SMAD4 was first reported in relation to autosomal dominant pulmonary arterial hypertension (PAH) in 2011 (Nasim et al., PMID:21898662) in a cohort of PAH patients without BMPR2 variants and screened for variants in SMAD candidate genes. In total, four SMAD4 variants (missense, non-canonical splice, and in frame deletion) have been reported (PMIDs: 21898662, 31727138). However, none of the variants were scorable. The relationship between SMAD4 and PAH is supported by SMAD4 biochemical function in rats with pulmonary hypertension (PMID:18367643). However, the gene-disease relationship betwen SMAD4 and PAH is classified as disputed due to insufficient genetic evidence over multiple years of research. This classification was approved by the ClinGen PH Gene Curation Expert Panel on 8/30/2022 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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