February 5, 2022

A very interesting finding of the paper published February 2 discussing the mechanism for loss of smell in COVID-19 found a very great downregulation of the ADCY3 gene. They identified interchromosomal compartments containing ADCY3 and other genes with key functions in olfaction that also dissipate in infected samples.

This gene is involved in far more than olfaction. In fact, it is involved in obesity, male fertility, diabetes and sudden cardiac death.

A paper from 2018 identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population.

Very interestingly, it also catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis. Required for the perception of odorants. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet.

Regarding sudden cardiac death (perhaps via dilated cardiomyopathy) and the gene expression of gap junctions in cardio-myopathic tissues, the up-regulated genes included GJA1 (Cx43), GJA5 (Cx40), GJA3, TJP1, GJA8, GJC2, GRB2, MAPK3, MAPK7 and PRKCG, whereas the only down-regulated gene was ADCY3.

Referenced/Related Papers

PATHWAY: hsa05414

Cardiomyopathy-Associated Gene 1-Sensitive PKC-Dependent Connexin 43 Expression and Phosphorylation in Left Ventricular Noncompaction Cardiomyopathy

Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes

Non-cell autonomous disruption of nuclear architecture as a potential cause of COVID-19 induced anosmia

Compartmentalization of Distinct cAMP Signaling Pathways in Mammalian Sperm

Molecular modelling of novel ADCY3 variant predicts a molecular target for tackling obesity