Autoimmune genetics: greatest hits

Reviewing every GO annotation on 20 shared autoimmune risk genes

AI Gene Review · projects/AUTOIMMUNE · 2026

Bottom line

  • 20 immune-regulation genes carry risk variants for several autoimmune diseases at once (T1D, RA, MS, IBD, SLE).
  • We reviewed 2,291 GO annotation rows (2,275 existing plus 16 proposed NEW); every row is actioned and all 20 reviews validate.
  • 1,464 accepted, 174 removed (144 of them generic protein binding, mostly on STAT3 and SMAD3), 16 NEW. Review files are not all finalised: 9 COMPLETE, 6 DRAFT, 5 IN_PROGRESS.

Where the genes act

Why these genes

  • Chosen as the most strongly replicated, functionally validated autoimmune risk loci (Tier 1: 11 genes) plus well-established risk genes (Tier 2: 9).
  • Six pathway groups: T cell activation and inhibition, Th1/Th2 polarisation, Th17/Treg balance, NF-κB/TNF, tolerance, ER sphingolipid control.
  • Several are among the most heavily annotated immune genes: STAT3 456 rows, SMAD3 349, GATA3 258.

Actions per gene

What a review looks like

ORMDL3 review page: sphingolipid biosynthesis (IBA) accepted as core; ORMDL3 is the ceramide-sensing regulatory subunit of serine palmitoyltransferase.

Findings

  1. protein binding IPI removed en masse: 144 of 174 REMOVEs; STAT3 66, SMAD3 68, GATA3 7.
  2. Propagation errors removed: IL23R prolactin receptor activity (IBA) and prolactin signaling pathway (IEA).
  3. ORMDL3 gets its real function as NEW terms: enzyme inhibitor activity, ceramide binding, negative regulation of sphingolipid biosynthetic process; generic TAS membrane locations removed.
  4. UNDECIDED resolved for IL4, IL7R, CD28 and IL10 once publications were cached; 11 remain.

Status and next steps

  • ✅ 20/20 reviews actioned and validating (0 errors).
  • ⬜ Finalise review status: 6 DRAFT, 5 IN_PROGRESS.
  • ⬜ Supporting-text warnings, mostly IL2RA, IL10, TNFAIP3.
  • The STAT3 deep-research to-do is already done (STAT3-deep-research-falcon.md).

Read more: projects/AUTOIMMUNE.md · genes/human/<GENE>/