CD274
Chr 9ARCD274 molecule
Also known as: ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1, PDL1, hPD-L1
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]
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
22 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 1 | 0 | 1 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 10 | 0 | 0 | 10 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 3 | 2 | 5 |
| Total | 0 | 12 | 4 | 2 | 18 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →163 pathogenic / likely-pathogenic (of 173) ClinVar copy-number / structural variants overlap CD274 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
CD274 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer
RECRUITINGStudy on the Safety and Tolerability of PD-1 Knockout Tumor-infiltrating T Cells (TILs) in the Treatment of Advanced Colorectal Cancer
RECRUITINGMYLUNG Consortium Study Protocol 2
ACTIVE NOT RECRUITINGAn Open-label, Single-arm Clinical Study of Stapokibart Injection in Combination with Tislelizumab Injection in Patients with Non-Small Cell Lung Cancer
NOT YET RECRUITINGOlaparib in Combination With Pembrolizumab and Carboplatin as First-Line Treatment of Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma
ACTIVE NOT RECRUITINGA Phase Ib Study of Tislelizumab Plus SYS6010 in Immunotherapy-Pretreated Locally Advanced or Metastatic NSCLC
NOT YET RECRUITINGPHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC
NOT YET RECRUITINGConstruction of a Prognostic and Prediction Model for Perioperative Immunotherapy in NSCLC: A Multi - Omics Perspective
NOT YET RECRUITINGTiragolumab and Atezolizumab in Advanced Pan-cancer Patients
RECRUITINGIn-depth Characterization of Circulating and Infiltrating Immune Subsets and Tumor Cells in Cancer Patients
NOT YET RECRUITINGNP137 Clinical and Biological Activities Assessment in Patients With Advanced/Metastatic Solid Tumors Treated by Standard Anti PD-1/PD-L1 Immunotherapies
ACTIVE NOT RECRUITINGA Trial to Learn How the Combination of Fianlimab With Cemiplimab and Chemotherapy Works Compared With Cemiplimab and Chemotherapy for Treating Adult Patients With Advanced Non-small Cell Lung Cancer
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools