SPOPL
protein-codingspeckle type BTB/POZ protein like, the group of BTB domain containing
Gene summary
Enables identical protein binding activity. Involved in negative regulation of protein ubiquitination and proteasome-mediated ubiquitin-dependent protein catabolic process. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~72.7 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 SPOPL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001001664.3. 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 | 54 | 3 | 57 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 58 | 3 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001001664.1 | 10 | MANE Select | |
| Ensembl | ENSP00000280098.4 | 10 | MANE Select | |
| Ensembl | ENSP00000396006.1 | 5 | Standard | |
| Ensembl | ENSP00000410201.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Hedgehog signaling pathway - Homo sapiens (human)
- Hedgehog Signaling Pathway
- Signal Transduction
- Hedgehog ,on, state
- Signaling by Hedgehog
Biological Process
- ubiquitin-dependent protein catabolic process
- protein ubiquitination
- regulation of proteolysis
- negative regulation of protein ubiquitination
- proteasome-mediated ubiquitin-dependent protein catabolic process
Molecular Function
- protein binding
- ubiquitin protein ligase binding
Cellular Component
- nucleus
- cytoplasm
- Cul3-RING ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000280098
- Coding exons
- 10
- Length
- 71747
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125744
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.960 | 171 | 210 | 0.814 | 0.0000106 | 2602 |
| Missense (PolyPhen) | 54 | 77.692 | 0.69505 | 1016 | ||
| Synonymous | 0.155 | 66 | 67.6 | 0.976 | 0.00000324 | 699 |
| Loss of Function | 3.15 | 8 | 25.0 | 0.320 | 0.00000145 | 274 |
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 | 0.00022 | 0.00022 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, but with relatively low efficiency. Cullin-RING-based BCR (BTB-CUL3- RBX1) E3 ubiquitin-protein ligase complexes containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL are less efficient than ubiquitin ligase complexes containing only SPOP. May function to down-regulate the activity of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain SPOP. {ECO:0000269|PubMed:22632832}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.483
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.635
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |