	939
CD86	IFNG	P01579	932
CD86	CD8A	P01732	924
CD86	TNF	P01375	914
CD86	CD83	Q01151	913
CD86	IL4	P05112	908
CD86	IL6	P05231	905
CD86	ITGAX	P20702	883
CD86	MRC1	P22897	881
CD86	ITGAM	P11215	880
CD86	CD40LG	P29965	878

IntAct

Human interaction partners of CD86 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
CTLA4	direct interaction	0.840	6
CD28	physical association	0.610	2
FSTL5	physical association	0.400	1
ECE2	physical association	0.370	1
PARP1	physical association	0.370	1
CD80	proximity	0.270	1

BioGRID (16 interactions; top human partners by supporting records): MARCH1 (Affinity Capture-Western; 4 records), ATR (Affinity Capture-Western; 3 records), CTLA4 (Co-localization; 3 records), CD80 (Co-localization), DDX58 (Affinity Capture-RNA), ECE2 (Two-hybrid), MARCH8 (Affinity Capture-Western), PARP1 (Two-hybrid), TMEM173 (Affinity Capture-MS)

SIGNOR signaling

3 signaling 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

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CD28	ligand
CTLA4	ligand

Disease & clinical

Genetic variants

Variant evidence for CD86: 70 ClinVar records (0 pathogenic / likely pathogenic); 16 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 572):

Position(s)	Effect	Δscore	Sites
3:122079815	donor_gain	0.9800
3:122103804	donor_gain	0.9800
3:122055504–122055505	donor_loss	0.9700	4
3:122103510–122103511	acceptor_loss	0.9700	6
3:122119437	acceptor_gain	0.9700
3:122055505	donor_loss	0.9600
3:122109363	acceptor_gain	0.9600
3:122103823	donor_gain	0.9500
3:122103848–122103849	donor_loss	0.9500	4
3:122103848–122103849	donor_loss	0.9400	2

AlphaMissense

324 missense substitutions predicted likely pathogenic (of 2,203 scored), across 102 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D104	8	0.942	0.984
C110	7	0.981	0.994
C218	7	0.976	0.990
C40	7	0.972	0.989
C157	7	0.972	0.992
F136	7	0.964	0.991
W57	7	0.939	0.989
F56	7	0.929	0.986
F42	7	0.833	0.956
E67	7	0.809	0.897
G162	6	0.927	0.986
P139	6	0.913	0.989
P164	6	0.888	0.938
R85	6	0.886	0.995
G71	6	0.811	0.957
M169	6	0.766	0.936
G106	6	0.763	0.912
S137	6	0.763	0.845
Y82	5	0.952	0.976
Y108	5	0.942	0.988

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:601020 | disease phenotypes:

GWAS associations

16 associations:

Study	Trait	p-value
GCST005531_115	Multiple sclerosis	1e-24
GCST90002382_136	Eosinophil percentage of white cells	7e-15
GCST90002381_7	Eosinophil count	4e-13
GCST001198_61	Multiple sclerosis	1e-11
GCST009597_174	Multiple sclerosis	8e-10
GCST003566_10	Multiple sclerosis	1e-9
GCST007847_83	Type 2 diabetes	5e-9
GCST001198_78	Multiple sclerosis	2e-8
GCST010571_25	Autoimmune thyroid disease	3e-8
GCST001198_79	Multiple sclerosis	6e-8
GCST002636_8	Diffuse large B cell lymphoma	8e-8
GCST001341_9	Multiple sclerosis	2e-7
GCST002643_8	Follicular lymphoma	2e-7
GCST003814_4	Selective IgA deficiency	2e-7
GCST003854_16	Gut microbiota (functional units)	2e-6
GCST004867_22	Systemic lupus erythematosus	6e-6

EFO canonical traits (from GWAS)

3 canonical traits:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CD86 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
ABATACEPT	Protein	4
BELATACEPT	Protein	4

PharmGKB: 1 entry (CPIC guideline: no)

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

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases reaction, decreases expression, affects response to substance, affects expression, affects reaction (+2 more)	20
Dinitrochlorobenzene	affects expression, affects reaction, decreases reaction, increases expression	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	affects expression, affects reaction, decreases reaction, increases expression	5
Eugenol	decreases activity, decreases reaction, increases expression	5
Particulate Matter	affects reaction, increases expression, increases reaction, decreases reaction, decreases expression	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	increases expression, decreases expression, affects cotreatment, decreases reaction	3
Calcitriol	increases expression, affects cotreatment, decreases expression	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	decreases reaction, affects expression, affects cotreatment, decreases expression	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	decreases reaction, increases expression	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)

Via MONDO — disease-level, not drug-specific.