Oncofusion

start / graph / gene-vim

Geneweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q90-pan-fusion-core3

VIM / vimentin (P08670) - a pan-MLL-fusion prey with a clean negative control, and separately a genuine KMT2A rearrangement partner in sarcoma, which are two different facts

also called VIM · vimentin · P08670 · VIME_HUMAN

Vimentin is a rope-like filament protein that gives cells their internal scaffolding; it is one of the most abundant proteins in many cells and is a classic thing to find by accident in a fishing experiment. It showed up attached to all seven MLL fusion proteins tested - and, quite separately, the vimentin gene is genuinely broken and joined to the KMT2A gene in a rare kind of sarcoma, which is a different claim about a different molecule.

The same thing, for a scientist

Vimentin (P08670, 466 aa) is the type III intermediate filament of mesenchymal and haematopoietic cells. It co-purified with all seven Strep-HA-tagged MLL fusions in Skucha 2018 (MLL-AF4 p = 0.0109, 4|3, negative control 0|0), sits at rank 16 of the 42 pan-fusion proteins, and is in the authors' post-filter 128 and the shRNA library. UniProt's human record places it in cytoplasm and cytoskeleton on three and two experimental citations respectively; the 'Nucleus matrix' line is ECO:0000250 by similarity to RAT P31000 and there is NO human experimental nuclear annotation (fetched live 2026-09-21). Measured here: VIM is the ONLY intermediate filament in the entire 960-protein network - NES, LMNA, LMNB1, DES and every keratin are absent - though keratin absence is by construction, because the paper's Methods state keratin and trypsin were removed as known MS contaminants. SEPARATELY AND IMPORTANTLY: VIM::KMT2A is a recurrent, named sarcoma entity. That is a genomic rearrangement, the breakpoint joins VIM exon 4 to KMT2A exon 2, and it therefore preserves almost the whole of KMT2A rather than replacing its C-terminus - so it is not an MLL fusion oncoprotein of the leukaemia type and it is not evidence that vimentin protein binds an MLL fusion. This entry keeps the two claims apart.

Go deeper
The Skucha row, stated in full

7 of 7 fusions. MLL-AF1p 0.00446 (7|3), MLL-AF4 0.0109 (4|3), MLL-AF9 6.28e-05 (20|20), MLL-CBP 8.4e-06 (8|30), MLL-EEN 0.000219 (21|21), MLL-ENL 2.06e-09 (36|37), MLL-GAS7 3.78e-05 (28|20); negative control 0|0 1. Rank 16 of the 42 by MLL-AF4 p. MLL-AF4 spectral total 7, rank 7 of seven baits, against 73 under MLL-ENL.

The clean negative control is not the exculpating fact the deferral treated it as

This tranche was deferred partly on the observation that VIM's negative control is clean (0|0) while ACTB's is dirty (3|3), read as the two classic cytoskeletal contaminants behaving differently. Measured over all 960 rows on 2026-09-21, that difference has a simpler explanation than specificity: the control column tracks abundance. Spearman(neg_ctrl total, maximum per-bait spectral total) = +0.461; median maximum spectra 42 for the 145 dirty-control proteins against 8 for the 815 clean ones. ACTB reaches 388 spectra under one bait and VIM reaches 73, so they sit on opposite sides of the detection boundary of a two-replicate mock purification. They are one abundance gradient, not two behaviours. And 32 of the 42 pan-fusion proteins (76.2%) have a clean 0|0 control, so a clean control is the base rate for this set and carries almost no information (rule 84) 1.

VIM::KMT2A sarcoma - a real KMT2A rearrangement, and a different molecule

Of 14,680 sarcomas profiled, 34 (0.2%) carry a KMT2A fusion; YAP1 is the predominant partner at 16 of 34, and two carried VIM-KMT2A, histologically spindle-to-round blue cell tumours with concurrent CTNNB1, SMARCB1 and ARID1A mutations 2. Two further cases confirmed the entity, with RNA-seq placing the breakpoint at VIM exon 4 to KMT2A exon 2 3.

Why this is not evidence for the interactome row. The leukaemia MLL fusions - including the index KMT2A::AFF1 - retain the KMT2A N-terminus (AT-hooks, CxxC, the menin-binding motifs) and replace the C-terminus with the partner. VIM::KMT2A is the other orientation: it joins four VIM exons onto KMT2A exon 2 and so preserves essentially the entire KMT2A protein, the same structural logic Massoth describes for YAP1-KMT2A-YAP1 preserving the CxxC domain. The VIM contribution is a short N-terminal head-domain segment and a promoter. So this establishes that the VIM and KMT2A loci recombine; it says nothing about whether the vimentin protein contacts an MLL fusion protein 23.

No intermediate filament module, and the keratin absence is by construction

Checked against the full 960 on 2026-09-21: NES, LMNA, LMNB1, DES and all keratins are absent. VIM is the only intermediate filament present. That looks like specificity until you read the Methods, which state: 'Known MS contaminants, such as trypsin and keratin were removed from the results.' Keratin absence is therefore a filtering decision, not a measurement, and cannot be used as evidence that the prep was free of cytoskeletal carryover. Vimentin was not on that removal list 1.

The literature bound, and what the query actually returns

VIM[tiab] AND (KMT2A[tiab] OR MLL[tiab] OR "MLL-AF4"[tiab] OR "MLL-AF9"[tiab] OR "t(4;11)"[tiab]) returns 11; the spelled-out vimentin[tiab] against the same clause returns 7. Every on-topic record in both is either a VIM::KMT2A sarcoma report or an immunohistochemistry panel in which vimentin is a staining marker. ZERO records tie vimentin protein to an MLL-fusion protein complex. The identical clause with MEN1 returns 85. Bounded to titles and abstracts; querytranslation recorded.

Verdict

Probably contamination, as an interactor. Vimentin is abundant, has no human experimental nuclear annotation, has no module in this network, and has no independent tie of the protein to any MLL fusion. What stops this being a confident call is that its negative control is clean and that this dataset's contaminants - CCT/TRiC, the tubulins, ACTN4, NCL - carry dirty ones. Separately, this entry is worth having for a reason that has nothing to do with the deferral: VIM::KMT2A is a real, named KMT2A entity that appears nowhere in this graph's 1,924 nodes, and the graph holds no sarcoma entry of any kind.

Facts and figures
uniprotP08670
length AA466
accession resolutionResolved live 2026-09-21: `gene_exact:VIM AND organism_id:9606 AND reviewed:true` returns exactly ONE reviewed row; gene_primary VIM, P08670, entry name VIME_HUMAN, 466 aa, protein name 'Vimentin', no gene synonyms. Matches the accession in Skucha's own table.
identifier hazardREAL, AND NOT PREVIOUSLY IN THE REGISTRY. `data/symbol-collisions.json` (98 collisions + 7 non-gene antigens, read 2026-09-21 before any search, per rule 88) has a VIM-2 row - the antibody clone defining the CD65s epitope, colliding with Verona integron-encoded metallo-beta-lactamase 2 - but NO row for the bare token VIM. Three live hazards for VIM itself, measured this session: (1) 'VIM' is also the standard abbreviation for the Verona integron-encoded metallo-beta-lactamase carbapenemase family, an entire antimicrobial-resistance literature; (2) inside a KMT2A-scoped query the token returns the VIM::KMT2A SARCOMA literature rather than vimentin biology - 5 of 11 records, which is a register collision in the same family as the ACTB and B2M rows; (3) in immunohistochemistry papers 'vimentin' is a staining reagent, not a subject. A row should be added; see the memo. The UniProt record itself is clean - one reviewed row, no synonyms - so this is a literature-register trap, not a resolution trap.
localizationCYTOPLASM AND CYTOSKELETON. UniProt P08670, fetched live 2026-09-21 with per-location evidence codes read individually: 'Cytoplasm' ECO:0000269 PubMed:19386766, 21465480, 29496907; 'Cytoplasm, cytoskeleton' ECO:0000269 PubMed:18408015, 29496907. 'Nucleus matrix' is ECO:0000250 by similarity to RAT P31000 - there is NO human experimental nuclear annotation. 'Cell membrane' and 'Cell projection, axon' are ECO:0000250 from P20152 (mouse). Per rule 91 the by-similarity lines were read rather than discarded, and the nuclear one is the only inferred compartment relevant here.
subnuclear localizationNOT APPLICABLE. Vimentin's only human experimental compartments are cytoplasmic. Recorded as not applicable rather than as an unmeasured absence, following the HLA-A / NRAS / B2M / PROM1 / CD33 / ELOVL1 precedent, so it does not enter the denominator of unmeasured subnuclear compartments. The 'Nucleus matrix' by-similarity line from rat is recorded in `localization` and is deliberately NOT used to open a subnuclear slot: an ECO:0000250 inference from another species is not a measurement of a human compartment.
localization shown for fusionNO - nobody has imaged or fractionated vimentin in any cell expressing any KMT2A fusion. Note the separate register trap: vimentin IS routinely stained by immunohistochemistry in KMT2A-rearranged sarcomas, but as a diagnostic marker of mesenchymal differentiation, which is not a localisation measurement about the interaction.
shown for fusionTwo different things, kept apart. (1) INTERACTION: co-purification with all seven MLL fusions including MLL-AF4 in Jurkat (p = 0.0109); shRNA-screened against MLL-AF9 in MOLM-13, score unpublished; NO independent experiment ties vimentin protein to any KMT2A fusion. (2) REARRANGEMENT: VIM::KMT2A is a recurrent sarcoma fusion, VIM exon 4 to KMT2A exon 2, 4 published cases - a genomic fact about the loci, with no functional characterisation of the resulting protein anywhere.
selectivityUNKNOWN, and BARRED from any target list. Not named among the paper's controls and not known to be among the 40 re-screened. Vimentin is one of the most abundant proteins in a mesenchymal or haematopoietic cell with structural roles in migration, adhesion and mechanics; there is no selective window and this entry's own verdict is that the interaction is probably an artefact.
absence classnever-measured
absence class noteFor the INTERACTION: no instrument has been pointed at vimentin in a KMT2A-rearranged cell outside the two screen hosts. The MOLM-13 shRNA score is measured-not-reported. For the VIM::KMT2A FUSION PROTEIN: never-measured - no functional experiment of any kind has been published on it. PRIDE checked: PXD009338 is the only relevant deposition.
graph contextVIM appears in ZERO of this graph's 1,924 node files as a gene before this entry. The two matches on the token are `target-cd65-vim2-neutral-glycolipid` and `target-cd65s-sialylated-vim2-ganglioside`, which are the VIM-2 antibody CLONE and a different molecule entirely - the collision the registry already warns about.
verdictPROBABLY CONTAMINATION as an interactor. Abundant, no human experimental nuclear annotation, no module, no independent protein-level tie to any MLL fusion. Held back from a confident call only by the clean negative control - which this beat measured to be the base rate (76.2% of the 42) rather than a discriminator. The entry earns its place on the second fact, not the first.
skucha 2018
{
  "bait": "MLL-AF4 (= KMT2A::AFF1)",
  "p_value": 0.0109,
  "spectral_counts": "4|3",
  "n_fusions_of_seven": 7,
  "negative_control_counts": "0|0",
  "per_bait": {
    "MLL-AF1p": "0.00446 (7|3)",
    "MLL-AF4": "0.0109 (4|3)",
    "MLL-AF9": "6.28e-05 (20|20)",
    "MLL-CBP": "8.4e-06 (8|30)",
    "MLL-EEN": "0.000219 (21|21)",
    "MLL-ENL": "2.06e-09 (36|37)",
    "MLL-GAS7": "3.78e-05 (28|20)"
  },
  "af4_spectral_rank_of_seven": 7,
  "af4_p_rank_within_the_42_pan_fusion": 16,
  "clean_control_is_the_base_rate": "32 of the 42 pan-fusion proteins (76.2%) carry 0|0, counted by this beat from the neg_ctrl column 2026-09-21.",
  "source": "analyses/skucha-mll-fusion-interactome/results.json, re-derived from the cached MOESM4 xlsx 2026-09-21; run.py re-run, both controls PASS"
}
is itself a kmt2a rearrangement partner
{
  "answer": "YES, in sarcoma - and this is a separate fact from the interactome row",
  "entity": "VIM::KMT2A-rearranged sarcoma",
  "frequency": "2 of 34 KMT2A-fusion sarcomas in a 14,680-sarcoma profiling database (KMT2A fusions themselves 0.2%); 4 published cases total across Massoth 2020 and Almohsen 2023",
  "breakpoint": "VIM exon 4 :: KMT2A exon 2 (RNA-seq, both Almohsen cases)",
  "orientation_note": "KMT2A is the 3' partner. Nearly the entire KMT2A coding sequence is retained and only exon 1 is replaced, so this is NOT an MLL-fusion oncoprotein of the leukaemia type, where KMT2A is 5' and the partner supplies the C-terminus. Structurally it is the same class as YAP1-KMT2A-YAP1, which Massoth notes preserves the CxxC domain.",
  "graph_gap": "Neither VIM::KMT2A nor any KMT2A-rearranged sarcoma has an entry in this graph's 1,924 nodes (checked 2026-09-21). `fusion-kmt2a-maml2-thymoma` shows non-leukaemic KMT2A entities are in scope."
}
complex membership
{
  "complex": "type III intermediate filament",
  "partners_in_the_960": {},
  "absent_from_the_960": [
    "NES",
    "LMNA",
    "LMNB1",
    "DES",
    "all keratins",
    "ACTL6A",
    "GSN",
    "CFL1",
    "PFN1"
  ],
  "reading": "ISOLATED, but the isolation is partly manufactured. Keratins were removed by the authors as known MS contaminants (Methods, verbatim), so their absence is a filtering decision. Vimentin is not a member of any of the twelve complexes tested in analyses/mll-fusion-interactome-complexes/, and no cytoskeletal module was tested there at all - which is itself a gap in that analysis."
}
cell types and states
[
  "Jurkat (human T-ALL) - the AP-MS host, nuclear lysate, tagged single-copy transgene",
  "MOLM-13 (human MLL-AF9 AML) - shRNA screen host, six shRNAs, per-gene score unpublished",
  "adult deep soft tissue sarcoma - the VIM::KMT2A entity, 4 published cases, all adults",
  "no B-lineage cell, no infant cell, and no KMT2A::AFF1 cell of any kind"
]
functionally screened in the source paper
{
  "screened": true,
  "shrnas_for_this_gene": 6,
  "design": "Supplementary Table 6 / MOESM5 is the shRNA library for the negative-selection screen: 768 data rows, 128 unique gene symbols, EXACTLY 6 shRNAs each - counted with openpyxl by this beat on 2026-09-21. Host is MLL-AF9-expressing MOLM-13, a human myeloid line.",
  "set_identity_measured_by_this_beat": "The 128 symbols in the shRNA library are the SAME SET as the 128 rows of MOESM4 with n_fusions >= 5, checked by set difference on 2026-09-21: the only four mismatches are alias spellings (JADE2/PHF15, JADE3/PHF16, KMT2A/MLL, NIFK/MKI67IP). This matters for the contamination question. The paper says 'Seven proteins were manually removed as these were either frequently observed contaminants or were not detected in human hematopoietic cell lines. The final set was comprised of 128 proteins.' Because the table's >=5 set is already exactly 128, those seven are NOT recoverable from Supplementary Table 5 - and every protein in this tranche is in the post-removal 128 and was carried into the functional screen.",
  "what_this_does_NOT_establish": "A per-gene result. Scores are presented only as heatmaps (Fig. 2c/2d); no per-gene depletion value is tabulated anywhere in the paper or its supplementary files, so for any individual gene the outcome is measured-not-reported. It is also MLL-AF9 MOLM-13, a myeloid line, not the index fusion and not B-lineage.",
  "the_filter_is_leaky_and_here_is_the_proof": "'Survived the authors' manual contaminant removal' is weaker than it sounds. CCT3 is also in the 128 and was also screened, and the CCT/TRiC chaperonin is the canonical AP-MS contaminant - the companion analysis analyses/mll-fusion-interactome-complexes/ uses it as its NEGATIVE control and it is still significant against a nuclear background (q = 2.7e-05, 8 of 9 subunits in the MLL-AF4 column). The authors' own named essentiality controls were RFC1, SF3A3 and CCT3. So the manual removal did not remove a canonical contaminant complex, and membership in the 128 is not the authors certifying a protein as a real partner.",
  "absence_class_for_the_per_gene_score": "measured-not-reported",
  "library_symbol": "VIM"
}
bounded literature
{
  "query": "VIM[tiab] AND (KMT2A[tiab] OR MLL[tiab] OR \"MLL-AF4\"[tiab] OR \"MLL-AF9\"[tiab] OR \"t(4;11)\"[tiab])",
  "querytranslation": "\"VIM\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract] OR \"t 4 11\"[Title/Abstract])",
  "count": 11,
  "on_topic_for_an_interaction": 0,
  "second_query": "vimentin[tiab] AND the identical KMT2A clause",
  "second_querytranslation": "\"vimentin\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract] OR \"t 4 11\"[Title/Abstract])",
  "second_count": 7,
  "what_the_18_records_actually_are": "Title-checked individually by this beat on 2026-09-21. VIM::KMT2A or KMT2A-rearranged sarcoma reports: 40944346 (LDB1::KMT2A sarcoma), 40879254 (YAP1::KMT2A sarcoma), 37713130 (CBX6::KMT2A::PYGO1), 37575084 (VIM::KMT2A, Naous), 36959690 (VIM::KMT2A, Almohsen), 32461620 (Massoth pan-sarcoma), 31136005 (KMT2A fusions in aggressive sarcomas). Vimentin-as-IHC-marker or EMT-marker papers: 36978050, 35249285, 31814569, 30221689, 30102091, 28274311, 37142078. Historical t(4;11) immunophenotyping: 3118100, 3017476. Other: 31558671 (NUP98-KMT2A). ZERO records report a vimentin protein interaction with an MLL fusion.",
  "date": "2026-09-21",
  "tool": "NCBI esearch db=pubmed",
  "names_tried": [
    "VIM",
    "vimentin"
  ],
  "positive_control": "MEN1[tiab] AND the identical five-term KMT2A clause returns 85.",
  "bound": "Titles and abstracts only; supporting figures not searched (rule 80). Cytogenetic term quoted, querytranslation read back and shows \"t 4 11\"[Title/Abstract] with no injected [UID] term (rule 95). One tag per term (rule 94). Not searched: the metallo-beta-lactamase register, deliberately, since it cannot be on topic."
}
what would settle it
[
  "Nuclear/cytoplasmic fractionation blot of vimentin in SEM or RS4;11, with a lamin and a tubulin control. One gel.",
  "Retrieve the CRAPome frequency for P08670 across the ~400 deposited control purifications. Free, and it is the external control Skucha 2018 did not run.",
  "Reciprocal co-IP: pull endogenous vimentin from a KMT2A::AFF1 line and blot for the fusion. If the interaction is real at 4|3 spectra it will not survive this, which is the point."
]
vim kmt2a coordinate corrections 2026 09 22
{
  "_found_by": "Q92 while building the sarcoma beat; CDS arithmetic verified independently by the king against Ensembl ENST00000534358 and ENST00000544301.",
  "error_1_was": "This entry said the VIM::KMT2A chimera 'preserves essentially the entire KMT2A protein'.",
  "error_1_correction": "It does not preserve exon 1. KMT2A exon 1 CDS is 432 bp = aa 1-144, so a chimera starting at KMT2A exon 2 is aa 145-3969 and LOSES the menin-binding motif (6-25) and IBM1 (123-134). IBM2 (147-152) sits in exon 2 and is retained. The same sentence listed 'the menin-binding motifs' among what leukaemia fusions retain, so a reader took the sarcoma fusion to retain them too -- which is the opposite of the finding.",
  "error_2_was": "This entry described the VIM contribution as 'a short vimentin head-domain segment and a promoter'.",
  "error_2_correction": "VIM exon 1 is untranslated; CDS exons 2-4 are 563+61+96 = 720 bp = aa 1-240 of 466, which is 52% of vimentin -- the head, coil 1A, linker 1 and most of coil 1B. Not a short segment. RefSeq NM_003380.5 has the same untranslated exon 1 and identical CDS lengths, so the exon numbering is not ambiguous.",
  "what_is_untouched": "This entry's interactome verdict on VIM -- probably contamination as a KMT2A::AFF1 interactor -- is a separate claim on separate evidence and stands. The sarcoma fusion is a different molecule and the entry already keeps the two apart.",
  "see": "fusion-vim-kmt2a and ana-kmt2a-exon-to-domain-map in data/graph/nodes/kmt2a-sarcoma/"
}
How this could bite us back
  • Vimentin must never reach a target list from this entry. It is structural, abundant, and the interaction is probably not real.
  • The reverse risk is the one worth watching: because vimentin is a standard IHC marker, a reader skimming the KMT2A-sarcoma literature will see 'vimentin positive' constantly and may read it as corroboration of the interactome row. It is not - it is a staining reagent doing its job.
  • If VIM::KMT2A is ever modelled, note that it retains nearly the whole KMT2A protein including the SET domain, so a menin inhibitor's predicted effect there is not the same as in a leukaemia MLL fusion and should not be assumed.
Still open
  1. VIM::KMT2A sarcoma has no entry in this graph and no functional characterisation anywhere in the literature. Does the VIM::KMT2A protein behave like an MLL fusion - is it menin-dependent, does it occupy HOXA? Nobody has expressed it.
  2. Two of the nine deferred pan-fusion preys - VIM and MAPRE1 - are recurrent KMT2A rearrangement partners, and neither of the other 33 pan-fusion proteins is. Is that anything? This beat did NOT compute the null (what fraction of any protein set are recurrent fusion partners), so it is an observation and explicitly not an enrichment claim.
  3. Does vimentin have a nuclear pool in a human haematopoietic cell? The human record has no experimental nuclear annotation and the rat-derived nuclear-matrix inference has never been tested in human cells.
  4. Does the abundance-driven negative control mean this whole table's 'clean control' group is systematically under-controlled? 815 of 960 proteins have 0|0, and for all of them the GLM's baseline is a regularised floor rather than data.
Every source behind this entry (3)
  1. E1weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper

    Vimentin co-purified with all seven Strep-HA-tagged MLL fusions from nuclear lysates of isogenic human Jurkat T-ALL cells; for MLL-AF4 (= KMT2A::AFF1) the combined p-value is 0.0109 with spectral counts 4|3 and a negative control of 0|0, and it is in the paper's final set of 128 conserved interactors that entered the MOLM-13 shRNA screen.

    MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity. · Skucha A, Ebner J, Schmoellerl J, Roth M, Eder T, Cesar-Razquin A, Stukalov A, Vittori S, Muhar M, Lu B, Aichinger M, Jude J, Mueller AC, Gyorffy B, Vakoc CR, Valent P, Bennett KL, Zuber J, Superti-Furga G, Grebien F · Nature Communications 2018
    PMID 29777171DOI
    What this evidence cannot show

    SYSTEM: the AP-MS host is JURKAT, a human T-ALL line, while KMT2A::AFF1 disease is B-lineage infant leukaemia; a partner requiring a B-cell or infant proteome cannot appear here and a T-lineage partner can appear spuriously. The bait is a Strep-HA-tagged, SINGLE-COPY, doxycycline-induced transgene at an FRT/Flp cassette, not the endogenous fusion. Prey came from bulk nuclear lysate after a single STREP-Tactin step, so co-purification is NOT evidence of a direct contact and is not evidence that the two proteins are ever in the same complex. INCLUSION RULE: the paper kept a fixed number of top-ranked interactions per bait rather than applying a p threshold. Methods, read verbatim from the PMC full text by this beat on 2026-09-21: "All the identified bait-prey pairs were ranked by the combined p-value. The 300 most significant interactions per bait were retained." Measured by this beat from the cached MOESM4 xlsx: within the MLL-AF4 column 186 of 291 listed p-values (63.9%) exceed 0.05, and that column's maximum p is 0.175. BAIT DEPTH: for all nine proteins in this tranche the MLL-AF4 spectral total is rank 7 of the seven baits - measured protein by protein - so a low MLL-AF4 count is a bait property (transgene expression, purification depth, or the GLM normalisation) and must not be read as a weaker association than the same protein's count under another bait. HOW TO READ THE NEGATIVE CONTROL, measured by this beat on 2026-09-21 over all 960 rows of MOESM4: the Spearman correlation between a protein's neg_ctrl spectral total and its maximum per-bait spectral total is +0.461, and the median maximum per-bait spectral count is 42 for the 145 proteins (15.1%) with a non-zero negative control against 8 for the 815 with 0|0. A dirty negative control in this table is therefore substantially a statement about protein ABUNDANCE, not about specificity, and a clean 0|0 is substantially a statement that two control replicates were not deep enough to see the protein at all. Two consequences. (1) PSIP1/LEDGF - the one pan-fusion partner with a solved co-crystal against the KMT2A N-terminus - carries 0|5, the second-dirtiest control of the 42, so a non-zero control cannot be used to call a protein a contaminant. (2) A 0|0 control is not purity; it is an unestimated baseline. The paper's GLM estimates each prey's baseline abundance A0,j from the control purifications, so a prey the controls never saw has its baseline set by a floor rather than by data, which is the direction that inflates apparent specificity. WHERE THIS ROW SITS AMONG THE 42, measured by this beat on 2026-09-21: ranked by MLL-AF4 p-value the pan-fusion set runs from MEN1 at 9.75e-16 to SMC3 at 0.174. The three WEAKEST MLL-AF4 calls in the whole pan-fusion set - SMC3 0.174, NOLC1 0.134, TRIM28 0.129 - all already have entries in this graph, and gene-nolc1 and gene-trim28 both carry confidence_overall 'weak' with those p-values recorded. So p > 0.05 in the index-fusion column is not a disqualifier in this corpus; it is a confidence tier that two existing entries already occupy. SPECIFIC TO THIS PROTEIN: MLL-AF4 p = 0.0109, rank 16 of 42. Measured by this beat on 2026-09-21: 32 of the 42 pan-fusion proteins (76.2%) carry a clean 0|0 negative control, so VIM's clean control is the BASE RATE for this set and carries essentially no information (rule 84); the informative tail is the other direction, where ACTB at 3|3 is the single dirtiest of the 42. VIM is the only intermediate filament in the 960 - NES, LMNA, LMNB1, DES and all keratins absent - but the keratin absence is a FILTERING decision stated in the Methods ('Known MS contaminants, such as trypsin and keratin were removed from the results'), not a measurement, so it cannot be cited as evidence the prep was clean. SELECTIVITY: not named among the paper's controls (RFC1, SF3A3, CCT3 non-selective; MEN1 selective), not known to be among the unpublished list of 40 re-screened. Recorded as unknown. Values re-read from the cached MOESM4 xlsx on 2026-09-21; run.py re-run, both controls PASS.

    Evidence that argues against this (2)
    • The negative-control asymmetry this tranche was deferred on dissolves on measurement. Over the 960 rows, Spearman(neg_ctrl, max per-bait spectral total) = +0.461, median max spectra 42 for dirty controls against 8 for clean. VIM's maximum is 73 and ACTB's is 388, so the two sit on opposite sides of a two-replicate mock purification's detection limit rather than behaving differently. PSIP1/LEDGF, which has a co-crystal with the KMT2A N-terminus, carries 0|5. Raw spectra at PXD009338 have not been reanalysed here and IntAct has never curated this dataset. ProteomeXchange/PRIDE 2018
    • Cytoskeletal and filament proteins are among the most frequently observed background proteins in affinity purification-mass spectrometry, and the CRAPome authors state explicitly that small-scale studies with limited negative controls do not capture a complete background protein set. Skucha 2018 used its own control purifications and did not consult a contaminant repository; a CRAPome frequency for vimentin was not retrieved by this beat and would be the cheapest external check available. Mellacheruvu D et al. 2013
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    In a comprehensive genomic profiling database of 14,680 sarcomas, 34 (0.2%) carry a KMT2A fusion; YAP1 is the predominant partner (16 of 34, usually as a complex YAP1-KMT2A-YAP1 rearrangement preserving the KMT2A CxxC domain), and two cases carry VIM-KMT2A fusions, presenting as spindle-to-round blue cell sarcomas with concurrent CTNNB1, SMARCB1 and ARID1A mutations.

    Pan-sarcoma genomic analysis of KMT2A rearrangements reveals distinct subtypes defined by YAP1-KMT2A-YAP1 and VIM-KMT2A fusions. · Massoth LR, Hung YP, Nardi V, Nielsen GP, Hasserjian RP, Louissaint A, Fisch AS, Deshpande V, Zukerberg LR, Lennerz JK, Selig M, Glomski K, Patel PJ, Williams KJ, Sokol ES, Alexander BM, Vergilio JA, Ross JS, Pavlick DC, Chebib I, Williams EA · Mod Pathol 2020
    PMID 32461620DOI
    What this evidence cannot show

    This is a genomic finding about the VIM and KMT2A LOCI and says nothing about a protein-protein interaction. The disease is adult soft-tissue sarcoma, not infant B-lineage leukaemia, and the fusion orientation is the opposite of the leukaemia MLL fusions: KMT2A is the 3' partner and almost the whole KMT2A coding sequence is retained. Retrospective analysis of a commercial sequencing database, n = 2 for VIM specifically. Read from the abstract.

    Evidence that argues against this (1)
    • Two cases out of 14,680 sarcomas is a rare event, and the co-occurring CTNNB1, SMARCB1 and ARID1A mutations in both mean the fusion is not the only driver in either tumour. More importantly for this entry, a recurrent genomic partnership does not imply a protein interaction: the leukaemia MLL fusions retain the KMT2A N-terminus and swap the C-terminus, whereas the VIM::KMT2A breakpoint at VIM exon 4 / KMT2A exon 2 preserves nearly all of KMT2A and contributes only a short vimentin head-domain segment and a promoter. Almohsen SS et al. 2023
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    Two further VIM::KMT2A-rearranged sarcomas were reported in adult males, RNA-sequencing placing the fusion at VIM exon 4 to KMT2A exon 2 in both; the tumours are uniformly cellular spindle-cell neoplasms that lack the sclerosing epithelioid fibrosarcoma-like background of KMT2A::YAP1 tumours, and have no specific immunohistochemical profile.

    VIM::KMT2A-rearranged sarcomas: A report of two new cases confirming an entity with distinct histologic features. · Almohsen SS, Griffin AM, Dickson BC, Demicco EG · Genes Chromosomes Cancer 2023
    PMID 36959690DOI
    What this evidence cannot show

    n = 2 case reports; a morphological entity claim built on four total published cases across this and the Massoth series. Adult deep soft tissue, not leukaemia and not paediatric. The value here for this graph is the precise breakpoint - VIM exon 4 to KMT2A exon 2 - which is what establishes that this is an N-terminal swap preserving KMT2A rather than a C-terminal MLL-fusion-type event. Read from the abstract.

    Evidence that argues against this (1)
    • No functional work exists on the VIM::KMT2A protein: no transformation assay, no occupancy, no menin dependency. Compare MLL-EB1, the other cytoskeletal KMT2A partner in this tranche, where a mouse bone-marrow transplantation model does exist. Until someone expresses VIM::KMT2A, whether it behaves like an MLL fusion at all is unknown, and this entry does not assert that it does. Fu JF et al. 2019
Connected to