BCORL1 — the BCOR paralogue that is in the only crystal structure of the PRC1.1 core, and is the one PRC1.1 subunit nobody has tested in KMT2A-rearranged leukaemia
also called BCORL1 · CXXC10 · BCL-6 corepressor-like protein 1 · BCoR-L1
BCORL1 is a near-twin of BCOR, and one of the two interchangeable arms that hold the PRC1.1 gene-silencing machine together. It is the version that appears in the only solved picture of that machine's core, yet no one has ever asked what it does in a KMT2A-rearranged leukaemia.
The same thing, for a scientist
BCORL1 (Q5H9F3, 1785 aa) is the paralogue of BCOR and an alternative PRC1.1 corepressor arm [E1]. It carries the structure of the beat: the **only crystal structure of the assembled PRC1.1 core, PDB 5JH5 at 2.55 A, is KDM2B/SKP1/BCORL1/PCGF1** — not BCOR [E2][E3]. In that structure the **BCORL1 PUFD domain (modelled aa 1668-1785)** positions residues immediately preceding the PCGF1 RAWUL domain (modelled aa 150-255) so that the two together create an extended interface for KDM2B (modelled aa 1059-1336) that is **unique to PCGF1-containing PRC1.1** [E2][E3]. The same work notes that KDM2B might simultaneously function in PRC1.1 and in an SCF ubiquitin ligase, which is why SKP1 is present at all [E2]. Functionally BCORL1 is where the beat runs out of evidence: **no published experiment tests BCORL1 in a KMT2A-rearranged model**, the KMT2A-resistance work names PCGF1 and BCOR and not BCORL1 [E4], and DepMap gives BCORL1 a difference of **+0.061** with a positive pan-essentiality of +0.077, i.e. effectively dispensable everywhere [E5]. It is nonetheless recurrently mutated in myeloid malignancy [E6].
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.
Why the structure matters more than it looks
Wong et al. reconstituted a minimal four-component PRC1.1 in vitro by combining two separately isolated subcomplexes — a DNA-binding KDM2B/SKP1 heterodimer and a BCORL1/PCGF1 heterodimer — and then solved the crystal structure of all four together 2. That establishes three things the graph previously asserted only by analogy:
- PRC1.1 targeting is hierarchical, not a single bipartite contact. BCORL1 PUFD does not merely bind PCGF1; it re-orders the residues N-terminal to PCGF1's RAWUL so a composite KDM2B-binding surface exists that neither protein has alone.
- The composite surface is specific to PCGF1. This is the structural reason PRC1.1 is a distinct complex from BMI1-PRC1, consistent with the PUFD binding-preference result 1.
- SKP1 is a bona fide structural member, not a contaminant of the purification, and its presence is a hint that KDM2B is shared with an SCF ligase 2.
A later study by the same group showed the BCOR PUFD behaves differently: BCOR PUFD alone does not stably assemble with KDM2B and needs additional N-terminal residues, and NMR shows the BCOR PUFD termini are disordered until PCGF1 binds 7. So BCOR and BCORL1 are not freely interchangeable, and a PRC1.1 built on BCORL1 may assemble by a different route from one built on BCOR. This project's PRC1.1 reasoning has so far treated them as interchangeable; on this evidence that is an approximation.
The gap this entry exists to record
The beat's enumeration searched (MLL OR KMT2A) AND (BCORL1 OR CXXC10) and got 7 records, none of which is a functional test of BCORL1 in a KMT2A-rearranged model 8. The menin-resistance work that this project's PRC1.1 reasoning rests on names PCGF1 and BCOR and does not report BCORL1 4.
That is a real, cheap experiment sitting open: if PRC1.1 loss is the resistance mechanism, and BCORL1 can substitute for BCOR in the complex, then BCORL1 status should modify the phenotype of BCOR loss. A BCOR-null KMT2A-rearranged line that retains BCORL1 is not PRC1.1-null. Nobody has checked, and the resistance claim is weaker than it appears until someone does.
Cell type, cell state, localisation and epigenetic readout
| Axis | Documented | Where |
|---|---|---|
| Cell type | Not established in any KMT2A-rearranged system. Mutations reported in adult AML and other myeloid malignancy. | 68 |
| Cell state | Not established. | — |
| Subcellular | Nuclear by inference from complex membership; no direct imaging cited here. | 1 |
| Subnuclear | Not established. | — |
| Epigenetic readout | Indirect: BCORL1 carries no catalytic activity; the mark is H2AK119ub deposited by RING1A/B within the same complex. | 1 |
| Structural localisation within the complex | Modelled aa 1668-1785 (PUFD), contacting PCGF1 RAWUL and forming a composite KDM2B interface | 3 |
This row of blanks is the point of the entry. Stating them explicitly is more useful than filling them by analogy with BCOR.
| uniprot | Q5H9F3 |
|---|---|
| gene symbol | BCORL1 |
| protein name | BCL-6 corepressor-like protein 1 |
| length AA | 1785 |
| alphafold ID | AF-Q5H9F3-F1 |
| accession resolution | UniProt REST query gene_exact:BCORL1 AND organism_id:9606 AND reviewed:true, run 2026-09-19; one reviewed hit; primary gene name read back as BCORL1 and length 1785 confirmed from the same fetched record. The same length is independently consistent with the RCSB alignment, which models BCORL1 residues 1668-1785 in 5JH5. |
| complex | PRC1.1 (non-canonical PRC1), as the alternative corepressor arm to BCOR |
| paralogue | BCOR - not freely interchangeable; the two PUFD domains differ in KDM2B assembly behaviour (PMID 32628469) |
| classification | structural PRC1.1 subunit; NOT a demonstrated interactor of KMT2A::AFF1, and untested in any KMT2A-rearranged model |
| classification reason | no co-IP, proximity or genetic result links BCORL1 to a KMT2A fusion; membership in PRC1.1 is established structurally |
| interaction evidence class | in-vitro reconstitution; X-ray crystallography (5JH5); NMR (PMID 32628469) |
| shown for fusion | none |
| epigenetic readout | none of its own; H2AK119ub is deposited by RING1A/B in the same complex |
PDB IDS
[ "5JH5" ]
aliases retired or alternate
[ "CXXC10", "BCoR-L1" ]
complex partners
[ "gene-pcgf1", "gene-kdm2b", "gene-skp1", "gene-rnf2" ]
domains — the numbers behind the chart
[
{
"name": "PUFD (PCGF Ub-like fold discriminator)",
"start": 1668,
"end": 1785,
"source": "UniProt Q5H9F3 fetched 2026-09-19; identical to the modelled range in PDB 5JH5 entity 4"
},
{
"name": "ANK 1 (ankyrin repeat)",
"start": 1529,
"end": 1558,
"source": "UniProt Q5H9F3, fetched 2026-09-19"
},
{
"name": "ANK 2 (ankyrin repeat)",
"start": 1562,
"end": 1591,
"source": "UniProt Q5H9F3, fetched 2026-09-19"
},
{
"name": "ANK 3 (ankyrin repeat)",
"start": 1595,
"end": 1623,
"source": "UniProt Q5H9F3, fetched 2026-09-19"
}
]localization
{
"subcellular": "nucleus, inferred from complex membership; not directly imaged in any cited work",
"subnuclear": "not established",
"chromatin_targeting": "indirect, via the KDM2B ZF-CxxC domain within PRC1.1"
}essentiality
{
"depmap_scan": "analyses/depmap-kmt2a-selective-scan-full",
"pan_essentiality_all_lines": 0.0771,
"n_all_lines": 1208,
"mean_kmt2a_rearranged": 0.1031,
"mean_other_leukemia": 0.0422,
"kmt2a_selectivity_difference": 0.0609,
"rank": 15515,
"n_scanned": 17728,
"percentile": 87.517,
"interpretation": "dispensable in bulk culture; paralogue-buffered by BCOR, which also scores positive"
}enumeration record count
{
"query": "(MLL OR KMT2A) AND (BCORL1 OR CXXC10)",
"records": 7,
"date": "2026-09-19",
"functional_tests_in_kmt2a_models": 0
}depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": 0.1031,
"chronos_mean_other_leukaemia": 0.0422,
"difference": 0.0609,
"pan_essentiality_all_lines": 0.0771,
"selectivity_rank": 15515,
"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."
}- If BCORL1 buffers BCOR, then a therapeutic strategy aimed at restoring PRC1.1 function - or any biomarker that reads BCOR status alone - would misclassify patients.
- The PUFD-RAWUL interface is a plausible small-molecule target, but disrupting it would phenocopy the PRC1.1 loss that confers menin-inhibitor resistance, so it points in the wrong therapeutic direction.
- BCORL1 is X-linked; any loss-of-function phenotype will differ between male and female patients, and the infant ALL population is not large enough to power that stratification.
- This entry has more blanks than data. Acting on it as if it were a characterised node would be the mistake it exists to prevent.
- Does BCORL1 substitute for BCOR in KMT2A-rearranged cells? If it does, then BCOR-null lines used to model menin-inhibitor resistance are not PRC1.1-null, and the published resistance phenotype is a partial loss of function rather than a clean one.
- Is a BCOR/BCORL1 double knockout more resistant to menin inhibition than BCOR single knockout? That single experiment would either strengthen or dismantle the PRC1.1 resistance model.
- Are BCORL1 mutations present in KMT2A-rearranged infant ALL at all? The mutation literature is adult myeloid.
- Does the 5JH5 composite KDM2B interface survive with BCOR in place of BCORL1, and if not, do BCOR-PRC1.1 and BCORL1-PRC1.1 occupy different genes?
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
A protein interaction domain in BCOR named PUFD binds the RAWUL domain of PCGF1 and PCGF3 but not PCGF2 (MEL18) or PCGF4 (BMI1), and the crystal structure of BCOR PUFD bound to PCGF1 shows that the ability to discriminate among RAWUL domains stems from the identity of specific residues within the interaction surfaces.
Structure of the polycomb group protein PCGF1 in complex with BCOR reveals basis for binding selectivity of PCGF homologs · Junco SE, Wang R, Gaipa JC, Taylor AB, Schirf V, Gearhart MD, Bardwell VJ, Demeler B, Hart PJ, Kim CA · Structure 21(4):665-71 2013What this evidence cannot show
Abstract fetched and read on 2026-09-19. This structure is of the **BCOR** PUFD, not BCORL1; BCORL1's equivalent behaviour is asserted by homology and by the later four-component structure, not by this paper.
Evidence that argues against this (1)
- The paralogues are not equivalent in assembly behaviour. BCOR PUFD alone does not stably assemble with KDM2B and requires additional N-terminal residues, whereas the four-component reconstitution used BCORL1 PUFD directly. Treating a BCOR result as a BCORL1 result, or vice versa, is not safe. Wong SJ et al. 2020
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
A minimal four-component PRC1.1 can be assembled in vitro by combining a DNA-binding KDM2B/SKP1 heterodimer with a BCORL1/PCGF1 heterodimer; the crystal structure of the KDM2B/SKP1/BCORL1/PCGF1 complex shows the BCORL1 PUFD domain positioning residues preceding the PCGF1 RAWUL domain to create an extended interface for interaction with KDM2B that is unique to the PCGF1-containing PRC1.1 complex, and suggests how KDM2B might simultaneously function in PRC1.1 and in an SCF ubiquitin ligase complex.
KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1 · Wong SJ, Gearhart MD, Taylor AB, Nanyes DR, Ha DJ, Robinson AK, Artigas JA, Lee OJ, Demeler B, Hart PJ, Bardwell VJ, Kim CA · Structure 24(10):1795-1801 2016What this evidence cannot show
Abstract fetched and read on 2026-09-19; full text not read. In-vitro assembly of truncated constructs and a crystal structure; no cellular validation in this paper, and no leukaemia system. The complex lacks RING1A/B, so it is the targeting module and not a catalytically competent PRC1.1.
Evidence that argues against this (1)
- Recruitment in cells is not governed only by this interface. A 2024 study reports that the tethering of the BCOR-PRC1.1 enzymatic core to KDM2B is calcium-modulated and involves liquid-liquid phase separation, a regime a static crystal structure of truncated constructs cannot represent. Chen R et al. 2024
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
RCSB PDB entry 5JH5, 'Structural Basis for the Hierarchical Assembly of the Core of PRC1.1', X-ray diffraction at 2.55 A, contains four polymer entities mapping to UniProt Q8NHM5 (KDM2B, modelled 1059-1336), P63208 (SKP1, modelled 2-163), Q9BSM1 (PCGF1, modelled 150-255) and Q5H9F3 (BCORL1, modelled 1668-1785); the primary citation is PMID 27568929, DOI 10.1016/j.str.2016.07.011.
RCSB PDB entry 5JH5 - Structural Basis for the Hierarchical Assembly of the Core of PRC1.1 · RCSB Protein Data Bank; entry and polymer-entity alignment records queried via data.rcsb.org 2016What this evidence cannot show
Entry, entity descriptions, UniProt accessions and per-entity modelled reference ranges were all fetched from data.rcsb.org on 2026-09-19 and copied out of the same fetched records; none was typed from recall. Modelled ranges are the aligned regions reported by RCSB and are shorter than the crystallised constructs. Crystal contacts and truncation can distort interface geometry.
Evidence that argues against this (1)
- There is no structure of PRC1.1 containing RING1A/B, a nucleosome, or full-length BCORL1, so the 'core of PRC1.1' in this entry is the targeting module only. Any inference about how the complex sits on chromatin, or about how BCOR internal tandem duplications disrupt it in tumours, is modelling beyond what 5JH5 shows. Wong SJ et al. 2020
- E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
The KMT2A-rearranged AML menin-inhibitor resistance work names loss of the PRC1.1 subunits PCGF1 and BCOR as the resistance-conferring events; BCORL1 is not reported among them.
Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia · Zhou X, Zhang L, Aryal S, Veasey V, Tajik A, Restelli C, Moreira S, Zhang P, Zhang Y, Hope KJ, Zhou Y, Cheng C, Bhatia R, Lu R · Blood 144(19):2018-2032 2024What this evidence cannot show
Abstract fetched and read on 2026-09-19; full text not read. **This is an argument from silence in an abstract**, which is the weakest kind of negative evidence. BCORL1 may well appear in the full screen data without reaching the abstract, and this entry's claim is only that BCORL1 is not among the named subunits, not that the screen tested and excluded it.
Evidence that argues against this (1)
- The absence may be methodological rather than biological. BCORL1 is X-linked and large, and chromatin-focused CRISPR libraries vary in paralogue coverage; a gene that is poorly represented or that is buffered by its paralogue will not emerge from a screen even if it is functionally relevant. Reading 'not named' as 'not involved' would be an error. Wong SJ et al. 2016
- 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, BCORL1 ranks 15,515 (87.517th percentile) with a difference of +0.0609 (KMT2A-rearranged mean +0.1031 against other-leukaemia mean +0.0422) and a pan-essentiality of +0.0771 across 1,208 lines - i.e. positive everywhere, dispensable in bulk culture.
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
Numbers read out of analyses/depmap-kmt2a-selective-scan-full/results.json on 2026-09-19. A positive gene effect in a paralogue pair is exactly what buffering looks like; BCOR scores +0.1019 in the same scan, so neither single knockout is informative about PRC1.1 function and a double knockout has not been run.
Evidence that argues against this (1)
- BCORL1 is recurrently somatically mutated in adult AML, which is hard to reconcile with a gene that is dispensable in every cell line tested. Either the mutations are passengers, or the relevant phenotype is one bulk proliferation does not measure - and the same ambiguity applies to BCOR. Tiacci E et al. 2012
- E6moderate confidence 3 of 5: One strong study, or several smaller consistent ones.review
BCOR and BCORL1 are recognised as recurrently somatically mutated transcriptional corepressors in acute myeloid leukaemia.
The corepressors BCOR and BCORL1: two novel players in acute myeloid leukemia · Tiacci E, Grossmann V, Martelli MP, Kohlmann A, Haferlach T, Falini B · Haematologica 97(1):3-5 2012What this evidence cannot show
**This is an editorial and PubMed carries no abstract for it**, so the claim above is taken from the title and MeSH terms (Leukemia Myeloid Acute; Mutation; Co-Repressor Proteins) rather than from read content. No mutation frequency, cohort size or KMT2A-rearrangement breakdown is asserted here because none was read. A primary cohort paper should replace this citation when the beat next touches BCORL1.
Evidence that argues against this (1)
- Recurrent mutation in adult AML says nothing about infant KMT2A::AFF1 B-ALL, which is this project's disease and which has among the quietest genomes in paediatric oncology. A corepressor that is a co-mutation in adult myeloid disease may simply be absent from the infant disease entirely. Broad Institute DepMap / Open Targets Platform; analyses/depmap-kmt2a-selective-scan-full 2026
- E7strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
The PUFD domains of BCOR and BCORL1 differ in their ability to assemble with KDM2B: BCORL1 PUFD suffices, whereas BCOR PUFD alone does not stably assemble with KDM2B and requires additional N-terminal residues; NMR structure determination and 15N relaxation measurements show the termini of the BCOR PUFD, which are critical for binding PCGF1 and KDM2B, are disordered, implying hierarchical assembly in which BCOR PUFD termini become ordered on PCGF1 binding. Internal tandem duplications causing paediatric kidney and brain tumours map to the PUFD termini and are predicted to disrupt PRC1.1 assembly.
Structure and Role of BCOR PUFD in Noncanonical PRC1 Assembly and Disease · Wong SJ, Senkovich O, Artigas JA, Gearhart MD, Ilangovan U, Graham DW, Abel KN, Yu T, Hinck AP, Bardwell VJ, Kim CA · Biochemistry 59(29):2718-2728 2020What this evidence cannot show
Abstract fetched and read on 2026-09-19; full text not read. Purified domains and NMR; the ITD consequence is a binding-study inference, not a cellular or tumour measurement. The tumours in question are paediatric kidney and brain tumours, not leukaemia.
Evidence that argues against this (1)
- The asymmetry could be an artefact of construct design rather than biology: 'BCOR PUFD alone' and 'BCORL1 PUFD' are different boundary choices made by the same group at different times, and the conclusion that the paralogues assemble differently rests on comparing across those constructs rather than on a side-by-side titration reported in one figure. Wong SJ et al. 2016
- E8moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
PubMed returns 7 records for '(MLL OR KMT2A) AND (BCORL1 OR CXXC10)' as of 2026-09-19, and none of them is a functional test of BCORL1 in a KMT2A-rearranged leukaemia model.
PubMed E-utilities esearch record count for (MLL OR KMT2A) AND (BCORL1 OR CXXC10), run for this beat · NCBI PubMed, queried 2026-09-19 2026What this evidence cannot show
A counted-absence claim is only as good as its symbol set. Searched here: BCORL1 and the alias CXXC10. **BCoR-L1 with internal punctuation is not covered by this query**, and PubMed's own term mapping expands BCORL1 to the supplementary-concept record, which may or may not catch older spellings. The 'none is a functional test' half of the claim rests on reading titles and abstracts, not full texts.
Evidence that argues against this (1)
- This project has already been burned once by a counted-absence claim run on current symbols: for the septin partners, retired symbols returned ten to twenty times more records than current ones. Seven records for BCORL1 should therefore be read as a floor, not a measurement, and a reviewer who finds a functional BCORL1 paper under another spelling would be right and this entry wrong. NCBI PubMed, queried 2026-09-19; finding originally made by this project's non-elongation-partners beat, cycle 40 2026
alternative corepressor arm; PUFD aa 1668-1785 modelled in PDB 5JH5
BCORL1 PUFD binds PCGF1 RAWUL and orders the residues preceding it into a composite KDM2B interface
composite BCORL1-PCGF1 surface contacts KDM2B; unique to PCGF1-containing PRC1.1
- related to →BCOR — the other side of the CBX8 conflict, and a target you would be inhibiting in the direction of disease
paralogues that are NOT interchangeable: BCORL1 PUFD assembles with KDM2B alone, BCOR PUFD does not
- related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
NOT an interactor and entirely untested: 7 PubMed records for (MLL OR KMT2A) AND (BCORL1 OR CXXC10), none a functional test