CD80

Summary

CD80 (CD80 molecule, HGNC:1700) is a protein-coding gene on chromosome 3q13.33, encoding T-lymphocyte activation antigen CD80 (P33681). Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation.

The protein encoded by this gene is a membrane receptor that is activated by the binding of CD28 or CTLA-4. The activated protein induces T-cell proliferation and cytokine production. This protein can act as a receptor for adenovirus subgroup B and may play a role in lupus neuropathy.

Source: NCBI Gene 941 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 36 total
• Druggable target: yes
• MANE Select transcript: NM_005191

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1700
Approved symbol	CD80
Name	CD80 molecule
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	B7.1, B7-1
Ensembl gene	ENSG00000121594
Ensembl biotype	protein_coding
OMIM	112203
Entrez	941

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000264246, ENST00000383669, ENST00000463729, ENST00000478182, ENST00000853991, ENST00000853992

RefSeq mRNA: 1 — MANE Select: NM_005191 NM_005191

CCDS: CCDS2989

Canonical transcript exons

ENST00000264246 — 7 exons

Exon	Start	End
ENSE00000823622	119544550	119544867
ENSE00000967524	119537137	119537418
ENSE00000967525	119529842	119529937
ENSE00001074119	119557629	119557928
ENSE00001074125	119527733	119527841
ENSE00001333600	119524293	119525749
ENSE00001878576	119559440	119559614

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 92.84.

FANTOM5 (CAGE): breadth broad, TPM avg 6.0206 / max 570.6848, expressed in 309 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43995	2.9953	267
43994	1.2062	179
43996	0.8184	172
43992	0.3922	69
43997	0.2778	101
43998	0.1285	48
43999	0.1055	39
43990	0.0624	42
43991	0.0343	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.84	gold quality
lower lobe of lung	UBERON:0008949	73.97	gold quality
pancreatic ductal cell	CL:0002079	73.67	silver quality
tibialis anterior	UBERON:0001385	73.63	silver quality
vermiform appendix	UBERON:0001154	70.18	gold quality
lymph node	UBERON:0000029	70.12	gold quality
spleen	UBERON:0002106	67.03	gold quality
upper lobe of lung	UBERON:0008948	66.83	gold quality
upper lobe of left lung	UBERON:0008952	66.46	gold quality
ileal mucosa	UBERON:0000331	65.88	gold quality
diaphragm	UBERON:0001103	65.43	gold quality
caecum	UBERON:0001153	65.40	gold quality
superficial temporal artery	UBERON:0001614	65.09	silver quality
oocyte	CL:0000023	64.67	gold quality
lung	UBERON:0002048	63.01	gold quality
tonsil	UBERON:0002372	62.66	gold quality
rectum	UBERON:0001052	61.91	gold quality
right lung	UBERON:0002167	61.47	gold quality
upper leg skin	UBERON:0004262	59.11	gold quality
deltoid	UBERON:0001476	58.94	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	58.74	gold quality
gall bladder	UBERON:0002110	58.47	gold quality
decidua	UBERON:0002450	56.55	gold quality
cranial nerve II	UBERON:0000941	56.34	gold quality
hair follicle	UBERON:0002073	55.78	gold quality
smooth muscle tissue	UBERON:0001135	55.68	gold quality
mucosa of paranasal sinus	UBERON:0005030	55.65	gold quality
leukocyte	CL:0000738	55.42	gold quality
mononuclear cell	CL:0000842	55.31	gold quality
colonic epithelium	UBERON:0000397	54.87	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BCL6, CTCF, GATA1, GATA3, IL33, IRF1, IRF6, IRF7, LILRB1, MAX, MYC, NFKB1, NFKB, RELA, RELB, SPI1, TRERF1

miRNA regulators (miRDB)

87 targeting CD80, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6124	99.87	69.78	3551

Literature-anchored findings (GeneRIF, showing 40)

• Thus, this study is the first demonstration of a distinct signaling event induced by CD80 and CD86 molecules in B cell lymphoma. (PMID:11726649)
• specific small molecule inhibitors of human B7.1 were identified and characterized. These compounds inhibit the binding of B7.1 to both CD28 and CTLA4. (PMID:11741888)
• 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)
• colocalization of ICAM-1 and B7.1 molecules was demonstrated in Hashomoto’s thyroiditis whereas no B7.1 expression was observed in Graves’ disease (PMID:11936473)
• 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)
• Leishmania major infection of macrophages cocultured with neutrophils results in a neutrophil-macrophage interaction via CD80 leading to IFN-gamma secretion and restriction of Leishmania growth. (PMID:12097397)
• expansion of CD5- B cells in multiple sclerosis correlates with CD80 (B7-1) expression (PMID:12100477)
• CD40 and CD80 molecules were observed to play a specific role in the induction of cytotoxic function but not in IFN-gamma production of IL-2-activated NK effectors. (PMID:12149421)
• with ctla4 pathway, is essential for generating regulatory cells after intratracheal delivery of alloantigen in mice (PMID:12352894)
• CD80 and CD86 differ in their interactions with CTLA-4 and that CD80 appears to be the preferential inhibitory ligand for CTLA-4 working via a population of CD4(+) CD25(+) CTLA-4(+) regulatory T cells. (PMID:12355442)
• After B7-1 and B7-2 induction, proximal tubular epithelial cells costimulate CD28 on T lymphocytes resulting in cytokine production. (PMID:12372936)
• data suggest that CD80 acquisition by human T cells might play a role in the immunoregulation of T cell responses (PMID:12444120)
• 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)
• On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases. (PMID:12569387)
• combined use of a vector driving the expression of OX40L with three other costimulatory molecules (B7-1, ICAM-1, and LFA-3) both enhances initial activation and then further potentiates sustained activation of nai;ve and effector T cells. (PMID:12798307)
• ICOS-B7H costimulatory pathway may be involved in the negative regulation of cell-mediated immune responses. (PMID:12800259)
• expression profiles and relative contribution in the porcine-human xenogeneic response (PMID:12829914)
• effect of PGE2 on the expression of ICAM-1 and B7 in the human mixed leukocyte reaction (MLR) in the presence or absence of IL-18 (PMID:12829919)
• results show that BCL6 prevents CD40-induced expression of CD80 by binding its promoter region in vivo and suppressing its transcriptional activation by NF-kappaB (PMID:12860928)
• 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)
• The CD80 immunoglobulin constant-like (C)-domain has a negative/regulatory effect on the immune response to a plasmid DNA vaccine; loss of the CD80 C-domain prevents modulation of the immune activation signal. (PMID:14530356)
• results confirm that both the CD80 and CD86 molecules play an important role in the maintenance and amplification of the inflammatory process (PMID:14692664)
• 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)
• CD80 and CD86 have opposite roles in the functioning of human regulatory T cells via CD28 and CTLA-4, an observation that has significant implications for manipulation of immune responses and tolerance in vivo. (PMID:14978077)
• 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)
• 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)
• B7-1 gene transduction might be effective against peritoneal metastases of gastric cancer. (PMID:15201958)
• CD80 has a role in activating cytotoxic T lymphocytes in hepatocellular carcinoma cells (PMID:15254713)
• CD80 driven by NF-kappaB is regulated by the enzymatic actions of caspases, which allows monocytes to participate in massive T-cell activation (PMID:15254772)
• data demonstrated a correlation between HIV infection and impairment of CD80 by circulating monocytes (PMID:15272203)
• There is a potential role of B7 co-stimulatory molecules in facilitating hepatocellular carcinoma escape from immune surveillance without the involvement of IL-10. (PMID:15377288)
• CD80 binding polyproline helical peptide has a role inhibiting T cell activation (PMID:15598660)
• Upregulation in the colonic mucosa of patients with ulcerative colitis. (PMID:15628695)
• 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)
• LPS-induced B7.1 transcription in human monocytic cells may be regulated by JNK-mediated activation of the IRF-7 transcription factor. (PMID:16237059)
• Th2 cytokine predominant in tumor microenvironment might be related to the expression of B(7)H(1),B(7)H(2) co-signal molecules in tumor cells and TIL (PMID:16237760)
• CD80 transfection can lower malignant phenotype of hepatocarcinoma cells and has a down-regulatory effect to activated T cells in vitro. (PMID:16521215)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd80	ENSMUSG00000075122
rattus_norvegicus	Cd80	ENSRNOG00000001527

Paralogs (12): CD86 (ENSG00000114013), CD274 (ENSG00000120217), 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 CD80 — P33681 (reviewed: P33681)

Alternative names: Activation B7-1 antigen, BB1, CTLA-4 counter-receptor B7.1

All UniProt accessions (2): A0N0P2, P33681

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. In turn, activates different signaling pathways such as NF-kappa-B or MAPK leading to the production of different cytokines. 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. In addition, CD28/CD80 costimulatory signal stimulates glucose metabolism and ATP synthesis of T-cells by activating the PI3K/Akt signaling pathway. Also acts as a regulator of PDL1/PDCD1 interactions to limit excess engagement of PDL1 and its inhibitory role in immune responses. Expressed on B-cells, plays a critical role in regulating interactions between B-cells and T-cells in both early and late germinal center responses, which are crucial for the generation of effective humoral immune responses. (Microbial infection) Acts as a receptor for adenovirus subgroup B.

Subunit / interactions. Homodimer. Interacts with PDL1/CD274; this interaction blocks PDL1/PDCD1 binding and thus PDL1/CD274 inhibitory function. Interacts with CD28. (Microbial infection) Interacts with adenovirus subgroup B fiber proteins. (Microbial infection) Interacts with Orthopoxvirus OPG038/M2 protein, inhibiting the interaction with CTLA4/CD152.

Subcellular location. Cell membrane.

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

Post-translational modifications. Palmitoylated by ZDHHC20; palmitoylation protects CD80 from ubiquitin-mediated degradation, regulating the protein stability, and ensures its accurate plasma membrane localization.

Miscellaneous. Soluble isoform. Expressed in unstimulated B-cells and monocytes, but not T-cells. Soluble isoform. Expressed in T-cells activated by ConA, non-activated monocytes and monocytes activated with IFN-c.

Isoforms (3)

UniProt ID	Names	Canonical?
P33681-1	1	yes
P33681-2	2, s1CD80
P33681-3	3, s2CD80

RefSeq proteins (1): NP_005182* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037676	CD80_IgC	Domain
IPR042711	CD80_IgV	Domain
IPR051713	T-cell_Activation_Regulation	Family

Pfam: PF07686, PF08205

UniProt features (51 total): strand 17, glycosylation site 8, lipid moiety-binding region 4, mutagenesis site 4, splice variant 3, helix 3, topological domain 2, disulfide bond 2, turn 2, domain 2, signal peptide 1, chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8FXW	ELECTRON MICROSCOPY	2.7
8FXZ	ELECTRON MICROSCOPY	2.86
1DR9	X-RAY DIFFRACTION	3
1I8L	X-RAY DIFFRACTION	3
8HXA	ELECTRON MICROSCOPY	3.04
7TPS	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33681-F1	86.17	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 266, 271, 284, 261, 262

Disulfide bonds (2): 50–116, 162–216

Glycosylation sites (8): 53, 89, 98, 186, 207, 211, 226, 232

Mutagenesis-validated functional residues (4):

Position	Phenotype
261	loss of costimulatory function upon t-cell activation; when associated with s-262, s-266 and s-271.
262	loss of costimulatory function upon t-cell activation; when associated with s-261, s-266 and s-271.
266	loss of costimulatory function upon t-cell activation; when associated with s-261, s-262 and s-271.
271	loss of costimulatory function upon t-cell activation; when associated with s-261, s-262 and s-266.

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: 405 (showing top): GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE

GO Biological Process (21): negative regulation of T cell mediated immunity (GO:0002710), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), positive regulation of signal transduction (GO:0009967), T cell costimulation (GO:0031295), positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725), positive regulation of interleukin-2 production (GO:0032743), intracellular signal transduction (GO:0035556), positive regulation of T cell proliferation (GO:0042102), T cell activation (GO:0042110), negative regulation of T cell proliferation (GO:0042130), positive regulation of T-helper 1 cell differentiation (GO:0045627), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), 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), immune system process (GO:0002376), regulation of immune system process (GO:0002682), symbiont entry into host cell (GO:0046718)

GO Molecular Function (4): virus receptor activity (GO:0001618), coreceptor activity (GO:0015026), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), protein complex involved in cell adhesion (GO:0098636), 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
signal transduction	4
immune system process	2
positive regulation of T cell activation	2
positive regulation of cytokine production	2
T cell proliferation	2
regulation of T cell proliferation	2
T cell receptor signaling pathway	2
regulation of T cell receptor signaling pathway	2
cellular anatomical structure	2
T cell mediated immunity	1
negative regulation of lymphocyte mediated immunity	1
regulation of T cell mediated immunity	1
negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
response to stimulus	1
regulation of signal transduction	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of response to stimulus	1
lymphocyte costimulation	1
granulocyte macrophage colony-stimulating factor production	1
regulation of granulocyte macrophage colony-stimulating factor production	1
positive regulation of protein metabolic process	1
interleukin-2 production	1
regulation of interleukin-2 production	1
intracellular anatomical structure	1
positive regulation of lymphocyte proliferation	1
lymphocyte activation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
positive regulation of immune effector process	1
T-helper 1 cell differentiation	1
positive regulation of T-helper cell differentiation	1
regulation of T-helper 1 cell differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of protein phosphorylation	1
peptidyl-tyrosine phosphorylation	1
regulation of peptidyl-tyrosine phosphorylation	1
negative regulation of antigen receptor-mediated signaling pathway	1

Protein interactions and networks

STRING

3542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD80	CD28	P10747	999
CD80	CTLA4	P16410	999
CD80	CD40	P25942	999
CD80	CD40LG	P29965	998
CD80	ICAM1	P05362	997
CD80	PDCD1	Q15116	997
CD80	ICOS	Q9Y6W8	997
CD80	CD58	P19256	994
CD80	TNFRSF4	P43489	994
CD80	PDCD1LG2	Q9BQ51	993
CD80	CD86	P42081	990
CD80	LAG3	P18627	989
CD80	CD27	P26842	989
CD80	CD274	Q9NZQ7	989
CD80	CD276	Q5ZPR3	987

IntAct

38 interactions, top by confidence:

A	B	Type	Score
CD80	CD274	psi-mi:“MI:0407”(direct interaction)	0.950
CD274	CD80	psi-mi:“MI:0407”(direct interaction)	0.950
CD80	CD274	psi-mi:“MI:0915”(physical association)	0.950
CD274	CD80	psi-mi:“MI:0915”(physical association)	0.950
CD80	CTLA4	psi-mi:“MI:0407”(direct interaction)	0.880
CD80	CTLA4	psi-mi:“MI:0915”(physical association)	0.880
CTLA4	CD80	psi-mi:“MI:0407”(direct interaction)	0.880
CTLA4	CD80	psi-mi:“MI:0915”(physical association)	0.880
CD80	NGFR	psi-mi:“MI:0915”(physical association)	0.800
CD80	NGFR	psi-mi:“MI:0407”(direct interaction)	0.800
NGFR	CD80	psi-mi:“MI:0915”(physical association)	0.800
CD80	NGFR	psi-mi:“MI:0403”(colocalization)	0.800
CD28	CD80	psi-mi:“MI:0915”(physical association)	0.710
CD80	CD28	psi-mi:“MI:0915”(physical association)	0.710

BioGRID (84): CD80 (Reconstituted Complex), CD80 (Co-localization), CD80 (Synthetic Lethality), CD80 (Reconstituted Complex), CD80 (Reconstituted Complex), CD80 (Affinity Capture-RNA), SLC25A5 (Affinity Capture-MS), ABCB8 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), DNAAF5 (Affinity Capture-MS), DPH6 (Affinity Capture-MS), FASTKD3 (Affinity Capture-MS), MTX1 (Affinity Capture-MS), GPD1L (Affinity Capture-MS), TTI2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E4BZH1, A2A7V7, A5D7B2, A5D7V5, A7TZE6, A7TZF0, A7TZF3, A7XUX6, A7XV04, A7XV07, G3X8R9, O75144, P0DMS9, P12318, P31994, P31995, P33681, P42070, P55803, Q16653, Q29ZQ1, Q5R960, Q5RFR2, Q60513, Q61885, Q63345, Q63994, Q68D85, Q6Q8B3, Q6QLQ4, Q6SJQ5, Q6XJV4, Q6XJV6, Q7TST0, Q8BTP3, Q8HZR8, Q8K249, Q8SPV8, Q8TD46, Q8VCH2

Diamond homologs: P33681, P42070, Q00609, Q868Z9, Q9H6B4, P42081, Q92823, A2AJ76, A2ASS6, P0C673, P97792, Q03142, Q08DK1, Q29RR6, Q498D6, Q4KLY3, Q5DTJ9, Q5DX21, Q5U2P2, Q640U3, Q86TC9, Q86XK7, Q8K1G0, Q8R373, Q8WMV3, Q8WX93, Q90Y50, Q96AP7, Q96IQ7, Q96LA5, Q99795, Q9D2J4, Q9JKA5, Q9PWR4, Q9R066

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NfKb-p65/p50	“up-regulates quantity by expression”	CD80	“transcriptional regulation”
sirolimus	“down-regulates quantity by repression”	CD80
BCL6	“down-regulates quantity by repression”	CD80	“transcriptional regulation”
NFKB1	“up-regulates quantity by expression”	CD80	“transcriptional regulation”
RELA	“up-regulates quantity by expression”	CD80	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1189 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119537133:TTAC:T	donor_loss	1.0000
3:119537134:TA:T	donor_loss	1.0000
3:119537135:A:AC	donor_gain	1.0000
3:119537135:A:C	donor_loss	1.0000
3:119537136:C:CA	donor_gain	1.0000
3:119537136:CT:C	donor_gain	1.0000
3:119537136:CTT:C	donor_gain	1.0000
3:119537136:CTTG:C	donor_gain	1.0000
3:119537136:CTTGT:C	donor_gain	1.0000
3:119537419:C:CC	acceptor_gain	1.0000
3:119544547:AAC:A	donor_loss	1.0000
3:119544548:ACCT:A	donor_loss	1.0000
3:119544549:C:T	donor_loss	1.0000
3:119544864:ACAC:A	acceptor_gain	1.0000
3:119544865:CAC:C	acceptor_gain	1.0000
3:119544865:CACC:C	acceptor_gain	1.0000
3:119544867:CCTA:C	acceptor_gain	1.0000
3:119544868:C:CC	acceptor_gain	1.0000
3:119544868:C:CG	acceptor_loss	1.0000
3:119544869:T:G	acceptor_loss	1.0000
3:119544870:A:AC	acceptor_gain	1.0000
3:119544870:A:C	acceptor_gain	1.0000
3:119557794:T:TA	donor_gain	1.0000
3:119557795:C:A	donor_gain	1.0000
3:119559435:CTTA:C	donor_gain	1.0000
3:119559436:TTA:T	donor_loss	1.0000
3:119559437:TAC:T	donor_loss	1.0000
3:119559438:A:AC	donor_gain	1.0000
3:119559438:ACT:A	donor_loss	1.0000
3:119559438:ACTTG:A	donor_gain	1.0000

AlphaMissense

1898 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119537312:C:A	W175C	0.997
3:119537312:C:G	W175C	0.997
3:119544699:C:G	R90P	0.997
3:119537412:A:C	F142C	0.996
3:119544768:T:G	Q67P	0.996
3:119544621:C:G	C116S	0.995
3:119544622:A:T	C116S	0.995
3:119544770:C:A	W66C	0.995
3:119544770:C:G	W66C	0.995
3:119537314:A:G	W175R	0.994
3:119537314:A:T	W175R	0.994
3:119537352:C:G	C162S	0.994
3:119537353:A:T	C162S	0.994
3:119537190:C:G	C216S	0.993
3:119537191:A:T	C216S	0.993
3:119537351:G:C	C162W	0.993
3:119544622:A:G	C116R	0.993
3:119537353:A:G	C162R	0.992
3:119544620:A:C	C116W	0.992
3:119544780:C:G	R63P	0.992
3:119544639:T:A	D110V	0.991
3:119537411:G:C	F142L	0.990
3:119537411:G:T	F142L	0.990
3:119537413:A:G	F142L	0.990
3:119544639:T:G	D110A	0.990
3:119537191:A:G	C216R	0.989
3:119544628:A:C	Y114D	0.989
3:119544772:A:G	W66R	0.989
3:119544772:A:T	W66R	0.989
3:119537352:C:T	C162Y	0.988

dbSNP variants (sampled 300 via entrez): RS1000213010 (3:119545406 T>G), RS1000244113 (3:119543558 G>A), RS1000533706 (3:119529740 A>C,G), RS1000679202 (3:119539635 G>C), RS1000881304 (3:119556523 A>C), RS1000910681 (3:119556201 A>T), RS1000984698 (3:119561535 A>T), RS1001114056 (3:119539286 A>G,T), RS1001210630 (3:119537485 T>A), RS1001234818 (3:119558626 G>A), RS1001260669 (3:119552403 C>G,T), RS1001300164 (3:119533507 G>A), RS1001364509 (3:119546685 G>A), RS1001432882 (3:119558481 G>A,C), RS1001526138 (3:119540046 G>A)

Disease associations

OMIM: gene MIM:112203 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000612_22	Celiac disease	8.000000e-09
GCST001010_11	Primary biliary cholangitis	3.000000e-11
GCST001509_7	Vitiligo	4.000000e-10
GCST001685_4	Primary biliary cholangitis	3.000000e-09
GCST001795_3	Systemic lupus erythematosus	3.000000e-16
GCST002266_1	Lobular breast cancer (menopausal hormone therapy interaction)	5.000000e-06
GCST002845_1	Systemic lupus erythematosus	5.000000e-08
GCST003129_25	Primary biliary cholangitis	4.000000e-15
GCST004145_1	Primary biliary cholangitis	1.000000e-06
GCST004162_39	Carotid plaque burden	6.000000e-06
GCST004302_6	Primary biliary cholangitis	3.000000e-13
GCST004785_13	Vitiligo	5.000000e-15
GCST005528_1	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	4.000000e-07
GCST005581_44	Primary biliary cirrhosis	7.000000e-16
GCST009131_7	Systemic sclerosis	2.000000e-10
GCST010042_124	Asthma	3.000000e-08
GCST010043_114	Asthma	3.000000e-08
GCST010571_21	Autoimmune thyroid disease	3.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0003961	hormone replacement therapy
EFO:0006501	carotid plaque build

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364157 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs34394661	CD80		0.00	0

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

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects reaction, decreases reaction, increases expression, affects cotreatment, decreases expression (+2 more)	10
lipopolysaccharide, E coli O55-B5	increases expression	4
Particulate Matter	affects reaction, increases expression, increases reaction, decreases reaction, increases abundance	4
Vehicle Emissions	increases reaction, decreases reaction, increases abundance, affects reaction, increases expression	3
(+)-JQ1 compound	increases expression, decreases expression, decreases reaction	2
Calcitriol	decreases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression, affects binding, increases reaction, decreases expression	2
helenalin	decreases reaction, increases expression	1
triptolide	increases expression, affects cotreatment, decreases reaction	1
quinone	increases expression	1
lasiocarpine	increases expression	1
imidazolidinyl urea	increases expression	1
bisphenol A	increases expression	1
diethyl maleate	affects cotreatment, increases expression	1
hydroxycitronellal	increases expression	1
nickel chloride	increases expression	1
4-methylhistamine	decreases reaction, increases expression	1
glucuronoxylomannan	increases expression	1
24,25-epoxycholesterol	decreases expression	1
nickel sulfate	increases expression	1
Ribomunyl	increases expression	1
heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
Bandrowski’s base	increases expression	1
3,5-di-tert-butylchalcone 4’-carboxylic acid	decreases expression	1
chromium hexavalent ion	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
LW 50020	increases expression	1
hexyl cinnamic aldehyde	affects cotreatment, increases expression	1
MF59 oil emulsion	decreases reaction, increases expression, affects cotreatment	1

Cellosaurus cell lines

25 cell lines: 21 cancer cell line, 2 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5AM	A904L-CD80	Cancer cell line	Male
CVCL_A5AN	A904L-A26	Cancer cell line	Male
CVCL_A5AP	A904L-B39	Cancer cell line	Male
CVCL_A5AQ	A529L-CD80	Cancer cell line	Male
CVCL_A5AR	B1203L-CD80	Cancer cell line	Male
CVCL_A5AS	B203L-CD80	Cancer cell line	Sex unspecified
CVCL_A5AT	B901L-CD80	Cancer cell line	Female
CVCL_B1BN	Abcam Raji CD80 KO	Cancer cell line	Male
CVCL_B8D9	Abcam HCT 116 CD80 KO	Cancer cell line	Male
CVCL_B8TS	Abcam MCF-7 CD80 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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