KMT2B has no haematopoietic cell-state result, and two of the seven records that look like one are about a different gene in muscle
also called KMT2B cell-state absence · MLL4 alias contamination
Nobody has shown what cell condition KMT2B maintains in blood. Worse, a search for it returns papers about muscle stem cells that are really about a different gene, because both genes share the nickname MLL4.
The same thing, for a scientist
Bounded query on 2026-09-20: `(KMT2B OR MLL2 OR MLL4 OR WBP7 OR TRX2 OR HRX2)[tiab] AND <18-term cell-state clause> AND <leukaemia clause>` returns **7**, of which **0** are haematopoietic cell-state results [E1]. Two of the seven — PMIDs 39710699 and 39649158, *Mll4 in skeletal muscle fibers maintains muscle stem cells* — are about **KMT2D**, reached through the shared `MLL4` alias [E2]. Brief rule 66 governs this gene and this is the measured cost of ignoring it: a count of seven contains at least two records about a different gene in a different tissue. DepMap adds a weak broad dependency with no lineage restriction [E3].
The rule-66 trap, measured rather than described
KMT2B is Q9UMN6, 2,715 aa, and carries both MLL2 and MLL4 as UniProt gene synonyms. So does KMT2D, O14686, 5,537 aa — and each one's protein name carries the other one's number. Brief rule 66 calls this the worst identifier trap in the project.
What this beat adds is the retrieval consequence. Searching MLL4 for KMT2B returns skeletal-muscle stem-cell papers that are KMT2D work, and searching MLL2 returns the Armstrong-lab murine Mll1;Mll2 co-deletion work that is KMT2B. There is no lookup that separates them: the source documents are ambiguous. Every hit must be resolved individually, and this entry records how each one used in the graph was resolved.
The one genuine KMT2B result, and how it was resolved
PMID 30315824 shows that in murine MLL-AF9 leukaemia, Men1 deletion produces cellular and molecular consequences distinct from Mll1;Mll2 co-deletion, and that Mll1;Mll2-deficient cells are MORE sensitive to menin-interaction inhibitors, consistent with complementary pathways 4.
Resolution: Mll2 there is Kmt2b, not Kmt2d. The decisive argument is biological rather than nomenclatural — the paper's subject is the menin-MLL N-terminal interaction, and menin binds the KMT2A and KMT2B N-termini through the MBM motifs; KMT2D has no menin-binding motif and does not belong in a menin-interaction experiment. The pairing with Mll1 as the closest menin-binding paralogue settles it. Recorded per rule 66 part 2.
A second, independent datum from a different paper points the same way: PMID 26167872 tests 'MLL4/Wbp7', and WBP7 is a KMT2B synonym only. So when a paper pairs MLL4 with Wbp7 it means KMT2B; when it pairs MLL4 with muscle or with enhancers it means KMT2D.
What is adjacent and must not be mis-assigned
PMID 42118696, MLL3 and MLL4 sustain hematopoietic stem cell multipotency by opposing a B-cell default state (2026), is a genuine haematopoietic cell-state result and is not about KMT2B. MLL3/MLL4 there are KMT2C/KMT2D, the enhancer-methyltransferase pair. It is recorded here so a future reader who re-finds it does not assign it to this gene.
| gene | gene-kmt2b |
|---|---|
| symbol | KMT2B |
| uniprot | Q9UMN6 |
| length AA | 2715 |
| ensembl | ENSG00000272333 |
| status | run |
| query | (KMT2B[tiab] OR "MLL2"[tiab] OR "MLL4"[tiab] OR "WBP7"[tiab] OR "TRX2"[tiab] OR "HRX2"[tiab]) AND <cell-state clause> AND <leukaemia clause> |
| count | 7 |
| on topic after title check | 0 |
| records about a different gene | 2 |
| gene clause alone control | 1310 |
| result summary | No haematopoietic cell-state result for KMT2B. The MLL4 alias contaminates the count with KMT2D muscle papers. |
| absence class | measured-not-analysed |
| absence class basis | ARCHIVE CHECK RUN 2026-09-21 (king), which is what moved this off unclassified-not-checked. GEO holds 760 human bone-marrow single-cell RNA-seq DataSets (query: "Homo sapiens"[Organism] AND "bone marrow"[All Fields] AND ("single cell" OR "scRNA-seq")[All Fields] AND "expression profiling by high throughput sequencing"[DataSet Type]; translation recorded, ran clean). GSE120221 was verified individually: 25 samples, Homo sapiens, human bone marrow by scRNA-seq with matched mass and flow cytometry. WHAT THAT DATA CAN SETTLE: which haematopoietic populations express KMT2B and whether its expression tracks a state such as HSC quiescence versus cycling - the associative placement this entry's own literature queries were looking for. WHAT IT CANNOT: function. A functional placement needs perturbation in the state, and that remains never-measured. So the entry is split - the descriptive half is a desk job on deposited data, the functional half still needs an experiment. |
| absence class assigned | 2026-09-21 (cycle 47, king) |
contaminating pmids
[ "39710699", "39649158" ]
rule 66 resolutions — the numbers behind the chart
[
{
"pmid": "30315824",
"string": "Mll2",
"resolved_to": "KMT2B",
"how": "the paper's subject is the menin-MLL N-terminal interaction; menin binds KMT2A and KMT2B N-termini, KMT2D has no menin-binding motif",
"title": "Distinct pathways affected by menin versus MLL1/MLL2 in MLL-rearranged acute myeloid leukemia.",
"authors": "Chen Y, Jones KL, Anastassiadis K, et al.",
"venue": "Exp Hematol",
"year": 2019,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
},
{
"pmid": "26167872",
"string": "MLL4/Wbp7",
"resolved_to": "KMT2B",
"how": "WBP7 is a synonym of KMT2B only, so the compound label disambiguates itself",
"title": "Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia.",
"authors": "Grebien F, Vedadi M, Getlik M, et al.",
"venue": "Nat Chem Biol",
"year": 2015,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
},
{
"pmid": "42118696",
"string": "MLL4",
"resolved_to": "KMT2D",
"how": "paired with MLL3 as the enhancer-methyltransferase pair in HSC multipotency; not this gene",
"title": "MLL3 and MLL4 sustain hematopoietic stem cell multipotency by opposing a B-cell default state.",
"authors": "Wang HC, Chen R, Yang W, et al.",
"venue": "Blood",
"year": 2026,
"title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}
]archive checked
{
"archive": "GEO DataSets",
"date": "2026-09-21",
"datasets_matching": 760,
"verified_example": "GSE120221 (25 samples, Homo sapiens, human bone marrow scRNA-seq)",
"closes_the_descriptive_half": true,
"closes_the_functional_half": false
}- A KMT2B-directed idea drawn from an MLL4-keyed search would rest partly on KMT2D muscle biology - the swap here does not produce a wrong protein, it produces a wrong tissue.
- Mll1;Mll2-deficient cells are MORE sensitive to menin inhibitors, so removing KMT2B would not be a resistance mechanism but could be a sensitiser - an under-explored combination and an under-explored toxicity.
- Does KMT2B contribute to the differentiation block in KMT2A-rearranged cells? The Mll1;Mll2 co-deletion work tests menin pathway complementarity, not cell state.
- Is there any assay that can attribute a phenotype to KMT2B rather than to KMT2A in a cell where both are present? The co-deletion design cannot.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
A bounded PubMed query pairing KMT2B and its aliases with an eighteen-term cell-state clause and a leukaemia clause returns 7 records, none of which is a haematopoietic cell-state result; the gene clause alone returns 1,310 and the state clause alone 96,743.
NCBI PubMed E-utilities esearch, db=pubmed, queried 2026-09-20 · NCBI Entrez Programming Utilities 2026What this evidence cannot show
Bounded by titles and abstracts; supporting figures not searched. Counts as of 2026-09-20. The alias set deliberately includes MLL2 and MLL4, which is what produces the contamination measured in E2.
Evidence that argues against this (1)
- PMID 30315824 is a genuine KMT2B result in murine MLL-AF9 leukaemia and shows that Mll1;Mll2 co-deletion has distinct consequences from Men1 loss. It is a pathway result rather than a cell-state result, but anyone reading this entry as 'KMT2B is unstudied in leukaemia' would be wrong. Chen Y et al. 2019
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
Two of the seven records returned are 'Mll4 in skeletal muscle fibers maintains muscle stem cells' (PMIDs 39710699 and 39649158), which concern KMT2D rather than KMT2B and are reached only through the shared MLL4 alias.
NCBI PubMed E-utilities esearch, db=pubmed, queried 2026-09-20 · NCBI Entrez Programming Utilities 2026What this evidence cannot show
The gene assignment for those two papers was made from the tissue and the enhancer-methyltransferase framing, not from a database lookup, because the source documents are ambiguous by construction (rule 66). Titles read; full texts not opened.
Evidence that argues against this (1)
- METHODOLOGICAL DEFEATER: the contamination runs in more directions than the MLL4 alias, and naming only the KMT2D leak understates the problem. KMT2B's own largest clinical literature is NEUROLOGICAL - Meyer et al. reported heterozygous KMT2B variants in 27 unrelated individuals with complex progressive childhood-onset dystonia responsive to deep brain stimulation, explicitly noting the gene is 'also known as MLL4'. So the bare symbol pulls muscle-stem-cell papers about KMT2D through the MLL4 alias in one direction and movement-disorder genetics about KMT2B itself in the other, and an eighteen-term cell-state clause does not exclude either, since 'progenitor', 'differentiation' and 'stem cell' appear throughout the dystonia and muscle literatures. The measured cost of ignoring rule 66 is larger than two of seven. Meyer E et al. 2017
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
In DepMap fetched 2026-09-20, KMT2B is depleted below -0.5 in 11.8% of 1,258 screened lines (mean -0.290) and its mean across eleven KMT2A-rearranged lines is -0.395, a difference of -0.105 with no lineage restriction.
Open Targets Platform - DepMap CRISPR gene essentiality (depMapEssentiality), queried by Ensembl gene id 2026-09-20 · Open Targets Platform GraphQL API 2026What this evidence cannot show
A weak contrast on a small arm. Cancer lines in culture. KMT2B's Ensembl id ENSG00000272333 was resolved through HGNC on 2026-09-20 and read back.
Evidence that argues against this (1)
- NAMED METHODOLOGICAL DEFEATER for a -0.105 contrast on this gene in particular. Alicea-Velazquez et al. showed that every human SET1-family member binds WDR5 through the Win motif, that the interface strength differs between them, and that disrupting it disturbs MLL1 and SETD1A severely while disturbing MLL2/4 - i.e. KMT2B and KMT2D - only MODESTLY, without significantly altering their enzymatic activity in vitro. A KMT2B knockout in a cell that retains KMT2A, SETD1A, SETD1B, KMT2C and KMT2D at shared H3K4 targets is buffered by construction, and a small negative difference across eleven lines measures how much of that buffering fails, not how much the fusion needs KMT2B. Alicea-Velázquez NL et al. 2016
- E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In murine MLL-AF9 leukaemia cells, Men1 deletion produces cellular and molecular consequences distinct from Mll1;Mll2 co-deletion, and Mll1;Mll2-deficient cells are more sensitive to menin-interaction inhibitors.
Distinct pathways affected by menin versus MLL1/MLL2 in MLL-rearranged acute myeloid leukemia. · Chen Y, Jones KL, et al. · Experimental hematology 2019What this evidence cannot show
Murine MLL-AF9 myeloid leukaemia (brief rule 73), not human infant B-lineage KMT2A::AFF1. Abstract read in full in this beat via efetch XML. RULE 66 RESOLUTION: Mll2 here is Kmt2b, decided from the menin-N-terminal-interaction subject matter, since KMT2D carries no menin-binding motif; recorded as required by rule 66 part 2.
Evidence that argues against this (1)
- PUBLISHED CONFLICTING RESULT against the direction this item is usually read in. 'Distinct pathways affected by menin versus MLL1/MLL2' is routinely carried as evidence that the methyltransferase arm can be set aside relative to the menin interface. Cao et al. show it cannot: MM-401, which blocks MLL1-WDR5 and therefore prevents assembly of the MLL1 core complex rather than deleting the protein, specifically blocks MLL-cell proliferation with cell-cycle arrest, apoptosis and myeloid differentiation, spares normal bone marrow and non-MLL cells, and produces transcriptome changes SIMILAR TO MLL1 DELETION. A co-deletion experiment and an interface inhibitor therefore give different verdicts on the same arm, and 'Mll1;Mll2-deficient cells are more sensitive to menin inhibitors' is a statement about epistasis in a co-deleted background, not about whether the arm is dispensable. Cao F et al. 2014
the bounded cell-state absence for this gene, with the MLL4/MLL2 alias resolutions recorded
Mll1;Mll2-deficient murine MLL-AF9 cells are MORE sensitive to menin-interaction inhibitors
- related to →KMT2A / MLL1 — the gene that breaks
the rule-66 pair that makes every MLL2/MLL4 citation ambiguous
SURVIVES at full text: the tight phrase intersection (13 records) was read in full and contains no haematopoietic cell-state result
the alias contamination runs both ways and is larger than two of seven: KMT2B's own largest clinical literature is complex early-onset DYSTONIA in 27 individuals, published under 'KMT2B, also known as MLL4' (PMID 27992417), and an eighteen-term cell-state clause does not exclude movement-disorder genetics