BIRC5
protein-codingbaculoviral IAP repeat containing 5, the group of Baculoviral IAP repeat containing|Chromosomal passenger complex
Gene summary
This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors, yet low in adult tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2011]
- API4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.5 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 BIRC5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001168.3. 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 | 15 | 2 | 17 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 15 | 3 | 0 | 18 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001159.2 | 4 | MANE Select | |
| Ensembl | ENSP00000324180.4 | 4 | MANE Select | |
| RefSeq | NP_001012270.1 | 3 | Standard | |
| RefSeq | NP_001012271.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| birc5b | Danio rerio | Structure: erythroid lineage cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Apoptosis - multiple species - Homo sapiens (human)
- Hippo signaling pathway - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- Hepatitis B - Homo sapiens (human)
- Apoptosis - Homo sapiens (human)
Biological Process
- protein phosphorylation
- apoptotic process
- cell cycle
- chromosome segregation
- sensory perception of sound
Molecular Function
- cysteine-type endopeptidase inhibitor activity
- protein binding
- microtubule binding
- Ran GTPase binding
- enzyme binding
Cellular Component
- nuclear chromosome
- chromosome, centromeric region
- condensed chromosome kinetochore
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000301633
- Coding exons
- 5
- Length
- 11451
- Individuals with no LoFs
- 123737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 123738
- p
- 0.00000404
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.473 | 73 | 85.3 | 0.856 | 0.00000464 | 1074 |
| Missense (PolyPhen) | 19 | 29.476 | 0.64459 | 398 | ||
| Synonymous | 0.271 | 31 | 33.0 | 0.940 | 0.00000198 | 289 |
| Loss of Function | 1.51 | 3 | 7.43 | 0.404 | 3.53e-7 | 101 |
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 | 0.000055 | 0.000055 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:9859993, PubMed:21364656, PubMed:20627126). Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis (PubMed:16322459). Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules (PubMed:20826784). Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis (PubMed:20929775). The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255). May counteract a default induction of apoptosis in G2/M phase (PubMed:9859993). The acetylated form represses STAT3 transactivation of target gene promoters (PubMed:20826784). May play a role in neoplasia (PubMed:10626797). Inhibitor of CASP3 and CASP7 (PubMed:21536684). Isoform 2 and isoform 3 do not appear to play vital roles in mitosis (PubMed:12773388, PubMed:16291752). Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform (PubMed:10626797). {ECO:0000269|PubMed:10626797, ECO:0000269|PubMed:12773388, ECO:0000269|PubMed:16291752, ECO:0000269|PubMed:16322459, ECO:0000269|PubMed:18591255, ECO:0000269|PubMed:20627126, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:20929775, ECO:0000269|PubMed:21364656, ECO:0000269|PubMed:21536684, ECO:0000269|PubMed:9859993}.;
Recessive Scores
- pRec
- 0.626
Intolerance Scores
- LoFtool
- 0.889
- RVIS EVS
- 0.79
- RVIS percentile EVS
- 87.4
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.384
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Low | Medium |