TNFRSF10B
protein-codingTNF receptor superfamily member 10b, the group of CD molecules|Tumor necrosis factor receptor superfamily
Gene summary
The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces an apoptosis signal. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for this gene. [provided by RefSeq, Mar 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0010150
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0010150
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0010150
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Oncologic
Intervention: Oncologic
Rationale: Surveillance and early diagnosis could potentially be beneficial to allow prompt management of detected neoplasms
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TNFRSF10B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003842.5. 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 | 9 | 12 | |||
| missense | 56 | 7 | 1 | 64 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 1 | 1 | 65 | 16 | 1 | 84 |
Highest pathogenic variant AF is 0.00022924696
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003833.4 | 9 | MANE Select | |
| Ensembl | ENSP00000276431.4 | 9 | MANE Select | |
| RefSeq | NP_671716.2 | 10 | Standard | |
| Ensembl | ENSP00000317859.3 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- p53 signaling pathway - Homo sapiens (human)
- Influenza A - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- Natural killer cell mediated cytotoxicity - Homo sapiens (human)
- Measles - Homo sapiens (human)
Biological Process
- apoptotic process
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- cell surface receptor signaling pathway
- activation of NF-kappaB-inducing kinase activity
- extrinsic apoptotic signaling pathway via death domain receptors
Molecular Function
- protein binding
- signaling receptor activity
- TRAIL binding
Cellular Component
- plasma membrane
- cell surface
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000276431
- Coding exons
- 9
- Length
- 49047
- Individuals with no LoFs
- 125648
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 100
- Defined
- 125748
- p
- 0.000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.670 | 270 | 241 | 1.12 | 0.0000128 | 2826 |
| Missense (PolyPhen) | 48 | 53.824 | 0.89179 | 721 | ||
| Synonymous | -0.224 | 102 | 99.2 | 1.03 | 0.00000584 | 892 |
| Loss of Function | 2.05 | 9 | 18.5 | 0.486 | 8.95e-7 | 221 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00055 | 0.00055 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00057 | 0.00057 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for the cytotoxic ligand TNFSF10/TRAIL (PubMed:10549288). The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis. {ECO:0000269|PubMed:10542098, ECO:0000269|PubMed:10549288, ECO:0000269|PubMed:15322075}.;
- Disease
- DISEASE: Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.196
- RVIS EVS
- 0.64
- RVIS percentile EVS
- 84.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.479
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |