TNFRSF10C
protein-codingTNF receptor superfamily member 10c, 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. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene. The expression of this gene was detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL. [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 ~14.5 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 TNFRSF10C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003841.5. 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 | 1 | 1 | 2 | 4 | ||
| missense | 24 | 6 | 30 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 25 | 7 | 2 | 34 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003832.3 | 5 | MANE Select | |
| Ensembl | ENSP00000349324.4 | 5 | MANE Select | |
| Ensembl | ENSP00000428235.1 | 3 | Standard | |
| Ensembl | ENSP00000547695.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Influenza A - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- Natural killer cell mediated cytotoxicity - Homo sapiens (human)
- Measles - Homo sapiens (human)
- Apoptosis - Homo sapiens (human)
Biological Process
- TRAIL-activated apoptotic signaling pathway
- regulation of apoptotic process
- positive regulation of apoptotic process
Molecular Function
- transmembrane signaling receptor activity
- TRAIL binding
Cellular Component
- plasma membrane
- cell surface
- anchored component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000356864
- Coding exons
- 5
- Length
- 33083
- Individuals with no LoFs
- 125014
- Homozygous LoFs
- 4
- Heterozygous LoFs
- 730
- Defined
- 125748
- p
- 0.00292
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.819 | 121 | 149 | 0.811 | 0.00000778 | 1677 |
| Missense (PolyPhen) | 41 | 35.854 | 1.1435 | 427 | ||
| Synonymous | 1.88 | 35 | 52.3 | 0.669 | 0.00000265 | 521 |
| Loss of Function | -0.235 | 8 | 7.31 | 1.09 | 3.08e-7 | 91 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0010 | 0.0010 | notable |
| Latino/Admixed American | 0.0018 | 0.0018 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00083 | 0.00083 | rare |
| European (Non-Finnish) | 0.0055 | 0.0054 | notable |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0.0031 | 0.0031 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for the cytotoxic ligand TRAIL. Lacks a cytoplasmic death domain and hence is not capable of inducing apoptosis. May protect cells against TRAIL mediated apoptosis by competing with TRAIL-R1 and R2 for binding to the ligand.;
Intolerance Scores
- LoFtool
- 0.605
- RVIS EVS
- 0.57
- RVIS percentile EVS
- 81.99
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.287
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |