TIGIT
protein-codingT cell immunoreceptor with Ig and ITIM domains, the group of V-set domain containing
Gene summary
This gene encodes a member of the PVR (poliovirus receptor) family of immunoglobin proteins. The product of this gene is expressed on several classes of T cells including follicular B helper T cells (TFH). The protein has been shown to bind PVR with high affinity; this binding is thought to assist interactions between TFH and dendritic cells to regulate T cell dependent B cell responses.[provided by RefSeq, Sep 2009]
- VSIG9
- VSTM3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TIGIT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173799.4. 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 | 1 | 2 | |||
| missense | 33 | 8 | 41 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 38 | 9 | 0 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_776160.2 | 4 | MANE Select | |
| Ensembl | ENSP00000373167.3 | 4 | MANE Select | |
| Ensembl | ENSP00000418917.1 | 3 | Standard | |
| Ensembl | ENSP00000420552.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
Biological Process
- negative regulation of interleukin-12 production
- positive regulation of interleukin-10 production
- negative regulation of T cell activation
Molecular Function
- signaling receptor binding
- protein binding
- identical protein binding
Cellular Component
- plasma membrane
- cell surface
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000486257
- Coding exons
- 4
- Length
- 33376
- Individuals with no LoFs
- 125691
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125706
- p
- 0.0000597
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0420 | 143 | 142 | 1.01 | 0.00000781 | 1560 |
| Missense (PolyPhen) | 32 | 32.354 | 0.98905 | 413 | ||
| Synonymous | 0.613 | 56 | 62.2 | 0.901 | 0.00000393 | 507 |
| Loss of Function | 1.48 | 4 | 8.71 | 0.459 | 4.39e-7 | 87 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds with high affinity to the poliovirus receptor (PVR) which causes increased secretion of IL10 and decreased secretion of IL12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells. {ECO:0000269|PubMed:19011627}.;
Intolerance Scores
- LoFtool
- 0.415
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.180
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |