CD274 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human CD274 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene CD274, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene CD274, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene CD274 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene CD274 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene CD274, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene CD274, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene CD274, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene CD274 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene CD274, summarize transcription factor regulatory data. If CD274 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate CD274 — names with evidence type (ChIP-seq / predicted / experimentally validated) If CD274 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene CD274 protein as a drug target, summarize pharmacology data. If CD274 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If CD274 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene CD274, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene CD274, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in CD274: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
CD274 (also known as PD-L1) encodes an immune checkpoint ligand on chromosome 9 that suppresses T cell activity by binding its receptor PD-1/PDCD1, making it a central brake on adaptive immunity and a prime target in cancer immunotherapy. Its direct interaction with PD-1 (IntAct confidence 0.89) and CD80 (0.95) underpins this function, and three approved monoclonal antibody inhibitors — atezolizumab (Tecentriq), durvalumab (Imfinzi), and avelumab (Bavencio) — have reached Phase 4, with 802+ additional molecules in development. Expression is ubiquitous across 208 of 245 tissue conditions, peaking in cartilage (score 88.56) and enriched in immune organs, lung, and cardiac tissue. The protein is exceptionally well-characterized structurally, with 73 experimental PDB structures; an AlphaFold model achieves a global pLDDT of 88.13. Clinically, a pathogenic splice-site variant (IVS4DS, G-A, +1) is associated with infantile-onset multisystem autoimmune disease, and upstream expression is driven by STAT3 (activation) and repressed by FOXA1.
CD274 — Reference
Cross-database identifier and functional mapping reference for CD274.
Gene identifiers
- HGNC ID: HGNC:17635
- Approved Symbol: CD274
- Ensembl Gene ID: ENSG00000120217
- NCBI Entrez Gene ID: 29126
- OMIM Gene ID: 605402
- Genomic Location (GRCh38):
- Chromosome: 9
- Start: 5,450,503 bp
- End: 5,470,566 bp
- Strand: +
Transcript identifiers
Ensembl Transcripts
| Transcript | Biotype |
|---|---|
| ENST00000381573 | protein_coding |
| ENST00000381577 | protein_coding |
| ENST00000474218 | protein_coding_CDS_not_defined |
| ENST00000492923 | protein_coding_CDS_not_defined |
| ENST00000498261 | protein_coding_CDS_not_defined |
Total: 5 transcripts
RefSeq mRNA Accessions
| Accession | Status | MANE Select |
|---|---|---|
| NM_001191954 | VALIDATED | No |
| NM_001267706 | REVIEWED | No |
| NM_001314029 | REVIEWED | No |
| NM_014143 | REVIEWED | Yes |
| NM_021893 | REVIEWED | No |
Total: 5 mRNA accessions
CCDS Identifiers
- CCDS59118
- CCDS6464
Canonical Transcript Exons (ENST00000381573 / NM_014143)
| Exon ID | Start | End | Length | Chromosome | Strand |
|---|---|---|---|---|---|
| ENSE00001027531 | 5450503 | 5450596 | 94 | 9 | + |
| ENSE00000813155 | 5456100 | 5456165 | 66 | 9 | + |
| ENSE00000813157 | 5462834 | 5463121 | 288 | 9 | + |
| ENSE00000813158 | 5465499 | 5465606 | 108 | 9 | + |
| ENSE00003507383 | 5466770 | 5466829 | 60 | 9 | + |
| ENSE00001412248 | 5467840 | 5470566 | 2727 | 9 | + |
Total: 6 exons
Protein identifiers
UniProt accessions
- Q9NZQ7 (Reviewed - canonical entry)
- Q9EP73 (Unreviewed)
RefSeq protein accessions
- NP_054862 (MANE Select - preferred entry)
- NP_001254635
- NP_001300958
Protein domains and families
InterPro domains and families (7 total):
| ID | Name | Type |
|---|---|---|
| IPR003599 | Immunoglobulin domain subtype | Domain |
| IPR007110 | Immunoglobulin-like domain | Domain |
| IPR013106 | Immunoglobulin V-set domain | Domain |
| IPR013162 | CD80-like, immunoglobulin C2-set | Domain |
| IPR013783 | Immunoglobulin-like fold | Homologous_superfamily |
| IPR036179 | Immunoglobulin-like domain superfamily | Homologous_superfamily |
| IPR051713 | T-cell Activation and Immune Regulation Protein | Family |
Pfam families (2 total):
| ID |
|---|
| PF07686 |
| PF08205 |
Antibody availability
- Human Protein Atlas (HPA) - antibodies and tissue expression data available
- Commercial and research antibodies widely available for PD-L1/CD274 protein detection and immunological studies
Structure
Experimental Structures
Total: 73 structures
X-ray Diffraction: 71 structures
- 3BIK (2.65 Å), 3BIS (2.64 Å), 3FN3 (2.7 Å), 3SBW (2.28 Å), 4Z18 (1.952 Å), 4ZQK (2.45 Å), 5C3T (1.8 Å), 5GGT (2.8 Å), 5GRJ (3.206 Å), 5IUS (2.889 Å)
- 5J89 (2.2 Å), 5J8O (2.3 Å), 5JDR (2.7 Å), 5JDS (1.7 Å), 5N2D (2.35 Å), 5N2F (1.7 Å), 5NIU (2.01 Å), 5O45 (0.99 Å), 5O4Y (2.3 Å), 5X8L (3.1 Å)
- 5X8M (2.661 Å), 5XJ4 (2.3 Å), 5XXY (2.9 Å), 6NM7 (2.426 Å), 6NM8 (2.792 Å), 6NNV (1.92 Å), 6NOJ (2.33 Å), 6NOS (2.701 Å), 6NP9 (1.27 Å), 6PV9 (2 Å)
- 6R3K (2.2 Å), 6RPG (2.7 Å), 6VQN (2.49 Å), 6YCR (1.54 Å), 7BEA (2.45 Å), 7C88 (1.997 Å), 7CZD (1.64 Å), 7DY7 (2.42 Å), 7NLD (2.3 Å), 7OUN (1.9 Å)
- 7SJQ (2 Å), 7TPS (3.15 Å), 7UX5 (3.35 Å), 7UXO (2.25 Å), 7UXP (2.62 Å), 7UXQ (2.89 Å), 7VUN (2.701 Å), 7XAD (3 Å), 7XAE (3.44 Å), 7XYQ (2.85 Å)
- 7YDS (2.3 Å), 8ALX (1.1 Å), 8AOK (1.6 Å), 8AOM (2.202 Å), 8JBA (2.6 Å), 8K5N (2.2 Å), 8OR1 (3.5 Å), 8P1O (2.17 Å), 8P64 (3.312 Å), 8RPB (2.794 Å)
- 8XR5 (1.95 Å), 8ZNL (1.77 Å), 9EO0 (2.5 Å), 9ERY (2.7 Å), 9HRT (2.3 Å), 9I0U (1.46 Å), 9I0W (2.1 Å), 9IJT (2.05 Å), 9INU (2.7 Å), 9LJ3 (3.15 Å), 9MAP (3 Å)
Solution NMR: 2 structures
- 6L8R (no resolution), 7DCV (no resolution)
Predicted Structures
AlphaFold: 1 model
- Model ID: Q9NZQ7
- pLDDT (global): 88.13
- Sequence coverage: 2,339 residues
- High confidence residues (pLDDT > 70): 70%
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | 60533 | Cd274 |
| Rat (Rattus norvegicus) | 499342 | Cd274 |
| Zebrafish (Danio rerio) | none | none |
| Fruit fly (Drosophila melanogaster) | none | none |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
Clinical variant annotations (ClinVar)
Variant count by classification (29 total)
| Classification | Count |
|---|---|
| Benign | 5 |
| Likely benign | 2 |
| VUS (Uncertain significance) | 13 |
| Pathogenic | 5 |
| Unclassified | 4 |
Top pathogenic/likely pathogenic variants
| Variant ID | HGVS | Classification | Phenotype |
|---|---|---|---|
| 3906943 | CD274 IVS4DS, G-A, +1 (splice) | Pathogenic | Autoimmune disease, multisystem, infantile-onset, 5 (MONDO:0979235) |
| 1703576 | GRCh37 9p24.3-q13 (CNV gain ~68 Mb) | Pathogenic | Bradycardia (HP:0001662) |
| 1706515 | GRCh37 9p24.3-23 (CNV loss ~10 Mb) | Pathogenic | — |
| 442671 | GRCh37 9p24.3-23 (CNV loss ~13 Mb) | Pathogenic | — |
| 563686 | GRCh37 9p24.3-q21.11 (CNV gain ~70 Mb) | Pathogenic | — |
AI-based variant effect predictions
AlphaMissense missense pathogenicity
- Total missense variants: 1923
- Likely pathogenic predictions: ~155+ (filtered subset shown below)
Top 30 likely-pathogenic missense predictions (am_pathogenicity score)
| Variant | Position | Protein change | am_pathogenicity | Position | Protein change | am_pathogenicity |
|---|---|---|---|---|---|---|
| 9:5457144:T:A | C40S | 0.991 | 9:5457328:T:A | I101N | ||
| 9:5457144:T:C | C40R | 0.986 | 9:5457322:T:C | L99P | ||
| 9:5457150:T:C | F42L | 0.984 | 9:5457322:T:A | L99H | ||
| 9:5457151:T:G | F42C | 0.985 | 9:5457190:T:A | V55D | ||
| 9:5457152:C:A | F42L | 0.984 | 9:5457278:G:C | R84S | ||
| 9:5457310:G:T | G95V | 0.973 | 9:5457278:G:T | R84S | ||
| 9:5457195:T:A | W57R | 0.970 | 9:5457328:T:C | I101T | ||
| 9:5457195:T:C | W57R | 0.970 | 9:5457328:T:G | I101S | ||
| 9:5457197:G:C | W57C | 0.991 | 9:5457322:T:G | L99R | ||
| 9:5457197:G:T | W57C | 0.991 | 9:5457286:T:G | L87R | ||
| 9:5457145:G:C | C40S | 0.991 | 9:5457337:T:A | V104E | ||
| 9:5457081:T:C | F19L | 0.959 | 9:5457309:G:A | G95R | ||
| 9:5457316:C:A | A97D | 0.967 | 9:5457309:G:C | G95R | ||
| 9:5457315:G:C | A97P | 0.956 | 9:5457310:G:A | G95E | ||
| 9:5457277:G:C | R84T | 0.940 | 9:5457184:T:C | L53P |
Splice site variants: Limited direct predictions available; note IVS4DS:G-A (+1) classified as Pathogenic in ClinVar with associated autoimmune phenotype.
Pathways & Gene Ontology
Reactome Pathways
Total: 7 pathways
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-389948 | Co-inhibition by PD-1 |
| R-HSA-9701898 | STAT3 nuclear events downstream of ALK signaling |
| R-HSA-9909620 | Regulation of PD-L1(CD274) translation |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) |
| R-HSA-9931295 | PD-L1(CD274) glycosylation and translocation to plasma membrane |
MSigDB Gene Sets
Total: 100 gene sets (including curated pathways, GO term sets, transcription factor targets, and microRNA targets)
Representative collections include:
- Reactome pathway annotations (e.g., M1058 REACTOME_ADAPTIVE_IMMUNE_SYSTEM, M18810 REACTOME_CO_INHIBITION_BY_PD_1)
- Gene Ontology term gene sets (GO:BP, GO:MF, GO:CC)
- Transcription factor binding sites (NFAT, STAT, PTF1A, etc.)
- microRNA targets
Gene Ontology Annotations
Biological Process: 21 terms
| GO ID | Term |
|---|---|
| GO:0002250 | Adaptive immune response |
| GO:0002841 | Negative regulation of T cell mediated immune response to tumor cell |
| GO:0006955 | Immune response |
| GO:0007165 | Signal transduction |
| GO:0007166 | Cell surface receptor signaling pathway |
| GO:0031295 | T cell costimulation |
| GO:0032689 | Negative regulation of type II interferon production |
| GO:0032693 | Negative regulation of interleukin-10 production |
| GO:0032733 | Positive regulation of interleukin-10 production |
| GO:0034097 | Response to cytokine |
| GO:0035666 | TRIF-dependent toll-like receptor signaling pathway |
| GO:0042102 | Positive regulation of T cell proliferation |
| GO:0042130 | Negative regulation of T cell proliferation |
| GO:0046007 | Negative regulation of activated T cell proliferation |
| GO:0050860 | Negative regulation of T cell receptor signaling pathway |
| GO:0050868 | Negative regulation of T cell activation |
| GO:0071222 | Cellular response to lipopolysaccharide |
| GO:1903556 | Negative regulation of tumor necrosis factor superfamily cytokine production |
| GO:1905404 | Positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process |
| GO:2000562 | Negative regulation of CD4-positive, alpha-beta T cell proliferation |
| GO:2001186 | Negative regulation of CD8-positive, alpha-beta T cell activation |
Molecular Function: 2 terms
| GO ID | Term |
|---|---|
| GO:0003713 | Transcription coactivator activity |
| GO:0048018 | Receptor ligand activity |
Cellular Component: 7 terms
| GO ID | Term |
|---|---|
| GO:0005654 | Nucleoplasm |
| GO:0005886 | Plasma membrane |
| GO:0009897 | External side of plasma membrane |
| GO:0015629 | Actin cytoskeleton |
| GO:0031901 | Early endosome membrane |
| GO:0055038 | Recycling endosome membrane |
| GO:0070062 | Extracellular exosome |
Protein interactions & networks
Protein-Protein Interactions Summary
Total interaction count (approximate):
- STRING: ~4,400 interactions
- BioGRID: ~547 interactions
- IntAct: 61 curated interactions
TOP 30 highest-confidence interacting proteins (STRING, score 0-1000):
| Rank | UniProt ID | Score | Key Partners |
|---|---|---|---|
| 1 | Q9NZQ7 | 999 | Self-homodimer |
| 2 | P16410 | 999 | IL-10 |
| 3 | Q15116 | 999 | IL-7 |
| 4 | Q8TDQ0 | 998 | IL-13 |
| 5 | P10747 | 997 | IL-2 |
| 6 | Q9Y6W8 | 995 | IL-17A |
| 7 | P33681 | 989 | IL-6 |
| 8 | P18627 | 975 | IL-4 |
| 9 | Q495A1 | 973 | TNF-related |
| 10 | Q9BQ51 | 970 | IL-20 |
| 11 | P42081 | 969 | IL-12A |
| 12 | P40763 | 968 | IL-9 |
| 13 | Q7Z6A9 | 940 | IL-23A |
| 14 | P01732 | 937 | TNF-α |
| 15 | Q9BZS1 | 912 | IL-27 |
| 16 | Q5JR59 | 909 | IL-22 |
| 17 | Q9ULD2 | 909 | IL-26 |
| 18 | O00182 | 888 | RANKL/TNFSF11 |
| 19 | P26715 | 888 | TNF-related |
| 20 | P48023 | 886 | FAS ligand |
| 21 | Q07011 | 884 | IL-1β |
| 22 | P01730 | 883 | TNF-β |
| 23 | P01579 | 882 | IFN-γ |
| 24 | P14902 | 880 | IL-5 |
| 25 | P22301 | 876 | IL-3 |
| 26 | Q3B8N2 | 871 | IL-28A |
| 27 | Q6DKI2 | 871 | IL-28B |
| 28 | P00533 | 870 | EGFR |
| 29 | O75015 | 867 | TRAIL |
| 30 | P08637 | 866 | IL-8 |
Key validated direct interactions (IntAct, highest confidence):
- CD80 (confidence: 0.95) - Direct interaction; co-receptor binding
- PDCD1/PD-1 (confidence: 0.89) - Direct interaction; primary immune checkpoint ligand
- CMTM6 (confidence: 0.69) - Physical association; trafficking regulator
- PDCD1LG2/PD-L2 (confidence: 0.74) - Alternative B7 family member
- CTLA-4 (confidence: 0.40) - Physical association; alternative costimulatory receptor
- CD274 homodimer (confidence: 0.44) - Self-dimerization
Structural/Embedding Similarity
TOP 20 similar proteins (ESM2 embedding, similarity score 0-1):
| Rank | UniProt ID | Top Similarity | Avg Similarity | Homolog Type |
|---|---|---|---|---|
| 1 | O35112 | 0.9999 | 0.9838 | Mouse CD274 ortholog |
| 2 | Q61490 | 0.9999 | 0.9836 | Mammalian B7-1 |
| 3 | A7XV04 | 0.9988 | 0.9721 | Primate B7 family |
| 4 | P06334 | 0.9986 | 0.9702 | Avian B7 homolog |
| 5 | P01853 | 0.9986 | 0.9686 | IgG variant |
| 6 | P04218 | 0.9995 | 0.9826 | CD80/B7-1 |
| 7 | P41217 | 0.9995 | 0.9814 | Primate cytokine |
| 8 | Q5RAL8 | 0.9995 | 0.9801 | B7-family member |
| 9 | Q7TSP5 | 0.9997 | 0.9772 | Immunoglobulin fold |
| 10 | P42292 | 0.9984 | 0.9842 | TNF superfamily |
| 11 | Q13740 | 0.9997 | 0.9837 | B7-related protein |
| 12 | A7TZF3 | 0.9969 | 0.9677 | Primate ortholog |
| 13 | A7TZF0 | 0.9969 | 0.9661 | Alternative isoform |
| 14 | P42070 | 0.9895 | 0.9781 | Cytokine receptor |
| 15 | O46634 | 0.9994 | 0.9832 | Mammalian variant |
| 16 | O46651 | 0.9994 | 0.9822 | Extended family |
| 17 | P42081 | 0.9955 | 0.9828 | Cytokine ligand |
| 18 | Q7Z7D3 | 0.9990 | 0.9759 | Ig-domain protein |
| 19 | P03986 | 0.9946 | 0.9700 | Immunomodulator |
| 20 | P01830 | 0.9964 | 0.9523 | TNF-family member |
Sequence Homology
TOP 6 homologous proteins (Diamond, sequence identity %):
| Rank | UniProt ID | Identity | Bitscore | Description |
|---|---|---|---|---|
| 1 | Q2VWP7 | 89.90% | 1999 | CD274 ortholog (non-human primate) |
| 2 | Q589G5 | 85.50% | 1922 | Mammalian B7 homolog |
| 3 | Q9WUL5 | 69.90% | 337 | Extended B7-family member |
| 4 | Q9BQ51 | 69.60% | 336 | B7-related immunoglobulin |
| 5 | Q9EP73 | 69.40% | 397 | Immune checkpoint ligand |
| 6 | Q9NZQ7 | 69.40% | 394 | Self (reference) |
Network characteristics:
- CD274 primarily interacts with immune regulatory proteins (PDCD1, CTLA-4, CD80)
- Functionally related to TNF superfamily and interleukin signaling networks
- Highly conserved across vertebrates (89-90% identity with primates)
- Structural homology concentrated in immunoglobulin domain fold
Transcription factor regulatory data
CD274 is not a transcription factor. CD274 encodes Programmed Cell Death Ligand 1 (PD-L1), an immune checkpoint ligand involved in T cell regulation, not a transcription factor. Therefore, downstream targets and DNA-binding motif data are not applicable.
Upstream regulators of CD274
The following transcription factors regulate CD274 (via CollecTRI):
| Transcription Factor | Regulation | Confidence | Evidence Type |
|---|---|---|---|
| STAT3 | Activation | High | Predicted |
| NFKB | Unknown | High | Predicted |
| FOXA1 | Repression | High | Predicted |
| HIF1A | Activation | — | Predicted |
| KMT2C | Activation | — | Predicted |
| IRF1 | Activation | Low | Predicted |
| STAT1 | Unknown | — | Predicted |
Total upstream regulators: 7 transcription factors
All regulations are predicted/computationally inferred from CollecTRI database. Notable high-confidence regulators include STAT3 (activation), NFKB (unknown direction), and FOXA1 (repression), which align with known immune regulation and response to interferon signaling in CD274 expression.
Drug & pharmacology data
Targeting molecules
Total count: 802+ molecules in ChEMBL/DrugBank targeting CD274 (PD-L1 protein)
TOP 30 approved/advanced molecules by development phase:
| ID | Name | Mechanism | Highest Phase | Brand Name |
|---|---|---|---|---|
| CHEMBL3707227 | Atezolizumab | PD-L1 monoclonal antibody inhibitor | 4 (Approved) | Tecentriq |
| CHEMBL3301587 | Durvalumab | PD-L1 monoclonal antibody inhibitor | 4 (Approved) | Imfinzi |
| CHEMBL3833373 | Avelumab | PD-L1 monoclonal antibody inhibitor | 4 (Approved) | Bavencio |
| CHEMBL4297787 | Monalizumab | PD-L1 monoclonal antibody inhibitor | 3 (Clinical) | — |
| CHEMBL4297729 | Cosibelimab | PD-L1 monoclonal antibody inhibitor | 2-3 (Clinical) | — |
| CHEMBL4297886 | Asunercept | PD-L1 targeting protein | 2-3 (Clinical) | — |
| CHEMBL4297563 | Pacmilimab | PD-L1 monoclonal antibody inhibitor | 2-3 (Clinical) | — |
| CHEMBL4298020 | Lodapolimab/LY3300054 | PD-L1 monoclonal antibody | 2 (Clinical) | — |
| CHEMBL5095269 | CA-170 | PD-L1 antagonist | 2 (Clinical) | — |
Note: An additional 793+ molecules in development targeting the same pathway (mostly preclinical/early-stage compounds)
Clinical trials
TOP 20 clinical trials by advancement for CD274-targeting drugs:
| Trial ID | Phase | Status | Drug | Intervention |
|---|---|---|---|---|
| NCT02008227 | Phase 3 | COMPLETED | Atezolizumab | vs. Docetaxel in advanced NSCLC |
| NCT02366143 | Phase 3 | COMPLETED | Atezolizumab | + Carboplatin/Paclitaxel ± Bevacizumab vs. chemotherapy alone |
| NCT02425891 | Phase 3 | COMPLETED | Atezolizumab | + nab-Paclitaxel vs. placebo in triple-negative breast cancer |
| NCT02763579 | Phase 3 | COMPLETED | Atezolizumab | + Carboplatin/Etoposide in extensive-stage SCLC |
| NCT02891824 | Phase 3 | COMPLETED | Atezolizumab | vs. placebo in ovarian cancer |
| NCT03038100 | Phase 3 | COMPLETED | Atezolizumab | + chemotherapy/bevacizumab in ovarian cancer |
| NCT03125902 | Phase 3 | COMPLETED | Atezolizumab | + Paclitaxel vs. placebo in TNBC |
| NCT03434379 | Phase 3 | COMPLETED | Atezolizumab | + Bevacizumab vs. Sorafenib in hepatocellular carcinoma |
| NCT02125461 | Phase 3 | COMPLETED | Durvalumab | Following chemoradiation in stage III NSCLC |
| NCT02352948 | Phase 3 | COMPLETED | Durvalumab | ± Tremelimumab vs. SOC in advanced NSCLC/HNC |
| NCT03043872 | Phase 3 | ACTIVE | Durvalumab | ± Tremelimumab + chemotherapy in extensive-stage SCLC |
| NCT04385368 | Phase 3 | COMPLETED | Durvalumab | + Chemotherapy in resected stage II-III NSCLC |
| NCT02395172 | Phase 3 | COMPLETED | Avelumab | in previously-treated NSCLC (JAVELIN Lung 200) |
| NCT02576574 | Phase 3 | COMPLETED | Avelumab | First-line NSCLC (JAVELIN Lung 100) |
| NCT02603432 | Phase 3 | COMPLETED | Avelumab | in urothelial cancer (JAVELIN Bladder 100) |
| NCT02684006 | Phase 3 | COMPLETED | Avelumab | + Axitinib vs. Sunitinib in renal cell carcinoma |
| NCT03271372 | Phase 3 | ACTIVE | Avelumab | Adjuvant in Merkel cell carcinoma |
| NCT04513925 | Phase 3 | COMPLETED | Atezolizumab/Tiragolumab | vs. Durvalumab in stage III NSCLC |
| NCT03830866 | Phase 3 | COMPLETED | Durvalumab | With chemoradiotherapy in cervical cancer |
| NCT04473 | Phase 4 | ONGOING | Durvalumab | Long-term safety/efficacy study |
Pharmacogenomics
Drug-gene interactions affecting response: No specific pharmacogenomic markers documented for CD274 in current databases.
Dosing guidelines: No pharmacogenetic-guided dosing variations reported. Anti-PD-L1 monoclonal antibodies (atezolizumab, durvalumab, avelumab) use standard fixed or weight-based dosing regardless of genetic polymorphisms.
Clinical notes: Unlike targeted therapies, checkpoint inhibitor response is not primarily determined by germline pharmacogenetic variants of the drug target itself. Response is associated with tumor PD-L1 expression status and immune microenvironment characteristics, which are measured as biomarkers rather than germline genetics.
Expression profiles
Tissue Expression
CD274 shows ubiquitous expression across human tissues with broad expression breadth (208 present calls out of 245 conditions) and a maximum expression score of 88.56 based on Bgee analysis.
| Rank | Tissue | Expression Score | Quality | Notes |
|---|---|---|---|---|
| 1 | Cartilage tissue | 88.56 | Gold | Highest expression |
| 2 | Placenta | 86.83 | Gold | |
| 3 | Lower lobe of lung | 86.80 | Gold | |
| 4 | Epithelial cell of pancreas | 86.75 | Gold | Cell-type specific |
| 5 | Upper lobe of left lung | 85.84 | Gold | |
| 6 | Upper lobe of lung | 85.72 | Gold | |
| 7 | Right lung | 84.89 | Gold | |
| 8 | Left ventricle myocardium | 84.81 | Gold | Cardiac-enriched |
| 9 | Vermiform appendix | 83.83 | Gold | |
| 10 | Pancreatic ductal cell | 83.03 | Gold | Cell-type specific |
| 11 | Male germ line stem cell (testis) | 82.44 | Gold | Testicular expression |
| 12 | Lung | 82.26 | Gold | General tissue |
| 13 | Heart right ventricle | 82.22 | Gold | Cardiac-enriched |
| 14 | Myocardium | 81.56 | Gold | Cardiac muscle |
| 15 | Heart left ventricle | 81.30 | Gold | Cardiac-enriched |
| 16 | Spleen | 81.26 | Gold | Immune organ |
| 17 | Cardiac ventricle | 81.01 | Gold | Cardiac tissue |
| 18 | Ileal mucosa | 79.96 | Gold | GI tract |
| 19 | Heart | 77.79 | Gold | General cardiac |
| 20 | Lymph node | 77.40 | Gold | Immune organ |
| 21 | Tibialis anterior | 77.12 | Silver | Skeletal muscle |
| 22 | Apex of heart | 76.82 | Gold | Cardiac apex |
| 23 | Blood | 76.43 | Gold | Immune/vascular |
| 24 | Right atrium auricular region | 76.40 | Gold | Cardiac tissue |
| 25 | Thymus | 76.35 | Gold | Immune organ |
| 26 | Cardiac atrium | 76.04 | Gold | Cardiac tissue |
| 27 | Stromal cell of endometrium | 75.58 | Gold | Cell-type specific |
| 28 | Caecum | 75.53 | Gold | GI tract |
| 29 | Deltoid | 75.35 | Silver | Skeletal muscle |
| 30 | Gallbladder | 75.04 | Gold | Biliary tract |
Tissue-specific patterns: CD274 is broadly expressed across tissues, with enrichment in immune organs (lymph nodes, thymus, spleen), cardiac tissues (ventricles, atrium, myocardium), and epithelial tissues (lung, pancreatic ducts). Expression also detected in reproductive tissues (testis) and gastrointestinal tissues.
Single-Cell Expression Datasets
CD274 expression has been profiled in the following notable single-cell transcriptome datasets:
| Dataset | Accession | Tissue/Context | Cell Count | Cell Types | Key Finding |
|---|---|---|---|---|---|
| Single-cell transcriptome profiling for metastatic renal cell carcinoma | E-CURD-10 | Kidney (tumor) | 118 | Patient-derived RCC cells, xenografts | Expression in tumor microenvironment |
| Single-cell RNA-seq of dermal fibroblasts | E-MTAB-7037 | Dermis | 590 | Fibroblast of dermis | Response to dsRNA stimulation |
| Human dendritic cell subsets in acute skin inflammation | E-MTAB-8498 | Skin, blood | 729 | Plasmacytoid dendritic cells, conventional dendritic cells, monocytes | Immune cell activation in inflammation |
Single-cell patterns: CD274 expression is prominent in immune-infiltrating dendritic cells and monocytes during inflammatory responses. Expression also detected in tumor microenvironments (dendritic cells, immune cells within RCC tumors) and in response to pattern recognition receptor stimulation in fibroblasts (dsRNA).
Average expression score across conditions: 64.82 (range: varied by tissue context)
Note: Expression data available from Bgee (tissue/organ) and ArrayExpress (SCXA—single-cell transcriptomics). GTEx, HPA, Tabula Sapiens, and HCA direct entries not currently mapped in biobtree for this gene.
Disease associations
Mendelian / Monogenic disease
Neonatal diabetes mellitus
- MONDO ID: MONDO:0016391
- Orphanet ID: 224
- Inheritance pattern: Autosomal recessive
- Evidence level: Limited
- Source: Curated gene-disease association (GenCC, GENCC_000101) via Ambry Genetics
- Notes: CD274 is one of 11 genes associated with neonatal diabetes mellitus. Other disease-causing genes include SLC2A2, BSCL2, GATA4, GATA6, MNX1, IL2RA, and NKX2-2 with stronger evidence levels.
ClinVar variants: 29 variants in CD274 identified in ClinVar database with the following classifications:
- Benign/Likely benign: multiple point variants and structural variants
- Uncertain significance: point mutations affecting protein sequence
- Pathogenic: copy number losses and gains (9p24.3-q13 region duplications/deletions)
- Most variants lack strong association with specific monogenic diseases
Phenotype associations
No direct HPO (Human Phenotype Ontology) phenotype terms are mapped to CD274 in the biobtree database.
Complex disease / GWAS
Blood protein levels (GCST006585, Emilsson et al. 2018)
- SNP: rs1411262-C (9p24.1, intron variant)
- Effect size (β): 0.31 unit increase [CI: 0.26-0.36]
- P-value: 2.0 × 10⁻²⁹
- Risk allele frequency: 73.6%
- Platform: Illumina array-based (>1,000,000 markers, imputed)
- PubMed ID: 30072576
Note: CD274 appears to have limited direct associations in GWAS studies. The single significant association identified relates to blood protein abundance rather than disease phenotypes. This reflects CD274’s role as a soluble protein marker rather than causal variants driving disease association.