TNFSF14
protein-codingTNF superfamily member 14, the group of CD molecules|Tumor necrosis factor superfamily
Gene summary
The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells. This protein is also reported to prevent tumor necrosis factor alpha mediated apoptosis in primary hepatocyte. Two alternatively spliced transcript variant encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.5 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 TNFSF14 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001376887.1. 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 | 3 | 3 | ||||
| missense | 34 | 3 | 37 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 34 | 3 | 3 | 40 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001363816.1 | 4 | MANE Select | |
| Ensembl | ENSP00000502837.1 | 4 | MANE Select | |
| RefSeq | NP_003798.2 | 4 | Standard | |
| RefSeq | NP_742011.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- NF-kappa B signaling pathway - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- Herpes simplex infection - Homo sapiens (human)
- TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
- TNFR2 non-canonical NF-kB pathway
Biological Process
- apoptotic process
- immune response
- signal transduction
- regulation of signaling receptor activity
- positive regulation of T cell chemotaxis
Molecular Function
- signaling receptor binding
- cytokine activity
- tumor necrosis factor receptor binding
- protein binding
- cysteine-type endopeptidase inhibitor activity involved in apoptotic process
Cellular Component
- extracellular space
- cytoplasm
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000599359
- Coding exons
- 4
- Length
- 7452
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125744
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.638 | 135 | 158 | 0.857 | 0.0000107 | 1500 |
| Missense (PolyPhen) | 33 | 52.689 | 0.62631 | 555 | ||
| Synonymous | 0.845 | 57 | 65.7 | 0.867 | 0.00000402 | 543 |
| Loss of Function | 2.04 | 4 | 11.5 | 0.349 | 6.66e-7 | 107 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Activates NFKB, stimulates the proliferation of T-cells, and inhibits growth of the adenocarcinoma HT-29. Acts as a receptor for Herpes simplex virus.;
Recessive Scores
- pRec
- 0.264
Intolerance Scores
- LoFtool
- 0.185
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 34.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.869
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |