SMAD1 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 the candidate SMAD genes. One missense variant with MAF <=0.0001 was identified. In total, two SMAD1 missense variants with MAF <=0.0001 have been reported in two HPAH/IPAH probands in 2 publications (PMIDs: 21898662, 33007923). Experimental evidence for a relationship between SMAD1 and PAH is supported by biochemical function from three publications (PMIDs: 18367643, 23478097, 21898662) and in conditional kock out mice in which a subset of KO mice developed pulmonary hypertension. However, the gene-disease relationship betwen SMAD1 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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