Table 1.
TMC mutations in diseases of humans and rodents
| Gene | Mutations | Predicted effect | Ex/in number | Phenotype | References |
|---|---|---|---|---|---|
| Human | |||||
| TMC1 | c.16 + 1G > T, | Splice disruption | Intron 5 | Hearing impairment | [7, 68–95] |
| c.100C > T, | p.R34X nonsense | Exon 7 | |||
| c.1543T > C, | p.C515R missense | Exon 17 | |||
| c.2004T > G, | p.S668R missense | Exon 21 | |||
| c.64 + 2T > A, | Splice disruption | Intron 6 | |||
| c.1330G > A, | p.G444R missense | Exon 16 | |||
| c.1333C > T, | p.R445C missense | Exon 16 | |||
| c.2030T > C, | p.I677T missense | Exon 21 | |||
| c.1696_2283del, | 431 kb deletion | Exon 19 | |||
| c.195_16del, | 27 kb deletion | Exon 5 | |||
| c.295delA, | p.K99KfsX4 | Exon 8 | |||
| c.536-8T > A, | Splice disruption | Intron 10 | |||
| c.884 + 1G > A, | Splice disruption | Intron 13 | |||
| c.1534C > T, | p.R512X nonsense | Exon 17 | |||
| c.1960A > G, | p.M654V missense | Exon 20 | |||
| c.776 + 1G > A, | Splice disruption | Exon 7 | |||
| c.767delT, | p.F255FfsX14 | Exon 13 | |||
| c.1166G > A, | p.R389Q missense | Exon 15 | |||
| c.1810C > T, | p.R604X nonsense | Exon 20 | |||
| c.1165C > T, | p.R389X nonsense | Exon 15 | |||
| c.1764G > A, | p.W588X nonsense | Exon 20 | |||
| c.237-6T > G, | Splice disruption | Intron 7 | |||
| c.453 + 2T > C, | Splice disruption | Intron 9 | |||
| c.628_630delATC, | p.I210del | Exon 11 | |||
| c.800G > A, | p.G267E missense | Exon 13 | |||
| c.1114G > A, | p.V372M missense | Exon 15 | |||
| c.1566 + 1G > A, | Splice disruption | Intron 17 | |||
| c.596A > T, | p.N199I missense | Exon 11 | |||
| c.1404 + 1G > T, | Splice disruption | Intron 16 | |||
| c.1788C > A, | p.S596R missense | Exon 20 | |||
| c.150delT, | p.N50KfsX25 | Exon 7 | |||
| c.362 + 18A > G, | p.Glu122Tyrfs*10 | Exon 8 | |||
| c.1714G > C, | p.D572N missense | Exon 9 | |||
| c.1714G > A, | p.D572H missense | Exon 9 | |||
| c.236 + 1G > C, | Splice disruption | Intron 7 | |||
| c.458G > A, | p.W153X nonsense | Exon 10 | |||
| c.582G > A, | p.W194X nonsense | Exon 11 | |||
| c.589G > A, | p.G197R missense | Exon 11 | |||
| c.776A > G, | p.Y259C missense | Exon 13 | |||
| c.797T > C, | p.I266T missense | Exon 13 | |||
| c.821C > T, | p.P274Lmissense | Exon 13 | |||
| c.830A > G, | p.Y277C missense | Exon 13 | |||
| c.1083_1087del, | p.R362PfsX6 | Exon 15 | |||
| c.1107C > A, | p.N369K missense | Exon 15 | |||
| c.1171C > T, | p.Q391X nonsense | Exon 15 | |||
| c.1209G > C, | p.W403C missense | Exon 15 | |||
| c.1334G > A, | p.R445H missense | Exon 16 | |||
| c.1396_1398AAC, | p.N466del | Exon 16 | |||
| c.1312G > A, | p.A438T missense | Exon 16 | |||
| c.1253T > A, | p.M418K missense | Exon 16 | |||
| c.1249G > A, | p.G417R missense | Exon 16 | |||
| c.1247T > G, | p.L416R missense | Exon 16 | |||
| c.1589_1590delCT, | p.S530X frameshift | Exon 18 | |||
| c.1718T > A, | p.I573N missense | Exon 19 | |||
| c.1714G > A, | p.D572N missense | Exon 19 | |||
| c.1714G > C, | p.D572H missense | Exon 19 | |||
| c.1763 + 3A > G, | p.W588WfsX81 | Intron 19 | |||
| c.IVS19 + 5G > A, | splice disruption | Intron 19 | |||
| c.1939T > C, | p.S647P missense | Exon 20 | |||
| c.1959C > G, | p.Y653X missense | Exon 20 | |||
| c.1979C > T, | p.P660L missense | Exon 20 | |||
| c.2035G > A, | p.E679K missense | Exon 21 | |||
| c.2050G > A, | p.D684N missense | Exon 21 | |||
| c.2130_1delG, | splice disruption | Exon 22 | |||
| c.2210_2211insCT, | p.E737HfsX2 | Exon 23 | |||
| c.2260 + 2T > A | splice disruption | Intron 23 | |||
| TMC2 | Unknown | Unknown | Unknown | Unknown | |
| TMC3 | Unknown | Unknown | Unknown | Unknown | |
| TMC4 | Unknown | Unknown | Unknown | Unknown | |
| TMC5 | Up-regulated | Unknown | Unknown | Intrahepatic cholangiocarcinoma (ICC) | [96] |
| TMC6 (EVER1) | c.280C → T, | p.R94X nonsense | Exon 5 | Epidermodysplasia verruciformis (EV) | [97, 98] |
| c.1726G → T | p.G576X nonsense | Exon 14 | |||
| TMC7 | Unknown | Unknown | Unknown | Unknown | |
| TMC8 (EVER2) | c.754/755delT, | p.F252fs X283 | Exon 7 | Epidermodysplasia verruciformis (EV) | [97, 98] |
| c.1084G → T | p.E362X nonsense | Exon 9 | |||
| Rodents | |||||
| TMC1 | c.1235T > A (Beethoven mutation), | p.M412K missense | Exon 13 | Deafness | [7, 8, 38, 99, 100] |
| c.1387_1557del (deafness mutation), | p.I463_Q519del | Exon 14 | |||
| c.545A > G (baringo mutation), | p.Y182C missense | Exon 8 | |||
| c.1345T > C (nice mutation), | p.Y449H missense | Exon 13 | |||
| c.1661G > T (stitch mutation), | p.W554L missense | Exon 15 | |||
| Tmc1Δ/Δ | Targeted deletion | ||||
| TMC2 | Unknown | Unknown | Unknown | Unknown | |
| TMC3 | Unknown | Unknown | Unknown | Unknown | |
| TMC4 | Unknown | Unknown | Unknown | Unknown | |
| TMC5 | Unknown | Unknown | Unknown | Unknown | |
| TMC6 | Unknown | Unknown | Unknown | Unknown | |
| TMC7 | Unknown | Unknown | Unknown | Unknown | |
| TMC8 | Unknown | Unknown | Unknown | Unknown | |
All annotations are based on cDNAs (c.) of TMC proteins
p protein, del deletion, fs frame shift, ex exon, in intron