SPSB3
protein-codingsplA/ryanodine receptor domain and SOCS box containing 3
Gene summary
Enables ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including negative regulation of cGAS/STING signaling pathway; negative regulation of epithelial to mesenchymal transition; and protein K48-linked ubiquitination. Part of Cul5-RING ubiquitin ligase complex. Is active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
- C16orf31
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.0 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 SPSB3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_080861.4. 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 | 3 | 2 | 1 | 6 | ||
| missense | 81 | 5 | 86 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 86 | 7 | 1 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_543137.2 | 6 | MANE Select | |
| Ensembl | ENSP00000457206.1 | 6 | MANE Select | |
| RefSeq | NP_001311010.1 | 6 | Standard | |
| Ensembl | ENSP00000301717.4 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Neddylation
Biological Process
- ubiquitin-dependent protein catabolic process
- protein ubiquitination
- proteasome-mediated ubiquitin-dependent protein catabolic process
- post-translational protein modification
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
Cellular Component
- cytosol
- SCF ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000566339
- Coding exons
- 6
- Length
- 16989
- Individuals with no LoFs
- 125374
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125393
- p
- 0.0000758
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.785 | 219 | 254 | 0.862 | 0.0000180 | 2310 |
| Missense (PolyPhen) | 59 | 94.844 | 0.62208 | 849 | ||
| Synonymous | -3.16 | 156 | 113 | 1.38 | 0.00000866 | 720 |
| Loss of Function | 2.37 | 5 | 14.8 | 0.337 | 7.19e-7 | 156 |
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 | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00013 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.480
- RVIS EVS
- -0.44
- RVIS percentile EVS
- 24.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.980
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |