TNFRSF18
protein-codingTNF receptor superfamily member 18, the group of CD molecules|Tumor necrosis factor receptor superfamily
Gene summary
This gene encodes a member of the TNF-receptor superfamily. The encoded receptor has been shown to have increased expression upon T-cell activation, and it is thought to play a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells. Knockout studies in mice also suggest the role of this receptor is in the regulation of CD3-driven T-cell activation and programmed cell death. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.1 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 TNFRSF18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004195.3. 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 | 6 | 7 | |||
| missense | 43 | 8 | 51 | |||
| nonsense | 1 | 2 | 3 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 45 | 16 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004186.1 | 5 | MANE Select | |
| Ensembl | ENSP00000368570.2 | 5 | MANE Select | |
| RefSeq | NP_683699.1 | 4 | Standard | |
| RefSeq | NP_683700.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
- Gene expression (Transcription)
- Generic Transcription Pathway
- TNFR2 non-canonical NF-kB pathway
Biological Process
- positive regulation of leukocyte migration
- apoptotic process
- signal transduction
- tumor necrosis factor-mediated signaling pathway
- positive regulation of tyrosine phosphorylation of STAT protein
Molecular Function
- tumor necrosis factor-activated receptor activity
- protein binding
Cellular Component
- extracellular region
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000328596
- Coding exons
- 4
- Length
- 3184
- Individuals with no LoFs
- 124996
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125028
- p
- 0.000128
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.567 | 175 | 155 | 1.13 | 0.00000940 | 1596 |
| Missense (PolyPhen) | 42 | 42.78 | 0.98178 | 453 | ||
| Synonymous | -0.866 | 77 | 67.9 | 1.13 | 0.00000461 | 535 |
| Loss of Function | -0.598 | 8 | 6.37 | 1.26 | 2.72e-7 | 70 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00057 | 0.00056 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.00010 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000098 | 0.000098 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for TNFSF18. Seems to be involved in interactions between activated T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B activation via the TRAF2/NIK pathway.;
Recessive Scores
- pRec
- 0.164
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |