"Franken-CARD9": chimeric proteins for high-resolution studies of activating mutations in CARD10, CARD11 and CARD14 https://www.biorxiv.org/content/10.1101/2023.03.06.531260v1?med=mas
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The most exciting of the two at the moment is CARD9, where the disease associations in #Genebass to the first activated variant we identified (G111E) (#constipation #IBS #fibromyalgia #depression #anxiety ...) led to more activated variants.
Especially #fibromyalgia was able to identify CARD9 activated variants:
We could identify the natural variants G111R, K165E, K165del, S172N, E523Q, E523Q and *537Qext59 as activating, strong confirmation.
With the advent of public health data correlated with genetic data (#Genebass from @uk_biobank
and #FinnGen), we have the possibility now to start screening variants in vitro for functional effects - then mine interesting natural variants for disease phenotypes!
And also in honor of #InternationalWomensDay I should probably point out that #fibromyalgia is 2-9 times more common in #women. This is in a way another argument in favor of #inflammation as a cause of the disease.
@biorxivpreprint
A project that started as a fun little side-project (structure-function comparisons in the CARD-CC family: CARD9, CARD10, CARD11 and CARD14). Then #serendipity happened: identification of activated CARD9 and CARD10 natural variants and novel disease association in #Genebass.
Activated CARD11 (causing B cell #lymphomas or #BENTA) and CARD14 (causing #psoriasis or #PRP) already known. With activated CARD9 and CARD10, we have activated variants in all 4 CARD-CC family members.