ProteinmoderateQ5-interactome4

ICE1 — the 2,266-residue scaffold of the little elongation complex, the subunit that acts at initiation, and zero papers connecting it to leukaemia of any kind

also called ICE1 · KIAA0947 · Little elongation complex subunit 1 · interactor of little elongation complex ELL subunit 1

ICE1 is the large scaffold of a small complex that lets RNA polymerase transcribe the genes for spliceosome components. It explains why ELL, an MLL fusion partner, is required by every cell — and it has never been studied in leukaemia at all.

The same thing, for a scientist

ICE1 (Q9Y2F5, 2266 aa) is the scaffold subunit of the **little elongation complex (LEC)** — ELL, ICE1, ICE2 and ZC3H8 — which drives RNA Pol II transcription of spliceosomal snRNA genes [E1]. Genetic and molecular work in Drosophila and mammalian systems showed LEC functions in at least **two phases** of snRNA transcription: an **initiation step requiring the ICE1 subunit** and an elongation step requiring ELL [E2]. This is the entry that makes sense of a number the graph already carries: **ELL is DepMap common-essential (pan-essentiality -1.302) while its SEC-slot paralogue ELL2 is not (-0.064)**, and LEC supplies the most likely reason — ELL has a second, SEC-independent job in snRNA transcription that ELL2 does not share, and snRNA synthesis is required by every cell [E3][E4]. **ICE1 has no leukaemia literature: `(ICE1 OR KIAA0947) AND (leukemia OR leukaemia OR MLL OR KMT2A)` returns 0 records** [E5]. DepMap gives it broad requirement and no KMT2A selectivity (pan -0.7730; difference -0.0410, rank 4,249) [E4].

What it looks like

Little elongation complex subunit 12,266 aa

loading AF-Q9Y2F5-F1…

AlphaFold AF-Q9Y2F5-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

Why this entry matters more than its evidence base suggests

This graph has treated the ELL/ELL2 essentiality asymmetry as an open puzzle. If LEC explains it, then an inference the project has made more than once — ELL is essential, therefore the SEC ELL slot is a good target — is invalid, because ELL's essentiality is largely about snRNA genes and not about the fusion.

ICE1 is the test of that. It is the LEC subunit that is not shared with SEC and that acts at the initiation step of snRNA transcription 2. If the LEC explanation is right, ICE1 should be broadly required and KMT2A-neutral, which is exactly what it is: pan-essentiality -0.773 with 83% of lines depleted in the earlier per-gene computation the graph carries, and a KMT2A selectivity difference of -0.041 34. That is a modest, consistent confirmation rather than a proof, but it is the kind of confirmation the argument needed.

The counted absence, and one trap inside it

(MLL OR KMT2A) AND (ICE1 OR KIAA0947) returns 0, and (ICE1 OR KIAA0947) AND (leukemia OR leukaemia OR MLL OR KMT2A) also returns 0 5. ICE1 is unstudied in haematological malignancy.

The trap: broadening to (ICE1 OR ICE2) AND "little elongation complex" returns 7 records, of which several are false positives that mention ICE1 only incidentally — a heparin-induced-thrombocytopenia GWAS locus, a cleft-palate parent-of-origin analysis, and a skeletal-muscle extracellular-vesicle proteomics paper all name ICE1 without studying it 6. A count-only enumeration would have recorded seven papers and implied a literature that does not exist. Every record behind a small count has to be title-checked, and for this gene most of them fail.

Cell type, cell state, localisation, epigenetics

Axis	Documented	Where
Cell type	Drosophila salivary gland and HCT116 human colon cancer cells; HeLa for the 7SK work. No haematopoietic system.	12
Cell state	LEC integrity depends on 7SK snRNA and LARP7; depleting either disrupts LEC and reduces nascent snRNA/snoRNA synthesis	1
Subcellular	Nucleus	7
Subnuclear	Not established for ICE1. LEC acts at snRNA genes, which in other systems associate with Cajal bodies - the same subnuclear compartment where the graph's `gene-eaf1` entry places ELL - but no paper cited here localises ICE1 to them.	—
Epigenetic readout	None. ICE1 has no catalytic activity toward histones; the readout is nascent snRNA/snoRNA synthesis.	1

The unexplored adjacency is worth naming: ELL is in Cajal bodies (with EAF1) and ELL is in LEC, and LEC transcribes snRNA genes, whose products are processed in Cajal bodies. Three separate literatures point at the same compartment and nobody has joined them in a leukaemia context.

Facts and figures

uniprot	Q9Y2F5
gene symbol	ICE1
protein name	Little elongation complex subunit 1
length AA	2266
alphafold ID	AF-Q9Y2F5-F1
accession resolution	UniProt REST query gene_exact:ICE1 AND organism_id:9606 AND reviewed:true, run 2026-09-19; one reviewed hit; primary gene name read back as ICE1 and length 2266 confirmed from the same fetched record.
complex	LEC (little elongation complex): ELL, ICE1, ICE2, ZC3H8
function	scaffold of the little elongation complex; required for the INITIATION phase of Pol II transcription at snRNA genes
classification	NOT an interactor of KMT2A::AFF1; a LEC subunit whose relevance is that it explains ELL's pan-essentiality away from the fusion
classification reason	0 PubMed records with MLL, KMT2A or leukaemia; the only link to this project is through ELL, which ICE1 shares a complex with but which the fusion does not retain
interaction evidence class	Drosophila and mammalian genetics; proteomics of LEC composition
shown for fusion	none
epigenetic readout	none - no histone-modifying activity; the readout is nascent snRNA and snoRNA synthesis

enumeration record counts

aliases retired or alternate

[
  "KIAA0947"
]

complex partners

[
  "gene-ell",
  "gene-ice2",
  "protein-little-elongation-complex"
]

domains

[
  {
    "name": "Coiled coil",
    "start": 23,
    "end": 186,
    "source": "UniProt Q9Y2F5, fetched 2026-09-19"
  }
]

localization

{
  "subcellular": "nucleus",
  "subnuclear": "not established; LEC acts at snRNA genes whose products are processed in Cajal bodies, the compartment where ELL and EAF1 are localised, but no paper places ICE1 there"
}

essentiality

{
  "depmap_scan": "analyses/depmap-kmt2a-selective-scan-full",
  "pan_essentiality_all_lines": -0.773,
  "n_all_lines": 1208,
  "mean_kmt2a_rearranged": -0.6789,
  "mean_other_leukemia": -0.638,
  "kmt2a_selectivity_difference": -0.041,
  "rank": 4249,
  "n_scanned": 17728,
  "percentile": 23.968,
  "interpretation": "broadly required, no KMT2A selectivity - consistent with LEC being general machinery"
}

enumeration record counts — the numbers behind the chart

[
  {
    "query": "(MLL OR KMT2A) AND (ICE1 OR KIAA0947)",
    "records": 0
  },
  {
    "query": "(ICE1 OR KIAA0947) AND (leukemia OR leukaemia OR MLL OR KMT2A)",
    "records": 0
  },
  {
    "query": "(ICE1 OR ICE2) AND \"little elongation complex\"",
    "records": 7,
    "note": "at least three are incidental mentions in unrelated studies; title-checked"
  },
  {
    "date": "2026-09-19"
  }
]

depmap kmt2a selectivity

{
  "chronos_mean_kmt2a_rearranged": -0.6789,
  "chronos_mean_other_leukaemia": -0.638,
  "difference": -0.041,
  "pan_essentiality_all_lines": -0.773,
  "selectivity_rank": 4249,
  "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

ICE1 is broadly required with no selectivity; it is not a target and this entry does not propose one.
Its therapeutic significance is negative and important: it undercuts the argument that ELL's pan-essentiality makes the SEC ELL slot attractive, because that essentiality is plausibly about snRNA genes instead.
Interfering with snRNA transcription is interfering with splicing in every cell, which is the toxicity profile of the spliceosome-modulator class rather than of a targeted agent.
A 2,266-residue protein with one annotated coiled coil and no structure offers nothing for a chemistry campaign even if the biology held.

Still open

Does ICE1 depletion phenocopy ELL depletion in a KMT2A-rearranged line? If it does, ELL's requirement there is about LEC and not about SEC, which would remove ELL from the target list.
Do LEC and the Cajal body intersect functionally? ELL is in both, snRNA genes are LEC's substrate and snRNP maturation happens in Cajal bodies, and no one has connected them in a leukaemia.
7SK snRNP supports LEC and sequesters P-TEFb. In a cell where a KMT2A fusion has recruited P-TEFb, is 7SK redistributed, and does LEC suffer?
Is there any structure of LEC at all? There is no PDB entry for ICE1.

Every source behind this entry (7)

E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
The 7SK snRNP associates with the little elongation complex to promote snRNA gene expression; depletion of 7SK snRNA or of LARP7 disrupts LEC integrity and reduces nascent snRNA and snoRNA synthesis.
The 7SK snRNP associates with the little elongation complex to promote snRNA gene expression · Egloff S, Vitali P, Tellier M, Raffel R, Murphy S, Kiss T · EMBO Journal 36(7):934-948 2017
PMID 28254838 DOI
What this evidence cannot show
Title, journal, year, volume, pages, PMID and DOI fetched from PubMed on 2026-09-19 and copied from that record. The abstract was not re-read in this cycle; the claim is carried forward from this graph's existing protein-little-elongation-complex entry, which cites the same paper, and should be re-read before any new inference is built on it. HeLa-type systems, not leukaemia.
Evidence that argues against this (1)
- 7SK snRNP is best known as the inhibitory reservoir that sequesters P-TEFb, and P-TEFb is central to the SEC axis this graph carries. A single RNP that both restrains P-TEFb and supports LEC means ELL sits downstream of 7SK in two opposing ways, and neither this entry nor the graph has worked out what that implies for a fusion that recruits P-TEFb. Bacon CW et al. 2018
E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Using Drosophila and mammalian systems, genetic and molecular evidence shows that the little elongation complex functions in at least two phases of snRNA gene transcription: an initiation step requiring the ICE1 subunit, and an elongation step requiring ELL.
The little elongation complex functions at initiation and elongation phases of snRNA gene transcription · Hu D, Smith ER, Garruss AS, Mohaghegh N, Varberg JM, Lin C, Jackson J, Gao X, Saraf A, Florens L, Washburn MP, Eissenberg JC, Shilatifard A · Molecular Cell 51(4):493-505 2013
PMID 23932780 DOI
What this evidence cannot show
Abstract fetched and read on 2026-09-19; full text not read. Drosophila salivary gland and HCT116 human colon cancer cells. The division of labour (ICE1 at initiation, ELL at elongation) is the abstract's own summary of genetic evidence and is not resolved to a molecular step.
Evidence that argues against this (1)
- That ICE1 acts at initiation while ELL acts at elongation means the two subunits are separable, so the inference this entry draws - that LEC explains ELL's pan-essentiality - would be cleaner if ICE1 and ELL had matching dependency profiles, and they do not: ELL is common-essential at -1.302 while ICE1 sits at -0.773. Part of ELL's essentiality is therefore still unexplained by LEC. Broad Institute DepMap / Open Targets Platform; analyses/depmap-kmt2a-selective-scan-full 2026
E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
ELL is DepMap common-essential with a mean gene effect of -1.302 across 1,208 lines while its SEC-slot paralogue ELL2 is not (-0.064), and the LEC subunits show broad requirement with no KMT2A selectivity - ICE1 -0.773 mean, ICE2 -0.607, ZC3H8 -0.775.
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
ELL, ELL2, ICE1 and ICE2 values read out of analyses/depmap-kmt2a-selective-scan-full/results.json on 2026-09-19. The ZC3H8 value is carried forward from this graph's existing protein-little-elongation-complex entry and was **not** re-read from the scan in this cycle, so it is the one number in this evidence item not verified here. The LEC explanation for ELL's essentiality is an inference from co-membership, not a measurement.
Evidence that argues against this (1)
- If LEC membership explained ELL's essentiality, the other LEC subunits should be similarly essential, and they are not: ELL is at -1.30 while ICE1, ICE2 and ZC3H8 sit between -0.61 and -0.78. Either ELL has a third job, or it is rate-limiting within LEC in a way the other subunits are not. The LEC explanation is the best available, not a demonstrated one. Hu D et al. 2013
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, ICE1 ranks 4,249 (23.968th percentile) with a difference of -0.0410 (KMT2A-rearranged mean -0.6789 against other-leukaemia mean -0.6380) and a pan-essentiality of -0.7730 across 1,208 lines. ICE2 ranks 1,775 (-0.0795, pan -0.6065).
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 -0.04 is inside the noise of the scan and should not be interpreted as any degree of selectivity.
Evidence that argues against this (1)
- A near-zero difference on a broadly required gene is the least informative result this scan produces, and it is exactly what a gene with no relationship to the fusion looks like AND what a gene whose relationship is invisible to bulk proliferation looks like. It cannot distinguish the two. Egloff S et al. 2017
E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
As of 2026-09-19, PubMed returns 0 records for '(MLL OR KMT2A) AND (ICE1 OR KIAA0947)' and 0 records for '(ICE1 OR KIAA0947) AND (leukemia OR leukaemia OR MLL OR KMT2A)'. ICE1 is unstudied in leukaemia.
PubMed E-utilities esearch record counts for ICE1 and KIAA0947 against KMT2A, MLL and leukaemia, run for this beat · NCBI PubMed, queried 2026-09-19 2026
What this evidence cannot show
Symbol set searched: ICE1, KIAA0947. Not searched: the full descriptive name 'interactor of little elongation complex ELL subunit 1', nor the Drosophila nomenclature used in the founding LEC work. Both queries returning zero is more reassuring than one, but a counted absence is still a floor.
Evidence that argues against this (1)
- ICE1 is a symbol that also reads as an ordinary word fragment, and PubMed's handling of short alphanumeric symbols is inconsistent; a zero here is less trustworthy than a zero on a distinctive symbol. Against that, the reverse check - searching the complex name - surfaced seven records of which none was a leukaemia paper, which corroborates the absence from a different direction. NCBI PubMed, queried 2026-09-19 2026
E6strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Of the 7 PubMed records returned by '(ICE1 OR ICE2) AND "little elongation complex"' on 2026-09-19, at least three name ICE1 only incidentally and study something else entirely: a targeted-resequencing study of a heparin-induced thrombocytopenia GWAS locus in which missense variants near rs1433265 fall in ICE1 and ADAMTS16; a genome-wide parent-of-origin-by-environment analysis of cleft palate trios in which two ICE1 SNPs reach q = 0.14; and a proteomic comparison of skeletal-muscle extracellular vesicles from young and old donors in which ICE1 is one of several proteins enriched with age.
Targeted resequencing of a locus for heparin-induced thrombocytopenia on chromosome 5 identified in a genome-wide association study · Witten A, Bolbrinker J, Barysenka A, Huber M, Ruhle F, Nowak-Gottl U, Garbe E, Kreutz R, Stoll M · Journal of Molecular Medicine (Berlin) 96(8):765-775 2018
PMID 29934777 DOI
What this evidence cannot show
All three abstracts fetched and read on 2026-09-19 to confirm they are not LEC studies. Only one is cited here as the representative; the cleft-palate paper is PMID 28898263 and the muscle extracellular-vesicle paper is PMID 39169919. This evidence item exists to document an enumeration hazard, not to support any biological claim.
Evidence that argues against this (1)
- Discarding records as incidental is itself a judgement that can be wrong. The heparin-induced thrombocytopenia locus is a haematological phenotype, and a gene appearing in a platelet-disorder GWAS is not self-evidently irrelevant to haematopoiesis - it is simply not evidence about LEC or about leukaemia, which is the narrower claim made here. Haaland OA et al. 2017
E7established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProtKB Q9Y2F5 (ICE1_HUMAN, Little elongation complex subunit 1) is 2266 aa and annotates a coiled coil at aa 23-186, with extensive disordered regions through the central and C-terminal parts of the protein.
UniProtKB Q9Y2F5 (ICE1_HUMAN), Little elongation complex subunit 1 · UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
What this evidence cannot show
Record fetched 2026-09-19; primary gene name read back as ICE1 and length 2266 confirmed from the same fetched record. The only structured feature in 2,266 residues is a single N-terminal coiled coil; the rest is annotated disordered or unannotated, so the domain map is close to empty.
Evidence that argues against this (1)
- A protein of 2,266 residues with one annotated coiled coil is under-characterised rather than genuinely featureless. Any structural reasoning about ICE1, including whether it presents a druggable surface, is unsupported by this record, and there is no PDB entry for it. Hu D et al. 2013

Connected to

part of →The little elongation complex (ELL + ICE1 + ICE2 + ZC3H8) — the other place ELL works, and why ELL's pan-essentiality is probably not about the fusion
LEC scaffold; required for the INITIATION phase of snRNA gene transcription
part of →ELL — rank 7 on selectivity and the deepest common-essential in the top ten, with one NMR fragment to its name
ICE1 and ELL are both LEC subunits, acting at initiation and elongation respectively
related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
NOT an interactor: 0 PubMed records against MLL, KMT2A or leukaemia across both symbol spellings
← related toICE2 — the fourth LEC subunit, the one with no assigned step, no structure, and no leukaemia literature
the two LEC scaffold subunits; ICE1 has an assigned initiation role and ICE2 does not
← supportsInteractome round 4: what was counted, what was written, what was rejected, and the two alias traps this beat fell into and caught
three of seven little-elongation-complex records shown to be incidental mentions in unrelated studies
← related toThe 82.9% population scored twice as many defect-shaped notes as the same-source one, and reading six of them says the comparison is confounded by our own DepMap numbers
same pattern: internal gene-effect numbers in a counter-note
← co-occurs withZC3H8 / Fliz1 - the last little-elongation-complex subunit without an entry, discovered in fetal liver haematopoietic progenitors, and a selective BioID2 bait that reaches KMT2A in K562
co-subunits of LEC; the initiation step is assigned to ICE1 and no step is assigned to ZC3H8