BIRC3
protein-codingbaculoviral IAP repeat containing 3, the group of Ring finger proteins|Baculoviral IAP repeat containing|Caspase recruitment domain containing
Gene summary
This gene encodes a member of the IAP family of proteins that inhibit apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. The encoded protein inhibits apoptosis induced by serum deprivation but does not affect apoptosis resulting from exposure to menadione, a potent inducer of free radicals. It contains 3 baculovirus IAP repeats and a ring finger domain. Transcript variants encoding the same isoform have been identified. [provided by RefSeq, Aug 2011]
- API2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.9 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 BIRC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001165.5. 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 | 2 | 3 | |||
| missense | 4 | 54 | 5 | 63 | ||
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 6 | 56 | 6 | 2 | 70 |
Highest pathogenic variant AF is 0.0000013697579
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001156.1 | 8 | MANE Select | |
| Ensembl | ENSP00000263464.4 | 8 | MANE Select | |
| RefSeq | NP_892007.1 | 8 | Standard | |
| Ensembl | ENSP00000501119.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Focal adhesion - Homo sapiens (human)
- Small cell lung cancer - Homo sapiens (human)
- Apoptosis - multiple species - Homo sapiens (human)
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- TNF signaling pathway - Homo sapiens (human)
Biological Process
- apoptotic process
- cell surface receptor signaling pathway
- I-kappaB kinase/NF-kappaB signaling
- spermatogenesis
- regulation of tumor necrosis factor-mediated signaling pathway
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- transferase activity
- cysteine-type endopeptidase inhibitor activity involved in apoptotic process
- metal ion binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263464
- Coding exons
- 8
- Length
- 21920
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125743
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.15 | 254 | 311 | 0.817 | 0.0000158 | 3963 |
| Missense (PolyPhen) | 57 | 105.06 | 0.54254 | 1353 | ||
| Synonymous | 0.460 | 109 | 115 | 0.945 | 0.00000634 | 1131 |
| Loss of Function | 3.37 | 7 | 25.3 | 0.277 | 0.00000116 | 350 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00013 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin- protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin- protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase- independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. {ECO:0000269|PubMed:21931591, ECO:0000269|PubMed:23453969}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving BIRC3 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with MALT1. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.;
Recessive Scores
- pRec
- 0.286
Intolerance Scores
- LoFtool
- 0.509
- RVIS EVS
- -0.53
- RVIS percentile EVS
- 20.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |