Chimeric mRNA trans-fusions in immunity

One protein, two genes: what GSDMD:TMEM106A means for gene-function curation

AI Gene Review · projects/CHIMERIC_MRNA_IMMUNITY · 2026

Bottom line

  • Inflamed mouse macrophages make a trans-spliced GSDMD:TMEM106A chimera that speeds GSDMD pore formation and IL-1β release (PMID:42686912).
  • We reviewed both human parents, GSDMD (77 rows) and TMEM106A (10 rows), and recorded the chimera as a knowledge gap, not as an annotation of either.
  • No human chimera has been shown; the remaining work is a set of open questions.

How the chimera forms and acts

Why it matters for curation

  1. Attribution. GO assumes one gene → one set of products. A chimera's function is not an annotation of either parent.
  2. The wrong-frame trap. The TMEM106A part is an out-of-frame peptide, so canonical TMEM106A function does not transfer.
  3. Ortholog scope. Characterized in mouse only; human reviews must flag it as unresolved.
Phenomenon DNA change? Parent loci Mechanism
Trans-spliced chimera No often different chromosomes RNA trans-splicing
cis read-through No adjacent, same strand transcription past gene 1
DNA fusion gene Yes any translocation

Where the function is recorded

Status and open questions

  • ✅ GSDMD and TMEM106A reviews COMPLETE (54 ACCEPT, 18 non-core, 15 over-annotated across 87 rows).
  • ⬜ Does a human GSDMD:TMEM106A chimera exist and function?
  • ⬜ What specifies which transcript pairs are trans-spliced during inflammation?
  • ⬜ By what criteria should a chimera be curated as a distinct gene product for GO?
  • Source is abstract-only in the cache; no catalogue size is quoted.

Read more: projects/CHIMERIC_MRNA_IMMUNITY.md · genes/human/GSDMD/ · genes/human/TMEM106A/