Table 2.  Missense mutation overview for the Connexin47 protein: molecular modelling analysis.

Mutation a	Position b	Modelling analysis prediction	References c
p.Ile33Met (Ile36Met)	TMD	Possible interference of the long 33Met side chain with the canonical hydrogen bonding between the adjacent helices. 33Met, being in short contact with the Trp3 side chain, might cause the displacement of the N-terminal helix of each Cx47 monomer towards the inner side of the hemichannel thus (partially) blocking the pore.	14
p.Ile43Met (Ile46Met)	TMD	The replaced 43Met might interact with Arg257, thus perturbing the salt bridge formed between Asp46, Arg257 and Glu260, and possibly misplacing the extracellular loop of the connexon.	9
p.Pro87Ser (Pro90Ser)	TMD	The new Pro87, inducing a 30° kink in α-helix could alter the transport properties.	2
p.Gly146Ser (Gly149Ser)	ICD	146Ser introduces less flexible residues in place of a glycine adding a polar group within the cytoplasmatic region of the protein.	7
p.Gly233Ser (Gly236Ser)	ECD	233Ser introduces less flexible residues in place of a glycine adding a polar group between the extracellular and the membrane region of the protein.	4
p.Gly233Arg (Gly236Arg)	ECD	233Arg introduces less flexible residues in place of a glycine adding a charged group between the extracellular and the membrane region of the protein. This could mildly interfere with the correct formation of the pore.	7
p.Glu260Lys	ECD	See legend of Figure 2.	Present study
p.Thr262Ala (Thr265Ala)	TMD	The new hydrophobic 262Ala residue, replacing a polar threonine, is supposed to prevent a H-bond formation with Glu235.	7
p.Tyr269Asp (Tyr272Asp)	TMD	The new 269Asp adds a negative charge in the membrane deleting at the same time, the contribution of the aromatic ring of the tyrosine.	2
p.Met283Thr (Met286Thr)	TMD	283Thr changes the local hydrophobic properties of a transmembrane helix by introducing a polar residue.	2

Abbreviations: ECD, Extracellular domain; ICD, Intracellular domain; TMD, Transmembrane domain.

^aAll mutations are described according to Orthmann-Murphy et al.¹⁶ Traditional amino-acid residue numbering has nevertheless also been provided in parentheses. Note that p.Thr395Ile (Thr398Ile), occurring in a region of the model having low homology (see Material and Methods), was excluded from this analysis.

^bPosition is given according to UniProtKB http://www.uniprot.org/.²⁷

^cReferred to the first report.