UTP18 / WDR50 (Q9Y5J1) - the SSU processome subunit that recruits the exosome helicase MTREX to rRNA fragments; in three MLL-fusion interactomes but not the index fusion's, and separately the subject of a 21-year-old IntAct curation error in this graph

THE INDEX FUSION DID NOT RECOVER THIS PROTEIN. UTP18 is absent from the MLL-AF4 column of Supplementary Table 5 entirely -- there is no p-value and no spectral count for it under the index bait. It is an MLL-FUSION interactor, not a demonstrated KMT2A::AFF1 interactor, and nothing in this entry should be read as a KMT2A::AFF1 contact. The 3 baits that did recover it are MLL-AF9, MLL-EEN, MLL-ENL. Negative control: ZERO spectra. THE HEADLINE OF THIS ENTRY: this protein is NOT in the MLL-AF4 column. It is an MLL-FUSION interactor and NOT a demonstrated KMT2A::AFF1 interactor. Six of the eleven nucleolar-block proteins written by this beat are in that position - RRP12, WDR18, UTP14A, RRP9, UTP18 and FTSJ3. The 'thirteen-protein nucleolar block' is a POOLED statement over seven baits; in the index fusion's own column there are seven members and four below p = 0.05. AND IT IS BELOW THE SCREEN THRESHOLD TOO: the source paper's shRNA library covers only the 128 interactors shared by at least five baits, so this protein was never functionally tested against any MLL fusion either. Both records - binding and function - are empty for the index fusion. SCOPING AGAINST THE EXISTING GRAPH ENTRY, which matters more here than anywhere else in this beat: this row is from Skucha 2018 (PMID 29777171), a different paper, bait set, cell line and method from PMID 15199122, whose IntAct curation of a KMT2A-UTP18 association was shown by ana-utp18-is-not-in-the-mll-complex-it-is-wdr5-miscurated to be a WDR5 substitution. That finding stands and is NOT weakened by this row; this row is NOT rehabilitated by it. Two independent statements about the same protein. FUNCTIONAL SCREEN -- NOT SCREENED. The shRNA library (MOESM5) covers the 128 interactors shared by at least five of the seven baits: 768 rows, 128 symbols, exactly six shRNAs each, counted with openpyxl by this beat on 2026-09-21. This protein's symbol is NOT in that library, because it falls below the five-bait threshold. So unlike the seven-plus-bait members of this block it has never been functionally tested against any MLL fusion, even in the source paper. That is a stronger absence than measured-not-reported. THE BLOCK, re-measured by this beat on 2026-09-21 by re-running analyses/mll-fusion-interactome-complexes/run.py. A 26-subunit nucleolar / ribosome-biogenesis set returns 15 of 26 present in the 960-protein network against 1.25 expected by chance, hypergeometric p = 6.99e-14, q(BH) = 8.39e-13 across the twelve complexes tested -- the TOP-RANKED complex in the whole interactome, ahead of the CCT/TRiC negative control (q = 1.4e-09) and the SEC positive control (q = 1.5e-09). The fifteen are FBL, FTSJ3, GNL2, LYAR, NOLC1, NOP2, NOP58, PA2G4, RRP12, RRP9, TBL3, TCOF1, UTP14A, UTP18, WDR18. BUT THE BACKGROUND IS THE ~20,000-PROTEIN PROTEOME, not the ~4,600 proteins the study actually recovered before filtering, so every q here is an UPPER BOUND on significance and it is loosest for a complex of abundant nuclear proteins -- which this one is, more than any other row in that table. AND THE POOLED NUMBER IS NOT THE PER-BAIT NUMBER. Subunits of the block recovered per bait, out of 26: MLL-AF1p 8, MLL-AF4 7, MLL-AF9 12, MLL-CBP 10, MLL-EEN 12, MLL-ENL 11, MLL-GAS7 7. The index fusion is TIED LAST. In its column there are seven members and only four at p<0.05 -- GNL2, NOP2, PA2G4 and TBL3; LYAR (0.141), NOLC1 (0.134) and TCOF1 (0.163) are above it. So the strongest complex-level signal in this entire interactome is weakest in the fusion this project studies. 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. INCLUSION RULE: the paper kept the top 300 interactions per bait by combined p-value rather than applying a p threshold (Methods, verbatim: "All the identified bait-prey pairs were ranked by the combined p-value. The 300 most significant interactions per bait were retained."). In the MLL-AF4 column 186 of 291 listed p-values (63.9%) exceed 0.05; the pooled rate over all baits is 26.6%, and the pooled rate must NOT be quoted for a per-bait claim. BAIT DEPTH: MLL-AF4 is the shallowest of the seven baits by spectral counts, so a low or absent MLL-AF4 count is a property of the bait (transgene expression, purification depth, normalisation) and must not be read as a weaker association. ABUNDANCE IS THE LEADING ALTERNATIVE EXPLANATION. The nucleolus is the densest compartment in the nucleus, every bait here is a tagged nuclear protein, and the complex-level analysis in this repo exists to make exactly that point: its strongest per-bait signature in the index fusion's own column is CCT/TRiC, a canonical AP-MS contaminant, at 8 of 9 subunits with 6 at p<0.05 -- BETTER represented in MLL-AF4's column than the nucleolar block is. Complex-wide enrichment is not by itself evidence of specific binding. THE ARGUMENT ON THE OTHER SIDE: all thirteen members of the nucleolar block, this protein included, have a negative control of ZERO spectra. A non-specific sticky abundant protein would be expected to appear in the control purification too, and none of them does. That is the strongest single fact about this block and it is not explained by abundance alone. SELECTIVITY: the paper's own named NON-selectivity controls are RFC1, SF3A3 and CCT3 -- knockdown inhibited MLL-wild-type K562 and HL-60 as much as MOLM-13 -- against MEN1 as the selective positive. This protein is not among them. That is NOT evidence of selectivity: only 40 of the 128 entered the MLL-r versus MLL-wild-type re-screen and the paper does not say which 40, so absence from the control list is equally consistent with never having reached the second screen. Recorded as UNKNOWN. This entry does not nominate a target. Per-bait membership re-derived by this beat on 2026-09-21 by re-running analyses/skucha-mll-fusion-interactome/run.py (both controls PASS: 128 shared by >=5 baits, 42 by all seven, MEN1 present with all seven) and analyses/mll-fusion-interactome-complexes/run.py. n_fusions and the MLL-AF4 p-value were supplied pre-verified by the coordinator from the cached MOESM4 xlsx and were independently reproduced by this beat's re-run of the complex analysis.

• IntAct has never curated this dataset, so no independent curator has re-examined these calls and no interactome-coverage metric built on IntAct can see them; the raw spectra at ProteomeXchange PXD009338 have not been reanalysed here. The authors themselves removed seven proteins from the shared set by hand as frequently observed contaminants, which concedes that a rank cutoff lets contaminants through. ProteomeXchange/PRIDE 2018
• The same paper that motivates the nucleolar reading supplies its null hypothesis: MLL-AF4 is reported predominantly nucleolar, so every abundant nucleolar protein becomes a high-probability co-purification partner on compartment grounds alone. And the prediction that reading makes fails -- if nucleolar residency of the bait drove recovery, the index fusion should pull MORE of the block than the other six baits, and it pulls the FEWEST (7 of 26, tied last with MLL-GAS7). The report is also an ectopic-overexpression system, which this project treats as weak evidence about an endogenous protein. Siemund AL et al. 2022
• The strongest reason for caution about ANY UTP18 row in this literature is that one already turned out to be a curation error that survived twenty-one years and propagated into a 2026 coverage recount in this very project. UTP18's synonym is WDR50, 'WD repeat-containing protein 50', against WDR5, 'WD repeat-containing protein 5' - a collision live in the exact literature this entry belongs to. This beat's row comes from a supplementary table read directly rather than from a curated database, which is why it is not exposed to that specific failure - but the base rate for UTP18 claims in this corpus is one error out of two. IntAct / EMBL-EBI 2026

YEAST plus in vitro reconstitution, 2015 Cell. Not human cells in the arm cited here, not leukaemia, not a fusion. Read from the abstract only. The motif and the arch-domain docking are the abstract's own stated results. Cited because it is the one function in this block that physically connects two of the network's independently enriched complexes - the nucleolar block and NEXT/exosome - and that is a structural observation about the AP-MS network, NOT evidence of anything about a fusion.

• The bridge observation cuts against specificity as hard as it cuts for coherence. Two co-enriched complexes joined by a documented adaptor is the configuration in which one genuine association drags in many passengers, which is precisely how an AP-MS experiment manufactures a coherent-looking non-specific block. The negative control on this repo's own complex table is CCT/TRiC, which is internally coherent at 8 of 9 subunits and is a contaminant. Skucha A et al. 2018

HUMAN cancer cells and copy-number data, 2015 Oncogene. Not leukaemia-specific, not a fusion, not haematopoietic; the cancer-gain analysis is pan-cancer and this beat did not check whether any leukaemia cohort is included. Read from the abstract only. Note the finding that a SUBSET of cells show cytoplasmic UTP18 and that serum withdrawal shifts it - so UTP18's compartment is condition-dependent, which matters for interpreting a nuclear-lysate co-purification from cells in an undefined state.

• A protein 'frequently gained and overexpressed in cancer' is a protein whose abundance is elevated in transformed cells generally - the single most common reason a prey appears in an AP-MS network without binding the bait. For UTP18 specifically this is the second independent abundance argument, alongside its membership of the nucleolus, and it applies to the three baits that recovered it just as much as to the four that did not. Skucha A et al. 2018

HUMAN cultured cells, 2014 Biochemistry and Cell Biology; GFP fusions and photobleaching, with the protein set originally defined from a nuclear-matrix fraction. A GFP fusion of a structural nucleolar protein can perturb the assembly it reports on, and 'very low mobility' measures exchange rather than stoichiometry. Not haematopoietic, not a fusion system. Read from the abstract only. This is the ONLY published human sub-nucleolar assignment for UTP18 that this beat found, and it is the same source gene-tbl3 cites for TBL3 - deliberately, so the two entries are consistent; gene-tbl3 was read before this entry was written and was NOT edited.

• If UTP18 is a structurally immobilised nucleolar component with very low exchange, then its recovery from a 420 mM nuclear extract means it was solubilised out of a dense structure, and what co-purifies after that treatment is harder to interpret than a soluble interaction would be. The same objection is recorded in gene-tbl3 against the same source, and it applies to UTP18 identically. Skucha A et al. 2018

CITATION SCOPE, stated plainly rather than hidden: the adjudication summarised in this claim is the work of the existing graph entry ana-utp18-is-not-in-the-mll-complex-it-is-wdr5-miscurated, which this beat READ IN FULL before writing, and whose primary sources are PMID 15199122 (read there via PMC HTML) and live IntAct MITAB queries. This beat did NOT independently re-run those IntAct queries and did NOT re-read PMID 15199122. The citation attached here is the Skucha paper, which is the source of THIS entry's own row and the reason the scoping note is necessary; it is not the source of the miscuration finding. The miscuration finding is attributed to the sibling entry and should be read there. Recorded this way to avoid re-asserting another entry's primary result as though this beat had verified it.

• The sibling entry's verdict line reads 'no entry written for UTP18 - the partner does not exist'. Read out of context that could be taken to mean UTP18 has no relationship to MLL fusions at all, which the Skucha table contradicts at three of seven baits. The two are compatible - the verdict is scoped to the IntAct/PMID 15199122 row - but the wording is quotable in a misleading way, and this beat reports that to the coordinator as a clarification owed on an entry it does not own, NOT as an error. IntAct / EMBL-EBI 2026