UTP14A (Q9BVJ6) - an SSU processome component that binds and destabilises p53, in four MLL-fusion interactomes but NOT the index fusion's and below the screen threshold

THE INDEX FUSION DID NOT RECOVER THIS PROTEIN. UTP14A 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 4 baits that did recover it are MLL-AF9, MLL-CBP, MLL-EEN, MLL-ENL. Negative control: ZERO spectra. THE HEADLINE OF THIS ENTRY, AND IT BELONGS IN EVERY QUOTATION OF IT: 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 of its records - binding and function - are empty for the index fusion. 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

HUMAN cultured cells, 2011 Journal of Biological Chemistry. Not leukaemia, not a fusion, not haematopoietic. Read from the abstract only. This is a single-laboratory result and this beat did not find an independent replication of the p53-degradation arm; the SSU-processome arm is corroborated separately (PMID 27798105, the EMG1/NOP14/NOC4L subcomplex). The p53 connection is used in this entry to generate a hypothesis and is explicitly NOT used as evidence about any KMT2A fusion.

• A protein reported to destabilise p53 is one whose knockdown would be expected to activate p53 and impair growth in ANY p53-wild-type line, fusion or not - so a growth phenotype in a KMT2A-rearranged cell would not by itself demonstrate fusion-specificity, and the control that matters is a p53-null comparator. Note also that MLL-rearranged cells are reported to respond to ribosome-subunit attrition via p53-MDM4, which means the p53 axis is a general feature of that response rather than a UTP14A-specific one. Siemund AL et al. 2022

HUMAN cultured cells, 2016 Human Molecular Genetics. Not leukaemia, not a fusion. Read from the abstract only. CRITICAL SCOPING, and it is why this item is phrased the way it is: the disease gene is EMG1, NOT UTP14A. This is a link from UTP14A to a marrow-failure ribosomopathy THROUGH A PARTNER. No UTP14A loss-of-function human disease is reported and this beat found no UTP14A knockout haematopoietic phenotype in any organism. Cited as a toxicity/context statement about the sub-complex, not as a phenotype of this protein.

• Recorded so the inference is not made silently: membership of a complex whose disruption causes marrow failure says nothing about whether THIS subunit is the limiting one, and Bowen-Conradi is caused by a specific hypomorphic missense change (D86G) rather than by loss of the complex. The relevant contrast inside this block is TBL3, where the haematopoietic phenotype belongs to the protein itself rather than to a partner. Skucha A et al. 2018

A counted negative with a date, the exact query, the querytranslation and the tool. Bounded by TITLES AND ABSTRACTS ONLY - supporting figures not searched (rule 80). The aliases SDCCAG16 and NY-CO-16 were searched deliberately because UTP14A's older literature is cancer-serology literature under those names. A SEPARATE HAZARD recorded for future beats: UTP14A has a retrogene paralogue, UTP14C, an intronless chromosome-13 copy expressed in testis and ovary, so any wildcard or prefix search on UTP14 will mix the two genes - this beat searched the exact symbol only. Bare operand 26, so the instrument can return a one.

• For this protein the usual 'it was screened but not reported' counter does NOT apply, and that is the point: UTP14A is at four baits, below the five-bait threshold of the 128-gene shRNA library, so unlike RRP12, WDR18 and the seven-plus-bait members it was never functionally tested against an MLL fusion at all. The absence class is therefore never-measured rather than measured-not-reported, which is three orders of magnitude more expensive to close. Skucha A et al. 2018