{"entity":{"id":"spen","kind":"target","name":"SPEN","aka":["spen family transcriptional repressor","Msx2-interacting protein","KIAA0929","SHARP","RBM15C"],"tldr":"SPEN (Msx2-interacting protein) is a protein that switches other genes on and off. 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 Breast cancer, Non-Hodgkin lymphoma, Renal cell carcinoma and 5 more.","summary":"May serve as a nuclear matrix platform that organises and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergises with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.73 (direct and indirect evidence; datatypes literature 0.89, genetic association 0.21, somatic mutation 0.86). IntOGen calls it a driver in 20 cohorts (1 activating, 18 loss-of-function), covering Acute Myeloid Leukaemia, Invasive Breast Carcinoma, Renal Clear Cell Carcinoma, Cervical Squamous Cell Carcinoma, Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma, Diffuse Large B-Cell Lymphoma, NOS and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:17575","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:17575"},{"label":"UniProt Q96T58","url":"https://www.uniprot.org/uniprotkb/Q96T58/entry"},{"label":"NCBI Gene 23013","url":"https://www.ncbi.nlm.nih.gov/gene/23013"},{"label":"Ensembl ENSG00000065526","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000065526"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["breast-cancer","non-hodgkin-lymphoma","rcc","cervical","nasopharyngeal","prostate","salivary-gland","skin-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"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 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 18 cohorts; CIViC holds 1 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":"SPEN","role":["oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:17575","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:17575","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q96T58","url":"https://www.uniprot.org/uniprotkb/Q96T58/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SPEN","url":"https://civicdb.org/features/9216","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000065526","url":"https://platform.opentargets.org/target/ENSG00000065526/associations","note":"association with cancer (MONDO_0004992) 0.73; per-cancer scores at or above 0.5: colorectal cancer 0.51, melanoma 0.56, acute lymphoblastic leukaemia 0.52, non-Hodgkin lymphoma 0.57, skin cancer 0.56, breast cancer 0.53 (GraphQL API, CC0)"},{"label":"IntOGen SPEN","url":"https://www.intogen.org/search?gene=SPEN","note":"driver in 20 cohorts (Act 1, LoF 18); 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 SPEN: RNA low tissue specificity; high antibody staining in 32 normal tissues; highest cancer staining carcinoid (4 of 4 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Lymphoma, Renal cell carcinoma, Cervical cancer, Nasopharyngeal carcinoma, Prostate cancer, Salivary gland cancers and more); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt Q96T58","url":"https://www.uniprot.org/uniprotkb/Q96T58/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SPEN","url":"https://civicdb.org/features/9216","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen SPEN","url":"https://www.intogen.org/search?gene=SPEN","note":"driver in 20 cohorts (Act 1, LoF 18); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas SPEN tissue","url":"https://www.proteinatlas.org/ENSG00000065526-SPEN/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000065526 associations","url":"https://platform.opentargets.org/target/ENSG00000065526/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:17575","ensembl":"ENSG00000065526","uniprot":"Q96T58","entrez":"23013","firstDescribed":1999,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Rhodes et al, 1999.","firstDescribedSource":"https://www.uniprot.org/uniprotkb/Q96T58/entry","biology":"May serve as a nuclear matrix platform that organises and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergises with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signalling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. Location: Nucleus (UniProt). Locus 1p36.21-p36.13 (HGNC).","whereFound":["Breast cancer: Open Targets association 0.53 with breast cancer (MONDO_0007254); IntOGen driver in 5 cohorts (BRCA)","Non-Hodgkin lymphoma: Open Targets association 0.57 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 1 cohort (MLYM)","Renal cell carcinoma: IntOGen driver in 1 cohort (CCRCC)","Cervical cancer: IntOGen driver in 1 cohort (CESC)","Nasopharyngeal carcinoma: IntOGen driver in 1 cohort (NPC)","Prostate cancer: IntOGen driver in 1 cohort (PRAD)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/spen/","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":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"nasopharyngeal","kind":"cancer","name":"Nasopharyngeal carcinoma","route":"/cancers/nasopharyngeal/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}]}}