SRCAP - the other H2A.Z-loading motor, whose entire PubMed intersection with MLL is five neurodevelopmental gene panels
also called SRCAP · Snf2-related CREBBP activator protein · KIAA0309 · Domino homolog · Q6ZRS2
SRCAP is one of two motors that install the H2A.Z histone variant at gene switches. Nothing connects it to this leukaemia, and the only papers that mention it alongside MLL are gene panels for childhood developmental disorders that happen to test both.
The same thing, for a scientist
SRCAP (Q6ZRS2, 3,230 aa) is the Snf2-related ATPase that, with p400/TIP60, deposits H2A.Z-H2B handed to it by the YL1/VPS72 chaperone [E1]. Unlike EP400 it has **no leukaemia literature at all**: `SRCAP AND (MLL OR KMT2A)` returns 5 records and every one is a clinical sequencing panel for short stature, intellectual disability or chromatin-related disorders in which both genes are simply on the panel [E2]. SRCAP's own disease association is **Floating-Harbor syndrome**, a developmental disorder, and that is what nearly all of its human genetics is about. In DepMap SRCAP is one of the three genes **least** required in KMT2A-rearranged lines among the 29 scanned here: difference **+0.118** at a pan-essentiality of -0.927 [E3]. **This entry exists to close the gene, not to open it.** It is written so the next cycle does not spend a day rediscovering that SRCAP is a developmental-syndrome gene with an H2A.Z function and nothing in between - and so that the five panel papers are recorded as a checked rejection rather than as an unexamined count of five.
A counted five that is really a zero, and why that is worth a section
SRCAP AND (MLL OR KMT2A) returns 5. Read as a number, five records looks like a small but real literature - enough to justify a paragraph in a review, or to make a gap-finding instrument skip the gene as covered.
The five, title-checked 2:
- genotypes and phenotypes of short stature caused by epigenetic modification gene variants
- de novo variants underlying monogenic syndromes with intellectual disability, India cohort
- a longitudinal genetics-of-cognition review
- a customised NGS multigene panel for chromatin-related disorders
- exome sequencing in prenatal-onset syndromic short stature
All five are gene-panel co-mentions. The real number is zero. This project has documented the opposite failure - a real literature hidden behind retired symbols - and this is the mirror: a co-mention literature that inflates a count. Both produce a confident wrong number, and only title-checking distinguishes them.
| uniprot | Q6ZRS2 |
|---|---|
| gene symbol | SRCAP |
| length AA | 3230 |
| function | Snf2-family ATPase depositing H2A.Z-H2B received from VPS72/YL1 |
| human disease | Floating-Harbor syndrome (developmental, not oncological) |
| kmt2a literature records title checked | 0 |
| raw count before title check | 5 |
depmap — the numbers behind the chart
{
"index_mean": -0.8978,
"other_leukaemia_mean": -1.0155,
"difference": 0.1177,
"pan_essentiality": -0.9266,
"myeloid_difference": 0.1444,
"lymphoid_difference": 0.0763,
"n_index": 11
}depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": -0.8978,
"chronos_mean_other_leukaemia": -1.0155,
"difference": 0.1177,
"pan_essentiality_all_lines": -0.9266,
"selectivity_rank": 17179,
"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."
}- SRCAP is required across cell lines at a pan-essentiality of -0.93 and germline SRCAP variants cause a developmental syndrome, so inhibiting it in a child has a foreseeable developmental toxicity and no selectivity argument.
- Its function is redundant with p400/TIP60 for H2A.Z deposition, so a selective SRCAP inhibitor has a built-in compensation route and would probably not move H2A.Z levels at all.
- Re-run the SRCAP absence against the complex name 'SRCAP complex' and against the phrase 'H2A.Z deposition', since a symbol-bounded zero in this beat has already been shown to miss a real result.
- Do SRCAP and p400/TIP60 divide H2A.Z deposition by locus class in a haematopoietic cell? If so, only one of them is relevant to HOXA and this beat cannot say which.
- Is the coherent positive difference across SRCAP, EP400, ANP32E and the FACT subunits real? A permutation null on the positive tail has never been run in this project.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
The YL1/VPS72 chaperone delivers H2A.Z-H2B for transfer to the nucleosome by the ATP-dependent chromatin-remodelling complexes SRCAP and P400-TIP60.
Molecular basis and specificity of H2A.Z-H2B recognition and deposition by the histone chaperone YL1. · Latrick CM, Marek M, Ouararhni K, et al. · Nature Structural & Molecular Biology 2016What this evidence cannot show
Abstract read from efetch 2026-09-20; full text not read (no PMCID). The two-remodeller statement is the authors' framing of the field plus their structural inference, not a measurement of either remodeller's activity in this paper. No leukaemia.
Evidence that argues against this (1)
- Which of the two remodellers acts at which locus is not resolved by a structure of the shared chaperone, and neither has been localised at KMT2A-fusion target genes. The only published variant-exchange event in this disease runs through the p400/TIP60 arm, not SRCAP. Yamagata K et al. 2021
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
As of 2026-09-20, PubMed returns 5 records for 'SRCAP AND (MLL OR KMT2A)' and all 5 are clinical gene-panel or exome studies in which both genes appear on a panel: a study of genotypes and phenotypes of short stature caused by epigenetic modification gene variants, a de novo variant study of monogenic intellectual-disability syndromes in an Indian neurodevelopmental cohort, a longitudinal cognitive-genetics review, a customised NGS multigene panel for chromatin-related disorders, and exome sequencing in prenatal-onset syndromic short stature. None studies SRCAP in a leukaemic cell.
NCBI E-utilities esearch over PubMed for SRCAP against KMT2A and MLL, with title checking of all returned records, run 2026-09-20 · US National Library of Medicine 2026What this evidence cannot show
Query translation captured; no [UID] term. All 5 titles fetched in full from efetch XML. **Bounded by the primary symbol only**; SRCAP's alias KIAA0309 and the phrase 'Floating-Harbor' were not crossed with the leukaemia terms, and the complex-name route ('SRCAP complex') was not run. This project has twice found a complex-level framing unreachable from subunit symbols.
Evidence that argues against this (1)
- The complex-name blind spot is real in this beat: the generic phrase 'histone chaperone' found an MLL paper that no gene-symbol query in the beat retrieved. A zero for SRCAP bounded only by its symbol is weaker than it looks. Shimoyama T et al. 2005
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
SRCAP is UniProt Q6ZRS2 (SRCAP_HUMAN), chromatin remodeling protein SRCAP / Domino homolog, 3,230 amino acids, with alias symbol KIAA0309. In DepMap its mean effect is -0.898 in 11 KMT2A-rearranged leukaemia lines against -1.016 in 43 other leukaemia lines (difference +0.118) at a pan-essentiality of -0.927; myeloid difference +0.144, lymphoid difference +0.076.
UniProtKB Q6ZRS2 (SRCAP_HUMAN), Chromatin remodeling protein SRCAP, 3230 aa · UniProt Knowledgebase, reviewed (Swiss-Prot) 2026What this evidence cannot show
UniProt fetched 2026-09-20 with `gene_primary` requested and read back per rule 62. DepMap from this beat's run the same day. **A positive difference at a pan-essentiality of -0.93 is floor-compressed** and is reported as a negative result rather than as a claim that KMT2A-rearranged cells need SRCAP less. No permutation null.
Evidence that argues against this (1)
- SRCAP and EP400 have nearly identical profiles in this scan (+0.118 and +0.121 at pan-essentialities of -0.93), which is either evidence that the H2A.Z deposition module behaves coherently or evidence that both numbers are driven by the same line-level noise. Coherence across two genes is not a null. Oncofusion knowledge graph (internal analysis) 2026
ATP-dependent deposition of H2A.Z-H2B delivered by YL1/VPS72
SWR1-family remodeller that deposits H2A.Z