ICE2 — the fourth LEC subunit, the one with no assigned step, no structure, and no leukaemia literature
also called ICE2 · NARG2 · C16orf80 · Little elongation complex subunit 2 · NMDA receptor-regulated protein 2
ICE2 is the second scaffold protein of the little elongation complex, which lets RNA polymerase make the genes for spliceosome parts. Unlike its partners, nobody has assigned it a specific job, and like them it has never been studied in leukaemia.
The same thing, for a scientist
ICE2 (Q659A1, 982 aa) is a subunit of the **little elongation complex** — ELL, ICE1, ICE2 and ZC3H8 — which drives Pol II transcription of spliceosomal snRNA genes and whose integrity depends on the 7SK snRNP [E1]. Where the LEC literature assigns ICE1 to an **initiation** step and ELL to an **elongation** step [E2], **ICE2 has no assigned step**: it is present in the complex and is not the subunit either of the two mechanistic results is about. It has no PDB entry and UniProt annotates no domains at all across 982 residues, only five disordered regions [E3]. Its leukaemia literature is empty: `(ICE2 OR NARG2) AND (leukemia OR leukaemia OR MLL OR KMT2A)` returns **0 records** [E4]. DepMap gives it broad requirement and no meaningful selectivity (pan-essentiality -0.6065; difference -0.0795, rank 1,775 of 17,728) [E5].
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.
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.
What this entry contributes
Completeness, and one number. The graph carries protein-little-elongation-complex and reasons from it that ELL's pan-essentiality is about LEC rather than about the KMT2A fusion, which invalidates a target argument the project made earlier. That reasoning is only as good as the subunit-level data behind it, and before this beat two of the four subunits had no entry.
ICE2's contribution to that argument is a mild complication. Its rank of 1,775 of 17,728 (10.0th percentile) is the most KMT2A-leaning of the LEC subunits — ICE1 sits at 23.97th percentile and ELL2 at 20.85th — though at a difference of only -0.0795 it is still inside the noise 5. If the LEC story were purely general machinery, one would expect the subunits scattered around the middle rather than all four on the same side of it. That is a weak observation and is recorded as one.
Cell type, cell state, localisation, epigenetics
Every axis is not established for ICE2: no cell type in any disease relevant to this project, no cell state, no subnuclear localisation, and no epigenetic readout because ICE2 has no catalytic activity. Subcellular is nuclear by inference from complex membership. The only structured fact available is the DepMap row 5 and the UniProt record 3.
The alias NARG2 ('NMDA receptor-regulated protein 2') is a relic of the gene's discovery in a neuronal screen and is the sort of name that hides a protein from a haematology search. It was included in this beat's queries and changed nothing 4.
| uniprot | Q659A1 |
|---|---|
| gene symbol | ICE2 |
| protein name | Little elongation complex subunit 2 |
| length AA | 982 |
| alphafold ID | AF-Q659A1-F1 |
| accession resolution | UniProt REST query gene_exact:ICE2 AND organism_id:9606 AND reviewed:true, run 2026-09-19; one reviewed hit; primary gene name read back as ICE2 and length 982 confirmed from the same fetched record. |
| complex | LEC (little elongation complex): ELL, ICE1, ICE2, ZC3H8 |
| domains note | UniProt annotates no domains across 982 residues and there is no PDB entry. No domain lane is contributed rather than inventing boundaries. |
| function | subunit of the little elongation complex; no phase of snRNA transcription is assigned to it in the primary literature read here |
| classification | NOT an interactor of KMT2A::AFF1; a LEC subunit with no leukaemia literature |
| interaction evidence class | proteomics of LEC composition; Drosophila and mammalian genetics at complex level |
| shown for fusion | none |
| epigenetic readout | none - no histone-modifying activity |
PDB IDS
[]
aliases retired or alternate
[ "NARG2", "C16orf80" ]
complex partners
[ "gene-ell", "gene-ice1", "protein-little-elongation-complex" ]
domains
[]
localization
{
"subcellular": "nucleus, by inference from complex membership",
"subnuclear": "not established"
}essentiality
{
"depmap_scan": "analyses/depmap-kmt2a-selective-scan-full",
"pan_essentiality_all_lines": -0.6065,
"n_all_lines": 1208,
"mean_kmt2a_rearranged": -0.3985,
"mean_other_leukemia": -0.319,
"kmt2a_selectivity_difference": -0.0795,
"rank": 1775,
"n_scanned": 17728,
"percentile": 10.012,
"interpretation": "broadly required; the rank sounds selective and the difference is not - recorded as noise"
}enumeration record counts
[
{
"query": "(MLL OR KMT2A) AND (ICE2 OR NARG2 OR C16orf80)",
"records": 0
},
{
"query": "(ICE2 OR NARG2) AND (leukemia OR leukaemia OR MLL OR KMT2A)",
"records": 0
},
{
"date": "2026-09-19"
}
]depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": -0.3985,
"chronos_mean_other_leukaemia": -0.319,
"difference": -0.0795,
"pan_essentiality_all_lines": -0.6065,
"selectivity_rank": 1775,
"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."
}- ICE2 is broadly required with no selectivity, no structure and no annotated domain. It is not a target and nothing in this entry suggests otherwise.
- Interfering with LEC is interfering with snRNA production and therefore with splicing in every cell - a general toxicity, not a targeted one.
- The main value of this entry is to complete a complex so that complex-level reasoning is not done on a partial roster. Used any other way it would be over-read.
- What does ICE2 actually do within LEC? No phase of snRNA transcription is assigned to it, and the question appears to be genuinely open rather than merely unread.
- Does ICE2 depletion phenocopy ICE1 or ELL depletion? If LEC is to be used as the explanation for ELL's pan-essentiality, the subunits' phenotypes should be compared and they have not been.
- Is there any structure of any part of LEC? ICE2 has no PDB entry and neither does ICE1.
- Why do all four LEC-associated genes fall on the KMT2A-leaning side of the scan median? Almost certainly chance with n = 4, but it is checkable.
- 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, and depletion of 7SK snRNA or LARP7 disrupts LEC integrity and reduces nascent snRNA and snoRNA synthesis; LEC comprises ELL, ICE1, ICE2 and ZC3H8.
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 2017What 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, and the four-subunit composition statement is carried forward from this graph's existing protein-little-elongation-complex entry, which cites the same paper. No leukaemia system.
Evidence that argues against this (1)
- The four-subunit roster is stated at complex level and this paper's experiments are about 7SK and LARP7, not about ICE2 specifically. Nothing cited here demonstrates that ICE2 is required for LEC function as opposed to merely present in it, and no ICE2 depletion result appears anywhere in this entry. Hu D et al. 2013
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Genetic and molecular evidence in Drosophila and mammalian systems shows 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. No step is assigned to ICE2 in this work.
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 2013What this evidence cannot show
Abstract fetched and read on 2026-09-19; full text not read. **The statement that no step is assigned to ICE2 is an argument from absence in an abstract**, which is weak: the full text may well contain ICE2 experiments the abstract does not summarise. Drosophila salivary gland and HCT116 cells; no haematopoietic system.
Evidence that argues against this (1)
- Reading 'ICE2 is not named in the abstract' as 'ICE2 has no assigned function' is exactly the inference this beat criticised when the BCORL1 entry made it about a CRISPR screen. It is flagged here for the same reason: the claim is about what has been summarised, not about what has been tested. UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProtKB Q659A1 (ICE2_HUMAN, Little elongation complex subunit 2) is 982 aa and annotates no domains, zinc fingers, repeats or coiled coils - only five disordered regions, at aa 410-450, 473-504, 595-623, 672-697 and 930-982.
UniProtKB Q659A1 (ICE2_HUMAN), Little elongation complex subunit 2 · UniProt Knowledgebase, reviewed (Swiss-Prot) 2026What this evidence cannot show
Record fetched 2026-09-19; primary gene name read back as ICE2 and length 982 confirmed from the same fetched record. An absence of annotated domains reflects the state of curation and not an absence of structure; there is no PDB entry for ICE2 to check against.
Evidence that argues against this (1)
- Because there is no annotated domain and no structure, this entry contributes no domain lane and no structural reasoning is possible. That is a limit of the evidence, and any downstream figure or ligandability assessment that treated ICE2 as characterised would be inventing content. Hu D et al. 2013
- E4moderate 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 (ICE2 OR NARG2 OR C16orf80)' and 0 records for '(ICE2 OR NARG2) AND (leukemia OR leukaemia OR MLL OR KMT2A)'. ICE2 is unstudied in leukaemia.
PubMed E-utilities esearch record counts for ICE2 and its aliases against KMT2A, MLL and leukaemia, run for this beat · NCBI PubMed, queried 2026-09-19 2026What this evidence cannot show
Symbol set searched: ICE2, NARG2, C16orf80. Not searched: the descriptive names 'little elongation complex subunit 2' or 'NMDA receptor-regulated protein 2' as phrases. Two independent zero-returning queries are more reassuring than one, but a counted absence remains a floor.
Evidence that argues against this (1)
- ICE2 is also a gene symbol in yeast for an unrelated endoplasmic-reticulum protein, and short symbols shared across organisms are a known source of both false positives and indexing inconsistency. A zero on such a symbol is less trustworthy than a zero on a distinctive one, even though here it is corroborated by the complex-name search returning no leukaemia papers. NCBI PubMed, queried 2026-09-19 2026
- E5moderate 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, ICE2 ranks 1,775 (10.012th percentile) with a difference of -0.0795 (KMT2A-rearranged mean -0.3985 against other-leukaemia mean -0.3190) and a pan-essentiality of -0.6065 across 1,208 lines. The other LEC-associated genes in the same scan are ICE1 -0.0410 (rank 4,249, pan -0.7730), ELL -0.2533 (rank 153, pan -1.3018) and ELL2 -0.0472 (rank 3,697, pan -0.0636).
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 2026What 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 -0.08 is well inside the range where nothing should be concluded; the 10th-percentile rank sounds meaningful and is not, because ranks compress hard near the centre of the distribution.
Evidence that argues against this (1)
- The observation that all four LEC-associated genes fall on the same side of the median is exactly the kind of pattern that looks like signal and is produced routinely by chance with n = 4. It is recorded in the prose as weak and should not be cited as evidence that LEC has any KMT2A-specific role. Egloff S et al. 2017
fourth LEC subunit; no phase of snRNA transcription assigned to it in the primary literature
the two LEC scaffold subunits; ICE1 has an assigned initiation role and ICE2 does not
- related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
NOT an interactor: 0 PubMed records against MLL, KMT2A or leukaemia across three symbol spellings
co-subunits of LEC