Oncofusion

start / graph / gene-syncrip

Genemoderate confidence 3 of 5: One strong study, or several smaller consistent ones.Q6-interactome-rna-layer

SYNCRIP (hnRNP Q) — required for MLL leukaemia stem cells in one paper and a tumour suppressor deleted in T-ALL in another

also called hnRNP Q · hnRNPQ · NSAP1 · HNRPQ · synaptotagmin binding cytoplasmic RNA interacting protein

SYNCRIP is an RNA-binding protein that keeps the HOXA9 message being translated, and myeloid MLL leukaemia stem cells need it. Confusingly, the same gene is deleted in a different childhood leukaemia where losing it makes the disease worse.

The same thing, for a scientist

SYNCRIP was identified as the most differentially required gene between normal and myeloid leukaemia cells in a functional shRNA screen of the MSI2-interacting RNA-binding protein network: depletion increases apoptosis and differentiation, delays leukaemogenesis, and causes loss of the MLL and HOXA9 leukaemia stem-cell programme, with SYNCRIP maintaining HOXA9 translation and MSI2 or HOXA9 over-expression rescuing depletion [E1]. **The opposite sign exists in the same disease family**: SYNCRIP is one of two contiguous haploinsufficient genes at 6q14 whose combined silencing accelerates leukaemogenesis in a T-ALL mouse model and increases leukaemia-initiating activity of primary human cells [E2]. DepMap gives it a Chronos mean of -0.360 with 26.4% of lines depleted and lineage-concordant index-arm differences of -0.116 / -0.242, the 2.4th percentile of a 466-gene null [E3].

Go deeper
A gene that is oncogenic and tumour-suppressive in two childhood leukaemias

This is the sharpest contradiction in the beat and it is not an error in either paper.

In MLL-driven myeloid leukaemia, SYNCRIP sustains the HOXA9 stem-cell programme and its loss is anti-leukaemic 1. In T-ALL, SYNCRIP sits in the recurrently deleted 6q14 region, and co-silencing it with the neighbouring snoRNA host gene SNHG5 accelerates disease and raises leukaemia-initiating activity 2.

The reconciliation is that an RNA-binding protein has no intrinsic direction: its effect is set by which transcripts it occupies, and those differ by lineage and by what the cell is transcribing. HOXA9 is a substrate in a HOXA-high myeloid context and is not one in T-ALL.

The practical consequence is severe for anyone contemplating a drug. A systemic SYNCRIP inhibitor would be expected to help in one paediatric leukaemia and to promote another, and an infant with a KMT2A rearrangement can present with either lymphoid or myeloid disease and with mixed phenotype. This graph should not carry SYNCRIP as a target without that sentence attached.

Where the index disease sits

Neither paper is KMT2A::AFF1. 1 is myeloid MLL leukaemia and 2 is T-ALL. (MLL OR KMT2A) AND SYNCRIP AND leukemia returns 2 records and the aliases hnRNP Q, hnRNPQ and NSAP1 add 0 against MLL or KMT2A 4 - a case where alias expansion, which recovered a tenfold literature for the septins, recovers nothing.

The dependency data are at least consistent and concordant across the lineage split (-0.116 lymphoid, -0.242 myeloid) 3, which puts SYNCRIP among the better-behaved rows in the panel. It is still a fifth of menin's effect.

Facts and figures
uniprotO60506
length AA623
gene symbolSYNCRIP
uniprot resolutiongene_exact:SYNCRIP AND organism_id:9606 AND reviewed:true; one hit; primary gene name read back as SYNCRIP; length 623 aa checked
rna functionhnRNP-family RNA-binding protein; maintains translation of HOXA9 and interacts indirectly with MSI2 through shared mRNA targets
direction conflictoncogenic in myeloid MLL leukaemia (PMID 28436985); part of a two-gene haploinsufficient tumour-suppressor interval at 6q14 in T-ALL (PMID 30266814)
essentiality
{
  "depmap_common_essential": false,
  "chronos_mean": -0.3598,
  "pct_lines_depleted": 26.4,
  "n_lines": 1208,
  "kmt2a_r_lymphoid_diff": -0.1159,
  "kmt2a_r_myeloid_diff": -0.2418,
  "null_percentile": 2.36,
  "lineage_discordant": false
}
pubmed counts
{
  "SYNCRIP AND leukemia": 3,
  "(MLL OR KMT2A) AND (hnRNP-Q OR hnRNPQ OR NSAP1)": 0
}
depmap kmt2a selectivity
{
  "chronos_mean_kmt2a_rearranged": -0.6681,
  "chronos_mean_other_leukaemia": -0.4721,
  "difference": -0.1961,
  "pan_essentiality_all_lines": -0.3598,
  "selectivity_rank": 270,
  "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
  • SYNCRIP is required in myeloid MLL leukaemia and tumour-suppressive in T-ALL. A systemic inhibitor would be expected to promote one childhood leukaemia while treating another.
  • Infant KMT2A-rearranged disease includes lymphoid, myeloid and mixed-phenotype presentations, so lineage cannot be assumed at diagnosis - exactly the situation in which a direction-conflicted target is most dangerous.
  • The MLL result runs through HOXA9 translation, and infant t(4;11) is HOXA-low, so the mechanism may not even be present in the index disease.
Still open
  1. Which transcripts does SYNCRIP occupy in a KMT2A::AFF1 B-lymphoid cell, where HOXA9 expression is low in infant t(4;11)?
  2. Is SYNCRIP itself the 6q14 tumour suppressor, or the passenger beside SNHG5?
  3. Can a single agent be safe when the same gene is required in one paediatric leukaemia and suppressive in another?
Every source behind this entry (5)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    A functional shRNA screen of the MSI2-interacting RNA-binding protein network identified 24 genes required for in vivo leukaemia, of which Syncrip was the most differentially required between normal and myeloid leukaemia cells; SYNCRIP depletion increases apoptosis and differentiation while delaying leukaemogenesis, causes loss of the MLL and HOXA9 leukaemia stem-cell programme, and maintains HOXA9 translation, with MSI2 or HOXA9 over-expression rescuing the effects of depletion.

    PMID 28436985DOI
    What this evidence cannot show

    Abstract read; full text not read. Myeloid leukaemia throughout; the MLL programme referred to is the myeloid MLL leukaemia stem-cell programme, not KMT2A::AFF1 B-lymphoid disease.

    Evidence that argues against this (1)
    • The same gene is a haploinsufficient tumour suppressor at 6q14 in T-ALL, where combined silencing with SNHG5 accelerates leukaemogenesis and increases the leukaemia-initiating activity of primary human cells. A gene with opposite signs in two paediatric leukaemias cannot be carried as a target without lineage specification. Gachet S et al. 2018
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    SYNCRIP and the snoRNA host gene SNHG5 are two contiguous candidate haploinsufficient genes at 6q14 in T-ALL; combined silencing of both, but not either alone, accelerates leukaemogenesis in a Tal1/Lmo1/Notch1 mouse model, and co-extinction increases the leukaemia-initiating activity of primary human leukaemic cells in xenograft.

    PMID 30266814DOI
    What this evidence cannot show

    Abstract read; full text not read. T-ALL, a different lineage from the index disease. The effect requires BOTH genes to be silenced, so SYNCRIP alone is not established as the tumour suppressor - the two-gene region is.

    Evidence that argues against this (1)
    • That neither gene alone produces the effect substantially weakens the claim that SYNCRIP is a tumour suppressor. It may be the passenger in a two-gene interval, in which case the contradiction with the MLL result is smaller than it looks. Vu LP et al. 2017
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis

    DepMap CRISPR (Chronos) gives SYNCRIP a mean gene effect of -0.360 across 1,208 lines with 26.4% depleted below -0.5, and lineage-concordant index-arm differences of -0.116 (four B-lymphoid) and -0.242 (seven myeloid) against 43 other leukaemia lines, at the 2.4th percentile of a 466-gene null and not floor-compressed.

    What this evidence cannot show

    Eleven index lines. The percentile is driven by the myeloid half, where the literature is.

    Evidence that argues against this (1)
    • A negative Chronos in a gene reported as a tumour suppressor in T-ALL is a reminder that a cell-autonomous proliferation screen and an in vivo leukaemia-initiation model measure different things and can disagree in sign. Gachet S et al. 2018
  4. E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

    Counted absence for the alias set: `(MLL OR KMT2A) AND (hnRNP-Q OR hnRNPQ OR NSAP1)` returns 0 PubMed records, and `(MLL OR KMT2A) AND SYNCRIP AND leukemia` returns 2; `SYNCRIP AND leukemia` returns 3 in total.

    PubMed E-utilities esearch counts, alias-expanded and title-checked · NCBI PubMed (queries run 2026-09-20) 2026
    What this evidence cannot show

    Four spellings covered including the hyphenated variant PubMed tokenises separately. A three-record total literature means every count here is fragile.

    Evidence that argues against this (1)
    • One of the three SYNCRIP-leukaemia records is a t(8;21) single-cell sequencing paper in which SYNCRIP is an incidental mention, so the functional literature is two papers - and they disagree in sign. Gachet S et al. 2018
  5. E5established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    UniProtKB O60506 (HNRPQ_HUMAN) is human SYNCRIP, 623 amino acids; resolved by gene_exact query with the primary gene name read back as SYNCRIP and the length checked.

    What this evidence cannot show

    Single reviewed human hit whose primary gene name equals the query symbol. This project has logged six cases of gene_exact returning a protein that merely lists the queried symbol as a synonym, so the read-back is the point, not the query.

    Evidence that argues against this (1)
    • An accession establishes identity and length. It says nothing about whether this protein matters in KMT2A-rearranged leukaemia, which is what the rest of this entry is for. UniProt Consortium 2026
Connected to