{"entity":{"id":"hspa5","kind":"target","name":"HSPA5","aka":["heat shock protein family A (Hsp70) member 5","Endoplasmic reticulum chaperone BiP","BiP","GRP78"],"tldr":"HSPA5 (Endoplasmic reticulum chaperone BiP) is an enzyme. The public catalogues list it as a drug target and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer.","summary":"Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen. Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate. Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1-mediated unfolded protein response (UPR).\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant, naming Fluorouracil.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:5238","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:5238"},{"label":"UniProt P11021","url":"https://www.uniprot.org/uniprotkb/P11021/entry"},{"label":"NCBI Gene 3309","url":"https://www.ncbi.nlm.nih.gov/gene/3309"},{"label":"Ensembl ENSG00000044574","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000044574"}],"tags":["cancer-genes-wave"],"related":["civic"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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: CIViC lists 1 therapies; 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"HSPA5","role":["drug-target","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:5238","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:5238","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P11021","url":"https://www.uniprot.org/uniprotkb/P11021/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene HSPA5","url":"https://civicdb.org/features/2778","note":"1 evidence items, 0 assertions, 1 variants; diseases: Colorectal Cancer (GraphQL API, CC0)"}],"specificity":"broadly-expressed","distribution":"one-type","specificityNote":"Broadly expressed or essential: HPA lists HSPA5 among essential proteins and finds the RNA at low tissue specificity; a medicine acting on the wild-type protein would expose normal tissue too. HPA HSPA5: RNA low tissue specificity; high antibody staining in 13 normal tissues; highest cancer staining pancreatic cancer (11 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Colorectal cancer); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas HSPA5 tissue","url":"https://www.proteinatlas.org/ENSG00000044574-HSPA5/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000044574 associations","url":"https://platform.opentargets.org/target/ENSG00000044574/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:5238","ensembl":"ENSG00000044574","uniprot":"P11021","entrez":"3309","firstDescribed":1988,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Ting et al, DNA, 1988, \"Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2840249/","biology":"Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen. Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate. Acts as a key repressor of the EIF2AK3/PERK and ERN1/IRE1-mediated unfolded protein response (UPR). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerisation of ERN1/IRE1, thereby inactivating ERN1/IRE1. Also binds and inactivates EIF2AK3/PERK in unstressed cells. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1 and EIF2AK3/PERK, allowing their homodimerisation and subsequent activation. Location: Endoplasmic reticulum lumen; Melanosome; Cytoplasm; Cell surface (UniProt). Locus 9q33.3 (HGNC).","whereFound":["Colorectal cancer: CIViC evidence names this disease"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/hspa5/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}]}}