{"entity":{"id":"mcl1","kind":"target","name":"MCL1","aka":["MCL1 apoptosis regulator, BCL2 family member","Induced myeloid leukemia cell differentiation protein Mcl-1","BCL2L3","Mcl-1"],"tldr":"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.\n\nCIViC 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).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:6943","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6943"},{"label":"UniProt Q07820","url":"https://www.uniprot.org/uniprotkb/Q07820/entry"},{"label":"NCBI Gene 4170","url":"https://www.ncbi.nlm.nih.gov/gene/4170"},{"label":"Ensembl ENSG00000143384","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000143384"},{"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":["cancer-genes-wave"],"related":["civic"],"cancers":["multiple-myeloma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["omacetaxine"],"companies":[],"institutions":[],"pathways":["apoptosis-bcl2","mrna-translation-eif4f","transcription-addiction"],"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 \"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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"MCL1","role":["drug-target","biomarker"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:6943","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6943","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q07820","url":"https://www.uniprot.org/uniprotkb/Q07820/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene MCL1","url":"https://civicdb.org/features/3448","note":"1 evidence items, 0 assertions, 1 variants; diseases: Multiple Myeloma (GraphQL API, CC0)"}],"specificity":"broadly-expressed","distribution":"one-type","specificityNote":"Broadly expressed or essential: HPA lists MCL1 among essential proteins; the 1 medicine aimed at it (Omacetaxine mepesuccinate) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA MCL1: RNA tissue enhanced (bone marrow 647 nTPM); high antibody staining in 14 normal tissues; highest cancer staining thyroid cancer (4 of 4 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Multiple myeloma); approvals of single-target medicines aimed at it also list Leukaemia, not counted; 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 MCL1 tissue","url":"https://www.proteinatlas.org/ENSG00000143384-MCL1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000143384 associations","url":"https://platform.opentargets.org/target/ENSG00000143384/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:6943","ensembl":"ENSG00000143384","uniprot":"Q07820","entrez":"4170","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Kozopas K.M. et al, Proc. Natl. Acad. Sci. U.S.A, 1993, \"MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/7682708/","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).","whereFound":["Multiple myeloma: CIViC evidence names this disease"],"targetClass":"other","prevalence":[]},"route":"/targets/mcl1/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"}],"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"drug":[{"id":"omacetaxine","kind":"drug","name":"Omacetaxine mepesuccinate","route":"/drugs/omacetaxine/"}],"pathway":[{"id":"apoptosis-bcl2","kind":"pathway","name":"Intrinsic apoptosis (BCL-2 family)","route":"/pathways/apoptosis-bcl2/"},{"id":"mrna-translation-eif4f","kind":"pathway","name":"mRNA translation (eIF4F / mTOR)","route":"/pathways/mrna-translation-eif4f/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"biomarker":[{"id":"bcl2-g101v","kind":"biomarker","name":"BCL2 G101V and the other venetoclax binding-site mutations","route":"/biomarkers/bcl2-g101v/"}]}}