Oncofusion

start / graph / gene-hla-dra

Genemoderate confidence 3 of 5: One strong study, or several smaller consistent ones.Q48-surface-antigens

HLA-DRA - the non-polymorphic alpha chain, and the only HLA-DR chain any source on this beat names explicitly

also called HLA-DRA · HLA-DRA1 · MHC class II antigen DRA · P01903

HLA-DRA is one of the two genes whose proteins clip together to make the HLA-DR marker on a cell surface. It is the half that barely varies between people, which is why it is the half that experiments usually measure.

The same thing, for a scientist

HLA-DRA (UniProt **P01903**, DRA_HUMAN, **254 aa**, single reviewed human record, primary gene name HLA-DRA, synonym HLA-DRA1) encodes the alpha chain of the HLA-DR class II heterodimer [E1]. Unlike the beta chains it is essentially non-polymorphic, which makes it the tractable half for expression work. **It is the one chain a source on this beat named.** Koues and colleagues report that common MLL/COMPASS subunits bind inducible MHC-II and CIITA promoters, that overexpressing a single common subunit **significantly enhanced MHC-II HLA-DRA expression**, and that those subunits are required for H3K4 trimethylation at MHC-II and CIITA promoters [E2]. Every other source read on this beat says 'HLA-DR' and specifies no chain. **Why it has its own entry.** The granularity rule: HLA-DR the surface marker, HLA-DRA the gene and HLA-DRB1 the gene are three different things, and the whole point of this beat is that collapsing them is how a graph loses track of what was actually measured.

Go deeper
Regulation, which is where the KMT2A family appears

Class II genes including HLA-DRA are controlled by CIITA, the class II transactivator, whose pIV promoter is itself cytokine-inducible. Koues 2010 places common MLL/COMPASS subunits on both the MHC-II and the CIITA promoters and makes H3K4 trimethylation there dependent on them 2.

Read this carefully, because it is easy to over-claim. The paper's manipulation is overexpression of a common subunit, its system is cytokine-induced class II regulation, and it names 'common MLL/COMPASS subunits' without the abstract identifying which - so it could be a WDR5, RBBP5, ASH2L or DPY30 result as much as a KMT2A one. This entry claims a family-level regulatory link to HLA-DRA and explicitly does not claim a KMT2A-specific one, per rule 66.

Facts and figures
uniprotP01903
length AA254
gene primaryHLA-DRA
polymorphismessentially non-polymorphic
partner chainHLA-DRB1 (or DRB3/DRB4/DRB5) to form the surface HLA-DR heterodimer
resolution notegene_exact:HLA-DRA AND organism_id:9606 AND reviewed:true returned exactly one row on 2026-09-20 whose primary gene name equals HLA-DRA and whose length is 254. HLA-DRB1 is 266 and CLEC12A 265, so three unrelated proteins on this beat lie within 12 residues; only gene_primary discriminates.
regulatory linkcommon MLL/COMPASS subunits bind MHC-II and CIITA promoters and their overexpression enhances HLA-DRA expression (PMID 20181089); family-level, not KMT2A-specific
gene symbolHLA-DRA
gene symbol notepromoted from gene_primary 2026-09-20: verify-accessions.py reads data.gene_symbol, so a gene_primary-only entry was being length-checked or id-inferred rather than symbol-asserted
uniprot gene synonyms
[
  "HLA-DRA1"
]
depmap kmt2a selectivity
{
  "chronos_mean_kmt2a_rearranged": 0.0114,
  "chronos_mean_other_leukaemia": -0.0083,
  "difference": 0.0197,
  "pan_essentiality_all_lines": -0.0055,
  "selectivity_rank": 11674,
  "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
  • **An HLA-DRA result is not an HLA-DR result.** Surface HLA-DR requires an assembled dimer, so a transcriptional effect on the alpha chain need not change what a flow antibody sees.
  • **Family-level chromatin results do not transfer to a fusion.** KMT2A fusions lose the SET domain, so a wild-type H3K4-dependent mechanism may be absent rather than amplified in fusion-driven disease.
Still open
  1. Is HLA-DRA expression altered in KMT2A-rearranged blasts relative to other B-precursor ALL? Nothing read on this beat measures it and the data exist in every diagnostic flow archive.
  2. Which MLL/COMPASS subunits are the 'common subunits' of PMID 20181089? Full-text reading would settle whether this graph's WRAD layer or its KMT2A layer owns this result.
Every source behind this entry (2)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    The reviewed human UniProt record for HLA-DRA is P01903 (DRA_HUMAN), primary gene name HLA-DRA, synonym HLA-DRA1, 254 aa, protein name 'HLA class II histocompatibility antigen, DR alpha chain (MHC class II antigen DRA)'.

    UniProtKB reviewed entry P01903 (DRA_HUMAN) · UniProt Consortium · UniProtKB 2026
    What this evidence cannot show

    Fetched live from the UniProt REST API on 2026-09-20 with fields accession, gene_primary, gene_synonym, protein_name, length; exactly one reviewed human row whose primary gene name equals HLA-DRA. HLA-DRA is 254 aa and HLA-DRB1 is 266 aa - only 12 residues apart - so in this gene pair, as elsewhere on this beat, length does not protect against a swap and only the primary gene name does.

    Evidence that argues against this (1)
    • A UniProt canonical record for an MHC gene is a reference sequence. HLA-DRA is near-monomorphic so the approximation is mild here, but it would be severe for any DRB record and the same field name is used for both. UniProt Consortium 2026
  2. E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    Multiple common subunits of the MLL/COMPASS complexes bind the cytokine-inducible MHC-II and CIITA promoters; overexpressing a single common MLL/COMPASS subunit significantly enhanced promoter activity and MHC-II HLA-DRA expression; and these subunits are important for H3 lysine 4 trimethylation at MHC-II and CIITA promoters.

    PMID 20181089DOI
    What this evidence cannot show

    Abstract read in full from raw NCBI efetch XML on 2026-09-20; full text not read. Wild-type MLL/COMPASS biology in a cytokine-inducible class II system; **no fusion protein, no leukaemic cell, no KMT2A rearrangement anywhere in the abstract**. 'Common MLL/COMPASS subunits' are not named at abstract level, so the result cannot be attributed to KMT2A rather than to another family member or to a shared WRAD component. The manipulation is overexpression.

    Evidence that argues against this (1)
    • Attributing this to KMT2A specifically would be the exact MLL-family conflation rule 66 documents - MLL2 and MLL4 each name two genes with swapped protein names. The safe reading is family-level, and this entry takes it. Xiu Y et al. 2018
Connected to