SPOP
Chr 17ADspeckle type BTB/POZ protein
Also known as: BTBD32, NEDMACE, NEDMIDF, NSDVS1, NSDVS2, TEF2
The SPOP protein functions as a component of a cullin-RING-based E3 ubiquitin ligase complex that targets specific proteins for degradation or regulation, playing essential roles in transcriptional regulation, DNA replication, and cell proliferation. Mutations cause Nabais Sa-de Vries syndrome types 1 and 2 with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variation in the population, indicating that such mutations are likely to have significant clinical consequences.
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SPOP · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Testing the Effect of M1774 on Hard-to-Treat Refractory SPOP-mutant Prostate Cancer
ACTIVE NOT RECRUITINGCJNJ-67652000 and Prednisone for Treatment of Metastatic Castration-Resistant Prostate Cancer and SPOP Gene Mutations
ACTIVE NOT RECRUITINGNeoadjuvant Degarelix With or Without Apalutamide (ARN-509) Followed by Radical Prostatectomy
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools