# SHP2 (PTPN11)

Source: https://onco.cc/targets/shp2/  
OnCo record `shp2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

SHP2 is an enzyme that sits between growth-factor receptors and RAS and keeps the RAS signal flowing. Blocking it removes the route by which KRAS-driven tumours bounce back from a KRAS inhibitor, which is why SHP2 inhibitors are being paired with KRAS G12C drugs.

## Summary

PTPN11 (chromosome 12q24.13) encodes SHP2, a cytoplasmic tyrosine phosphatase that acts downstream of receptor and cytoplasmic tyrosine kinases, positively regulates MAPK signalling and dephosphorylates GAB1, EGFR, ROCK2, CDC73 and other substrates; it is also the effector recruited by phosphorylated PD-1 to dephosphorylate T-cell receptor signalling components (UniProt Q06124). In OnCo, SHP2 is the target of the second-generation allosteric inhibitor sitneprotafib (JAB-3312), combined with the KRAS G12C inhibitor glecirasib in NSCLC, colorectal and pancreatic cancer, and the combination partner named in the garsorasib and glecirasib records.

## Fields

- Kind: Target
- Last checked: 2026-09-22
- Also known as: SHP-2; PTP2C; SH-PTP2; protein tyrosine phosphatase non-receptor type 11
- Tags: wave5-target
- Symbol: PTPN11
- Class: enzyme
- Biology: Because SHP2 relays receptor signals into RAS, inhibiting it blocks the upstream reactivation that limits KRAS inhibitors, and its role in PD-1 signalling gives a second rationale in immunotherapy combinations. Sitneprotafib is described as allosteric, with more potent anti-tumour activity than earlier SHP2 inhibitors.
- Where found: KRAS G12C-mutant NSCLC and colorectal cancer (combination trials with KRAS inhibitors); Pancreatic cancer (sitneprotafib trials)

## Notes

- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.

## Sources

- HGNC HGNC:9644: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9644
- UniProt Q06124: https://www.uniprot.org/uniprotkb/Q06124/entry
- NCBI Gene 5781: https://www.ncbi.nlm.nih.gov/gene/5781

## Connected records

- drugs: [Garsorasib](https://onco.cc/drugs/garsorasib/), [Glecirasib](https://onco.cc/drugs/glecirasib/), [Sitneprotafib](https://onco.cc/drugs/sitneprotafib/), [Somatostatin analogues (octreotide, lanreotide)](https://onco.cc/drugs/octreotide-lanreotide/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- pathways: [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/), [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/)

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JSON: https://onco.cc/api/v1/entities/shp2.json