CD274
Chr 9ARCD274 molecule
Also known as: ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1, PDL1, hPD-L1
The protein is an immune inhibitory receptor ligand that regulates T-cell activation and maintains immune tolerance by limiting T-cell effector responses and preventing autoimmunity. Mutations cause autoimmune disease with multisystem involvement and infantile onset, inherited in an autosomal recessive pattern. The gene is not highly constrained against loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CD274 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Adding the Immunotherapy Drug Cemiplimab to Usual Treatment for People With Advanced Non-Small Cell Lung Cancer Who Had Previous Treatment With Platinum Chemotherapy and Immunotherapy (An Expanded Lung-MAP Treatment Trial)
RECRUITINGRC48 in Combination With AK104 and Bevacizumab in OCCC
RECRUITINGOpen-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer
ACTIVE NOT RECRUITINGTalimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
ACTIVE NOT RECRUITINGNeoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca
ACTIVE NOT RECRUITINGEarly Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy
RECRUITINGRamucirumab Plus Pembrolizumab vs Usual Care for Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer Following Immunotherapy, Pragmatica-Lung Study
ACTIVE NOT RECRUITINGRare Tumor Focused Platform Study of Innovative Therapies and Technologies (PLATFORM2)
NOT YET RECRUITINGGenomic Analysis to Identify a Predictive Biomarker for Immunotherapy
RECRUITINGStudy of the Effects of Pembrolizumab in Patients With Advanced Solid Tumors
ACTIVE NOT RECRUITINGEfficacy and Safety Analysis of First-Line ABCP Therapy in Advanced SMARCA4-Mutated NSCLC
NOT YET RECRUITINGA Phase I Study to Evaluate the Safety, Tolerability, and PK of HLX43 in Advanced/Metastatic Solid Tumors
RECRUITINGExternal Resources
Links to major genomics databases and tools