SPSB2
protein-codingsplA/ryanodine receptor domain and SOCS box containing 2
Gene summary
This gene encodes a member of a subfamily of proteins containing a central SPRY (repeats in splA and RyR) domain and a C-terminal suppressor of cytokine signaling (SOCS) box. This protein plays a role in cell signaling. This gene is present in a gene-rich cluster on chromosome 12p13 in the vicinity of the CD4 antigen and triosephosphate isomerase genes. Alternative splicing results in multiple transcript variants. [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 ~18.4 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 SPSB2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032641.4. 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 | 3 | ||||
| missense | 45 | 45 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 50 | 0 | 0 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_116030.1 | 2 | MANE Select | |
| Ensembl | ENSP00000428338.1 | 2 | MANE Select | |
| RefSeq | NP_001139788.1 | 2 | Standard | |
| RefSeq | NP_001306599.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Immune System
- Adaptive Immune System
- Antigen processing: Ubiquitination & Proteasome degradation
Biological Process
- ubiquitin-dependent protein catabolic process
- biological_process
- protein ubiquitination
- intracellular signal transduction
- proteasome-mediated ubiquitin-dependent protein catabolic process
Molecular Function
- molecular_function
- ubiquitin-protein transferase activity
- protein binding
- protein binding, bridging involved in substrate recognition for ubiquitination
Cellular Component
- cellular_component
- cytosol
- SCF ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000524270
- Coding exons
- 2
- Length
- 18424
- Individuals with no LoFs
- 125637
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 104
- Defined
- 125741
- p
- 0.000414
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.610 | 172 | 151 | 1.14 | 0.00000767 | 1641 |
| Missense (PolyPhen) | 70 | 59.837 | 1.1698 | 684 | ||
| Synonymous | -0.223 | 72 | 69.6 | 1.03 | 0.00000333 | 589 |
| Loss of Function | 1.58 | 4 | 9.14 | 0.437 | 3.95e-7 | 97 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00040 | 0.00040 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00087 | 0.00087 | rare |
| Finnish | 0.00061 | 0.00060 | rare |
| European (Non-Finnish) | 0.00039 | 0.00038 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable 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:0000269|PubMed:15601820}.;
Intolerance Scores
- LoFtool
- 0.726
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.824
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |