CD276

Summary

CD276 (CD276 molecule, HGNC:19137) is a protein-coding gene on chromosome 15q24.1, encoding CD276 antigen (Q5ZPR3). May participate in the regulation of T-cell-mediated immune response.

The protein encoded by this gene belongs to the immunoglobulin superfamily, and thought to participate in the regulation of T-cell-mediated immune response. Studies show that while the transcript of this gene is ubiquitously expressed in normal tissues and solid tumors, the protein is preferentially expressed only in tumor tissues. Additionally, it was observed that the 3’ UTR of this transcript contains a target site for miR29 microRNA, and there is an inverse correlation between the expression of this protein and miR29 levels, suggesting regulation of expression of this gene product by miR29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 80381 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 126 total
• Druggable target: yes
• MANE Select transcript: NM_001024736

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19137
Approved symbol	CD276
Name	CD276 molecule
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	B7-H3, B7H3, B7RP-2
Ensembl gene	ENSG00000103855
Ensembl biotype	protein_coding
OMIM	605715
Entrez	80381

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 38 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay

ENST00000318424, ENST00000318443, ENST00000537340, ENST00000557951, ENST00000558689, ENST00000559073, ENST00000559465, ENST00000559978, ENST00000560786, ENST00000560928, ENST00000560995, ENST00000561176, ENST00000561213, ENST00000561260, ENST00000561416, ENST00000563584, ENST00000564751, ENST00000567189, ENST00000567582, ENST00000864253, ENST00000864254, ENST00000864255, ENST00000864256, ENST00000864257, ENST00000864258, ENST00000864259, ENST00000864260, ENST00000864261, ENST00000921503, ENST00000921504, ENST00000921505, ENST00000921506, ENST00000921507, ENST00000921508, ENST00000921509, ENST00000921510, ENST00000921511, ENST00000921512, ENST00000953229, ENST00000953230, ENST00000953231, ENST00000953232, ENST00000953233, ENST00000953234

RefSeq mRNA: 4 — MANE Select: NM_001024736 NM_001024736, NM_001329628, NM_001329629, NM_025240

CCDS: CCDS10251, CCDS32288, CCDS86475

Canonical transcript exons

ENST00000318443 — 10 exons

Exon	Start	End
ENSE00001432716	73712934	73714514
ENSE00001563264	73684383	73684460
ENSE00003465476	73703659	73703997
ENSE00003479905	73704176	73704472
ENSE00003496861	73702255	73702593
ENSE00003496916	73711135	73711170
ENSE00003579894	73708339	73708473
ENSE00003619006	73709648	73709689
ENSE00003619218	73699586	73699718
ENSE00003647361	73702772	73703086

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.5643 / max 157.1529, expressed in 1634 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147609	18.1826	1572
147606	13.0646	1590
147608	2.0601	1185
147607	0.5388	330
207583	0.3873	237
147610	0.2240	108
147605	0.1069	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.03	gold quality
ganglionic eminence	UBERON:0004023	96.66	gold quality
ventricular zone	UBERON:0003053	96.00	gold quality
gall bladder	UBERON:0002110	95.91	gold quality
endocervix	UBERON:0000458	95.66	gold quality
adrenal tissue	UBERON:0018303	95.47	gold quality
right adrenal gland cortex	UBERON:0035827	95.21	gold quality
left adrenal gland	UBERON:0001234	94.98	gold quality
apex of heart	UBERON:0002098	94.86	gold quality
right adrenal gland	UBERON:0001233	94.76	gold quality
left adrenal gland cortex	UBERON:0035825	94.72	gold quality
cortical plate	UBERON:0005343	94.63	gold quality
islet of Langerhans	UBERON:0000006	94.57	gold quality
right coronary artery	UBERON:0001625	94.51	gold quality
adrenal gland	UBERON:0002369	94.35	gold quality
smooth muscle tissue	UBERON:0001135	94.31	gold quality
adrenal cortex	UBERON:0001235	94.30	gold quality
ectocervix	UBERON:0012249	93.98	gold quality
ascending aorta	UBERON:0001496	93.83	gold quality
thoracic aorta	UBERON:0001515	93.78	gold quality
descending thoracic aorta	UBERON:0002345	93.72	gold quality
aorta	UBERON:0000947	93.43	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.35	gold quality
skin of leg	UBERON:0001511	93.32	gold quality
popliteal artery	UBERON:0002250	93.27	gold quality
tibial artery	UBERON:0007610	93.27	gold quality
uterine cervix	UBERON:0000002	92.84	gold quality
minor salivary gland	UBERON:0001830	92.69	gold quality
body of uterus	UBERON:0009853	92.40	gold quality
right atrium auricular region	UBERON:0006631	92.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting CD276, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832

Literature-anchored findings (GeneRIF, showing 40)

• A novel structural variant of B7-H3 (named B7-H3b) with four Ig-like domains, is the major isoform expressed in several tissues and results from gene duplication and differential splicing. (PMID:12055244)
• B7-H3 enhances T lymphocyte proliferation and IL-10 secretion when expressed in E. coli in vitro (PMID:15188059)
• data suggest that 4Ig-B7-H3 molecules expressed at the neuroblastoma tumor cell surface can exert a protective role from natural killer-mediated lysis by interacting with a still undefined inhibitory receptor expressed on natural killer cells (PMID:15314238)
• B7-H3 might be another valuable molecule marker for dendritic cells derived from monocytes (PMID:16274630)
• Single nucleotide polymorphisms in the B7H3 gene are not associated with autoimmune myasthenia gravis. (PMID:17406098)
• Disease-free survival or overall survival of the gastric carcinoma patients with positive B7-H3 expression were significantly longer than those with negative B7-H3 expression. (PMID:17851789)
• B7-H3 may be important for the interactions between fibroblast-like synoviocytes and T cells in rheumatoid arthritis and other diseases; the outcome of such interactions depends on the activation state of the T cell. (PMID:18292521)
• analysis of an interaction between B7-H3 and TLT-2 that preferentially enhances CD8(+) T cell activation (PMID:18650384)
• B7-H3 is highly expressed in urothelial cell carcinoma across tumor stages, whereas B7-H1 and PD-1 expression are associated with advanced disease (PMID:18676751)
• Overexpression of B7H3 is associated with tumor cell migration and invasion. (PMID:18690846)
• Both tumor cell and tumor vasculature B7-H3 expression convey important information to predict clear cell renal cell carcinoma outcomes (PMID:18694993)
• Progenitor cells from the anterior pituitary gland containing 4Ig-B7-H3 may play a critical role in the immunoendocrine network. (PMID:18941196)
• results suggest circulating B7-H3 is a valuable biomarker for non-small cell lung cancer (NSCLC) and an elevated level of circulating B7-H3 suggests a poor clinical character for NSCLC. (PMID:19269710)
• Data do not point to a role for TREML2 as a receptor for B7-H3. (PMID:19544488)
• tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival;B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer. (PMID:20035626)
• higher expression in human colorectal carcinoma correlates with tumor progression (PMID:20333377)
• B7-H3 functions as a costimulator of innate immunity by augmenting proinflammatory cytokine release from bacterial cell wall product-stimulated monocytes/macrophages and may contribute positively to the development of sepsis. (PMID:20696859)
• B7-H3 protein expressed by primary breast cancer cells is associated with extent of regional nodal metastasis. (PMID:21107115)
• role of B7-H3 in the regulation of T-cell response; its potential role in antitumor immunity (Review) (PMID:21127709)
• B7-H3 appears to be a useful blood marker for predicting tumor progression in gastric cancer (PMID:21251161)
• B7-H3 plays a crucial role in hypopharyngeal squamous cell carcinoma progression, tumor metastasis resulting in poor prognosis and might be involved in the negative regulation of T-cell-mediated tumor immune response. (PMID:21344157)
• silencing of B7-H3 increased the sensitivity of multiple human breast cancer cell lines to paclitaxel as a result of enhanced drug-induced apoptosis. (PMID:21518725)
• Upregulation of B7-H3 is associated with induction of immunosuppressive phenotype of dendritic cells in Non-small cell lung cancer microenvironment. (PMID:21597388)
• our findings indicate a novel role for B7-H3 in the regulation of the metastatic capacity of melanoma cells (PMID:21671471)
• B7-H3 is aberrantly expressed in prostate cancer. In addition to modulating tumor immunity, B7-H3 may have a novel role in regulating PC-3 cell progression (PMID:21784485)
• Analysis of B7-H3 protein expression indicates that comparable levels of B7-H3 are expressed on both primary human mesothelial and malignant mesothelial cell types. (PMID:21792917)
• regulates differentiation of bone marrow stromal cells to osteoblasts (PMID:21893365)
• B7-H3 expression on cancer cells is correlated with the number of T cells infiltrating the tumor. Endometrium tumor development and progression may be associated with downregulation of T-cell-mediated antitumor immunity through B7-H3. (PMID:21982044)
• The reduced expression of B7-H3 in the livers might temper the inhibition of T-cell responses mediated by B7-H3 expressed on hepatocytes and thus promote the hepatic inflammation and hepatitis progression in the chronic HBV-infected patients. (PMID:22187944)
• B7-H3 expression in tumor-associated vasculature and fibroblasts was observed in the majority of samples. (PMID:22473715)
• high expression level in prostate cancer correlates with the expression of the proliferation marker Ki-67, biochemical failure and clinical relapse (PMID:22487487)
• The data suggested that B7-H3 was abundantly expressed in hepatocellular carcinoma and was associated with adverse clinicopathologic features and poor outcome. (PMID:22729558)
• In myasthenia gravis (MG) patients, down-regulation of sB7-H3 is finely correlated to the severity of the disease. (PMID:22863596)
• A review of B7-H3 and B7-H4 immune molecules and the role their overexpression plays in ovarian cancer. (PMID:22910694)
• Membrane B7-H3 may be a promising biomarker that associates with the pathogenesis of multiple sclerosis. (PMID:22996270)
• Data suggest that the immunomodulatory proteins B7-H1, B7-H3, and HLA-G5 are secreted from early and term placenta via exosomes and have important implications in mechanisms by which trophoblast immunomodulators modify maternal immunological milieu. (PMID:23107341)
• High B7-H3 expression in human breast cancer tissues may be important in tumor progression and invasiveness. This expression appeared to be correlated with the ability of B7-H3 to promote IL-10 secretion (PMID:23128494)
• The study investigates the role of B7-H3 in pancreatic cancer progression and shows that this protein promotes cancer cell migration and invasiveness in vitro and in vivo. (PMID:23242015)
• B7-H3 is a significant factor in melanoma progression and events of metastasis. (PMID:23474948)
• The level of sB7-H3 in HCC patients was significantly higher than that in healthy people, and B7-H3 expression was correlated with clinical pathological indexes. (PMID:23746248)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd276	ENSDARG00000003061
mus_musculus	Cd276	ENSMUSG00000035914
rattus_norvegicus	Cd276	ENSRNOG00000033608

Paralogs (15): BTN3A1 (ENSG00000026950), BTN3A3 (ENSG00000111801), BTN2A1 (ENSG00000112763), BTNL8 (ENSG00000113303), HHLA2 (ENSG00000114455), BTN2A2 (ENSG00000124508), BTN1A1 (ENSG00000124557), VTCN1 (ENSG00000134258), ICOSLG (ENSG00000160223), ERMAP (ENSG00000164010), BTNL9 (ENSG00000165810), BTNL3 (ENSG00000168903), BTN3A2 (ENSG00000186470), BTNL2 (ENSG00000204290), MOG (ENSG00000204655)

Protein

Protein identifiers

CD276 antigen — Q5ZPR3 (reviewed: Q5ZPR3)

Alternative names: 4Ig-B7-H3, B7 homolog 3, Costimulatory molecule

All UniProt accessions (11): A0A0C4DGH0, Q5ZPR3, H0YK40, H0YK59, H0YKQ9, H0YL10, H0YLT3, H0YLT8, H0YN29, H0YN85, H3BM68

UniProt curated annotations — full annotation on UniProt →

Function. May participate in the regulation of T-cell-mediated immune response. May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling.

Subunit / interactions. Interacts with TREML2 and this interaction enhances T-cell activation.

Subcellular location. Membrane.

Tissue specificity. Ubiquitous but not detectable in peripheral blood lymphocytes or granulocytes. Weakly expressed in resting monocytes. Expressed in dendritic cells derived from monocytes. Expressed in epithelial cells of sinonasal tissue. Expressed in extravillous trophoblast cells and Hofbauer cells of the first trimester placenta and term placenta.

Induction. By bacterial lipopolysaccharides (LPS) in monocytes and by ionomycin in T and B-lymphocytes. Up-regulated in cells mediating rejection of human transplants.

Miscellaneous. B7-H3 locus underwent genomic duplication leading to tandemly repeated immunoglobulin-like V and C domains (VC domains). The dominantly expressed human B7-H3 isoform contains tandemly duplicated VC domains. In contrast, mouse B7-H3 transcript contains only one single VC domain form due to an exon structure corresponding to V domain-(pseudoexon C)-(pseudoexon V)-C domain. This duplication appearing in primates is suggested to be very recent supporting a model of multiple independent emergence of tandem VC repeats within human and monkey species. Contains tandemly repeated immunoglobulin-like V and C domains. Minor transcript. Contains one single set of immunoglobulin-like V and C domains. Contains tandemly repeated immunoglobulin-like V and C domains. Contains tandemly repeated immunoglobulin-like V and C domains.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q5ZPR3-1	1, 4Ig-B7-H3	yes
Q5ZPR3-2	2, B7-H3
Q5ZPR3-3	3
Q5ZPR3-4	4

RefSeq proteins (4): NP_001019907, NP_001316557, NP_001316558, NP_079516 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003597	Ig_C1-set	Domain
IPR003598	Ig_sub2	Domain
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
IPR047318	CD276_IgV	Domain
IPR050504	IgSF_BTN/MOG-like	Family
IPR053896	BTN3A2-like_Ig-C	Domain

Pfam: PF07686, PF22705

UniProt features (37 total): sequence variant 9, glycosylation site 6, disulfide bond 4, splice variant 4, domain 4, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, compositionally biased region 1, modified residue 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9LME	X-RAY DIFFRACTION	2.4
9LY5	ELECTRON MICROSCOPY	2.98
9LY6	ELECTRON MICROSCOPY	3.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5ZPR3-F1	83.63	0.60

Functional residue map

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

Post-translational modifications (1): 525

Disulfide bonds (4): 50–122, 165–220, 268–340, 383–438

Glycosylation sites (6): 104, 189, 215, 322, 407, 433

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 141 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, WANG_CLIM2_TARGETS_UP, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_LEUKOCYTE_PROLIFERATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2

GO Biological Process (8): regulation of cytokine production (GO:0001817), positive regulation of type II interferon production (GO:0032729), positive regulation of T cell proliferation (GO:0042102), T cell activation (GO:0042110), regulation of immune response (GO:0050776), T cell receptor signaling pathway (GO:0050852), positive regulation of cytokine production (GO:0001819), regulation of type II interferon production (GO:0032649)

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

GO Cellular Component (2): external side of plasma membrane (GO:0009897), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

2202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD276	CD28	P10747	998
CD276	CD86	P42081	988
CD276	CD80	P33681	987
CD276	CTLA4	P16410	985
CD276	TREML2	Q5T2D2	953
CD276	CD40LG	P29965	935
CD276	TNFRSF9	Q07011	924
CD276	ICOS	Q9Y6W8	890
CD276	CD8A	P01732	873
CD276	CD4	P01730	871
CD276	ICOSLG	O75144	871
CD276	TNFRSF4	P43489	862
CD276	A0A087X1L8	A0A087X1L8	820
CD276	IL2	P01585	817
CD276	TNFSF4	P23510	813

IntAct

39 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CD68	LGALS1	psi-mi:“MI:0914”(association)	0.640
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
CLEC5A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
RYK	PCDH7	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	RAP1BL	psi-mi:“MI:0915”(physical association)	0.400
	VPS37C	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
SIGLECL1	RBFOX3	psi-mi:“MI:0914”(association)	0.350
RYK	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
NHLRC3	OGG1	psi-mi:“MI:0914”(association)	0.350
CEACAM21	MET	psi-mi:“MI:0914”(association)	0.350
TMPRSS11B	SCAMP3	psi-mi:“MI:0914”(association)	0.350
PCDHA9	PCDHGA12	psi-mi:“MI:0914”(association)	0.350
RYK	DUSP14	psi-mi:“MI:0914”(association)	0.350
PAIP1	SYNCRIP	psi-mi:“MI:0914”(association)	0.350
UBXN6	PSMD11	psi-mi:“MI:0914”(association)	0.350
LGALS3	SDCBP	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-MS), CD276 (Affinity Capture-RNA), CD276 (Affinity Capture-MS), CD276 (Proximity Label-MS), CD276 (Proximity Label-MS)

ESM2 similar proteins: A6QLN9, A8MXK1, D3Z7P3, D3ZTX0, O94925, P01135, P01860, P13264, P35790, P52875, P55244, Q00961, Q01098, Q06922, Q08DW9, Q14957, Q15768, Q28D01, Q2KI11, Q4V899, Q5R890, Q5ZPR3, Q642A6, Q66H54, Q67FW5, Q6AZB0, Q6IA17, Q6PCB0, Q6UXG2, Q7TPB4, Q8C6G8, Q8HXJ7, Q8N2K0, Q8N5I2, Q8N612, Q8NBT3, Q8R2Z5, Q8VE98, Q969P0, Q96N03

Diamond homologs: O75144, Q5ZPR3, Q62556, Q7TPB4, Q8VE98, Q9JHJ8, A0A8M2B818, B0JYH6, P15151, P32506, P32507, P41217, Q15223, Q5FWR8, Q92692, Q9GL76, Q9JKF6, Q9NQS3, A0A0E4BZH1, A4QPC6, A7TZE6, A7TZF0, A7TZF3, A7XUX6, A7XUY5, A7XUZ6, A7XV04, A7XV07, A8MVZ5, O00478, O00481, O70355, P18892, P55803, P78410, Q13410, Q16653, Q29ZQ1, Q5R7W8, Q5R960

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neutrophil degranulation	8	5.1×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
Ras protein signal transduction	5	20.6×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1734 predictions. Top by Δscore:

Variant	Effect	Δscore
15:73702251:CCAG:C	acceptor_loss	1.0000
15:73702252:CAG:C	acceptor_loss	1.0000
15:73702253:A:AC	acceptor_loss	1.0000
15:73702254:GGA:G	acceptor_gain	1.0000
15:73702591:CCG:C	donor_loss	1.0000
15:73702592:CGGT:C	donor_loss	1.0000
15:73702594:G:C	donor_loss	1.0000
15:73702594:G:GG	donor_gain	1.0000
15:73702595:T:G	donor_loss	1.0000
15:73702605:G:GT	donor_gain	1.0000
15:73703041:GA:G	donor_gain	1.0000
15:73703075:G:GT	donor_gain	1.0000
15:73703995:CCGGT:C	donor_loss	1.0000
15:73703996:CGGT:C	donor_loss	1.0000
15:73703998:G:C	donor_loss	1.0000
15:73703998:G:GG	donor_gain	1.0000
15:73703999:TGAG:T	donor_loss	1.0000
15:73704000:GA:G	donor_loss	1.0000
15:73704009:G:GT	donor_gain	1.0000
15:73704174:A:AG	acceptor_gain	1.0000
15:73704175:G:GG	acceptor_gain	1.0000
15:73704469:ACAGG:A	donor_loss	1.0000
15:73704470:CAGG:C	donor_loss	1.0000
15:73704472:GGTA:G	donor_loss	1.0000
15:73704473:G:GC	donor_loss	1.0000
15:73704474:T:G	donor_loss	1.0000
15:73708337:A:AG	acceptor_gain	1.0000
15:73708338:G:GG	acceptor_gain	1.0000
15:73712920:ATCAT:A	acceptor_gain	1.0000
15:73712921:T:G	acceptor_gain	1.0000

AlphaMissense

3463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:73703778:T:A	W285R	0.997
15:73703778:T:C	W285R	0.997
15:73703780:G:C	W285C	0.996
15:73703780:G:T	W285C	0.996
15:73703943:T:C	C340R	0.995
15:73704250:T:C	C383R	0.995
15:73708395:T:C	C476R	0.995
15:73703899:T:C	L325P	0.994
15:73703944:G:A	C340Y	0.994
15:73704291:G:C	W396C	0.994
15:73704291:G:T	W396C	0.994
15:73703945:C:G	C340W	0.993
15:73702374:T:A	W67R	0.992
15:73702374:T:C	W67R	0.992
15:73703727:T:C	C268R	0.992
15:73702495:T:C	L107P	0.991
15:73703727:T:A	C268S	0.991
15:73703728:G:C	C268S	0.991
15:73704289:T:A	W396R	0.991
15:73704289:T:C	W396R	0.991
15:73702376:G:C	W67C	0.990
15:73702376:G:T	W67C	0.990
15:73703986:T:C	L354P	0.990
15:73704415:T:C	C438R	0.990
15:73704252:C:G	C383W	0.989
15:73704415:T:A	C438S	0.989
15:73704416:G:C	C438S	0.989
15:73702887:G:C	W178C	0.988
15:73702887:G:T	W178C	0.988
15:73703943:T:A	C340S	0.987

dbSNP variants (sampled 300 via entrez): RS1000214282 (15:73698722 A>G), RS1000218822 (15:73705721 C>A), RS1000526777 (15:73699916 T>G), RS1000534374 (15:73693317 A>G,T), RS1000553553 (15:73700230 A>G), RS1000677980 (15:73705274 T>C), RS1000868147 (15:73699371 C>T), RS1001074807 (15:73714579 C>A), RS1001098828 (15:73686379 C>A), RS1001121622 (15:73693205 CAG>C), RS1001152364 (15:73698050 T>C), RS1001331311 (15:73684940 T>A,G), RS1001551647 (15:73692902 A>G), RS1001679529 (15:73709323 C>A), RS1001851828 (15:73704841 G>C)

Disease associations

OMIM: gene MIM:605715 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001135_6	Bipolar disorder	9.000000e-06
GCST001277_4	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-09
GCST004072_1	Cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) with severe ocular complications	2.000000e-08
GCST006019_7	Gamma glutamyl transferase levels	1.000000e-09
GCST007277_20	Tourette syndrome	7.000000e-06
GCST008103_138	Bipolar disorder	2.000000e-06
GCST011349_24	Gamma glutamyl transferase levels	8.000000e-12
GCST90011898_42	Alanine aminotransferase levels	2.000000e-19
GCST90011899_79	Aspartate aminotransferase levels	2.000000e-16
GCST90013405_110	Liver enzyme levels (alanine transaminase)	3.000000e-22
GCST90013407_13	Liver enzyme levels (gamma-glutamyl transferase)	6.000000e-70
GCST90013663_12	Alanine aminotransferase levels	2.000000e-17
GCST90013664_38	Aspartate aminotransferase levels	4.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0006997	response to cold medicine
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712879 (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
enoblituzumab	Binding	7.61	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	3
Particulate Matter	affects cotreatment, increases expression, decreases expression, increases abundance	3
FR900359	affects phosphorylation	1
deoxynivalenol	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acrolein	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Benztropine	decreases expression	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Cannabidiol	increases expression	1
Clozapine	decreases expression	1
Doxorubicin	decreases expression	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases expression	1

Cellosaurus cell lines

10 cell lines: 4 cancer cell line, 4 spontaneously immortalized cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1MN	Abcam HeLa CD276 KO	Cancer cell line	Female
CVCL_B2TS	Abcam HEK293T CD276 KO	Transformed cell line	Female
CVCL_C5QI	MS1-hCD276	Transformed cell line	Sex unspecified
CVCL_D7BC	Abeomics CHO-K1 B7-H3	Spontaneously immortalized cell line	Female
CVCL_D7M2	Ubigene A-549 CD276 KO	Cancer cell line	Male
CVCL_E0Z3	Ubigene MG-63 CD276 KO	Cancer cell line	Male
CVCL_E1T9	HAP1 CD276 (-)	Cancer cell line	Male
CVCL_E6AU	CHO-B7H3	Spontaneously immortalized cell line	Female
CVCL_E6PG	Genomeditech CHO-K1 H_CD276(B7H3)	Spontaneously immortalized cell line	Female
CVCL_KA47	CHO-K1/B7-H3	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea