CD274
protein-codingCD274 molecule, the group of V-set domain containing|CD molecules|C2-set domain containing|Receptor ligands|B7 family
Gene summary
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]
- PDCD1LG1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0016391
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CD274 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014143.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 3 | |||
| missense | 12 | 2 | 14 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 14 | 2 | 2 | 18 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_054862.1 | 6 | MANE Select | |
| Ensembl | ENSP00000370989.3 | 6 | MANE Select | |
| RefSeq | NP_001254635.1 | 5 | Standard | |
| RefSeq | NP_001300958.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- PD-1 signaling
- Costimulation by the CD28 family
- Immune System
- Adaptive Immune System
Biological Process
- positive regulation of tolerance induction to tumor cell
- immune response
- signal transduction
- cell surface receptor signaling pathway
- positive regulation of cell migration
Molecular Function
- protein binding
Cellular Component
- plasma membrane
- external side of plasma membrane
- cell surface
- integral component of membrane
- early endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381577
- Coding exons
- 6
- Length
- 20064
- Individuals with no LoFs
- 125698
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125703
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.898 | 123 | 154 | 0.797 | 0.00000753 | 1918 |
| Missense (PolyPhen) | 29 | 47.712 | 0.60781 | 625 | ||
| Synonymous | -1.39 | 71 | 57.6 | 1.23 | 0.00000286 | 541 |
| Loss of Function | 2.08 | 5 | 13.1 | 0.381 | 6.39e-7 | 164 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a critical role in induction and maintenance of immune tolerance to self. As a ligand for the inhibitory receptor PDCD1/CD279, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11015443). The PDCD1/CD279-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival (PubMed:28813417, PubMed:28813410). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077). {ECO:0000269|PubMed:10581077, ECO:0000269|PubMed:11015443, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417}.;
Recessive Scores
- pRec
- 0.220
Intolerance Scores
- LoFtool
- 0.547
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 75.12
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.450
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |