MAP7D1 (Q3KQU3) - the strongest index-fusion p-value of the nine deferred pan-MLL-fusion preys, on a protein UniProt places entirely outside the nucleus

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 = 0.00818 is rank 15 of the 42 pan-fusion proteins and the strongest of the nine deferred ones, with a clean 0|0 control and six of seven baits below 0.001. The weakness is entirely biological, not statistical: UniProt Q3KQU3 records NO nuclear compartment at all (cytoskeleton, spindle, centrosome, midbody only; fetched live 2026-09-21), and MAP7, MAP7D2 and MAP7D3 are absent from the 960 at any n, so there is no family module. SELECTIVITY: not named among the paper's controls (RFC1, SF3A3, CCT3 as non-selective; MEN1 as selective) and not known to be among the 40 re-screened, which the paper does not list. Recorded as unknown. This entry must not be read as nominating a target. All values re-read from the cached MOESM4 xlsx on 2026-09-21; run.py re-run the same day, both controls PASS (128 shared by >=5 baits, 42 by all seven, MEN1 present with all seven).

• The negative control the whole tranche was judged on is an abundance readout, not a purity readout. Measured by this beat over the 960 rows on 2026-09-21: Spearman(neg_ctrl, max per-bait spectral total) = +0.461; median max spectra 42 for dirty controls against 8 for clean ones. PSIP1/LEDGF, the pan-fusion partner with an actual co-crystal against the KMT2A N-terminus, carries 0|5. IntAct has never curated this dataset and the raw spectra at PXD009338 have not been reanalysed here. ProteomeXchange/PRIDE 2018
• An AP-MS prey list scores against a background that is largely bait-independent, and abundant cytoskeletal proteins are among the most frequently observed background proteins across published affinity purifications. A single study's own small set of negative controls is explicitly described by the CRAPome authors as failing to capture a complete background protein set; that is the condition this row was scored under, and no CRAPome frequency was consulted by the source paper. Mellacheruvu D et al. 2013

MOUSE N1-E115 neuroblastoma cells, not human and not haematopoietic; the paper's focus is Map7D2 and Map7D1 is the comparator arm. Nothing here is nuclear, and nothing here is a fusion system. Read from the abstract. This citation is here to establish what the protein is for, not to support any interaction claim.

• This is exactly the problem for the AP-MS row: a protein characterised entirely at the centrosome and along microtubules has no described function in the compartment the bait was purified from. Skucha's own Methods state the purifications were from NUCLEAR lysates, so the recovery has to be explained either by a nuclear pool nobody has reported or by carryover. Skucha A et al. 2018

n = 1 patient. Shwachman-Diamond syndrome is canonically an SBDS ribosome-maturation disorder, and this paper proposes MAP7D1 as an additional contributing gene on a single variant; the mechanistic work is in glioblastoma and embryonic kidney lines. It is included because it is the ONLY link this beat could find between MAP7D1 and a bone-marrow-failure phenotype, and because that class of disorder carries leukaemic transformation risk - not because it supports any statement about KMT2A. SBDS, EFL1 and RPS14 are all ABSENT from the Skucha 960, checked by this beat on 2026-09-21, so there is no corroborating module. Read from the abstract.

• A single-patient variant claim in a disease with an established different causal gene is the weakest form of human genetic evidence, and the source paper itself frames MAP7D1 as contributing rather than causal. Nothing in it concerns MLL, KMT2A or any fusion; the bounded PubMed query joining MAP7D1 to the KMT2A clause returns 0 records (querytranslation recorded in data.bounded_literature). Skucha A et al. 2018