TNFRSF12A
protein-codingTNF receptor superfamily member 12A, the group of CD molecules|Tumor necrosis factor receptor superfamily
Gene summary
Involved in positive regulation of extrinsic apoptotic signaling pathway and regulation of wound healing. Predicted to be located in cell surface; membrane; and ruffle. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.9 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 TNFRSF12A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016639.3. 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 | 1 | ||||
| missense | 17 | 1 | 18 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 17 | 1 | 1 | 19 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057723.1 | 4 | MANE Select | |
| Ensembl | ENSP00000326737.5 | 4 | MANE Select | |
| Ensembl | ENSP00000343894.5 | 3 | Standard | |
| Ensembl | ENSP00000343894.5 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway
- TWEAK
- TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
- TNFR2 non-canonical NF-kB pathway
Biological Process
- angiogenesis
- substrate-dependent cell migration, cell attachment to substrate
- tumor necrosis factor-mediated signaling pathway
- positive regulation of apoptotic process
- regulation of angiogenesis
Molecular Function
- protein binding
Cellular Component
- ruffle
- plasma membrane
- cell surface
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326577
- Coding exons
- 4
- Length
- 3939
- Individuals with no LoFs
- 106224
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 106227
- p
- 0.0000141
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.141 | 60 | 57.0 | 1.05 | 0.00000253 | 792 |
| Missense (PolyPhen) | 26 | 30.485 | 0.85288 | 369 | ||
| Synonymous | -1.40 | 33 | 24.2 | 1.36 | 0.00000109 | 290 |
| Loss of Function | 0.776 | 3 | 4.84 | 0.619 | 2.15e-7 | 62 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000031 | 0.000031 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for TNFSF12/TWEAK. Weak inducer of apoptosis in some cell types. Promotes angiogenesis and the proliferation of endothelial cells. May modulate cellular adhesion to matrix proteins. {ECO:0000269|PubMed:11728344}.;
Intolerance Scores
- LoFtool
- 0.275
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.541
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |