# HPK1 (MAP4K1)

Source: https://onco.cc/targets/hpk1/  
OnCo record `hpk1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

HPK1 is a brake inside immune cells: it dampens a T cell's response once the cell has recognised its target. Blocking it is meant to let T cells attack a tumour harder, and an HPK1 inhibitor is in an early trial, alone and with a checkpoint antibody.

## Summary

MAP4K1, better known as HPK1 (hematopoietic progenitor kinase 1, chromosome 19q13.2), is a serine/threonine kinase of the MAP4K family that acts upstream of the JUN N-terminal kinase pathway and may help regulate blood-cell lineage decisions (UniProt Q92918). Its expression is restricted to blood-forming cells. In mice, T cells lacking HPK1 made more Th1 cytokines after T-cell receptor engagement, proliferated faster, resisted suppression by prostaglandin E2, and protected recipients against lung tumour growth after adoptive transfer; dendritic cells lacking it presented antigen better (Immunologic Research 2012, doi:10.1007/s12026-012-8319-1). In OnCo, CFI-402411 is an oral HPK1 inhibitor tested alone and with pembrolizumab in advanced solid tumours.

## Fields

- Kind: Target
- Last checked: 2026-11-03
- Also known as: HPK1; hematopoietic progenitor kinase 1; mitogen-activated protein kinase kinase kinase kinase 1
- Tags: pipeline-gap-target
- Symbol: MAP4K1
- Class: kinase
- Biology: Hematopoietic cell-restricted MAP4K family serine/threonine kinase; a negative regulator of T-cell receptor signalling in the cited mouse studies, so inhibition is an immune-activating rather than a tumour-cell-killing strategy.
- Where found: T cells, B cells and dendritic cells (blood-forming lineage only); Advanced solid tumours (CFI-402411 trial, with pembrolizumab)

## Notes

- Prevalence not recorded: HGNC, UniProt and the paper cited give no positivity rate.

## Sources

- HGNC HGNC:6863: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6863
- UniProt Q92918: https://www.uniprot.org/uniprotkb/Q92918/entry
- NCBI Gene 11184: https://www.ncbi.nlm.nih.gov/gene/11184
- HPK1 as a novel target for cancer immunotherapy (Immunol Res 2012): https://doi.org/10.1007/s12026-012-8319-1

## Connected records

- cancers: [Metastatic cancer (cancer that has spread)](https://onco.cc/cancers/metastatic-cancer/)
- drugs: [CFI-402411](https://onco.cc/drugs/cfi-402411/)

---
JSON: https://onco.cc/api/v1/entities/hpk1.json