{"entity":{"id":"hpk1","kind":"target","name":"HPK1 (MAP4K1)","aka":["HPK1","hematopoietic progenitor kinase 1","mitogen-activated protein kinase kinase kinase kinase 1"],"tldr":"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.","asOf":"2026-11-03","links":[{"label":"HGNC HGNC:6863","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6863"},{"label":"UniProt Q92918","url":"https://www.uniprot.org/uniprotkb/Q92918/entry"},{"label":"NCBI Gene 11184","url":"https://www.ncbi.nlm.nih.gov/gene/11184"},{"label":"HPK1 as a novel target for cancer immunotherapy (Immunol Res 2012)","url":"https://doi.org/10.1007/s12026-012-8319-1"}],"tags":["pipeline-gap-target"],"related":[],"cancers":["metastatic-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["cfi-402411"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded: HGNC, UniProt and the paper cited give no positivity rate."],"provenance":{"editedBy":"OnCo gap audit, class 5 targets (HGNC REST, UniProt REST, Europe PMC, corpus drug records)","editedOn":"2026-11-03"},"symbol":"MAP4K1","role":["drug-target"],"sources":[],"specificitySources":[],"hgnc":"HGNC:6863","ensembl":"ENSG00000104814","uniprot":"Q92918","entrez":"11184","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.","whereFound":["T cells, B cells and dendritic cells (blood-forming lineage only)","Advanced solid tumours (CFI-402411 trial, with pembrolizumab)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/hpk1/","neighbours":{"cancer":[{"id":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-cancer/"}],"drug":[{"id":"cfi-402411","kind":"drug","name":"CFI-402411","route":"/drugs/cfi-402411/"}]}}