CTR9 — a PAF1C subunit the field assumes is a fusion partner, with no paper that tested it

This is a prediction, not a measurement. No one has seen this protein in this shape. The colours say how much the software trusts itself, and that is worth reading before anything else — the orange stretches are places the model is effectively saying this part has no fixed shape.

• Essential-function toxicity: required by 92.6% of cell lines, so the protein cannot be targeted.
• Evidence risk to this graph: an interactome entry whose support is complex-level only can propagate into downstream reasoning as if it were a validated direct contact. This entry is written specifically so that it cannot.

1. Does CTR9 make a direct contact with KMT2A, or is PAF1C's MLL contact made entirely by another subunit? Subunit-resolution crosslinking mass spectrometry on the MLL-PAFc interaction would answer it and would tell a structure-based campaign where to aim.
2. Is the graph's habit of listing whole complexes as interactors inflating the apparent size of the KMT2A::AFF1 interactome? CTR9 and LEO1 are two entries whose evidence is complex-level only; there may be others.
3. CTR9 is a recognised tumour-suppressor gene in some contexts. Does CTR9 loss occur in KMT2A-rearranged leukemia at relapse, and would that be compatible with the complex being required?
4. Can a CTR9 allele be made that assembles PAF1C normally but cannot bind the Rad6/UBE2A acidic tail? Without it, every H2Bub phenotype attributed to CTR9 is indistinguishable from complex loss, and the Rad6-dock assignment stays a biochemical result with no cellular test.
5. Is H2BK120ub reduced at MLL-fusion target genes when CTR9 is depleted in a KMT2A-rearranged line? This graph holds PAFc as a physical connector between MLL and the Super Elongation Complex and has never measured a mark under a PAF1C perturbation in that setting.
6. Do the H3K4me3 and H3K36me3 attributions to Paf1C survive at subunit level in human cells? They are recorded here as complex-level only, and this graph has been wrong before by promoting a complex property to a subunit claim.

1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   CTR9 is a constitutive subunit of the RNA polymerase II-associated factor complex, which binds MLL through sequences flanking the CxxC domain and synergises with MLL fusion proteins at HOX loci.

   The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis. · Muntean AG, Tan J, Sitwala K, Huang Y, Bronstein J, Connelly JA, Basrur V, Elenitoba-Johnson KSJ, Hess JL · Cancer Cell 2010
   PMID 20541477DOI
   ▸What this evidence cannot show

   The MLL contact is mapped to PAFc as a complex, not to CTR9. This paper does not test CTR9 individually.

   ▸Evidence that argues against this (1)

   • CTR9 is a germline tumour suppressor in a childhood cancer, which is a hard constraint on treating it as a target in paediatric leukemia. Inactivating germline CTR9 mutations were found in 3 of 35 Wilms tumour families by exome and Sanger sequencing and in none of 1,000 population controls (P < 0.0001); each mutation segregated with disease and a second mutational event was present in the available tumours, establishing CTR9 as a Wilms tumour predisposition gene acting as a tumour suppressor. A second family with a novel splice-acceptor CTR9 germline variant and tumour loss of heterozygosity was reported subsequently (PMID 29292210). Whatever CTR9 contributes to the MLL-PAFc interaction, pharmacologically reducing CTR9 function in a child is reducing a tumour suppressor. Hanks S et al. 2014
2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   The human PAF1 complex physically connects the Super Elongation Complex to RNA polymerase II on chromatin.

   Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin. · He N, Chan CK, Sobhian B, Chou S, Xue Y, Liu M, Alber T, Benkirane M, Zhou Q · Proceedings of the National Academy of Sciences USA 2011
   PMID 21873227DOI
   ▸What this evidence cannot show

   Biochemistry in non-leukemia cell systems; establishes complex topology rather than a fusion-specific requirement.

   ▸Evidence that argues against this (1)

   • Physically connecting the SEC to Pol II is a statement about the PAF1 complex as a whole. It does not identify CTR9 as the connecting subunit, and CTR9 is pan-essential, so its removal disrupts far more than that connection. Oncofusion knowledge graph (internal analysis) 2026
3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

   A targeted literature search for a primary study testing CTR9 individually in KMT2A-fusion leukemia returned no result, so CTR9's place in the KMT2A::AFF1 interactome is complex-inferred rather than subunit-validated.

   PubMed search for CTR9 in the context of KMT2A/MLL-fusion leukemia, conducted for this graph on 2026-09-18; no primary subunit-level study retrieved · Oncofusion Knowledge Graph project, using the NCBI PubMed E-utilities · Literature search 2026
   ▸What this evidence cannot show

   A negative literature search is bounded by the query terms used and by PubMed indexing. It is evidence of absence only to the degree the search was competent, and a CTR9-specific study may exist under different terminology, in a preprint, or as an unannotated figure inside a complex-level paper.

   ▸Evidence that argues against this (1)

   • Searched and nothing contradicting found, with one caveat that strengthens rather than weakens E3. Repeated targeted searches for a primary study testing CTR9 individually in KMT2A-fusion leukemia again returned nothing; the only CTR9-specific human genetics that exist point the other way, to CTR9 as a germline Wilms tumour suppressor. So the absence is real and the field has not quietly filled it. The practical consequence is that CTR9's place in this interactome remains complex-inferred, and the one well-powered human dataset about CTR9 loss describes cancer predisposition, not therapeutic benefit. Hanks S et al. 2014
4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

   CTR9 is DepMap common-essential with mean Chronos -0.873 across 1,258 lines and depletion in 92.6% of lines; gnomAD reports pLI ~1.0 and LOEUF 0.350 with 41 observed against 152.1 expected loss-of-function variants; HPA reports uniform low-specificity expression with bone marrow 22.4 nTPM.

   DepMap CRISPR (Chronos) gene effect via the Open Targets Platform GraphQL API; gnomAD v4 constraint via the gnomAD GraphQL API; Human Protein Atlas consensus tissue nTPM via the HPA API · Broad Institute DepMap; gnomAD; Human Protein Atlas; Open Targets Platform · Databases 2026
   ▸What this evidence cannot show

   DepMap release version not stated by the API.

   ▸Evidence that argues against this (1)

   • Pan-essentiality is the finding here and it argues against the target rather than for it. A gene depleted in more than 90% of all cell lines is required by the patient's normal marrow as much as by the leukaemia, so its appearance in a KMT2A complex is a statement about the complex and not a therapeutic opening. gnomAD, Broad Institute 2026
5. E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset

   Across 54 DepMap leukemia lines CTR9 correlates with MEN1 at r = 0.006, confidence interval -0.289 to 0.280, permutation p = 0.963.

   Leukemia-restricted co-dependency with MEN1, bootstrap and permutation testing; analyses/wrad-discrimination/ in this project · Broad Institute DepMap; Open Targets Platform; analysis run by this project · Database and derived analysis 2026
   ▸What this evidence cannot show

   Our own computation in 54 lines. A pan-essential gene has a flat profile and cannot correlate, so this null carries no biological information.

   ▸Evidence that argues against this (1)

   • Same objection as for the other sub-threshold correlations in this beat: the deeper 2,743-gene variance-matched null with Holm correction leaves only KMT2A, PSIP1, DOT1L, FLT3, MEF2C and KAT7 standing, with MEIS1 already failing at Holm 0.067. LEO1's r = 0.302 at Holm 0.286 in the 16-gene panel is well below the genes that fail in the deep pool, so it should not be described as a signal of any kind. Broad Institute DepMap; Open Targets Platform; analysis run by this project 2026
6. E6strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

   CTR9 has no domain annotated in its UniProt record and is resolved structurally only within Pol II elongation-complex cryo-EM models such as 6TED, 7OPC and 8A3Y.

   UniProtKB Q6PD62 (CTR9_HUMAN) feature table and PDB cross-references; RCSB entries 6TED, 7OPC and 8A3Y verified via the RCSB data API · UniProt Consortium; RCSB Protein Data Bank · Databases 2026
   ▸What this evidence cannot show

   Absence of a UniProt domain feature does not mean absence of structure; CTR9 is a tetratricopeptide-repeat protein and the repeats are recognisable in the cryo-EM models even though they are not annotated as a domain feature in this record.

   ▸Evidence that argues against this (1)

   • No annotated domain and structure only inside cryo-EM elongation complexes is the profile of a large scaffold that folds around its partners. There is no isolated site to target and no model of the protein alone. RCSB PDB 2026
7. E_q93_ctr9_loc1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

   Human CTR9's ONLY UniProt subcellular location is 'Nucleus speckle', carried on a single ECO:0000250 (by similarity) attributed to Q62018 = CTR9_MOUSE; the mouse record is 1,173 aa, identical in length to the human protein, and its own speckle call rests on one ECO:0000269, PubMed:8636124.

   UniProtKB Q6PD62 (CTR9_HUMAN) and Q62018 (CTR9_MOUSE), SUBCELLULAR LOCATION comments with evidence codes and sources, both fetched live 2026-09-21 · UniProt Consortium · Databases 2026
   ▸What this evidence cannot show

   This is a statement about the database record, not about the biology. ECO:0000250 means a curator propagated an annotation across orthologues; it is not an experiment in a human cell, and this graph's localization-dot1l-nucleus-measured-cytoplasm-by-similarity entry is the worked example of why the distinction is kept. The identical 1,173-aa length means verify-accessions.py cannot detect a human-for-mouse substitution in this pair.

   ▸Evidence that argues against this (1)

   • ARGUING THE OTHER WAY: an ECO:0000250 propagation between mouse and human CTR9 is about as defensible as such a propagation gets - the two proteins are the same length, PAF1C is conserved from yeast to human, and no source anywhere disputes that CTR9 is nuclear. The objection is narrower and sharper than 'the annotation is rodent-derived': it is that the SPECIFIC SUBNUCLEAR TERM, speckle, is more precise than the underlying observation, which was 'predominantly in the nucleus'. A propagated annotation inherits its source's precision, and this one gained precision in transit. Malek SN et al. 1996
8. E_q93_ctr9_loc2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   PubMed:8636124, the single experimental citation behind CTR9's speckle annotation, is the cloning paper for mouse Ctr9 under the name p150TSP - a TPR-containing SH2-binding phosphoprotein purified from the mouse B-cell lymphoma A20 - and its abstract's whole localisation statement is that the protein is located predominantly in the nucleus, naming no subnuclear compartment.

   p150TSP, a conserved nuclear phosphoprotein that contains multiple tetratricopeptide repeats and binds specifically to SH2 domains. · Malek SN, Yang CH, Earnshaw WC, Kozak CA, Desiderio S · J Biol Chem 1996
   PMID 8636124DOI
   ▸What this evidence cannot show

   This claim is bounded by the ABSTRACT. The full text was pursued through all five routes of the standing brief's unreadable test and could not be obtained: Europe PMC returns pmcid null and inEPMC N so routes 2-4 are structurally unavailable, and DOI resolution returns a 13-character Elsevier redirect stub. The paper may contain a speckled or punctate image in a figure; what is established is that no reachable text supports the speckle term, so the graph should not repeat it as though it were measured.

   ▸Evidence that argues against this (1)

   • The honest counter is that this is an argument from unreachability, which is the weakest kind, and the brief's own rule is that a paper found, on topic and unreadable is neither an absence nor a rejection. So the correct reading is NOT 'UniProt is wrong'. It is that a reader cannot currently check UniProt's only annotation for this protein, and that the one independent test available - the literature bound - returns zero for CTR9 against speckles. Against that, note the counter-direction risk: an apparently off-topic citation can contain the better measurement, and it was exactly by opening a 2005 yeast paper with no CTR9 in its title that this entry acquired a real subnuclear record. Porter SE et al. 2005
9. E_q93_ctr9_loc3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   In BUDDING YEAST, all five Paf1 complex components including Ctr9 are present in the nucleoplasm but NOT the nucleolus in wild-type cells, and in paf1 and rtf1 mutants - where the complex is dissociated from Pol II and chromatin - the remaining factors are found in the nucleolus as well as the nucleoplasm; the authors show this relocalisation is not the cause of the rRNA-processing defect also seen in the paf1 strain, because rtf1 loss relocalises the factors without reproducing it.

   Separation of the Saccharomyces cerevisiae Paf1 complex from RNA polymerase II results in changes in its subnuclear localization. · Porter SE, Penheiter KL, Jaehning JA · Eukaryot Cell 2005
   PMID 15643076DOI
   ▸What this evidence cannot show

   Saccharomyces cerevisiae, not human and not haematopoietic - brief rule 73 applies and the claim names the system in its first clause. It is a complex-level measurement: Ctr9 is one of five factors localised, so nothing here is subunit-resolved in the sense this entry's main argument asks for. Yeast has no nuclear speckles in the mammalian sense, so this paper cannot adjudicate UniProt's speckle term directly - it adjudicates the nucleolar question.

   ▸Evidence that argues against this (1)

   • Two objections, and the second bites harder. First, PAF1C's subnuclear behaviour is demonstrably not conserved in detail: Drosophila Ctr9 shows paralog-dependent specialisation for sex-chromosome gene regulation and male germline differentiation, so 'Paf1C does X in yeast' transfers no better than any other cross-phylum claim. Second, a conditional relocalisation observed in a MUTANT is a statement about a perturbed complex, and what this entry needs is where CTR9 sits in an unperturbed human leukaemic nucleus, which nobody has measured. The yeast result is valuable because it supplies a testable hypothesis - pull PAF1C off Pol II and it enters the nucleolus - not because it supplies an address. Kai T et al. 2025
10. E_q93_ctr9_loc4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

    Bounded 2026-09-21: CTR9[tiab] AND ("nuclear speckle"[tiab] OR speckles[tiab]) returns 0 records; the gene clause across CTR9, p150TSP and SH2BP1 returns 102; the gene clause against a nine-term KMT2A/MLL fusion clause returns 0; and the gene clause against a localisation clause AND the fusion clause returns 0.

    NCBI E-utilities esearch db=pubmed; querytranslation read back and stored for every count in data.localization_bounded_absence · NCBI E-utilities · Databases 2026
    ▸What this evidence cannot show

    Titles and abstracts only; supporting figures not searched (brief rule 80), which matters more than usual because the decisive paper's full text is unreachable. PubMed silently dropped KIAA0155 from the query translation, so the count is over three strings and not four. The fusion-clause zero is a statement about the literature reachable from this symbol, not about whether CTR9 is in the fusion complex - the graph's own position is that PAF1C membership rests on complex-level purifications that never name a subunit.

    ▸Evidence that argues against this (1)

    • This zero is exactly the class rule 64 was written about, and it fails in the way that rule predicts. A counted absence on a complex SUBUNIT is worthless without the complex form, and running the complex form is what produced this entry's only real subnuclear evidence: a 2005 paper with 'subnuclear localization' in its title that no CTR9 query reaches. So the defensible statement of the absence is narrow - nobody has published a CTR9-resolved compartment measurement in a human cell. The broader-sounding version, that nobody has studied where this protein sits, would be false, and would have been written if the subunit query had been trusted. Porter SE et al. 2005
11. E_q97_epi1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    PAF1C is required for Rad6/Bre1-mediated monoubiquitination of histone H2B, and the contributions are SUBUNIT-RESOLVED: Ctr9 acts as a hub and interacts with the carboxyl-terminal acidic tail of Rad6, which is required for PAF1C-induced stimulation of H2Bub; the Ras-like domain of Cdc73 accelerates ubiquitin discharge from Rad6; and the Rtf1 histone modification domain stimulates H2Bub, probably by accelerating ubiquitin discharge from Rad6 alone or in cooperation with Cdc73.

    Biochemical insights into Paf1 complex-induced stimulation of Rad6/Bre1-mediated H2B monoubiquitination. · Proc Natl Acad Sci U S A 2021
    PMID 34385316
    ▸What this evidence cannot show

    Abstract fetched and read in full 2026-09-21; full text not read. RECONSTITUTED BIOCHEMISTRY on the YEAST complex (Rad6/Bre1 are the yeast enzymes; the human orthologues are UBE2A/B and RNF20/RNF40, both of which this graph holds as gene-rnf20 and gene-rnf40). The authors state the Cdc73 mechanism MIGHT be conserved from yeast to humans, which is the paper's own hedge and is carried here. No mammalian cell, no haematopoietic system, no KMT2A fusion. This is cited for ONE thing: it is the source that assigns the H2Bub contribution to named PAF1C subunits rather than to the complex, which is what rule 64 demands before a subunit entry may claim the complex's mark.

    ▸Evidence that argues against this (1)

    • Subunit resolution obtained in a reconstituted yeast system is not subunit resolution in a human blast. Human PAF1C composition differs - notably RTF1 is only loosely associated with human PAF1C rather than being a stable core subunit, which this graph's gene-rtf1 entry already records from Warner's deletion series - so a contribution measured in a yeast complex where Rtf1 IS a stable subunit may not transfer. The direction of the possible error is that the human Rtf1 contribution could be larger (a separable, diffusible stimulatory module) or smaller (not present in the complex at the relevant time), and this abstract cannot distinguish them. Genetics 2011
12. E_q97_epi2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    The crystal structure of a quaternary Ctr9/Paf1/Cdc73/Rtf1 core module of S. cerevisiae PAF1C reveals interfaces between the tetratricopeptide-repeat module of Ctr9 and Cdc73 or Rtf1, and shows that the Ctr9/Paf1 subcomplex is the key scaffold for PAF1C assembly; Cdc73 binds the Ctr9/Paf1 subcomplex in a very similar conformation in thermophilic fungi and in human PAF1C.

    Crystal Structure of the Core Module of the Yeast Paf1 Complex. · J Mol Biol 2022
    PMID 34852272
    ▸What this evidence cannot show

    Abstract fetched and read in full 2026-09-21; full text not read. YEAST crystal structure; the human comparison is asserted for the Cdc73 binding conformation only. No residue ranges are recorded in this entry from the abstract, so nothing is added to data.domains and no coordinates are claimed (the joins rule: a domain with a null boundary is invisible, so it is better left out).

    ▸Evidence that argues against this (1)

    • This is the source of the confound rather than a support for a CTR9-specific function: if Ctr9/Paf1 is the assembly scaffold, then every mark phenotype after CTR9 loss is also a complex-loss phenotype, and the Rad6-docking assignment in [E_q97_epi1] cannot be tested in cells by depletion alone. A separation-of-function CTR9 allele that keeps the complex together and loses the Rad6 tail contact is the only clean test and does not exist. Proc Natl Acad Sci U S A 2021
13. E_q97_epi3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    Paf1C promotes H3K4 and H3K36 trimethylation and H2BK123 ubiquitination as well as RNA Pol II transcriptional termination and RNA-mediated gene silencing; Paf1 and Ctr9 are critical for overall complex integrity, and Drosophila Ctr9 mutants die at late embryogenesis or early larval life with increased neuroblast numbers and increased nervous-system proliferation.

    Ctr9, a Key Component of the Paf1 Complex, Affects Proliferation and Terminal Differentiation in the Developing Drosophila Nervous System. · G3 (Bethesda) 2016
    PMID 27520958
    ▸What this evidence cannot show

    Abstract fetched and read in full 2026-09-21; full text not read. DROSOPHILA nervous system - neither the organism, the lineage nor the disease of this graph (rule 73). The mark list is stated as a property of Paf1C in the introduction sense, i.e. it is a COMPLEX-level attribution carried in a review-like framing, not a measurement in this paper's own figures; it is recorded here as such and is why the confidence is moderate.

    ▸Evidence that argues against this (1)

    • A complex-level mark list is exactly the inference rule 64 exists to block. Naming H3K4me3, H3K36me3 and H2Bub as Paf1C outputs does not license writing them as CTR9 outputs, and this entry's readout separates the two registers deliberately: the only CTR9-BY-NAME assignment is the Rad6 dock in the reconstituted system. J Mol Biol 2005
14. E_q97_epi4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    In Neurospora, loss of the PAF-1, CTR-9 or RTF-1 subunit of Paf1C shortens the circadian period and advances phase, and the PAF-1 and CTR-9 subunits promote transcription of the clock gene frequency by enhancing the enrichment of histone H2B ubiquitination (H2BK131ub) at that locus.

    Paf1C regulates the Neurospora circadian clock by promoting the transcription elongation of frequency. · PLoS Genet 2025
    PMID 41129592
    ▸What this evidence cannot show

    Abstract fetched and read in full 2026-09-21; full text not read. NEUROSPORA CRASSA, a filamentous fungus, and the ubiquitylated residue is H2BK131 - a third organism-specific site after yeast H2BK123 and human H2BK120. Cited for one narrow purpose: it is a second organism in which CTR9 SPECIFICALLY, by name and by single-subunit deletion, is required for H2Bub enrichment at a named locus. The circadian biology is irrelevant here and is not imported.

    ▸Evidence that argues against this (1)

    • Two fungal systems agreeing is not evidence about a human blast, and the residue is different in all three organisms. The convergent finding also cannot escape the assembly confound: a ctr-9 deletion in Neurospora removes the subunit that holds the complex together, so it too is compatible with 'no complex' rather than 'no Rad6 dock'. J Mol Biol 2022

• part of →PAF1 — pan-essential subunit of a complex the fusion needs, where the window is in the interface and not in the protein

  Counter-evidence: CTR9 is a germline Wilms tumour suppressor, which constrains any PAF1C-directed agent in a paediatric population

• ← part ofSKIC8 (formerly WDR61) — the last PAF1C subunit, and a gene-symbol trap worth recording

  same complex

• ← related toA quarter of this graph's gene entries have a UniProt localization that nobody measured - and the subnuclear vocabulary UniProt does carry avoids the genes we care about most

  core elongation machinery whose localisation is by-similarity only

• related to →Nuclear speckles — the compartment everyone assumes KMT2A::AFF1 uses, on evidence that skips AFF1 itself

  UniProt's ONLY location for human CTR9 is 'Nucleus speckle' and it is ECO:0000250 from mouse, whose own call is one 1996 cloning paper saying 'predominantly in the nucleus' and naming no speckle (PMID 8636124). CTR9[tiab] AND speckles returns ZERO. The speckle term gained precision in transit and must not enter the SEC speckle argument as a measurement (Q93 2026-09-21)

• related to →PAF1 is annotated as punctate everywhere in the nucleus EXCEPT the nucleolus - and a 2024 proximity map puts it in the nucleolus

  CTR9's real subnuclear record is complex-level and in YEAST: wild-type Paf1C sits in the nucleoplasm and NOT the nucleolus, and dissociating it from Pol II by paf1 or rtf1 loss admits it to the nucleolus (PMID 15643076). That is a candidate reconciliation of this node's CONTESTED status - bulk exclusion plus a conditional nucleolar pool - and gene-paf1 currently states that no source reconciles them (Q93 2026-09-21)

• related to →PAF1 — pan-essential subunit of a complex the fusion needs, where the window is in the interface and not in the protein

  Same complex, and the two localisation records are complementary rather than independent: PAF1's uncited UniProt note describes nucleoplasmic puncta EXCLUDING nucleoli, and the yeast paper that measured all five subunits including Ctr9 found exactly that in wild-type cells (PMID 15643076). Neither protein has a human leukaemic compartment measurement (Q93 2026-09-21)

• related to →Transcription factories and Pol II clusters - no KMT2A::AFF1 imaging, condensate evidence for SEC and MLL-ENL, and 3D-FISH that actively contradicts the factory story for t(4;11)

  CTR9's subnuclear address is defined by Pol II ASSOCIATION rather than by a body: Paf1C is nucleoplasmic and nucleolus-excluded while attached to elongating Pol II, and enters the nucleolus when pulled off it (PMID 15643076, yeast) (Q93 2026-09-21)

• related to →DOT1L's localization record is a mouse kidney paper wearing a human label - and the one image of it in a leukaemia cell is a supporting figure a title search cannot see

  Same annotation pathology, one step worse. DOT1L's cytoplasmic call is by-similarity; CTR9's ENTIRE location record is by-similarity from mouse, and the propagated term (speckle) is more precise than the source observation (predominantly nuclear) (Q93 2026-09-21)

• related to →SGF29 — a SAGA reader with a Tudor pocket, intermediate essentiality, and the best unexploited profile in this beat

  Second consecutive tranche in which a chromatin-complex subunit's human compartment turns out to be a RODENT inference: SGF29 human-from-rat with one hepatocellular-carcinoma paper behind it (Q91), CTR9 human-from-mouse with one 1996 SH2-binding cloning paper behind it. Both have identical or near-identical orthologue lengths, so the length check protects neither (Q93 2026-09-21)

• ← related toCDC73 / parafibromin — the PAF1C subunit that was genetically tested, and a second tumour suppressor required by the fusion

  Two subunits of one complex with OPPOSITE database failures, and only opening the cited papers separates them: CTR9's single UniProt value is 'Nucleus speckle' resting on a source that says only 'predominantly in the nucleus' - precision gained in transit - while CDC73's single value is a bare 'Nucleus' although three nucleolar signals are mapped in the protein. Both are ECO:0000269; no evidence-code filter tells them apart (Q95 2026-09-22)

• ← related toWAC — the adaptor that hands RNF20/RNF40 to RNA polymerase II, and the only member of this axis whose knockdown alone killed MLL-rearranged ALL cells

  Third cross-species two-step compartment chain in this series and the tightest length pair: human WAC 647 aa against mouse Wac 646 aa, ONE residue apart, so verify-accessions.py cannot catch a swap (CTR9 was 1,173/1,173, CSNK2A2 350/350). WAC's chain INVERTS in the protein's favour where CTR9's did not - the source is a human paper titled for the localisation (Q95 2026-09-22)

• regulates →H2BK120ub (H2Bub1) — the ubiquitin tag on histone H2B that licenses H3K79 methylation, and the mark this graph was missing

  CTR9 is the Rad6 (E2) dock required for PAF1C-induced stimulation of H2B monoubiquitination; confounded in cells by CTR9's scaffold role

• part of →RTF1 — the PAF1C subunit the graph was missing, on a complex that does bind the retained KMT2A fragment

  Ctr9/Paf1 is the PAF1C assembly scaffold and the Ctr9 TPR module provides the Rtf1 and Cdc73 interfaces; the two subunits stimulate H2Bub by different steps

• ← testsAuditing the seven strikes before applying them: nine of ten decisions stand, four for different reasons than were given, and one clinical argument fails

  strike confirmed; germline-tumour-suppressor reasoning demoted to a caution because it would disqualify menin