Table 1.
PAH causal channelopathy genes and associated variant allele frequencies/characteristics across multiple studies.
| Gene | Gene Name | Number of Cases (%) | PAH Subclass 1 | Variant Type 2 | Mode of Inheritance 3 |
|---|---|---|---|---|---|
| ABCC8 | ATP-binding cassette subfamily C member 8 | 49/3521 (1.4%) [6,10,11,12,13] |
H/I/APAH APAH-CTD APAH-CHD APAH-HIV PPHN |
missense, LGD | AD |
| ATP13A3 | ATPase 13A3 | 27/4012 (0.7%) [6,8,12,14,15,16] |
H/IPAH APAH-CTD APAH-CHD APAH-MS/IFNβ-1a |
LGD, missense | Semi-dominant |
| KCNK3 | Potassium two-pore domain channel subfamily K member 3 | 14/4682 (0.3%) [6,17,18,19,20,21,22] |
H/IPAH | missense | AD |
1 H/IPAH, hereditary or idiopathic pulmonary arterial hypertension; APAH-CTD, PAH associated with connective tissue diseases; APAH-CHD, PAH associated with congenital heart disease; PAH associated with HIV; PPHN, persistent pulmonary hypertension of the newborn; APAH-MS/IFNβ-1a, PAH associated with interferon beta 1a treatment in multiple sclerosis; APAH-porto, PAH associated with portopulmonary disease. Bold typeface indicates primary PAH subclass. 2 Variants filtered by gnomAD allele frequency < 0.0001 and variant type likely gene disrupting (LGD, stopgain, frameshift, splicing) or damaging missense defined by CADD ≥ 20. Bold typeface indicates primary variant type. 3 MOI, mode of inheritance; AD, autosomal dominant.