Oncofusion

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Proteinweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q5-interactome4

NELFE (RDBP) — the RNA-binding subunit of the pausing brake, and the alias that inflated a record count fifty-fold before it was caught

also called NELFE · RDBP · NELF-E · RD · Negative elongation factor E · RD RNA-binding protein

NELFE is the part of the pausing brake that actually grips the new RNA as it emerges from the polymerase. Nothing connects it to KMT2A leukaemia — and finding that out required discarding a search that looked reasonable and was wrong by a factor of fifty.

The same thing, for a scientist

NELFE (P18615, 380 aa) is the RNA-binding subunit of NELF. It is the only NELF subunit with a nucleic-acid-binding module: an **RRM at aa 262-332**, preceded by 30 approximate two-residue R-[DSNE] tandem repeats at aa 184-243 (the 'RD' repeat that gave the protein its original name) and an N-terminal coiled coil at aa 7-36 [E1]. In the paused complex, NELF extends two flexible tentacles that can contact DSIF and the **exiting RNA**, and NELFE's RRM is the obvious candidate for the RNA contact [E2]. There is no KMT2A literature: `(MLL OR KMT2A) AND (NELFE OR RDBP OR NELF-E)` returns **2 records**, both reviews [E3]. DepMap places it mid-field among the NELF subunits with a difference of **+0.0583** at rank 15,340 (86.53rd percentile) on a pan-essentiality of -0.4482 — the shallowest of the four, and unremarkable [E4].

What it looks like
Negative elongation factor E380 aa
RRM (RNA recognition motif)RRM (RNA recognition motif) · residues 262–332Coiled coilCoiled coil · residues 7–36RD repeat regionRD repeat region · residues 184–2430100200300
loading AF-P18615-F1…
AlphaFold AF-P18615-F1 ↗
colourshape

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.

very high (90+)confident (70–90)low (50–70)very low (<50)
I have never read one of these pictures before

A protein is one long chain of amino acids that folds up. The ribbon traces that chain from one end to the other; it is not a wire, it is a simplification of where the backbone runs. Drag to rotate, scroll to zoom.

Domains are the stretches of chain that do a particular job, and they are what the coloured blocks above the picture mark out. Click one and the view flies to it. In this project the important question about any domain is usually whether the fusion still has it — the labels say lost where it does not.

Anything in yellow sticks is a bound small molecule, which is usually the drug.

Go deeper
The methodological finding this entry carries

NELFE's oldest alias is the two-letter symbol RD. Including it in an enumeration query looked like ordinary diligence — the standing brief for this project specifically instructs agents to search retired symbols — and it returned 115 records for (MLL OR KMT2A) AND (NELFE OR RDBP OR RD OR "NELF-E") where the corrected query returns 2 3.

That is the same failure the project documented for SEPT* matching 'September', arriving from the opposite direction. The brief's rule says search the retired symbol; this case shows the rule needs a companion: a retired symbol that is one or two characters, or that is a common English abbreviation, must be validated before its count is used. Fifty-seven-fold inflation from one alias would have produced a confident, completely wrong statement that NELF is well studied in this disease.

The general form: an enumeration's alias list needs both recall and precision checks, and only the recall half is currently written down.

What NELFE does, and the one thing that would make it interesting here

NELFE is where NELF touches RNA. The cryo-EM description of the paused complex has NELF binding the polymerase funnel with two flexible tentacles reaching toward DSIF and the exiting transcript 2, and NELFE's RRM (aa 262-332) is the module built for that job 1.

The reason that could matter for this graph is gene-aqr, already present: the ECAS complex joins an AFF4-ELL2-EAF1 elongation module to a U2 snRNP-associated intron binding complex, sits on promoter-proximal chromatin, and its perturbation impairs elongation and increases intron retention while leaving pause release unchanged 5. Two RNA-engaging assemblies at the same promoter-proximal position, one of them MLL-relevant, is a coincidence worth one experiment. No published work connects them, and this entry does not claim one.

Cell type, cell state, localisation, epigenetics

All not established in KMT2A-rearranged disease: no cell type, no cell state, no subnuclear localisation. Subcellular is nuclear 1. Epigenetic readout: none — NELFE has no histone-modifying activity, and the relevant measurement would be a pausing index or a nascent-RNA profile, neither of which exists for this disease with NELF perturbed.

Facts and figures
uniprotP18615
gene symbolNELFE
protein nameNegative elongation factor E
length AA380
alphafold IDAF-P18615-F1
accession resolutionUniProt REST query gene_exact:NELFE AND organism_id:9606 AND reviewed:true, run 2026-09-19; one reviewed hit; primary gene name read back as NELFE and length 380 confirmed from the same fetched record.
alias hazardThe two-letter alias RD inflates PubMed co-occurrence counts from 2 to 115 and must not be used in an enumeration query without title-checking.
complexNELF (negative elongation factor), with NELFA, NELFB and NELFCD
classificationNOT a documented interactor of KMT2A::AFF1; pausing machinery with a counted absence and no dependency signal
interaction evidence classcryo-EM of reconstituted Pol II complexes; unbiased DepMap scan
shown for fusionnone
epigenetic readoutnone - no histone-modifying activity
domains
Coiled coil7.000Coiled coil: 7RD repeat region184.0RD repeat region: 184RRM (RNA recognition moti…262.0RRM (RNA recognition motif): 262
aliases retired or alternate
[
  "RDBP",
  "NELF-E",
  "RD"
]
complex partners
[
  "gene-nelfb"
]
domains — the numbers behind the chart
[
  {
    "name": "RRM (RNA recognition motif)",
    "start": 262,
    "end": 332,
    "source": "UniProt P18615, fetched 2026-09-19"
  },
  {
    "name": "Coiled coil",
    "start": 7,
    "end": 36,
    "source": "UniProt P18615, fetched 2026-09-19"
  },
  {
    "name": "RD repeat region",
    "start": 184,
    "end": 243,
    "source": "UniProt P18615, fetched 2026-09-19; 30 approximate 2-aa R-[DSNE] repeats; the origin of the RDBP/RD name"
  }
]
localization
{
  "subcellular": "nucleus",
  "subnuclear": "not established"
}
essentiality
{
  "depmap_scan": "analyses/depmap-kmt2a-selective-scan-full",
  "pan_essentiality_all_lines": -0.4482,
  "n_all_lines": 1208,
  "mean_kmt2a_rearranged": -0.405,
  "mean_other_leukemia": -0.4633,
  "kmt2a_selectivity_difference": 0.0583,
  "rank": 15340,
  "n_scanned": 17728,
  "percentile": 86.53,
  "interpretation": "no meaningful selectivity; notable chiefly because it is the NELF subunit least affected by the essentiality floor and shows the smallest effect"
}
enumeration record count
{
  "query": "(MLL OR KMT2A) AND (NELFE OR RDBP OR NELF-E)",
  "records": 2,
  "both_reviews": true,
  "discarded_query": "(MLL OR KMT2A) AND (NELFE OR RDBP OR RD OR NELF-E) returned 115",
  "date": "2026-09-19"
}
depmap kmt2a selectivity
{
  "chronos_mean_kmt2a_rearranged": -0.405,
  "chronos_mean_other_leukaemia": -0.4633,
  "difference": 0.0583,
  "pan_essentiality_all_lines": -0.4482,
  "selectivity_rank": 15340,
  "rank_denominator": 17728,
  "provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
  "how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}
How this could bite us back
  • NELFE has no KMT2A selectivity and a pan-essentiality of -0.45; there is no therapeutic idea here and this entry should not be read as proposing one.
  • The real risk this entry guards against is methodological: an alias list assembled for recall can destroy precision, and a fifty-seven-fold inflated count would have supported the opposite conclusion with the same apparent rigour.
  • Suggesting an ECAS-NELF connection on the basis of shared genomic position is the kind of adjacency argument this project has elsewhere refused. It is flagged as an experiment, not a mechanism, and should stay that way until someone measures it.
Still open
  1. Does NELFE's RRM contact nascent RNA at KMT2A::AFF1 target genes? A CLIP experiment in a fusion-positive line would be the first NELF measurement in this disease.
  2. ECAS and NELF both engage RNA at promoter-proximal chromatin and one of them is MLL-relevant. Are they related at all? The ECAS paper's own result that AQR loss does not alter pause release argues no.
  3. How many of the 115 records returned by the RD-containing query are genuine? Reading those titles is a small job that would either confirm or overturn this entry's central negative.
  4. Is the alias-precision problem general enough to warrant a rule in the standing brief alongside the alias-recall rule?
Every source behind this entry (5)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    UniProtKB P18615 (NELFE_HUMAN, Negative elongation factor E) is 380 aa and annotates an RRM domain at aa 262-332, a coiled coil at aa 7-36, and 30 approximate 2-residue R-[DSNE] tandem repeats spanning aa 184-243, with disordered regions at aa 30-67 and 79-258.

    UniProtKB P18615 (NELFE_HUMAN), Negative elongation factor E · UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
    What this evidence cannot show

    Record fetched 2026-09-19; primary gene name read back as NELFE and length 380 confirmed from the same fetched record, and every coordinate copied from that record. The RD repeat region overlaps an annotated disordered region, so it will not appear in structures.

    Evidence that argues against this (1)
    • That an RRM is present does not establish that NELFE binds nascent RNA in the paused complex. The cryo-EM abstract attributes RNA contact to flexible NELF 'tentacles' without naming the subunit, so the assignment made in this entry's prose is an inference from domain architecture rather than a structural observation. Vos SM et al. 2018
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    In the cryo-EM structure of the paused transcription complex Pol II-DSIF-NELF at 3.2 A, NELF binds the polymerase funnel, bridges two mobile polymerase modules, contacts the trigger loop and restrains Pol II mobility required for pause release, prevents TFIIS binding, and possesses two flexible tentacles that can contact DSIF and exiting RNA.

    Structure of paused transcription complex Pol II-DSIF-NELF · Vos SM, Farnung L, Urlaub H, Cramer P · Nature 560(7720):601-606 2018
    PMID 30135580DOI
    What this evidence cannot show

    Abstract fetched and read on 2026-09-19; full text not read. Reconstituted complex with pig Pol II and human factors, no chromatin, no leukaemia. 'Can contact' is the authors' own hedged phrasing about the tentacles.

    Evidence that argues against this (1)
    • The tentacles are described as flexible, which in a cryo-EM reconstruction generally means poorly resolved. A functional claim about NELFE-RNA contact resting on a flexible, hedged feature of one structure is thinner support than the structure's overall quality suggests. UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

    As of 2026-09-19, PubMed returns 2 records for '(MLL OR KMT2A) AND (NELFE OR RDBP OR NELF-E)', both reviews, neither reporting a NELFE-KMT2A interaction. Including the historical two-letter alias 'RD' in the same query returns 115 records, almost all spurious matches to the letters RD in unrelated contexts; that query was discarded.

    What this evidence cannot show

    The 115-record figure was not title-checked record by record; 'almost all spurious' is an inference from the magnitude of the jump and from the known behaviour of two-letter tokens in PubMed All Fields, not from reading 115 titles. The corrected count of 2 is exact.

    Evidence that argues against this (1)
  4. E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

    In the project's genome-wide KMT2A-rearranged selectivity scan of 17,728 genes, NELFE ranks 15,340 (86.530th percentile) with a difference of +0.0583 (KMT2A-rearranged mean -0.4050 against other-leukaemia mean -0.4633) and a pan-essentiality of -0.4482 across 1,208 lines - the shallowest pan-essentiality of the four NELF subunits and the least extreme selectivity score after NELFCD.

    Genome-wide KMT2A-rearranged selectivity scan, 17,728 genes (DepMap Chronos via Open Targets) · Broad Institute DepMap / Open Targets Platform; analyses/depmap-kmt2a-selective-scan-full 2026
    What this evidence cannot show

    Rows read out of analyses/depmap-kmt2a-selective-scan-full/results.json on 2026-09-19. Eleven KMT2A-rearranged against 43 other leukaemia lines, AML-heavy, none infant-derived. A difference of +0.058 on a gene with pan-essentiality -0.45 is well inside the range where nothing should be concluded.

    Evidence that argues against this (1)
    • NELFE's near-neutral score is itself the best argument against the beat's NELF anti-dependency pattern. If KMT2A-rearranged cells genuinely needed less pausing brake, the subunit least compressed by the essentiality floor - which is NELFE - is where the effect should be cleanest, and it is absent there. Vos SM et al. 2018
  5. E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    Native chromatin proteomics identified ECAS, a bipartite assembly linking an AFF4-ELL2-EAF1 elongation module to a U2 snRNP-associated intron binding complex, occupying promoter-proximal chromatin and distinct from P-TEFb-containing SEC; acute perturbation of its AQR/XAB2-dependent functions impairs productive gene-body elongation without altering pause release and increases intron retention, and Aqr perturbation impairs leukaemia initiation, maintenance and leukaemia stem cell function in MLL-rearranged leukaemia.

    A dual-module ECAS complex couples transcription elongation and RNA processing · Xiang Y, Wang H, Yin Z, Xiao R, Song Z, Lu R, Dai R, Ye J, Li C, Cui Y, Wang M, Lv J, Li Q, Wang F, Li Z, Zhang K, Zhang Y, Wu D, Fang P, Liang K · Molecular Cell, online ahead of print 16 September 2026 2026
    PMID 42748909DOI
    What this evidence cannot show

    Abstract fetched and read on 2026-09-19; full text not read. Cited here only to establish that a second RNA-engaging, promoter-proximal, MLL-relevant assembly exists. **No connection between ECAS and NELF is reported in that paper or anywhere else**, and the juxtaposition in this entry is a suggestion for an experiment, not a claim.

    Evidence that argues against this (1)
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