Table 3.
Supporting evidence for the role of risk genes in PAH pathogenesis. Abbreviations: (+) indicates that the paper provides information in favour of the role of the given gene in the pathogenesis of PAH, (−) indicates that the paper does not provide support for the role of the given gene in the pathogenesis of PAH.
| Forward Genetics | Reverse Genetics | |||||
|---|---|---|---|---|---|---|
| Gene | Case-Control Data | Case-Level Data | Segregation Data | Functional Aberration | Disease Model | Rescue |
| MOI: Autosomal Dominant | ||||||
| BMPR2 | (+) [24,25] | (+) [101,114] | (+) [101,122] | (+) [123,124,125,126,127,128,129,130] | Animal: (+) [123,126,128,129,130,131] Cell culture: (+) [124,129,130] | (+) [128,129,130,131] (+) |
| ACVRL1 | (+) [24] | (+) [25,103,105,114] | (+) [103] | |||
| ENG | (−) [24,25] | (+) [24,75,104] | (+) [104] | Animal: (−) [132] | ||
| SMAD9 | (−) [24,25] | (+) [24,25,75,106,114] | (+) [54,106,133] | Animal: (+) [134] Cell culture: (+) [54,106,133] |
(+) [133,135] | |
| SMAD1 | (−) [24,25] | (+) [54], (−) [24,25] | (+) [54,136] | Animal: (+) [136] Cell culture: (+) [54] | ||
| SMAD4 | (−) [24,25] | (+) [25,54], (−) [24] | (+) [54], (−) [54] | Cell culture: (+) [54] | ||
| CAV1 | (+) [74] | (+) [25,75], (−) [24] | (+) [137] | Animal: (+) [138,139] Cell culture: (+) [137] | (+) [137] | |
| TBX4 | (+) [24,140] | (+) [75,108,114,141,142] | (+) [143,144] | |||
| KCNK3 | (+) [24,25,107] | (+) [107] | (+) [107,145] | Animal: (+) [146] Cell culture: (+) [107,145] | (+) [107] | |
| ATP13A3 | (+) [24] | (+) [147,148] | Animal: (+) [147,148] | |||
| AQP1 | (+) [24] | (+) [149,150] (−) [149] | Animal: (+) [149,151] Cell culture: (+) [150] | (+) [149] | ||
| GDF2 | (+) [24,25,26] | (+) [114] | (+) [115] | (+) [26,115] | Animal: (−) [152] Cell culture: (+) [26,115] | |
| SOX17 | (+) [24,75] | (+) [112] | (+) [153,154] | Animal: (+) [153] Cell culture: (+) [154] | ||
| ABCC8 | (+) [113] | (+) [113] | (+) [113] | Cell culture: (+) [113] | (+) [113] | |
| BMP10 | (+) [114,115] | |||||
| GGCX | (+) [25] | |||||
| KLK1 | (+) [25] | |||||
| KDR | (+) [30] | (+) [30,117] | (+) [155] | Animal: (+) [155] | ||
| FBLN2 | (+) [118] | |||||
| PDGFD | (+) [118] | |||||
| TET2 | (+) [55] | (+) [55] | Animal: (+) [55] | (+) [55] | ||
| BMPR1A | (+) [25,75] | (+) [156,157,158,159] | Animal: (+) [156,157,159] | (+) [156] | ||
| BMPR1B | (+) [24,25,75] | (+) [160] | Cell culture: (+) [160] | |||
| TOPBP1 | (+) [24] | |||||
| THBS1 | (+) [161] | Cell culture: (+) [161] | (+) [161] | |||
| KCNA5 | (+) [162] | (+) [163] | Cell culture: (+) [163] | (+) [163] | ||
| MOI: Autosomal Recessive | ||||||
| EIF2AK4 | (+) [111] | (+) [114] | (+) [109,110] | (+) [109] | Animal: (+) [164] | |
| Common Variation | ||||||
| enhancer near SOX17 | (+) [116] | (+) [116] | (+) [116] | |||
| locus within HLA-DPA1/DPB1 | (+) [116] | |||||
| CBLN2 | (+) [165] (−) [116] |
|||||
| SIRT3 | (+) [166] | (+) [166] | (+) [166] | Animal: (+) [166,167] | ||
| UCP2 | (+) [168] | Animal: (+) [167,169] | ||||
| EDN1 | (+) [170] | (+) [171] | ||||
| AGTR1 | (+) [34] | |||||
| TOPBP1 | (+) [172] | (+) [172] | Cell culture: (+) [172] | |||
| Endostatin | (+) [173] | |||||
| TRPC6 | (+) [174] | Cell culture: (+) [174] | ||||