{"entity":{"id":"spop","kind":"target","name":"SPOP","aka":["speckle type BTB/POZ protein","Speckle-type POZ protein","TEF2","BTBD32"],"tldr":"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.","summary":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11254","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11254"},{"label":"UniProt O43791","url":"https://www.uniprot.org/uniprotkb/O43791/entry"},{"label":"NCBI Gene 8405","url":"https://www.ncbi.nlm.nih.gov/gene/8405"},{"label":"Ensembl ENSG00000121067","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000121067"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["prostate","endometrial","non-hodgkin-lymphoma","ovarian","skin-cancer","uterine-carcinosarcoma","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012","paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020"],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 14 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 9 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"SPOP","role":["oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:11254","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11254","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt O43791","url":"https://www.uniprot.org/uniprotkb/O43791/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SPOP","url":"https://civicdb.org/features/6652","note":"9 evidence items, 0 assertions, 10 variants; diseases:  (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000121067","url":"https://platform.opentargets.org/target/ENSG00000121067/associations","note":"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)"},{"label":"IntOGen SPOP","url":"https://www.intogen.org/search?gene=SPOP","note":"driver in 15 cohorts (Act 14, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"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.)","specificitySources":[{"label":"UniProt O43791","url":"https://www.uniprot.org/uniprotkb/O43791/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SPOP","url":"https://civicdb.org/features/6652","note":"9 evidence items, 0 assertions, 10 variants; diseases:  (GraphQL API, CC0)"},{"label":"IntOGen SPOP","url":"https://www.intogen.org/search?gene=SPOP","note":"driver in 15 cohorts (Act 14, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas SPOP tissue","url":"https://www.proteinatlas.org/ENSG00000121067-SPOP/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000121067 associations","url":"https://platform.opentargets.org/target/ENSG00000121067/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11254","ensembl":"ENSG00000121067","uniprot":"O43791","entrez":"8405","firstDescribed":1997,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Nagai et al, FEBS Lett, 1997, \"Identification of a novel nuclear speckle-type protein, SPOP\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9414087/","biology":"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).","whereFound":["Prostate cancer: Open Targets association 0.72 with prostate cancer (MONDO_0008315); IntOGen driver in 12 cohorts (PRAD, PROSTATE)","Endometrial cancer: Open Targets association 0.62 with endometrial cancer (MONDO_0011962); IntOGen driver in 1 cohort (UCEC)","Non-Hodgkin lymphoma: IntOGen driver in 1 cohort (NHL)","Ovarian cancer: Open Targets association 0.52 with ovarian cancer (MONDO_0008170)","Skin cancer: Open Targets association 0.52 with skin cancer (MONDO_0002898)","Uterine carcinosarcoma: IntOGen driver in 1 cohort (UCS)","Prostate cancer: missense mutation in the substrate-binding cleft 6-14% depending on disease state"],"targetClass":"oncogene","prevalence":[{"cancerId":"prostate","pct":"6-14","measure":"Missense mutation in the substrate-binding cleft","source":"https://www.cbioportal.org/study/summary?id=prostate_msk_2024","note":"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)."}]},"route":"/targets/spop/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"},{"id":"uterine-carcinosarcoma","kind":"cancer","name":"Uterine carcinosarcoma","route":"/cancers/uterine-carcinosarcoma/"}],"paper":[{"id":"paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017","kind":"paper","name":"Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer","route":"/key-papers/paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017/"},{"id":"paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012","kind":"paper","name":"Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer","route":"/key-papers/paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012/"},{"id":"paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020","kind":"paper","name":"Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer","route":"/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/"},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/"},{"id":"paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018","kind":"paper","name":"The long tail of oncogenic drivers in prostate cancer","route":"/key-papers/paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018/"}],"biomarker":[{"id":"spop-mutation","kind":"biomarker","name":"SPOP mutation","route":"/biomarkers/spop-mutation/"}]}}