{"entity":{"id":"bim","kind":"target","name":"BIM (BCL2L11)","aka":["BIM","BH3-only protein BIM","BH3","BimEL","BimL","BimS","BCL2 like 11"],"tldr":"BIM is a pro-death protein that leukaemia cells keep clamped by BCL-2. Venetoclax and sonrotoclax are BH3 mimetics: they copy the part of BIM that binds BCL-2, so BIM is released, the mitochondria leak and the cell dies.","summary":"BCL2L11 (chromosome 2q13) encodes BIM, a BCL-2 family protein whose isoforms induce apoptosis and anoikis with differing potency: BimL is more potent than BimEL, the short Bim-alpha isoforms are weaker, and the BimAC and BimABC isoforms cannot induce apoptosis at all (UniProt O43521). The intrinsic apoptosis pathway record places BIM among the BH3-only proteins (with PUMA, NOXA and BAD) that either inhibit BCL-2, BCL-XL and MCL-1 or directly activate BAX and BAK. In OnCo the BH3 mimetics venetoclax and sonrotoclax occupy the BH3-binding groove of BCL-2 so that sequestered BIM and BAX are released, the mitochondrial outer membrane is permeabilised, cytochrome c triggers caspase activation and CLL, AML and mantle-cell lymphoma cells die within hours.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:994","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:994"},{"label":"UniProt O43521","url":"https://www.uniprot.org/uniprotkb/O43521/entry"},{"label":"NCBI Gene 10018","url":"https://www.ncbi.nlm.nih.gov/gene/10018"},{"label":"Tsujimoto et al., Science 1985: the t(14;18) translocation results from a mistake in VDJ joining","url":"https://doi.org/10.1126/science.3929382"},{"label":"Horn et al., Blood 2013: MYC, BCL2 and BCL6 rearrangement and expression in 442 RICOVER patients","url":"https://doi.org/10.1182/blood-2012-06-435842"}],"tags":["wave5-target"],"related":["venetoclax","sonrotoclax","bcl2","bax"],"cancers":["cll","aml","dlbcl","non-hodgkin-lymphoma"],"sections":[],"technologies":["bcl2-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["apoptosis-bcl2"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.","Lymphoma, BCL2 and t(14;18): The t(14;18) translocation puts BCL2 under the control of the immunoglobulin heavy-chain enhancer, so the cell makes an anti-apoptotic protein at a level a germinal-centre B cell is never meant to have. The sequencing of the breakpoints showed that the translocation is a mistake made by the VDJ recombinase at the pre-B-cell stage: the chromosome 18 segment recombines with the JH segment on chromosome 14, with extraneous N-region nucleotides at the junction and signal-like sequences near the chromosome 18 breakpoint (Tsujimoto 1985). The lesion is therefore not a late event in a lymphoma but the first event, made in the bone marrow years before. Frequency: BCL2 rearrangement in 13.5% of 442 unselected diffuse large B-cell lymphomas in the RICOVER trial (Horn 2013), and in the large majority of follicular lymphomas. A t(14;18)-bearing B cell can be found in the blood of healthy people, so the translocation alone is not a disease. What it changes about treatment: Less than it should. Venetoclax, which displaces the pro-apoptotic partners from BCL-2 directly, transformed chronic lymphocytic leukaemia and has not transformed follicular or diffuse large B-cell lymphoma, where the cells also depend on MCL1 and BCL-xL. A BCL2 rearrangement is used for diagnosis and, in combination with MYC, for risk, not for drug choice."],"provenance":{"editedBy":"OnCo content wave 5 (HGNC REST, UniProt REST, corpus drug and pathway records)","editedOn":"2026-09-22"},"symbol":"BCL2L11","role":[],"sources":[],"specificitySources":[],"hgnc":"HGNC:994","ensembl":"ENSG00000153094","uniprot":"O43521","entrez":"10018","firstDescribed":1998,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: O'Connor et al, EMBO J, 1998, \"Bim: a novel member of the Bcl-2 family that promotes apoptosis\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9430630/","biology":"BIM itself is not a drug target; the drugs mimic its BH3 domain. Sonrotoclax is recorded as more potent and shorter-acting than venetoclax and active against the venetoclax-resistant G101V BCL2 mutation in preclinical models; both need a ramp-up for tumour lysis precautions.","whereFound":["Chronic lymphocytic leukaemia and AML (venetoclax)","Mantle-cell lymphoma and DLBCL (sonrotoclax)"],"targetClass":"other","prevalence":[]},"route":"/targets/bim/","neighbours":{"drug":[{"id":"sonrotoclax","kind":"drug","name":"Sonrotoclax","route":"/drugs/sonrotoclax/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"target":[{"id":"bax","kind":"target","name":"BAX","route":"/targets/bax/"},{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"technology":[{"id":"bcl2-inhibitors","kind":"technology","name":"BCL-2 inhibitors","route":"/technologies/bcl2-inhibitors/"}],"pathway":[{"id":"apoptosis-bcl2","kind":"pathway","name":"Intrinsic apoptosis (BCL-2 family)","route":"/pathways/apoptosis-bcl2/"}]}}