Functional significance of ACVRL1 mutations
| Mutation location . | Mutation category . | Nucleotide change . | Amino acid change . | Location of mutation . | Novel mutation . | Conflicting mutation* . | Expression . | Localization . | BMP9 binding . | BMP9 response . |
|---|---|---|---|---|---|---|---|---|---|---|
| Exon 3 | Missense | c.152G → A | p.C51Y | Extracellular | — | — | Yes | Intracellular | No | No |
| Exon 3 | Missense | c.231C → G | p.C77W | Extracellular | — | — | Yes | Partial cell surface | No | No |
| Exon 3 | Missense | c.286A → G | p.N96D | Extracellular | — | — | Yes | Intracellular | No | No |
| Exon 5 | Missense | c.536A → C | p.D179A | GS domain | — | — | Yes | Cell surface | Yes | Yes |
| Exon 7 | Missense | c.1039G → C | p.A347P | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Missense | c.1121G → A | p.R374Q | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Missense | c.1120C → T | p.R374W | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Frameshift | c.1112_1113dupG | p.G371fsX391 | Kinase domain | — | — | Yes | Cell surface | No | No |
| Exon 8 | Missense | c.1142T → C | p.L381P | Kinase domain | Yes | Yes | Yes | Not tested | Not tested | No |
| Exon 8 | Missense | c.1156C → T | p.R386C | Kinase domain | Yes | Yes | Yes | Not tested | Not tested | Yes |
| Exon 8 | Missense | c.1232G → C | p.R411P | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Missense | c.1232G → A | p.R411Q | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Missense | c.1231C → T | p.R411W | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 9 | Missense | c.1360C → T | p.R454W | Kinase domain | Yes | Yes | Yes | Not tested | Not tested | Yes |
| Exon 10 | Missense | c.1436G → A | p.R479Q | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 10 | Missense | c.1445C → T | p.A482V | Kinase domain | — | Yes | Yes | Not tested | Not tested | Yes |
| Exon 10 | Missense | c.1451G → A | p.R484Q | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 10 | Missense | c.1451C → T | p.R484W | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 10 | Missense | c.1453A → T | p.I485F | Kinase domain | Yes | — | Yes | Cell surface | Yes | No |
| Mutation location . | Mutation category . | Nucleotide change . | Amino acid change . | Location of mutation . | Novel mutation . | Conflicting mutation* . | Expression . | Localization . | BMP9 binding . | BMP9 response . |
|---|---|---|---|---|---|---|---|---|---|---|
| Exon 3 | Missense | c.152G → A | p.C51Y | Extracellular | — | — | Yes | Intracellular | No | No |
| Exon 3 | Missense | c.231C → G | p.C77W | Extracellular | — | — | Yes | Partial cell surface | No | No |
| Exon 3 | Missense | c.286A → G | p.N96D | Extracellular | — | — | Yes | Intracellular | No | No |
| Exon 5 | Missense | c.536A → C | p.D179A | GS domain | — | — | Yes | Cell surface | Yes | Yes |
| Exon 7 | Missense | c.1039G → C | p.A347P | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Missense | c.1121G → A | p.R374Q | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Missense | c.1120C → T | p.R374W | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Frameshift | c.1112_1113dupG | p.G371fsX391 | Kinase domain | — | — | Yes | Cell surface | No | No |
| Exon 8 | Missense | c.1142T → C | p.L381P | Kinase domain | Yes | Yes | Yes | Not tested | Not tested | No |
| Exon 8 | Missense | c.1156C → T | p.R386C | Kinase domain | Yes | Yes | Yes | Not tested | Not tested | Yes |
| Exon 8 | Missense | c.1232G → C | p.R411P | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Missense | c.1232G → A | p.R411Q | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 8 | Missense | c.1231C → T | p.R411W | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 9 | Missense | c.1360C → T | p.R454W | Kinase domain | Yes | Yes | Yes | Not tested | Not tested | Yes |
| Exon 10 | Missense | c.1436G → A | p.R479Q | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 10 | Missense | c.1445C → T | p.A482V | Kinase domain | — | Yes | Yes | Not tested | Not tested | Yes |
| Exon 10 | Missense | c.1451G → A | p.R484Q | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 10 | Missense | c.1451C → T | p.R484W | Kinase domain | — | — | Yes | Cell surface | Yes | No |
| Exon 10 | Missense | c.1453A → T | p.I485F | Kinase domain | Yes | — | Yes | Cell surface | Yes | No |
Patients with another described mutation in ENG or ACVRL1.