Oncofusion

start / graph / interface-kmt2a-oasl-declined-an-isg-with-an-uncoded-nucleolus

Interfaceweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q129-the-never-discussed-partners-of-kmt2a-and-psip1

KMT2A-OASL is one spoke-expanded BioPlex 3.0 AP-MS row with OASL as bait and KMT2A as prey; OASL is the only partner in the beat natively expressed in blood leukocytes, and its nucleolar annotation is uncoded - declined, with the compartment argument unavailable

also called KMT2A-OASL · MLL-OASL · p59OASL · EBI-54531862

A database lists OASL, an interferon-induced antiviral protein, as a KMT2A partner. The one supporting experiment tagged OASL in kidney cells and found KMT2A in the catch; unlike most partners on this list OASL really is made by blood cells, so the usual objection - wrong compartment, wrong tissue - does not apply and the decline rests only on how thin the evidence is.

The same thing, for a scientist

**Verdict: DECLINED, and the reason is weaker than for the other BioPlex partners, which is worth stating rather than hiding. Detection method is anti-tag co-immunoprecipitation (AP-MS) in BioPlex 3.0, spoke-expanded, with OASL as bait and KMT2A as prey** [E1]. One IntAct record, EBI-54531862, PMID 33961781, HEK293T only, intact-miscore 0.35 - the floor band that also contains the experimentally secreted ANOS1 and FGFBP1 [E1]. **The two arguments used against the other partners both fail here.** OASL's recorded tissue specificity is *'most tissues, with the highest levels in primary blood leukocytes and other hematopoietic system tissues'* - the right lineage for this project - and its location comments include **Nucleus, nucleolus** alongside Cytoplasm [E3]. So there is no compartment mismatch and no lineage mismatch. **What is left is the evidence itself: one record, one publication, one method, one cell line, spoke-expanded, at the floor score, with reciprocal confirmation structurally impossible because KMT2A is a prey-only node in BioPlex** [E1]. Note also that every OASL location comment is **UNCODED** - no ECO:0000269 - so 'nucleolar OASL' is a curator statement without a cited experiment [E3].

Go deeper
An interferon cluster runs through this list, and it is an observation rather than a finding

Three of the thirteen never-discussed partners are interferon-pathway proteins: OASL (an interferon-stimulated gene), PRKRA (the PKR activator PACT) and IRF2 (interferon regulatory factor 2). OASL and PRKRA arrive from BioPlex 3.0; IRF2 arrives from an entirely different publication, the Hubel ISG interaction network (PMID 30833792), where IRF2 was one of 104 tagged ISG baits.

This is offered as a pattern and explicitly not as a result, for two reasons that this project has been burned by before.

  1. No base rate has been computed. Interferon-stimulated genes are a large, heavily studied, highly expressed set, and one of the three sources is a dedicated ISG screen - so ISGs are over-represented in the source material, not necessarily in KMT2A's neighbourhood. Until somebody counts what fraction of all 24 KMT2A BioPlex baits, and of the whole IntAct KMT2A partner list, is interferon-annotated, 'three of thirteen' is a number without a null (rule 84).
  2. The three do not agree on anything mechanistic. OASL is a dsRNA-binding antiviral effector, PRKRA is a translational-control kinase activator, IRF2 is a DNA-binding transcriptional repressor. They share an annotation term, not a complex.

The pattern is recorded so a later cycle can test it rather than rediscover it. The test is cheap: count interferon-annotated proteins among KMT2A's 101 human IntAct partners against the genome background.

Why this one is declined anyway, and what would reverse it fastest

The record is a single spoke-expanded AP-MS row. Spoke expansion means the binary KMT2A-OASL pair was never observed; it was inferred by joining every prey in an OASL pull-down to the bait 1. It did not replicate in BioPlex's HCT116 arm, and reciprocal confirmation cannot be attempted because all 31 BioPlex rows touching Q03164 have KMT2A as prey - the 3,969-residue protein is not among the 10,128 baits 12.

OASL is also a natural frequent flier in this kind of experiment for a mundane reason: it is strongly interferon-inducible and abundant in the cells where it is expressed, and HEK293T over-expression of a tagged dsRNA-binding protein will capture RNA-associated background.

What would reverse this fastest, in order of cost: (1) the BioPlex portal's own CompPASS-Plus probability for the pair, which is published and was not retrieved here; (2) whether OASL appears in any KMT2A-bait pull-down anywhere - it does not, but no KMT2A-bait experiment has been curated into IntAct since 2015 1; (3) an interferon-stimulated haematopoietic cell, which is the only context in which both proteins are simultaneously present at physiological levels, and in which nobody has looked.

Facts and figures
partner agene-kmt2a
partner a uniprotQ03164
partner a length AA3969
partner bOASL
partner b uniprotQ15646
partner b length AA514
verdictDECLINED
adjudicated byQ129, cycle 92, 2026-09-23
decline strengthweakest decline in the beat - no compartment mismatch and no lineage mismatch; declined on evidence thinness alone
source publication pmid33961781
source datasetBioPlex 3.0
detection methodanti-tag co-immunoprecipitation (AP-MS)
experimental role partnerbait
experimental role kmt2aprey
kmt2a was never the baittrue
expansion methodspoke expansion
intact miscore0.35
replicated in second bioplex linefalse
reciprocally confirmedfalse
reciprocal confirmation possiblefalse
n publications1
n methods1
orthogonal method existsfalse
partner tissuemost tissues, highest in primary blood leukocytes and other haematopoietic tissues
compartment mismatchfalse
lineage mismatchfalse
interferon cluster base rate computedfalse
druggabilityNot assessable. No residue, domain or region is mapped on either side and no structure of the pair exists.
absence classnever-measured
absence class noteNo experiment has tested KMT2A against OASL with KMT2A as the bait, and none has tested the pair in an interferon-stimulated haematopoietic cell - the one context where both proteins are simultaneously at physiological levels. Closing it needs wet work. A cheaper secondary gap is measured-not-searched: the BioPlex portal publishes the CompPASS-Plus probability for this bait-prey pair and it was not retrieved.
shown for fusionNO - nobody has looked in any KMT2A fusion. Full-length KMT2A as prey in embryonic kidney cells.
epigenetic readoutnone - no chromatin, histone-mark or occupancy measurement exists for this pair.
host cell lines
[
  "HEK293T embryonic kidney"
]
records
[
  "EBI-54531862"
]
partner compartments
[
  "Nucleus, nucleolus [UNCODED]",
  "Cytoplasm [UNCODED]"
]
interferon cluster members in this beat
[
  "OASL",
  "PRKRA",
  "IRF2"
]
interface residues a
[]
structures
[]
ligands
[
  "drug-revumenib",
  "drug-ziftomenib"
]
How this could bite us back
  • If KMT2A does have interferon-pathway partners, menin inhibitors given to patients with active infection or inflammation could behave differently from the trial population, and no trial stratifies on interferon tone.
  • Interferon-stimulated genes are induced by many cytotoxic and epigenetic drugs, including hypomethylating agents used with menin inhibitors. A KMT2A-ISG contact, if real, would be a drug-induced interaction rather than a constitutive one, which is the kind of thing a baseline interactome cannot see.
Still open
  1. What fraction of KMT2A's 101 human IntAct partners is interferon-annotated, against a genome background? Three of thirteen never-discussed partners are interferon-pathway proteins and nobody has computed the null, so the pattern is currently uninterpretable (rule 84).
  2. Does interferon stimulation change anything about KMT2A in a haematopoietic cell? The question is unasked in this graph and is the only context in which an OASL-KMT2A contact could be physiological.
  3. Has any KMT2A-bait interaction experiment been published since 2015? IntAct's most recent KMT2A-bait publication is PMID 25751424; whether that reflects the field or only IntAct's curation queue has not been checked.
Every source behind this entry (3)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    IntAct curates one record of a KMT2A-OASL association, EBI-54531862, from PMID 33961781 (BioPlex 3.0), annotated to Supplementary table 1. Detection method anti-tag co-immunoprecipitation, interaction type 'association', expansion method SPOKE EXPANSION, host Homo sapiens HEK293T embryonic kidney cell. OASL (Q15646) is the BAIT and KMT2A (Q03164) is the PREY. intact-miscore 0.35, the same value as ANOS1, FGFBP1, ABT1, KRR1 and the ribosomal proteins, against 0.96/0.95/0.91 for WDR5/RBBP5/ASH2L. Across all 376 IntAct records touching Q03164, KMT2A is a bait in 18 publications, the most recent of which is PMID 25751424 (Nat Struct Mol Biol, April 2015), and a prey in 40.

    What this evidence cannot show

    Read live from IntAct REST on 2026-09-23, not PSICQUIC (rule 93). The BioPlex supplementary table was not opened. The '18 bait publications, most recent 2015' figure counts IntAct curation, not the literature: a KMT2A-bait experiment published after 2015 and not curated by IntAct would be invisible to it, so this bounds IntAct and not the field.

    Evidence that argues against this (1)
    • The floor score is a pair-level aggregate driven by how many publications support a pair, so it cannot distinguish a weak experiment from a strong experiment that nobody has repeated. For a protein like OASL, which no chromatin laboratory would think to test against KMT2A, 'nobody has repeated it' is close to guaranteed regardless of whether the interaction is real. IntAct (EMBL-EBI) 2026
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    In human HEK293T and HCT116 epithelial cell lines, BioPlex 3.0 affinity-purified 10,128 tagged human proteins plus 5,522 HCT116 immunoprecipitations, scored by CompPASS-Plus against a GFP control at 1% protein-level FDR with entropy-based dataset-level filtering, and names replication in the second cell line, reciprocal confirmation and co-fractionation as its confirmations, reporting about 60% of interactions in both networks confirmed by one of them.

    Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. · Huttlin EL, Bruckner RJ, Navarrete-Perea J, Cannon JR, Baltier K, Gebreab F, et al. (28 authors), Gygi SP · Cell 2021
    PMID 33961781DOI
    What this evidence cannot show

    Full text read 2026-09-23 through the PMC HTML route (PMC8165030) after fullTextXML returned HTTP 500. Neither 'KMT2A' nor 'OASL' appears in the paper's text; the row is a supplementary-table entry not opened here.

    Evidence that argues against this (1)
    • BioPlex recovered WDR5, RBBP5 and ASH2L on KMT2A at 0.91-0.96, so the dataset demonstrably reports true KMT2A biology and is not being dismissed wholesale. IntAct (EMBL-EBI) 2026
  3. E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    UniProtKB Q15646 is 514 aa, primary gene name OASL, recommended name "2'-5'-oligoadenylate synthase-like protein". Its subcellular-location comments are Nucleus, nucleolus and Cytoplasm, and ALL of them are UNCODED - no ECO:0000269 or other evidence code is attached to any of them. Function: does not have 2'-5'-OAS activity but binds double-stranded RNA; displays antiviral activity against encephalomyocarditis virus and hepatitis C virus by an RNase L-independent pathway. Tissue specificity: expressed in most tissues, with the highest levels in primary blood leukocytes and other hematopoietic system tissues, colon, stomach and to some extent testis.

    What this evidence cannot show

    Rule 91 applies in its second form here: the uncoded comments are the interesting ones and must be recorded as uncoded rather than discarded. 'Nucleus, nucleolus' with no evidence code means a curator asserted it without a cited experiment in the record, so it can be neither used as support nor treated as absent. The cited function papers were not opened.

    Evidence that argues against this (1)
    • An uncoded UniProt location is not a weak location - this project measured in ana-uniprot-localization-is-not-a-measurement-in-a-quarter-of-this-graph that about 10.7% of entries rest on uncoded annotations, and rule 91 found that filtering on ECO:0000269 discards the fragment- and condition-specific lines that are usually the informative ones. So the uncoded nucleolar OASL comment may well be correct; it simply cannot be cited as a measurement. UniProt Consortium 2026
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