KHDRBS3 (SLM2/T-STAR) — the third STAR paralogue, also zero leukaemia records, also flat in DepMap
also called SLM2 · SLM-2 · TSTAR · T-STAR · etoile · Sam68-like mammalian protein 2 · KH domain containing, RNA binding, signal transduction associated 3
KHDRBS3 is the third member of the Sam68 family, the group of proteins that slow down production of the MLL-AF4 fusion protein. Like its sibling KHDRBS2 it has never been studied in any leukaemia.
The same thing, for a scientist
KHDRBS3/SLM2/T-STAR completes the KH-domain STAR family implicated collectively in translational repression of MLL-AF4 [E1]. `(KHDRBS3 OR SLM2 OR TSTAR) AND (leukemia OR leukaemia)` returns **0 records** and `(MLL OR KMT2A) AND (KHDRBS3 OR SLM2 OR SLM-2 OR TSTAR OR etoile)` returns **0** [E2]. DepMap is flat: Chronos mean -0.033, 0.2% of 1,208 lines depleted, index-arm difference +0.044 lymphoid / +0.043 myeloid [E3]. Written as a bounded absence with the queries stated, for the same reason as `gene-khdrbs2`: the family is now on the fusion transcript and two of its three members are unexamined.
The alias set, and one that had to be included deliberately
etoile is a used synonym for this gene and is a common French word. It was included in the query but would be unusable as a standalone term for the same reason SEPT* is unusable as a PubMed wildcard - it matches text that has nothing to do with the gene. In an AND with MLL OR KMT2A it is safe; alone it would inflate a count exactly as RD inflated NELFE's from 2 to 115 in this project's cycle-40 audit.
TSTAR and T-STAR are separate PubMed terms because the parser treats the hyphen as a token boundary, so both were run. SLM2 and SLM-2 likewise.
What would make this entry stop being an absence
One measurement: which STAR-family member is expressed in a t(4;11) blast. The founding result is at family resolution 1, and the family has three members with different expression breadth. If KHDRBS3 is absent from B-lymphoid progenitors the absence closes honestly; if it is present, the literature gap becomes a real gap and this entry becomes a target-identification lead rather than a placeholder.
| uniprot | O75525 |
|---|---|
| length AA | 346 |
| gene symbol | KHDRBS3 |
| uniprot resolution | gene_exact:KHDRBS3 AND organism_id:9606 AND reviewed:true; one hit; primary gene name read back as KHDRBS3; length 346 aa checked |
absence claim
{
"queries_run": [
"(KHDRBS3 OR SLM2 OR TSTAR) AND (leukemia OR leukaemia)",
"(MLL OR KMT2A) AND (KHDRBS3 OR SLM2 OR SLM-2 OR TSTAR OR etoile)"
],
"records": [
0,
0
],
"date": "2026-09-20"
}essentiality
{
"depmap_common_essential": false,
"chronos_mean": -0.0332,
"pct_lines_depleted": 0.2,
"n_lines": 1208,
"kmt2a_r_lymphoid_diff": 0.0438,
"kmt2a_r_myeloid_diff": 0.0433
}depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": -0.022,
"chronos_mean_other_leukaemia": -0.0655,
"difference": 0.0435,
"pan_essentiality_all_lines": -0.0332,
"selectivity_rank": 14201,
"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."
}- Recorded as an absence, this entry is one careless citation away from being read as a negative result about KHDRBS3's importance.
- If the family buffers itself on the fusion transcript, the therapeutic reading - enhance repression - would require engaging all three, and no modality does that.
- Is KHDRBS3 expressed in B-lymphoid progenitors and in t(4;11) blasts at all?
- Do the three STAR paralogues compete for the same AU-rich sites on the fusion transcript, which would make single-member depletion uninformative and a triple depletion the only meaningful test?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
The KHDRBS family collectively inhibits MLL-AF4 translation through ribosomal stalling at AU-rich regulatory sites; synonymous mutations that disrupt the association restore translation and cause leukaemic transformation in vivo.
RNA-binding proteins of KHDRBS and IGF2BP families control the oncogenic activity of MLL-AF4 · Okuda H, et al. · Nat Commun 2022What this evidence cannot show
Family-level attribution only; the abstract does not identify which member carries the activity, and attributing it to KHDRBS3 would be unsupported. Abstract read; full text not read.
Evidence that argues against this (1)
- KHDRBS3's best-characterised biology is in testis and brain splicing regulation rather than in haematopoiesis, so the family-level result is at least as likely to be carried by the ubiquitously expressed KHDRBS1. UniProt Consortium 2026
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
Counted absence, queries run this session: `(KHDRBS3 OR SLM2 OR TSTAR) AND (leukemia OR leukaemia)` returns 0 records; `(MLL OR KMT2A) AND (KHDRBS3 OR SLM2 OR SLM-2 OR TSTAR OR etoile)` returns 0 records.
PubMed E-utilities esearch counts for KHDRBS3 aliases against leukaemia and against MLL/KMT2A · NCBI PubMed (queries run 2026-09-20) 2026What this evidence cannot show
Six spellings covered including the hyphenated variants PubMed tokenises separately. A paper framing the work at family level is invisible to every member-keyed query, which is why the family term was run separately and is reported in gene-khdrbs2.
Evidence that argues against this (1)
- A zero over six aliases still rests on the assumption that authors name the gene in the title or abstract. A splicing-factor screen reporting a hit only in a supplementary table would not appear in any of these counts. Okuda H et al. 2022
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
DepMap CRISPR (Chronos) gives KHDRBS3 a mean gene effect of -0.033 across 1,208 lines with 0.2% of lines depleted, and a positive index-arm difference of +0.044 (B-lymphoid) and +0.043 (myeloid) against 43 other leukaemia lines.
The RNA layer in KMT2A-rearranged leukaemia lines: panel-wide selectivity scan and IGF2BP family co-dependency test · Oncofusion knowledge graph (internal analysis) 2026What this evidence cannot show
Flat, and flat rows in DepMap are uninformative about tissue-restricted genes that may simply not be expressed in the screened lines.
Evidence that argues against this (1)
- All three KHDRBS paralogues are flat-to-positive in this scan, which is equally consistent with redundancy across the family - in which case no single knockout could ever show an effect and the screen is answering a question it cannot answer. Oncofusion knowledge graph (internal analysis) 2026
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProtKB O75525 (KHDR3_HUMAN) is human KHDRBS3, 346 amino acids; resolved by gene_exact query with the primary gene name read back as KHDRBS3 and the length checked.
UniProtKB O75525 (KHDR3_HUMAN), human KHDRBS3, 346 aa · UniProt Consortium 2026What this evidence cannot show
One reviewed human hit, primary gene name matching the query. Identity only.
Evidence that argues against this (1)
- Accession identity says nothing about whether this paralogue binds the AU-rich sites on the MLL-AF4 transcript, which is the only property that would matter here and has not been measured for any individual member. Okuda H et al. 2022
STAR-family paralogue sharing the KH domain architecture
- related to →RNA-binding proteins set how much KMT2A::AFF1 protein a cell makes from its own fusion transcript
Named only at family level by the founding result