Results - Ttc29

Ttc29:Eno2

Eno2 was predicted to bind Ttc29 approximately half-way through the polypeptide chain of Ttc29. Residues near the binding site are predicted with medium confidence.

Ttc29:Zmynd12

Zmynd12 is predicted to bind Ttc29 more towards the N-terminus than Eno2. Residues near the binding site are predicted with a higher degree of confidence.

Ttc29 mutant

c.977+1G>T (p.Ser326Pro fs*8)

The disease-causing patient allele Ser326Pro fs*8 causes a frame shift that truncates the protein, resulting in the loss of exon9 and missense of several amino acid residues. Pictured below is the wild type mutation with exon 9 highlighted in orange, next to the AlphaFold2 prediction of the mutant protein.

Mutant Ttc29 - Eno2 and Zmynd12

The truncation occurs on the C-terminus of the protein, and likely does not affect binding of Eno2 and Zmynd12. The highlighted truncation is pictured below, this time with binding partners included in green and magenta.

Wild Type Ttc29 Dimer

Because the disease allele truncates the C-terminus, some other protein-protein interaction may be disrupted. Candidate genes Dnah1 and Myh10 were too large to run on AlphaFold2 Multimer with current capabilities. Another possible behavior of Ttc29 is dimerization. Pictured below is the AlphaFold2 prediction of a Ttc29 dimer. The region involved in dimerization is predicted with a high confidence.

Mutant Ttc29 Dimer

To see if the truncating mutation affects Ttc29 dimerization, I ran the mutant isoform of Ttc29 on AlphaFold2 Multimer. While the C-termini are clearly lost, dimerization appears to remain largely unaffected, and the interacting regions are still predicted with high confidence.