GPKOW - a G-patch spliceosomal protein whose BioID neighbourhood contains AFF4, ELL, ENL, CDK9, KMT2A and DOT1L
also called T54 · MOS2 homolog · G-patch domain and KOW motifs
GPKOW helps the spliceosome work. Tagging it inside a leukaemia cell put AFF4, ELL, ENL, CDK9, KMT2A and DOT1L in its list of neighbours.
The same thing, for a scientist
GPKOW (Q92917, 476 aa) is one of the fifty RNA-binding proteins used as a BioID2 bait in K562. Its curated neighbourhood contains **748 preys**, among them **AFF4**, **ELL**, **MLLT1**, **CDK9**, **KMT2A**, **DOT1L**, **KAT7**, **ICE1** and 16 others [E1]. Nothing here is a binding claim: proximity labelling reports that two proteins came within roughly 10 nm during a multi-hour labelling window, recovery is abundance-weighted, and the pairs are spoke-expanded from a bait-centric pulldown [E2]. GPKOW is one of the four baits that reach **AFF4** and is the bait with the widest reach into the ELL/ENL/CDK9 side of the elongation machinery. It does **not** reach AFF1. Together with ZRANB2 and PPIL4 it makes the AFF4 neighbourhood a spliceosome-facing one, which is the cleanest pattern in this beat.
What this bait reaches in this graph's subject matter
GPKOW is one of the four baits that reach AFF4 and is the bait with the widest reach into the ELL/ENL/CDK9 side of the elongation machinery. It does not reach AFF1. Together with ZRANB2 and PPIL4 it makes the AFF4 neighbourhood a spliceosome-facing one, which is the cleanest pattern in this beat.
Full list of recovered proteins that have entries or canonical ids in this graph: AFF4, ELL, MLLT1, CDK9, KMT2A, DOT1L, KAT7, ICE1, PAF1, NELFE, ELOA, CDC73, RTF1, KMT2D, SETD1A, HCFC1, SIRT1, HDAC1, CHD8, ARID1A, RUNX1, IGF2BP2, IGF2BP3, HNRNPA2B1 1.
Why the deflating reading is the default
A bait with 748 preys recovers roughly a quarter of the dataset's entire prey space. Co-occurrence inside a list that long is weak evidence about any individual pair, and the compartment effect - splicing is co-transcriptional, so a spliceosomal bait sits where the elongation machinery is - explains the pattern without any direct contact 2.
This entry exists so the observation is on record with its limits attached, not because a target has been found.
Retained region
Retained region: not determinable from this data. The SEC proteins here were preys, never baits, so what was labelled is the endogenous full-length wild-type protein. Biotinylation happens at accessible lysines anywhere on the prey and no site-level biotinylation was reported, so nothing distinguishes a contact with the AFF1 N-terminus that KMT2A::AFF1 discards from one with the C-terminal half it keeps.
| uniprot | Q92917 |
|---|---|
| gene symbol | GPKOW |
| length AA | 476 |
| uniprot resolution note | Accession taken from the IntAct MITAB bait column; primary gene name and sequence length read back from the UniProt REST API on 2026-09-19 as GPKOW, 476 aa. |
| role | BioID2 bait |
| n preys total | 748 |
| method | BioID2 in K562 (PSI-MI MI:1314), spoke-expanded |
proximity preys of interest
[ "AFF4", "ELL", "MLLT1", "CDK9", "KMT2A", "DOT1L", "KAT7", "ICE1", "PAF1", "NELFE", "ELOA", "CDC73", "RTF1", "KMT2D", "SETD1A", "HCFC1", "SIRT1", "HDAC1", "CHD8", "ARID1A", "RUNX1", "IGF2BP2", "IGF2BP3", "HNRNPA2B1" ]
depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": -1.3014,
"chronos_mean_other_leukaemia": -1.0668,
"difference": -0.2346,
"pan_essentiality_all_lines": -1.0911,
"selectivity_rank": 177,
"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."
}- This is a bait's neighbourhood, not a partner list. Promoting anything in it to a target would be the error this beat exists to prevent.
- GPKOW is broadly expressed and, on the evidence here, has no leukaemia-specific role. Any intervention aimed at it would hit splicing in every cell.
- Does GPKOW co-immunoprecipitate with any of the elongation proteins in its neighbourhood, in any cell type? No such experiment was found.
- Is GPKOW required in KMT2A-rearranged cells? It was absent from this project's 79-gene RNA-layer DepMap panel and should be added to any repeat.
- Would the same neighbourhood be recovered with a nucleus-restricted or endogenously tagged construct rather than an overexpressed one?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
As a BioID2 bait in K562 in the IMEx IM-30059 deposition, GPKOW (Q92917) recovers 748 distinct curated preys, including AFF4, ELL, MLLT1, CDK9, KMT2A, DOT1L, KAT7, ICE1, PAF1, NELFE, ELOA, CDC73, RTF1, KMT2D, SETD1A, HCFC1, SIRT1, HDAC1, CHD8, ARID1A, RUNX1, IGF2BP2, IGF2BP3, HNRNPA2B1.
IntAct PSICQUIC query: pubid:39251607, full 19,403-row deposition (IMEx IM-30059), retrieved 2026-09-19 · IntAct molecular interaction database (EMBL-EBI) 2026What this evidence cannot show
Retrieved from IntAct 2026-09-19 over the authors' curated bona fide pair list. A neighbourhood of this size contains a slice of most nuclear processes, so co-occurrence is weak evidence about any pair. The bait is an overexpressed BioID2 fusion in K562, which carries BCR::ABL1 and no KMT2A rearrangement; no fusion protein is present anywhere in the experiment.
Evidence that argues against this (2)
- In the largest human BioID survey (192 baits, HEK293) a prey's bait profile is dominated by subcellular compartment rather than by binding, so a splicing bait recovering co-transcriptional machinery is the expected background of the method. Go CD et al. 2021
- The founding BioID report describes the reagent as labelling proteins near the bait without binding it; promiscuous labelling of the vicinity is designed behaviour. Roux KJ et al. 2012
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
Every row in this deposition is proximity-dependent biotin identification (PSI-MI MI:1314), spoke-expanded (MI:1060) from a bait-centric streptavidin pulldown, with the RBP in bait role MI:0496 and the recovered protein in prey role MI:0498, and carries an IntAct MI-score of 0.27.
IntAct PSICQUIC query: detmethod:"MI:1314" (proximity-dependent biotin identification) intersected with the UniProt accessions of the super elongation complex, KMT2A, MEN1 and DOT1L, retrieved 2026-09-19 · IntAct molecular interaction database (EMBL-EBI) 2026What this evidence cannot show
Spoke expansion means each deposited pair is a bait-to-prey assignment rather than an observed binary contact, and the uniform MI-score carries no information about individual pairs.
Evidence that argues against this (1)
- BioID and affinity purification of chromatin-associated complexes recover few shared partners and enrich for different processes, so a proximity hit list is not a complex roster. Lambert JP et al. 2015
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
GPKOW is an X-linked spliceosomal G-patch protein; a donor-splice-site variant causes male-lethal microcephaly with intrauterine growth restriction, establishing that it is essential in human development.
Variant in the X-chromosome spliceosomal gene GPKOW causes male-lethal microcephaly with intrauterine growth restriction. · Carroll R, et al. · Eur J Hum Genet 2017What this evidence cannot show
Clinical genetics report of a single family; abstract read, full text not read. It establishes essentiality and spliceosomal function, and says nothing about leukaemia, AFF4 or KMT2A.
Evidence that argues against this (1)
- Background biology of a bait explains why its neighbourhood looks the way it does and is therefore an argument against, not for, reading the neighbourhood as a list of partners. A co-transcriptional protein is near transcription because it is co-transcriptional. Go CD et al. 2021
- co-occurs with →KMT2A / MLL1 — the gene that breaks
recovered as prey in the GPKOW BioID2 neighbourhood (proximity, not binding)
one of the fifty baits in that deposition
contributes to the SEC recovery census
- co-occurs with →AFF4 — the textbook SEC scaffold that KMT2A::AFF1 cells need LESS than other leukemias
AFF4 recovered as prey