Fig. 2. The variable expression of chaperones across human tissues.

a The distribution of 43 chaperones with known aberrations that are causal for Mendelian diseases by the number of tissues expressing them at a level ≥1 transcripts per million (TPM) or above (denoted heredity disease chaperones), and the distribution of the respective 62 Mendelian diseases by the number of tissues in which they manifest clinically (denoted heredity diseases). We united sub-parts of the same tissue (e.g., adipose subcutaneous and adipose visceral omentum were united into a single adipose tissue), ending up with 20 united tissues. Most hereditary diseases are highly tissue-specific (Supplementary Data 3). In contrast, hereditary disease chaperones are expressed ubiquitously across tissues, also when considering other expression thresholds (Supplementary Fig. 1E). b A clustered heatmap showing the differential expression of 194 chaperones across tissues. Differential expression of a chaperone in a tissue was computed by comparing the expression profiles of that tissue to the expression profiles of all other tissues. Each entry reflects the log₂ fold-change value (log₂fc) of a chaperone (row) in a tissue (column); red and blue denote positive and negative log₂fc values, respectively. Physiologically related tissues often clustered together. c The overlap between 57 chaperones that were upregulated (log₂fc ≥ 1) in human skeletal muscle relative to other tissues, and the 10 chaperones with a known aberration that causes heritable muscle disorders. Seven chaperones were both upregulated and associated with muscle disorders (p = 0.0078, one-sided Fisher exact test). Source data are provided as a Source Data file.