Data from primary manuscripts and microscopy screenings were used to assign a confidence level to the likelihood of different subcellular locations expressing ACE2.  This study showed that the extracellular space and plasma membrane are the most likely places to express ACE2 (confidence = 5), and the Golgi apparatus is the least likely (confidence = 1) out of these listed locations.  

Subcellular Expression of ACE2

- drug mediators
- non-drug mediators
- genetic mediators
- disease states

Mediators that Infleunce ACE2 Expression

Pregnant mice were used to assess the expression levels of the following genes associated with SARS-CoV-2, inflammation, and other viral diseases:

- ACE2: cellular receptor for the SARS-CoV-2 virus
- TMPRSS2: serine protease involved in cellular entry of the SARS-CoV-2 virus
- St3gal4: related to the influenza virus
- St6gal1: related to the influenza virus
- Ifngr1: related to inflammation
- Tnfrsf1a: related to inflammation

Mice were sacrificed at the following timepoints:

- E12.5: embryonic day 12 (gravid females are sacrificed)
- E14.5: embryonic day 14 (gravid females are sacrificed)
- P1: day pups are born (pups are sacrificed)

Epithelium (Epi) and mesenchyme (Mes) tissue were collected from the soft pallets (SP) and tongues (T) of the different developmental stages.  Notably, ACE2 expression was only observed in large quantities in P1 mice, and TMPRSS2 expression increased throughout the developmental process.  FPKM: fragments per kilobase million reads

ACE2 and Other SARS-CoV-2 Related Gene Expression in Mouse Development

ACE2 is expressed throughout many human tissues and organs. This node organizes the tissue- and organ-level expression findings for ACE2, covering: expression in cancer tissue; expression in the human airway epithelium; expression in the human brain; ACE2 protein and mRNA expression levels across tissues; and the relationship between tissue ACE2 expression and COVID-19.

ACE2 Expression in Tissue and Organs

Comparing the expression of TMPRSS2 and ACE2 reveals their overlaps and differences across human tissues and demographics. Both genes are coexpressed in respiratory and intestinal cells, and their overall expression levels are largely similar across sexes. However, their primary expression sites differ significantly: TMPRSS2 is expressed most highly in the prostate and more than ACE2 in the lungs, whereas ACE2 is most highly expressed in the testes.

Comparison of TMPRSS2 and ACE2 Expression

This node organizes findings about circulating ACE2, including comparisons with circulating ACE and reported associations between circulating ACE2 levels and COVID-19 symptom severity.

Circulating ACE2: Levels and Association with COVID-19 Symptoms

- subcellular expression
- tissue and organ expression
- mediators that influence expression
- comparing to TMPRSS2 expression
- circulating expression
- expression in embryonic development

Michigan State University

Smith College

ACE2 is located on the X chromosome (Xp22), and belongs to a subset of genes that escapes X-inactivation, showing a heterogenous sex bias and evolutionary characteristics of tissue specificity and expression (Tukiainen et. al). However, expression differences in distinct tissues suggest presence of X-inactivation, though incomplete.

The figure below shows ACE2 preferential expression in males (blue). 

ACE2 Chromosomal Localization and Activation.

Allelic variants in the ACE2 gene has been observed in different ethinic populations, as well as in case-control studies within ethnic groups. However, these are present in relatively low frequencies. Functional studies are encouraged to characterize the relationship between ACE2 variants and COVID-19 severity, but no causal relationship can be made to date.

Learn Before

Related

Learn After

Learn After

Related