RRP12 (Q5JTH9) - a pre-40S export factor in six of seven MLL-fusion interactomes but NOT in the index fusion's, and the block's only member with a recessive human disease published in 2025

THE INDEX FUSION DID NOT RECOVER THIS PROTEIN. RRP12 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 6 baits that did recover it are MLL-AF1p, MLL-AF9, MLL-CBP, MLL-EEN, MLL-ENL, MLL-GAS7. 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. Five of the eleven nucleolar-block proteins written by this beat are in that position - RRP12, WDR18, UTP14A, RRP9 and FTSJ3 - plus UTP18, six in total. 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. TWO READINGS, NEITHER ESTABLISHED: MLL-AF4 is the shallowest bait, so absence may be a detection-depth artefact; or RRP12 may genuinely not associate with the index fusion. The experiment cannot distinguish them. FUNCTIONAL SCREEN. Supplementary Data 2 (MOESM5) is the shRNA library for the negative-selection screen: 768 data rows, 128 unique gene symbols, EXACTLY six shRNAs each -- counted with openpyxl by this beat on 2026-09-21, and this protein's symbol IS in it with six shRNAs. So it was functionally tested against an MLL fusion (MLL-AF9 in MOLM-13), which is more than a co-purification. But per-gene scores are published only as the heatmaps in Fig. 2c/2d with no table anywhere in the paper or its five supplementary files, so the outcome for this protein is not recoverable: 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

SACCHAROMYCES CEREVISIAE, 2014 PLoS Genetics. Not human, not leukaemia, not a fusion. Read from the abstract only. Cited for molecular function, which transfers reasonably across eukaryotes for a conserved ribosome-biogenesis factor, but the human protein's role has not been demonstrated to be identical. The Crm1 co-requirement is noted because this repo carries an export-axis/XPO1 thread - that is a TOPICAL ADJACENCY and not a connection: nothing here involves a fusion protein.

• A conserved export factor is required in every eukaryotic cell that makes ribosomes, so nothing about this function predicts a specific relationship with a leukaemia fusion. It also makes RRP12 abundant and constitutively associated with large pre-ribosomal particles, which is the profile most likely to be recovered non-specifically from a nuclear lysate. Skucha A et al. 2018

SACCHAROMYCES CEREVISIAE, 2011 Molecular and Cellular Biology, a single-author functional screen. Not human, not leukaemia, not a fusion. Read from the abstract only. Separating intra- from extra-ribosomal roles is explicitly stated by the paper as difficult, so an 'unrelated' function claimed from a screen in a ribosome-biogenesis mutant background should be held loosely - a cell-cycle phenotype is the expected downstream consequence of impaired ribosome production, which is the confound the paper is trying to exclude.

• The straightforward alternative explanation is the one the paper is arguing against: a cell that cannot make ribosomes properly will have cell-cycle and stress phenotypes for that reason alone. Calling them ribosome-synthesis-unrelated requires separating two things the paper concedes are hard to separate, and no human or vertebrate work this beat found replicates the extra-ribosomal claim. Moriggi G et al. 2014

HUMAN genetics, 2025 Movement Disorders. Not leukaemia, not a fusion, and NO HAEMATOPOIETIC PHENOTYPE IS REPORTED - this is a neurological and calcific disorder, and nothing in it supports a blood-lineage inference for RRP12. The discovery arm is two patients from two families, which is small; the cohort arms are the replication attempt and this beat read only the abstract, so how many additional cases the two cohorts yielded is NOT recorded here and must not be assumed. Cited for two things: RRP12 loss of function has human consequences, and this paper is the current experimental (ECO:0000269) citation behind UniProt's nucleolar localisation call for human RRP12.

• This entry deliberately does NOT parallel it with TBL3. TBL3's zebrafish mutant loses T cells and haematopoietic stem/progenitor cells, which is why that protein's loss-of-function phenotype is treated as lineage-relevant in this graph. RRP12's human phenotype is neurological with no blood component reported, so the two are not comparable and RRP12 must not inherit TBL3's relevance argument by association within the same block. 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 retired/clone symbol KIAA0690 was searched deliberately per the retired-symbol rule, because RRP12's older literature predates the current symbol. Bare operand 38, so the instrument can return a one.

• RRP12 is one of the 128 conserved interactors shRNA-screened in MLL-AF9 MOLM-13 with six shRNAs in the source paper itself, so a functional measurement against an MLL fusion exists and was never tabulated. Note the asymmetry this creates for this particular protein: it was functionally SCREENED against MLL-AF9 while never having been BOUND by the index fusion - the functional record here is stronger than the binding record, which is the reverse of the usual situation in this block. Skucha A et al. 2018