# SPEN

Source: https://onco.cc/targets/spen/  
OnCo record `spen` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: spen family transcriptional repressor; Msx2-interacting protein; KIAA0929; SHARP; RBM15C
- Tags: cancer-genes-wave
- Symbol: SPEN
- Class: transcription
- 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:17575: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:17575
- UniProt Q96T58: https://www.uniprot.org/uniprotkb/Q96T58/entry
- NCBI Gene 23013: https://www.ncbi.nlm.nih.gov/gene/23013
- Ensembl ENSG00000065526: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000065526

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Cervical cancer](https://onco.cc/cancers/cervical/), [Nasopharyngeal carcinoma](https://onco.cc/cancers/nasopharyngeal/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Salivary gland cancers](https://onco.cc/cancers/salivary-gland/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)

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JSON: https://onco.cc/api/v1/entities/spen.json