# BIM (BCL2L11)

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

## TL;DR

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.

## Fields

- Kind: Target
- Last checked: 2026-09-22
- Also known as: BIM; BH3-only protein BIM; BH3; BimEL; BimL; BimS; BCL2 like 11
- Tags: wave5-target
- Symbol: BCL2L11
- Class: other
- 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.
- Where found: Chronic lymphocytic leukaemia and AML (venetoclax); Mantle-cell lymphoma and DLBCL (sonrotoclax)

## 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.

## Sources

- HGNC HGNC:994: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:994
- UniProt O43521: https://www.uniprot.org/uniprotkb/O43521/entry
- NCBI Gene 10018: https://www.ncbi.nlm.nih.gov/gene/10018
- Tsujimoto et al., Science 1985: the t(14;18) translocation results from a mistake in VDJ joining: https://doi.org/10.1126/science.3929382
- Horn et al., Blood 2013: MYC, BCL2 and BCL6 rearrangement and expression in 442 RICOVER patients: https://doi.org/10.1182/blood-2012-06-435842

## Connected records

- drugs: [Sonrotoclax](https://onco.cc/drugs/sonrotoclax/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- targets: [BAX](https://onco.cc/targets/bax/), [BCL-2](https://onco.cc/targets/bcl2/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- technologies: [BCL-2 inhibitors](https://onco.cc/technologies/bcl2-inhibitors/)
- pathways: [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/)

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