SVIP
protein-codingsmall VCP interacting protein
Gene summary
Endoplasmic reticulum-associated degradation (ERAD) is the pathway by which misfolded proteins in the endoplasmic reticulum are targeted to the proteasome for degradation. Multiple specialized proteins interact with one another during ERAD to complete this process. The protein encoded by this gene is an inhibitor of ERAD, functioning to disrupt the interaction of these protein components. This downregulation of ERAD may be needed to protect the cell from overactive protein degradation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.5 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 SVIP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_148893.3. 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 | 0 | |||||
| missense | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 15 | 0 | 0 | 15 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_683691.1 | 4 | MANE Select | |
| Ensembl | ENSP00000346130.4 | 4 | MANE Select | |
| RefSeq | NP_001307269.1 | 4 | Standard | |
| RefSeq | NP_001307270.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- positive regulation of autophagy
- negative regulation of protein complex assembly
- neutrophil degranulation
- positive regulation of protein lipidation
- negative regulation of ER-associated ubiquitin-dependent protein catabolic process
Molecular Function
- protein binding
- protein self-association
- ATPase binding
Cellular Component
- Golgi membrane
- endoplasmic reticulum membrane
- plasma membrane
- secretory granule membrane
- smooth endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000354193
- Coding exons
- 4
- Length
- 16501
- Individuals with no LoFs
- 124728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 61
- Defined
- 124789
- p
- 0.000244
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.444 | 30 | 37.7 | 0.797 | 0.00000186 | 469 |
| Missense (PolyPhen) | 14 | 18.226 | 0.76812 | 231 | ||
| Synonymous | 0.680 | 10 | 13.1 | 0.761 | 5.78e-7 | 149 |
| Loss of Function | -0.170 | 5 | 4.61 | 1.09 | 1.93e-7 | 64 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00036 | 0.00032 | rare |
| Latino/Admixed American | 0.00043 | 0.00038 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00037 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0.00031 | 0.00029 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Intolerance Scores
- LoFtool
- 0.680
- RVIS EVS
- 0.01
- RVIS percentile EVS
- 54.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |