Table 1

Pathogenic BMPR2Mutations in PAH

LocationMutation CategoryDomainNucleotide ChangeAmino Acid ChangeFrequency in This StudyCommentReference
5′ UTRMissensec.*-944/5GC>AT1HAldred et al. (36)
5′ UTR and Exon 1Deletionc.?_-540_76+?del1HThis analysis
Exon 1Missensec.28C>Tp.T10W1IBaloira et al. (37)
Nonsensec.71C>Ap.A24E1IThis analysis
Intron 1Splice-sitec.76+5G>A1IThis analysis
Exon 2NonsenseECDc.124C>Tp.Q42X1IFujiwara et al. (38)
FrameshiftECDc.186insTACCp.G63fsX11HThis analysis
FrameshiftECDc.189_207delins14p.S64EfsX321ASD/PAHThis analysis
DeletionECDc.189-209del21p.del6470(STCYGLW)1HThis analysis
NonsenseECDc.201T>Gp.Y67X1HThis analysis
MissenseECDc.247G>Ap.G83R1IThis analysis
Exons 1–4DeletionECDc.1-?_419+?del1IThis analysis
Exons 1–8DeletionECDc.1-?_1128+?del1IThis analysis
Intron 2Splice-siteECDc.247+1delCAAGTG1HThis analysis
Splice-siteECDc.247+1_+4 delGTAAp.C84_S140del1IThis analysis
Splice-siteECDc.248-2A>G1HThis analysis
Splice-siteECDc. 248-5 delTATAGGinsAC1HThis analysis
Exon 3MissenseECDc.248G>Ap.G83E1HThis analysis
MissenseECDc.250T>Cp.C84R1HThis analysis
MissenseECDc.250T>Gp.C84G1IThis analysis
FrameshiftECDc.261insAp.87fsX91HThis analysis
MissenseECDc.295T>Cp.C99R1HThis analysis
MissenseECDc.296G>Tp.C99F1IThis analysis
MissenseECDc.296G>Ap.C99Y1HThis analysis
NonsenseECDc.339C>Ap.Y113X1IThis analysis
NonsenseECDc.339C>Gp.Y113X1IFujiwara et al. (38)
MissenseECDc.350G>Ap.C117Y1HThis analysis
NonsenseECDc.354-355TA>AGp.C118X1HThis analysis
MissenseECDc.367T>Cp.C123R1IFujiwara et al. (38)
MissenseECDc.370A>Gp.N124D1IThis analysis
MissenseECDc.377A>Gp.N126S1IThis analysis
DeletionECDc.248-?_418+?del2H,HThis analysis
Exon 2–3DeletionECDc.77-?_418+?del5H,H,H,H,IThis analysis
Intron 3Splice-siteECDc.418+1G>C1HThis analysis
Splice-siteECDc.418+5G>A2HThis analysis
Exons 4–5DeletionECDc.419-?_621+?del2H,IThis analysis
Exon 5NonsenseTMc.583G>Tp.E195X1PVODThis analysis
MissenseTMc.604A>Tp.N202Y1PVODThis analysis
Exon 6FrameshiftKDc.612delAp.L204fsX51HThis analysis
NonsenseKDc.631C>Tp.R211X2HThis analysis
FrameshiftKDc.660insGp.G220fsX41NKThis analysis
FrameshiftKDc.690-691delAGinsTp.K239fsX211HThis analysis
MissenseKDc.794A>Gp.E265G1IThis analysis
MissenseKDc.797G>Cp.R266T1NKThis analysis
MissenseKDc.806G>Tp.A268V1IBaloira et al. (37)
Intron 6Splice-siteKDc.852+1G>C1IThis analysis
Splice-siteKDc.853-1G>C1HThis analysis
Exon 7NonsenseKDc.928A>Tp.R310X1IThis analysis
MissenseKDc.932G>Ap.G311E1HThis analysis
Exon 8MissenseKDc.1019T>Cp.L340P1HThis analysis
NonsenseKDc.1189-1190delTGp.C347X1HThis analysis
MissenseKDc.1042G>Ap.V348E1HThis analysis
FrameshiftKDc.1095delCp.R365fsX81HThis analysis
FrameshiftKDc.1099-1103delGGGGAp.E368fsX11HThis analysis
DeletionKDc.968-?_1129+?del1HThis analysis
Intron 8Splice-siteKDc.968-5A>G1HThis analysis
Exon 9MissenseKDc.1157A>Tp.E386V1HFu et al. (39)
MissenseKDc.1171G>Ap.A391T1IThis analysis
NonsenseKDc.1207C>Tp.Q403X1HFujiwara et al. (38)
FrameshiftKDc.1214delAp.D405fsX61HThis analysis
NonsenseKDc.1248-1251delATTTp.F417X1HThis analysis
FrameshiftKDc.1271delTCCCAGinsCGGAGAp.F424fsX101HThis analysis
Intron 9Splice-siteKDc.1276+1G>A1HThis analysis
Splice-siteKDc.1277-9A>G1HThis analysis
Exon 10NonsenseKDc.1297C>Tp.Q433X2I,NKThis analysis
FrameshiftKDc.1392delAp.A465fsX91HThis analysis
Exon 11MissenseKDc.1460A>Tp.D487V1HThis analysis
MissenseKDc.1472G>Ap.R491Q1IThis analysis
Exon 12MissenseCDc.1598A>Gp.H533R1IThis analysis
FrameshiftCDc.2410-2413delGTCAp.V804fsX11HThis analysis
FrameshiftCDc.2441-2442delACp.H814fsX21HThis analysis
FrameshiftCDc.2504insAp.T835fsX61PAH+collagen diseaseThis analysis
FrameshiftCDc.2609del Tp.L870fsX11IThis analysis
NonsenseCDc.2626C>Tp.Q876X1HThis analysis
NonsenseCDc.2695C>Tp.R899X2IThis analysis
NonsenseCDc.2789C>Gp.S930X2IThis analysis
Exon 13MissenseCDc.2945A>Gp.L982R1HThis analysis

Numbering is based on +1 of the initiation methionine.

ASD = atrial-septal defect; CD = cytoplasmic domain; ECD = extracellular domain; F = familial; I = idiopathic; KD = kinase domain; NK = not known; PAH = pulmonary arterial hypertension; PVOD = pulmonary veno-occlusive disease; TM = transmembrane; UTR = untranslated region.