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SPOP (Speckle-type POZ protein) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Prostate cancer, Endometrial cancer, Non-Hodgkin lymphoma and 4 more.
Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation.
CIViC holds 9 clinical evidence items and 0 assertions across 10 variants. Open Targets scores its association with cancer at 0.77 (direct and indirect evidence; datatypes literature 1.00, genetic association 0.00, somatic mutation 0.92). IntOGen calls it a driver in 15 cohorts (14 activating, 1 loss-of-function), covering Non-Hodgkin Lymphoma, Prostate Adenocarcinoma, Prostate, Endometrial Carcinoma, Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumour.
In plain words · SPOP (Speckle-type POZ protein) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Prostate cancer, Endometrial cancer, Non-Hodgkin lymphoma and 4 more.
SPOP (Speckle-type POZ protein) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Prostate cancer, Endometrial cancer, Non-Hodgkin lymphoma and 4 more.
Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation.
No product in this corpus aims at SPOP yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA SPOP: RNA low tissue specificity; no normal tissue stained high. Distribution: 5 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Prostate cancer, Endometrial cancer, Lymphoma, Ovarian cancer, Skin cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (prostate adenocarcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt O43791; CIViC gene SPOP; IntOGen SPOP; Human Protein Atlas SPOP tissue; Open Targets ENSG00000121067 associations
First described 1997. Earliest sequence paper UniProt cites for the protein: Nagai et al, FEBS Lett, 1997, "Identification of a novel nuclear speckle-type protein, SPOP". Source.
Sources: HGNC HGNC:11254 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O43791 (protein name, function text, keywords and locations (REST API)); CIViC gene SPOP (9 evidence items, 0 assertions, 10 variants; diseases: (GraphQL API, CC0)); Open Targets ENSG00000121067 (association with cancer (MONDO_0004992) 0.77; per-cancer scores at or above 0.5: prostate cancer 0.72, ovarian cancer 0.52, endometrial cancer 0.62, melanoma 0.52, skin cancer 0.52 (GraphQL API, CC0)); IntOGen SPOP (driver in 15 cohorts (Act 14, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation. Inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL. Involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability. Location: Nucleus; Nucleus speckle; Cytoplasm (UniProt). Locus 17q21.33 (HGNC).
RNA: low tissue specificity, detected in all normal tissues.
No normal tissue stained high.
No cancer sample stained medium or high.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | 6-14% | Missense mutation in the substrate-binding cleft | cBioPortal: 318 of 2,260, 14.1%, in prostate_msk_2024; 260 of 2,069, 12.6%, in prad_msk_stopsack_2021; 166 of 1,465, 11.3%, in prad_cdk12_mskcc_2020; 55 of 494, 11.1%, in prad_tcga_pan_can_atlas_2018 and 37 of 333, 11.1%, in prad_tcga_pub; 14 of 112, 12.5%, in prad_broad; 53 of 424, 12.5%, in prad_mcspc_mskcc_2020; 92 of 1,013, 9.1%, in prad_p1000; 38 of 477, 8.0%, in prad_cpcg_2017; 25 of 444, 5.6%, in prad_su2c_2019; 11 of 65, 16.9%, in prad_eururol_2017. The discovery series put it at 6 to 15% across several independent cohorts (Barbieri 2012). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It fills the gap between the primary-tumour atlases and the castration-resistant series by describing the disease at the moment most treatment decisions are actually made, and it identifies SPOP as a favourable marker rather than a neutral one.
It is the quantitative answer to why prostate cancer has so few targeted therapies. The common events are not druggable, the druggable ones are individually rare, and no trial can be powered on a driver present in 2% of men without an international basket.
It is the study that justified using plasma instead of a bone biopsy in this disease, with the honest caveat attached: the concordance holds only above a tumour fraction threshold, and below it the test is uninformative rather than negative.
The reference classification of prostate cancer as it presents, and the source of the two numbers that drive most molecular treatment decisions in the disease: a quarter with a PI3K or MAPK lesion, which is the rationale for capivasertib in PTEN-deficient disease, and a fifth with DNA repair inactivation, which is the rationale for PARP inhibitors.
It established the fusion-negative side of the prostate cancer taxonomy and made SPOP the disease's signature point mutation, in a ubiquitin ligase adaptor rather than in a kinase, which is part of why prostate cancer has so few druggable drivers.
Query for this target: (TITLE:"SPOP" OR ABSTRACT:"SPOP" OR TITLE:"speckle type BTB/POZ protein" OR ABSTRACT:"speckle type BTB/POZ protein" OR TITLE:"Speckle-type POZ protein" OR ABSTRACT:"Speckle-type POZ protein" OR TITLE:"TEF2" OR ABSTRACT:"TEF2" OR TITLE:"BTBD32" OR ABSTRACT:"BTBD32") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about SPOP, not a curated reading list.
Shares Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, The long tail of oncogenic drivers in prostate cancer, TCGA: the molecular taxonomy of primary prostate cancer, CIViC.
Shares Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, The long tail of oncogenic drivers in prostate cancer, TCGA: the molecular taxonomy of primary prostate cancer, CIViC.
Shares Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer, Skin cancer (all types), CIViC, IntOGen.
Shares Uterine carcinosarcoma, IntOGen, Melanoma, Prostate cancer.
Shares Uterine carcinosarcoma, Skin cancer (all types), IntOGen, Open Targets Platform.
Shares TCGA: the molecular taxonomy of primary prostate cancer, CIViC, IntOGen, Open Targets Platform.
Shares The long tail of oncogenic drivers in prostate cancer, CIViC, IntOGen, Open Targets Platform.
Shares The long tail of oncogenic drivers in prostate cancer, CIViC, IntOGen, Non-Hodgkin lymphoma (all types).