Transmembrane (TM) proteins perform many essential biological roles. The presence of charged amino acids within the TM domain of human proteins has been shown to be functionally relevant. The objective of this research was to characterise this functional importance and gain a greater understanding of how electrostatic interactions within TM domains can influence protein structure, interactions, and overall functionality. Protein sequence and topological information was extracted from UniProtKB/Swiss-Prot to obtain a list of all human proteins containing charged TM amino acids. A heat map was generated to visualise the distribution of these residues along the TM. Information relating to rare genetic variants known to occur in humans was derived from ClinVar to evaluate the clinical significance of TM charge disturbances. Of 5,177 human TM proteins, 3,096 (59.80%) contained at least one charged amino acid within their TM sequence. There were 20,911 unique TM domains among these proteins, 9,678 (46.28%) of which contained a charged residue. These residues were distributed relatively sparsely in TM sequences compared to their hydrophobic counterparts. 34 proteins were identified sharing a total of 84 pathogenic point mutations involving a TM charged residue. Most TM proteins with reported variants were transport proteins, with the most clinically significant variants occurring in the cystic fibrosis transmembrane conductance regulator. Despite scarce distribution, there are many cases of TM charges playing key functional roles. This has implications for our understanding of health and disease processes, providing a basis for therapeutic targeting of these residues.