Here is an  interim update on some genes of my recent asthma exome paper coming now from 1 M  exomes published yesterday in a preprint.

Also ClinVar shows that the IL33 receptor is not “essential” making anti IL33 receptor antibodies like etokimab, itepekimab, tozorakimab a safe therapy although not being effective in the many LOF mutation carriers.

The most interesting thing in the preprint is in supplemental table 2 with all the s-het values for 16,704 genes. From that table  I have selected  my favorite target  IL33 receptor together with TLR1, ALOX15, GSDMA, IL13 and IKZF3. Only BTNL2 could not be found.

IKZF3 would be dangerous to be touched (see my 2008 commentary) while in the 2022 exome paper I  found only protective variants in the 5′-UTR but not any LOF variant  in IKZF3- probably as it is the only essential gene when looking at 1 M exomes.