CD274
Programmed cell death 1 ligand 1
Also known as: B7-H, B7-H1, B7H1, PD-L1, PD1L1_HUMAN, PDCD1LG1, PDL1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9NZQ7
- Gene
- CD274
- Ensembl
- ENSG00000120217
- Chromosome
- 9
- Canonical length
- 290 aa
- Protein class
- Cancer-related genes, CD markers, Disease related genes, FDA approved drug targets, Predicted membrane proteins, Transporters
- Subcellular location
- Nucleoplasm,Plasma membrane,Actin filaments
- Secretome location
- Secreted - unknown location
- Quaternary structure
- Homomultimer
OverviewNCBI Gene
This gene encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells and various types of tumor cells. The encoded protein is a type I transmembrane protein that has immunoglobulin V-like and C-like domains. Interaction of this ligand with its receptor inhibits T-cell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response. In tumor microenvironments, this interaction provides an immune escape for tumor cells through cytotoxic T-cell inactivation. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including colon cancer and renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
Canonical amino-acid sequenceUniProt
290 residues, UniProt reviewed canonical sequence.
>Q9NZQ7|CD274
1 MRIFAVFIFM TYWHLLNAFT VTVPKDLYVV EYGSNMTIEC KFPVEKQLDL AALIVYWEME
61 DKNIIQFVHG EEDLKVQHSS YRQRARLLKD QLSLGNAALQ ITDVKLQDAG VYRCMISYGG
121 ADYKRITVKV NAPYNKINQR ILVVDPVTSE HELTCQAEGY PKAEVIWTSS DHQVLSGKTT
181 TTNSKREEKL FNVTSTLRIN TTTNEIFYCT FRRLDPEENH TAELVIPELP LAHPPNERTH
241 LVILGAILLC LGVALTFIFR LRKGRMMDVK KCGIQDTNSK KQSDTHLEETLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CD274 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.37
- Highest tissue expression
- 16 nTPM
Expression across tissuesHPA
Tissue
- lung: 16 nTPM
- thymus: 12 nTPM
- appendix: 9.7 nTPM
- spleen: 9.7 nTPM
- heart muscle: 8.3 nTPM
- urinary bladder: 6.7 nTPM
Single-cell type
- syncytiotrophoblasts: 73 nCPM
- mast cells: 61 nCPM
- megakaryocyte progenitors: 56 nCPM
- extravillous trophoblasts: 48 nCPM
- neutrophils: 34 nCPM
- cdc: 33 nCPM
Immune cell
- basophil: 6.7 nTPM
- neutrophil: 3.6 nTPM
- memory CD4 T-cell: 1.4 nTPM
- MAIT T-cell: 1.2 nTPM
- memory CD8 T-cell: 1.1 nTPM
- gdT-cell: 0.7 nTPM
Brain region
- pons: 3.9 nTPM
- hypothalamus: 3.8 nTPM
- medulla oblongata: 3.5 nTPM
- spinal cord: 3.2 nTPM
- midbrain: 3.1 nTPM
- cerebral cortex: 2.2 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CD274.
Disease | AllUniProt
Conditions CD274 is implicated in, by any mechanism.
- Autoimmune disease, multisystem, infantile-onset, 5 (ADMIO5) MIM:621235
Disease | ImmuneIEDB
Conditions an epitope on CD274 was assayed in.
- melanoma T cell
- myeloproliferative neoplasm T cell
- head and neck squamous cell carcinoma T cell
ReferencesPubMed · IEDB
Publications for CD274 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
18 publications
- Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors.
2018 · Diabetes · RCR 16.9 · 483 citations - Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1.
2016 · Cancer Immunol Res · RCR 8.1 · 222 citations - B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance.
2010 · Blood · RCR 5.4 · 272 citations - Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis.
2003 · J Clin Invest · RCR 2.7 · 171 citations - [Physiopathological mechanisms of immune-related adverse events induced by anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies in cancer treatment].
2018 · Bull Cancer · RCR 2.3 · 70 citations
Show 13 more
- Promotion of an Antitumor Immune Program by a Tumor-specific, Complement-activating Antibody.
2024 · J Immunol · RCR 2.2 · 14 citations - Anti-PD-L1 immunoconjugates for cancer therapy: Are available antibodies good carriers for toxic payload delivering?
2022 · Front Pharmacol · RCR 1.8 · 25 citations - Involvement of inducible costimulator-B7 homologous protein costimulatory pathway in murine lupus nephritis.
2003 · J Immunol · RCR 1.5 · 96 citations - Anti-programmed cell death 1 antibody reduces CD4+PD-1+ T cells and relieves the lupus-like nephritis of NZB/W F1 mice.
2010 · J Immunol · RCR 1.4 · 70 citations - Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade.
2022 · J Clin Endocrinol Metab · RCR 1.4 · 19 citations - Lack of Conventional Acinar Cells in Parotid Salivary Gland of Patient Taking an Anti-PD-L1 Immune Checkpoint Inhibitor.
2020 · Front Oncol · RCR 0.9 · 19 citations - Adoptive transfer of antithyrotropin receptor (TSHR) autoimmunity from TSHR knockout mice to athymic nude mice.
2012 · Endocrinology · RCR 0.7 · 20 citations - Maturation of circulating Ly6ChiCCR2+ monocytes by mannan-MOG induces antigen-specific tolerance and reverses autoimmune encephalomyelitis.
2022 · Front Immunol · RCR 0.7 · 9 citations - Hypothalamic-Pituitary Autoimmunity in Patients Treated with Anti-PD-1 and Anti-PD-L1 Antibodies.
2021 · Cancers (Basel) · RCR 0.5 · 8 citations - A study of programmed death-1/programmed death ligand and iodine-induced autoimmune thyroiditis in NOD.H-2h4 mice.
2023 · Environ Toxicol · RCR 0.4 · 2 citations - Co-inhibitory Receptor Signaling in T-Cell-Mediated Autoimmune Glomerulonephritis.
2020 · Front Med (Lausanne) · RCR 0.3 · 7 citations - Elevated PD-1 and PDL-1 autoantibodies and association with tuberculosis.
2025 · J Infect · 2 citations - A case of irAE myositis with positive antistriational antibodies after anti-PD-L1 antibody administration: A case report.
2025 · Mod Rheumatol Case Rep · 1 citations
Reference: T cellIEDB
5 publications
- Staphylococcus aureus alpha-toxin inhibits CD8+ T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma.
2020 · Oncoimmunology · RCR 2.1 · 35 citations - An arginase1- and PD-L1-derived peptide-based vaccine for myeloproliferative neoplasms: A first-in-man clinical trial.
2023 · Front Immunol · RCR 1.5 · 14 citations - PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine.
2016 · Oncoimmunology · RCR 0.9 · 31 citations - PD-L1-specific helper T-cells exhibit effective antitumor responses: new strategy of cancer immunotherapy targeting PD-L1 in head and neck squamous cell carcinoma.
2019 · J Transl Med · RCR 0.7 · 17 citations - Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma.
2020 · Elife · RCR 0.6 · 17 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.8
- gnomAD pLI
- 0.02
- gnomAD missense Z
- 0.9
- DepMap mean gene effect
- 0.13
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adaptive immune response
- cell surface receptor signaling pathway
- cellular response to lipopolysaccharide
- immune response
- negative regulation of activated T cell proliferation
- negative regulation of CD4-positive, alpha-beta T cell proliferation
- negative regulation of CD8-positive, alpha-beta T cell activation
- negative regulation of interleukin-10 production
- negative regulation of T cell activation
- negative regulation of T cell mediated immune response to tumor cell
- negative regulation of T cell proliferation
- negative regulation of T cell receptor signaling pathway
- negative regulation of type II interferon production
- positive regulation of interleukin-10 production
- positive regulation of T cell proliferation
- response to cytokine
- signal transduction
- T cell costimulation
- TRIF-dependent toll-like receptor signaling pathway
- negative regulation of tumor necrosis factor superfamily cytokine production
- positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CD274 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CD274 as an antibody target. Whether an autoantibody or antibody against CD274 could matter depends on whether native CD274 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CD274 is annotated at the cell surface, where native CD274 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label CD274 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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