| General information | Literature | Expression | Regulation | Mutation | Interaction |
|
Basic Information |
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|---|---|
Gene ID | 4089 |
Name | SMAD4 |
Synonymous | DPC4|JIP|MADH4|MYHRS;SMAD family member 4;SMAD4;SMAD family member 4 |
Definition | MAD homolog 4|SMAD, mothers against DPP homolog 4|deleted in pancreatic carcinoma locus 4|deletion target in pancreatic carcinoma 4|mothers against decapentaplegic homolog 4|mothers against decapentaplegic, Drosophila, homolog of, 4 |
Position | 18q21.1 |
Gene type | protein-coding |
Source | Count: SMAD4; 4089 |
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Sentence |
Abstract |
| "A putative splice site mutation in SMAD4 resulted in moderate transcript loss due to compromised splicing efficiency in PAH, pulmonary arterial hypertension." | Heterozygous germline mutations of BMPR2 contribute to familial clustering of pulmonary arterial hypertension (PAH). To further explore the genetic basis of PAH in isolated cases, we undertook a candidate gene analysis to identify potentially deleterious variation. Members of the bone morphogenetic protein (BMP) pathway, namely SMAD1, SMAD4, SMAD5, and SMAD9, were screened by direct sequencing for gene defects. Four variants were identified in SMADs 1, 4, and 9 among a cohort of 324 PAH cases, each not detected in a substantial control population. Of three amino acid substitutions identified, two demonstrated reduced signaling activity in vitro. A putative splice site mutation in SMAD4 resulted in moderate transcript loss due to compromised splicing efficiency. These results demonstrate the role of BMPR2 mutation in the pathogenesis of PAH and indicate that variation within the SMAD family represents an infrequent cause of the disease.CI - (c) 2011 Wiley Periodicals, Inc. |