# MCL1

Source: https://onco.cc/targets/mcl1/  
OnCo record `mcl1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

MCL1 (Induced myeloid leukaemia cell differentiation protein Mcl-1) is a gene. The public catalogues list it as a drug target and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Multiple myeloma.

## Summary

Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis.

CIViC holds 1 clinical evidence item and 0 assertions across 1 variant, naming Mcl-1 Inhibitor MIK665. In OnCo, 1 product record names it (Omacetaxine mepesuccinate).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: MCL1 apoptosis regulator, BCL2 family member; Induced myeloid leukemia cell differentiation protein Mcl-1; BCL2L3; Mcl-1
- Tags: cancer-genes-wave
- Symbol: MCL1
- Class: other
- Biology: Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis. Location: Membrane; Cytoplasm; Mitochondrion; Nucleus, nucleoplasm (UniProt). Locus 1q21.2 (HGNC).
- Where found: Multiple myeloma: CIViC evidence names this disease

## 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 "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- 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:6943: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6943
- UniProt Q07820: https://www.uniprot.org/uniprotkb/Q07820/entry
- NCBI Gene 4170: https://www.ncbi.nlm.nih.gov/gene/4170
- Ensembl ENSG00000143384: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000143384
- 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

- collections: [CIViC](https://onco.cc/collections/civic/)
- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- drugs: [Omacetaxine mepesuccinate](https://onco.cc/drugs/omacetaxine/)
- pathways: [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/), [mRNA translation (eIF4F / mTOR)](https://onco.cc/pathways/mrna-translation-eif4f/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- biomarkers: [BCL2 G101V and the other venetoclax binding-site mutations](https://onco.cc/biomarkers/bcl2-g101v/)

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JSON: https://onco.cc/api/v1/entities/mcl1.json