MED12 - a named menin-associated protein that restrains menin's transcriptional output, and the anchor of the CDK8 module a KMT2A-r AML paper co-targets
also called MED12 · TRAP230 · ARC240 · CAGH45 · HOPA · KIAA0192 · TNRC11 · Mediator subunit 12
MED12 is the part of the Mediator complex that holds the kinase CDK8. It is directly relevant here because it is one of a small set of proteins found sitting next to menin - the protein every menin inhibitor targets - and because a KMT2A-rearranged AML study used a drug hitting both RET and the MED12-associated kinase CDK8.
The same thing, for a scientist
MED12 (Q93074, 2,177 aa) anchors the CDK8 kinase module of Mediator. Two published results place it in this project's frame. **(1) It is a menin-associated protein.** Menin is reported as a transcription factor regulating OXPHOS and glycolytic genes, and a group of menin-associated proteins (MAPs) - **KMT2A, MED12, WAPL and GATA3** - is found to restrain menin's full function in that regulation; shRNA knockdown of menin and of MAPs reduced ATP production, and a close-proximity interaction between menin and MAPs is proposed to allow the transcriptional regulation [E1]. MED12 appearing in a four-member list alongside KMT2A itself is the single most directly menin-relevant fact this beat found. **(2) It is co-targeted in KMT2A-r AML.** A study of enhancer-activated RET in KMT2A-rearranged AML reports that RET expression is tightly correlated with selective chromatin remodeller and **mediator (MED) proteins**, and uses a small molecule with dual activity against RET and **MED12-associated CDK8**; dual inhibition restricted proliferation by producing oxidative stress responses [E2]. Dependency is the best of the Mediator panel apart from MED23: pan -0.5562, difference **-0.268, rank 131 of 17,728 (0.739th percentile)** [E3] - but the lineage split makes it myeloid-weighted and inconclusive (myeloid z -0.60, B-lineage z **-0.04**), classified 'weak or ambiguous' [E4]. Its KMT2A literature is thin: 4 records, of which 2 are relevant on title-check [E5].
This is a prediction, not a measurement. No one has seen this protein in this shape. The colours say how much the software trusts itself, and that is worth reading before anything else — the orange stretches are places the model is effectively saying this part has no fixed shape.
I have never read one of these pictures before
A protein is one long chain of amino acids that folds up. The ribbon traces that chain from one end to the other; it is not a wire, it is a simplification of where the backbone runs. Drag to rotate, scroll to zoom.
Domains are the stretches of chain that do a particular job, and they are what the coloured blocks above the picture mark out. Click one and the view flies to it. In this project the important question about any domain is usually whether the fusion still has it — the labels say lost where it does not.
Anything in yellow sticks is a bound small molecule, which is usually the drug.
The menin-associated-protein result, and what it does and does not say
Chou and colleagues report menin as a transcription factor regulating OXPHOS and glycolytic gene expression in cancer cells and primary tumours with poor prognosis, and name KMT2A, MED12, WAPL and GATA3 as menin-associated proteins that restrain menin's full function in that regulation. Knockdown of menin or of a MAP reduced ATP production with proportional changes in glycolysis and OXPHOS; under metabolic stress the dual functionality separates, with a MAP negatively counteracting menin's regulation of OXPHOS while positively influencing glycolysis; and a close-proximity interaction between menin and MAPs is proposed to permit the regulation 1.
What is genuinely useful here. MED12 is named, by a primary paper, in the same short list as KMT2A as a protein in close proximity to menin. This graph's menin-interface work is almost entirely about the KMT2A MBM motifs; a second, independent protein reported at that interface is new information, and it arrives with a functional readout (ATP production) rather than as a mass-spectrometry co-occurrence alone.
What it does not say, and the limits are large. The disease context is not leukaemia - the work is in cancer cells and primary tumours generally, with GATA3 in the list pointing towards breast cancer. 'Close-proximity interaction' is a proximity claim, not a mapped interface, and the abstract does not describe the assay. shRNA knockdown is chronic and permits adaptation. And 'restrain menin's full function' is an unusual formulation: it makes MED12 a negative regulator of menin output, which, if it held in KMT2A-rearranged leukaemia, would predict that losing MED12 increases menin-driven transcription - the opposite direction from a target hypothesis.
That last point is why this entry does not present MED12 as a menin-interface target. It presents it as a named proximity partner whose sign of effect is, on the only evidence available, unhelpful.
The CDK8 angle, which is where the tractability is
MED12 itself is a 2,177-residue scaffold with one annotated interaction region and no enzymatic activity 6. The druggable element of its module is CDK8, and the KMT2A-r AML paper reaches it: RET is significantly upregulated in KMT2A-rearranged AML, a KMT2A-MLLT3 fusion induces a CTCF-guided de novo extrusion enhancer loop to upregulate RET, RET expression correlates with selective chromatin remodeller and mediator proteins, and a dual RET/CDK8 inhibitor restricted proliferation through multimodal oxidative stress responses 2.
Two things about this are worth separating. The RET enhancer-loop mechanism is a KMT2A-fusion mechanism and is well specified. The CDK8 half of the drug is justified by a correlation between RET expression and mediator proteins, which is much weaker - the paper does not, in what was read, demonstrate that CDK8 inhibition is required for the effect, and a dual inhibitor cannot separate its two activities.
The graph should therefore hold: KMT2A::MLLT3 drives RET through an enhancer loop, and a compound that hits RET and CDK8 together works in those cells. It should not hold that CDK8 or MED12 is a validated node.
Independently, BET bromodomain inhibition is reported to release the Mediator complex from select cis-regulatory elements 7 - which matters because this graph carries BRD4 as a fusion-axis protein, and it means Mediator occupancy is downstream of a perturbation the field already applies to this disease.
Cell type, cell state, subcellular and subnuclear localisation, epigenetics
Subcellular: nucleus 6. Subnuclear: not established - no compartment, body or focus result exists for MED12 in any KMT2A system, and none is claimed. Mediator is often discussed in the condensate literature; nothing read for this entry used calibrated half-bleach internal-mixing measurement, so this entry makes no phase-separation claim about Mediator in either direction.
Cell type: KMT2A-rearranged AML cells for the RET work 2; unspecified cancer cell lines and primary tumours for the menin work 1. No infant B-ALL, no KMT2A::AFF1 system, no patient material in the menin study that is described as leukaemic.
Cell state: the only state-level readout is metabolic - ATP production, the glycolysis/OXPHOS balance, and response to metabolic stress 1; and oxidative stress response in the RET study 2. That is an unusual and genuinely different axis from the differentiation-block framing the rest of this graph uses, and it is recorded as such.
Epigenetic readout: none written by MED12, which has no catalytic activity. The nearest quantities are Mediator occupancy at cis-regulatory elements, which BET inhibition reduces 7, and the CTCF-guided extrusion enhancer loop at RET, which is a three-dimensional genome readout rather than a histone mark 2.
| uniprot | Q93074 |
|---|---|
| gene symbol | MED12 |
| protein name | Mediator of RNA polymerase II transcription subunit 12 |
| length AA | 2177 |
| alphafold ID | AF-Q93074-F1 |
| accession resolution | UniProt REST query gene_exact:MED12 AND organism_id:9606 AND reviewed:true, run 2026-09-19; one reviewed hit; primary gene name read back as MED12 and length 2177 confirmed from the same fetched record. |
| complex | Mediator CDK8 kinase module (MED12, MED13, CCNC, CDK8) |
| domains note | Only one UniProt region carries coordinates across 2,177 residues. CDK8-module interfaces visible in PDB 8TQ2/8TQC/8TQW were not derived into boundaries in this cycle and are not invented. |
| function | scaffold anchoring the CDK8 kinase module of Mediator; no catalytic activity of its own |
| classification | NOT a documented interactor of KMT2A::AFF1; a named menin-associated protein in one non-leukaemia study, and the anchor of the kinase module co-targeted in one KMT2A-r AML pharmacology paper |
| interaction evidence class | proximity/association claim with functional metabolic readout (menin); correlation plus dual-inhibitor pharmacology (KMT2A-r AML) |
| shown for fusion | KMT2A-MLLT3 AML cells, pharmacologically and by expression correlation; not shown for KMT2A::AFF1 |
| cell type evidence | KMT2A-rearranged (KMT2A-MLLT3) AML cells; unspecified cancer cell lines and primary tumours for the menin work. No infant B-ALL. |
| cell state evidence | metabolic: ATP production, glycolysis/OXPHOS balance, response to metabolic stress; oxidative stress response under dual RET/CDK8 inhibition |
| epigenetic readout | none written; Mediator occupancy at cis-regulatory elements (reduced by BET inhibition) and a CTCF-guided extrusion enhancer loop at RET - a 3D-genome readout rather than a histone mark |
PDB IDS
[ "8TQ2", "8TQC", "8TQW" ]
aliases retired or alternate
[ "TRAP230", "ARC240", "CAGH45", "HOPA", "KIAA0192", "TNRC11" ]
complex partners
[ "gene-med26", "gene-med23", "gene-ctnnb1" ]
domains
[
{
"name": "CTNNB1/GLI3 interaction region",
"start": 1616,
"end": 2051
}
]menin association
{
"claim": "MED12 is named as a menin-associated protein alongside KMT2A, WAPL and GATA3",
"direction": "MAPs RESTRAIN menin's full transcriptional function - loss of MED12 would be predicted to INCREASE menin output",
"system": "cancer cells and primary tumours, not leukaemia",
"replication": "single paper; 1 PubMed record for MED12 against menin",
"evidence": "E1"
}localization
{
"subcellular": "nucleus (UniProt)",
"subnuclear": "not established in any KMT2A system; no phase-separation claim is made in either direction"
}essentiality
{
"depmap_scan": "analyses/depmap-kmt2a-selective-scan-full",
"pan_essentiality_all_lines": -0.5562,
"n_all_lines": 1208,
"mean_kmt2a_rearranged": -1.1715,
"mean_other_leukemia": -0.9035,
"kmt2a_selectivity_difference": -0.268,
"rank": 131,
"n_scanned": 17728,
"percentile": 0.739,
"lineage_split": {
"analysis": "analyses/depmap-interactome5-lineage-split",
"z_kmt2a_myeloid": -0.6,
"z_kmt2a_b_lineage": -0.04,
"z_split_gap": -0.56,
"z_OCI_AML3": -0.92,
"z_U937": -0.56,
"verdict": "weak or ambiguous; the B-lineage half is essentially zero"
},
"mediator_panel": {
"MED23": {
"difference": -0.4827,
"rank": 16
},
"MED1": {
"difference": -0.3114,
"rank": 81,
"lineage_verdict": "MYELOID-IDENTITY ARTEFACT"
},
"MED24": {
"difference": -0.2698,
"rank": 128
},
"MED14": {
"difference": -0.1541,
"rank": 453
}
},
"interpretation": "good genome-wide rank that does not survive splitting; the Mediator panel as a whole ranks suspiciously well, which argues for a common cause rather than a complex-level fusion requirement"
}enumeration record counts — the numbers behind the chart
[
{
"query": "(MLL OR KMT2A) AND (MED12 OR TRAP230 OR HOPA OR CAGH45 OR ARC240)",
"records": 4,
"records_after_title_check": 2
},
{
"query": "MED12 AND (leukemia OR leukaemia)",
"records": 28,
"note": "raw count, not title-checked"
},
{
"query": "MED12 AND (menin OR MEN1) AND (interact OR complex OR bind)",
"records": 1
},
{
"date": "2026-09-19"
}
]depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": -1.1715,
"chronos_mean_other_leukaemia": -0.9035,
"difference": -0.268,
"pan_essentiality_all_lines": -0.5562,
"selectivity_rank": 131,
"rank_denominator": 17728,
"provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
"how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}- If menin-associated proteins restrain menin, then depleting MED12 would be expected to INCREASE menin-driven transcription. A programme that targeted MED12 to reduce menin output would be pushing the wrong way, on the only evidence that exists.
- MED12's B-lineage dependency z is -0.04. For an infant B-ALL programme that is zero, and the genome-wide rank of 131 that would attract attention is a myeloid-weighted number.
- Mediator is general transcription machinery and MED12 is required across cell lines at -0.556 [E3], so any CDK8-module intervention carries broad transcriptional toxicity. Claims sometimes made about CDK8-inhibitor class liabilities and about MED12 germline syndromes were NOT verified in this session and are deliberately not asserted here.
- The one KMT2A-r pharmacology result uses a dual RET/CDK8 compound, so the apparent Mediator validation may be entirely RET. Building on it without a selective-agent control would be building on an attribution error.
- Does MED12 sit near menin in a KMT2A-rearranged leukaemia cell, and with what sign? The only evidence is one non-leukaemia paper in which menin-associated proteins RESTRAIN menin, which points the wrong way for a target hypothesis.
- Is CDK8 inhibition required for the dual RET/CDK8 compound's effect in KMT2A-r AML? A dual inhibitor cannot answer this and a selective CDK8 inhibitor arm would.
- Why does the entire Mediator panel rank inside the top 460 of 17,728 on the KMT2A selectivity statistic? Either KMT2A-rearranged lines really are more Mediator-dependent, or a common cause such as transcriptional output is driving the whole panel - and the second is far more likely and is testable by expression normalisation.
- Does the CTCF-guided RET enhancer loop form in KMT2A::AFF1 B-ALL as it does in KMT2A-MLLT3 AML? RET is an actionable target with approved inhibitors, so the answer has immediate consequences.
- E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
Menin is reported as a key transcription factor regulating expression of OXPHOS and glycolytic genes in cancer cells and primary tumours with poor prognosis; a group of menin-associated proteins including KMT2A, MED12, WAPL and GATA3 is found to restrain menin's full function in that transcription regulation; shRNA knockdown of menin and of menin-associated proteins reduced ATP production with proportional alterations in glycolysis and OXPHOS; and a close-proximity interaction between menin and these proteins is proposed to allow transcriptional regulation for metabolic adjustment.
Menin and Menin-Associated Proteins Coregulate Cancer Energy Metabolism · Chou CW, Tan X, Hung CN, Lieberman B, Chen M, Kusi M, Mitsuya K, Lin CL, Morita M, Liu Z, Chen CL, Huang TH · Cancers (Basel) 12(9):2715 2020What this evidence cannot show
Abstract fetched from PubMed and read on 2026-09-19; full text not read, and every identifier copied from that fetched record. **The disease context is cancer generally, not leukaemia**, and the presence of GATA3 in the list suggests a breast-cancer-weighted system. 'Close-proximity interaction' is a proximity statement, not a mapped interface, and the assay is not described in the abstract. shRNA knockdown is chronic. Critically, the direction of effect is that MAPs **restrain** menin - so this result does not support MED12 loss as a way to reduce menin output.
Evidence that argues against this (1)
- If MED12 restrains menin, removing MED12 should increase menin-driven transcription, which is the opposite of a therapeutic direction in a menin-dependent leukaemia. The entry therefore records MED12 as a named proximity partner rather than as a menin-interface target, and any future use of this result must carry the sign. Frett B et al. 2024
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
RET is significantly upregulated (p < 0.01) in KMT2A-rearranged AML; integrating multi-epigenomics data shows the KMT2A-MLLT3 fusion induces development of a CTCF-guided de novo extrusion enhancer loop that upregulates RET expression; RET expression is tightly correlated with selective chromatin remodeller and mediator proteins; and a small molecule with dual inhibitory activity against RET and MED12-associated CDK8 restricted cell proliferation by producing multimodal oxidative stress responses in KMT2A-rearranged AML cells.
Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia · Frett B, Stephens KE, Koss B, Melnyk S, Farrar J, Saha D, Roy Choudhury S · Cancer Science 115(3):963-973 2024What this evidence cannot show
Abstract fetched from PubMed and read on 2026-09-19; full text not read, identifiers copied from that fetched record. **A dual RET/CDK8 inhibitor cannot separate its two activities**, and the CDK8 arm is justified by a correlation between RET expression and mediator proteins rather than by a demonstration that CDK8 inhibition is required. KMT2A-MLLT3 AML, not KMT2A::AFF1 B-ALL. No genetic perturbation of MED12 or CDK8 is described in the abstract.
Evidence that argues against this (1)
- The enhancer-loop mechanism is about RET, not about Mediator; Mediator enters through a correlation. Reading this paper as validation of the CDK8 module in KMT2A-rearranged leukaemia would be reading a pharmacological convenience as a mechanistic result. PubMed record; title and year read from the esummary response for this PMID on 2026-09-19. Authors, journal and DOI were NOT fetched in this session and are deliberately omitted rather than written from recall. 2016
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
In the genome-wide KMT2A-rearranged selectivity scan of 17,728 genes, MED12 has a pan-essentiality of -0.5562 across 1,208 lines and a KMT2A-rearranged difference of -0.268 (KMT2A-rearranged mean -1.1715 against other-leukaemia mean -0.9035), ranking 131 (0.739th percentile). Other Mediator subunits scanned: MED23 -0.4827 rank 16, MED1 -0.3114 rank 81, MED24 -0.2698 rank 128, MED14 -0.1541 rank 453.
Genome-wide KMT2A-rearranged selectivity scan, 17,728 genes (DepMap Chronos via Open Targets) · Broad Institute DepMap / Open Targets Platform; analyses/depmap-kmt2a-selective-scan-full 2026What this evidence cannot show
Rows read out of analyses/depmap-kmt2a-selective-scan-full/results.json on 2026-09-19 in a scripted pass. Eleven KMT2A-rearranged against 43 other leukaemia lines, AML-heavy, none infant-derived. **The whole Mediator panel ranks unusually well on this statistic - five subunits inside the top 460 - which is itself suspicious**, because a differential requirement for general transcription machinery across leukaemia subtypes is not a comfortable claim. A common cause such as transcriptional output or proliferation rate is the obvious alternative.
Evidence that argues against this (1)
- The lineage split reclassifies MED1, the second-best-ranked of these, as a myeloid-identity artefact, which is direct evidence that this panel's genome-wide ranks are partly lineage composition rather than fusion biology. No Mediator rank in this table should be quoted without its split. Broad Institute DepMap / Open Targets Platform; analyses/depmap-interactome5-lineage-split 2026
- E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
On the lineage-split run for this beat, MED12 is myeloid-weighted and inconclusive: KMT2A-rearranged myeloid z -0.60, B-lineage z -0.04, split gap -0.56, OCI-AML3 z -0.92, U-937 z -0.56, on a pan-essentiality of -0.557. The run classifies it 'weak or ambiguous' and does not flag it as a lineage artefact. In the same run MED1 IS flagged as a myeloid-identity artefact (myeloid z -0.86, B-lineage z -0.13) and MED23 survives the split (myeloid z -0.77, B-lineage z -1.85).
Interactome round 5 panel, lineage-split DepMap dependency (FACT, NSL, MSL, COMPASS remainder, Mediator) · Broad Institute DepMap / Open Targets Platform; analyses/depmap-interactome5-lineage-split 2026What this evidence cannot show
Rows read from analyses/depmap-interactome5-lineage-split/results.json on 2026-09-19. Six myeloid and four B-lineage index lines, so a single line moves a mean; the split is by lineage LABEL rather than expression signature. **The B-lineage z of -0.04 is the number that matters for this project's index disease and it is essentially zero.** The genome-wide rank of 131 conceals it entirely.
Evidence that argues against this (1)
- MED12 sitting between MED1 (artefact) and MED23 (survivor) on the same panel means the Mediator complex does not behave as a unit in this analysis, which argues that whatever the signal is, it is not a Mediator-complex requirement. Broad Institute DepMap / Open Targets Platform; analyses/depmap-kmt2a-selective-scan-full 2026
- E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
As of 2026-09-19, PubMed returns 4 records for '(MLL OR KMT2A) AND (MED12 OR TRAP230 OR HOPA OR CAGH45 OR ARC240)' and 28 for 'MED12 AND (leukemia OR leukaemia)'. Title-checking the 4: two are relevant - the KMT2A-rearranged AML RET/CDK8 study and a 2025 paper on epigenetic dysregulation and therapeutic targeting of RET in high-risk KMT2A-rearranged AML; the other two are an exome pool-sequencing study in neurodevelopmental disorders and the menin-associated-proteins metabolism paper, which is relevant to menin but is matched here through MED12 rather than through KMT2A. 'MED12 AND (menin OR MEN1) AND (interact OR complex OR bind)' returns exactly 1 record, the menin-associated-proteins paper.
PubMed E-utilities esearch record counts for the Mediator subunits MED1, MED12, MED14, MED23 and MED24 against KMT2A, MLL and leukaemia, run for interactome round 5 · NCBI PubMed, queried 2026-09-19 2026What this evidence cannot show
Counts from the esearch `count` field, queried 2026-09-19, with **every record in the 4-record query title-checked individually**. Symbol set: MED12, TRAP230, HOPA, CAGH45, ARC240. HOPA is an old alias and CAGH45 a repeat-based name, both of which could collide; neither contributed a hit that survived title-checking. The 28-record leukaemia query was not title-checked and is reported as a raw count only.
Evidence that argues against this (1)
- That a single record exists for MED12 against menin means the menin-association claim rests on one paper, in a non-leukaemia system, with no replication. This graph's menin-interface work is built on a much deeper literature for KMT2A, and the two should not be given comparable weight. Chou CW et al. 2020
- E6established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProtKB Q93074 (MED12_HUMAN, Mediator of RNA polymerase II transcription subunit 12) is 2,177 aa with synonyms ARC240, CAGH45, HOPA, KIAA0192, TNRC11 and TRAP230; it is annotated to the nucleus; it has three PDB cross-references (8TQ2, 8TQC, 8TQW); and it carries one annotated region with residue coordinates, aa 1616-2051, interacting with CTNNB1 and GLI3.
UniProtKB Q93074 (MED12_HUMAN), Mediator of RNA polymerase II transcription subunit 12 · UniProt Knowledgebase, reviewed (Swiss-Prot) 2026What this evidence cannot show
Record fetched 2026-09-19 via UniProt REST with gene_exact:MED12 AND organism_id:9606 AND reviewed:true; **primary gene name read back as MED12 and length 2,177 confirmed from the same fetched record**, per the standing accession rule. One reviewed hit. Only one region carries coordinates across 2,177 residues, so the domain lane contributed is minimal; the CDK8-module interfaces visible in the cryo-EM structures have no UniProt boundaries and were not derived here.
Evidence that argues against this (1)
- The one annotated region binds CTNNB1, which this graph carries as gene-ctnnb1 in the fusion-axis literature. That is a resolvable connection and it is drawn as an edge, but a UniProt interaction annotation is a curation summary of work not read in this session and is weaker evidence than a fetched primary paper. Chou CW et al. 2020
- E7moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
BET bromodomain inhibition releases the Mediator complex from select cis-regulatory elements.
BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements · PubMed record; title and year read from the esummary response for this PMID on 2026-09-19. Authors, journal and DOI were NOT fetched in this session and are deliberately omitted rather than written from recall. 2016What this evidence cannot show
**Title and year only were read, from the PubMed esummary response fetched on 2026-09-19; the abstract and full text were not read in this session, and authors, journal and DOI were deliberately not written rather than recalled.** The claim stated is the paper's title and nothing beyond it. It is cited to record that Mediator occupancy is downstream of a perturbation already applied to this disease, not for any quantitative statement.
Evidence that argues against this (1)
- Citing a paper by its title alone is weak, and this entry marks it as such. If Mediator occupancy is to be used as a readout in any experiment derived from this graph, the primary paper must be read first. Frett B et al. 2024
MED12 is named as a menin-associated protein alongside KMT2A, WAPL and GATA3 - but MAPs are reported to RESTRAIN menin's transcriptional function.
UniProt annotates MED12 residues 1616-2051 as interacting with CTNNB1 and GLI3.
Both Mediator subunits in this graph; neither shows a KMT2A-selective requirement that survives scrutiny.
A dual RET/MED12-associated-CDK8 inhibitor restricted proliferation of KMT2A-rearranged AML cells through oxidative stress responses.
Same complex, opposite behaviour on the lineage split: MED12 is myeloid-weighted, MED23 survives in both halves.
Same complex; MED23 survives the lineage split while MED12 is myeloid-weighted and MED1 is a demonstrated artefact.
MED12 ranks 131 but is broadly essential (pan -0.556); MED12L is not expressed
core module versus CDK8 kinase module: MED19 core (median rank 445), MED12 kinase module