*4.7. Protein Expression in Human Tissues*

Expression levels of human RTT-related proteins in each tissue were extracted from the Human Protein Atlas (https://www.proteinatlas.org/; release 2019\_4) [45] and classified into 37 tissues. The protein expression level was determined using the TPM value, which was corrected for protein expression by gene length. Comparisons of protein expression levels were not shown as a ratio so that proteins with high expression did not skew the results (Equations (1)–(3)). The mean and standard deviation were derived from Equations (1) and (2), and the range was obtained from Equation (3). The range in Equation (3) was taken as the tissue for each of the specifically expressed proteins—i.e., the value was "1" when included in the range of Equation (3) and "0" when it was not included in the expression level of each protein expressed as a percentage. The procedure yielded human protein-specific expression profiles in the context of RTT.

$$\mu = \frac{1}{n} \sum\_{i=0}^{n} x\_i \tag{1}$$

$$s = \sqrt{\frac{1}{n} \sum\_{i=0}^{n} (\mathbf{x}\_i - \boldsymbol{\mu})^2} \tag{2}$$

$$
\mu + 1.65 \times s \quad \text{<} \tag{3}
$$

Here, μ, *s*, *n*, and *x* are the mean, standard deviation, number of samples, and one sample, respectively. The value of 1.65 in Equation (3) is the standard confidence factor for extracting data outside the 90% confidence interval.

### *4.8. GO Analysis*

Specific GO categories in the target protein group were obtained using the Panther tool [85]. Categories with an appearance frequency of *p* < 0.05 were defined as protein group-specific. In this study, we obtained GO categories specific for human proteins related to RTT that were classified based on defined functions.
