GPS2
Overview
GPS2 (G Protein Pathway Suppressor 2) encodes a component of the N-CoR (nuclear receptor co-repressor) transcriptional repressor complex. In medulloblastoma, GPS2 harbors somatic missense mutations within the NCOR2 interaction domain (amino acids 53–90) specifically in Group 3 tumors, implicating disruption of the N-CoR co-repressor complex in this aggressive medulloblastoma subgroup.
Alterations observed in the corpus
- Missense mutations within the NCOR2-interaction domain (aa 53–90) identified in Group 3 medulloblastoma by WES (Broad, 92 tumors) PMID:22820256
- Identified in a 173-gene targeted sequencing panel breast cancer study (n=2,433) as part of the mutational landscape analysis PMID:27161491
Cancer types (linked)
- MB (medulloblastoma): Mutations in Group 3 subtype; disrupts N-CoR/NCOR2 co-repressor complex; subtype-specific MutSig candidate PMID:22820256
Co-occurrence and mutual exclusivity
- Mutations cluster in the NCOR2 interaction domain, suggesting disruption of the same GPS2–NCOR2 protein interface as LDB1 and other N-CoR complex members altered in medulloblastoma PMID:22820256
Therapeutic relevance
- N-CoR complex disruption across multiple components (GPS2, LDB1, NCOR2) in medulloblastoma may indicate sensitivity to epigenetic therapies targeting nuclear co-repressor pathways.
Open questions
- Whether GPS2 mutations are sufficient to drive Group 3 medulloblastoma or require co-occurring alterations remains unknown.
- Functional validation of GPS2 missense mutations on N-CoR complex activity not yet performed.
Sources
This page was processed by entity-page-writer on 2026-05-06. - PMID:27161491
This page was processed by wiki-cli on 2026-05-14.