SIVA1
protein-codingSIVA1 apoptosis inducing factor
Gene summary
This gene encodes an E3 ubiquitin ligase that regulates cell cycle progression, cell proliferation and apoptosis. The N-terminus of this protein binds to the cytoplasmic tail of the CD27 antigen, a member of the tumor necrosis factor receptor (TNFR) superfamily. In response to UV radiation-induced DNA damage, this protein has been shown to mediate the ubiquitination of proliferating cell nuclear antigen (PCNA), an important step in translesion DNA synthesis. [provided by RefSeq, Sep 2018]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.3 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 SIVA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006427.4. 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 | 0 | |||||
| missense | 38 | 2 | 1 | 41 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 39 | 2 | 1 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006418.2 | 4 | MANE Select | |
| Ensembl | ENSP00000329213.6 | 4 | MANE Select | |
| RefSeq | NP_068355.1 | 3 | Standard | |
| Ensembl | ENSP00000329447.6 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- viral entry into host cell
- extrinsic apoptotic signaling pathway
Molecular Function
- virus receptor activity
- tumor necrosis factor receptor binding
- CD27 receptor binding
- protein binding
- metal ion binding
Cellular Component
- nucleoplasm
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000329967
- Coding exons
- 4
- Length
- 15395
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125737
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.00676 | 114 | 114 | 0.998 | 0.00000709 | 1109 |
| Missense (PolyPhen) | 31 | 40.58 | 0.76392 | 438 | ||
| Synonymous | -0.654 | 59 | 52.9 | 1.11 | 0.00000372 | 367 |
| Loss of Function | 1.68 | 4 | 9.61 | 0.416 | 6.64e-7 | 81 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Induces CD27-mediated apoptosis. Inhibits BCL2L1 isoform Bcl-x(L) anti-apoptotic activity. Inhibits activation of NF-kappa- B and promotes T-cell receptor-mediated apoptosis. {ECO:0000269|PubMed:12011449, ECO:0000269|PubMed:14739602, ECO:0000269|PubMed:15034012, ECO:0000269|PubMed:15958577, ECO:0000269|PubMed:16491128}.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.149
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.805