SMAD3 SMAD family member 3

Gene info


JV15-2, HsT17436

Previous symbol


External ID

HGNC: 6769
Entrez Gene: 4088
Ensembl: ENSG00000166949
UCSC: uc002aqj.4
OMIM: 603109
UniProtKB: P84022

Disease info


CHD Phenotype

  • Ventricular septal defect
  • Patent ductus arteriosus
  • Pulmonic stenosis
  • Hypoplastic left heart syndrome

Extra Cardiac Phenotype

Hypertelorism , Abnormal uvula , High-arched palate, Cleft palate, Dental malocclusion , Pectus deformity , Umbilical hernia , Inguinal hernia, Bowel prolapse , Uterine prolapse , Bladder prolapse, Osteoporosis , Intervertebral disc degeneration , Facet joint osteoarthritis , Uncovertebral (C3-C7) joint osteoarthritis , Dural ectasia , Scoliosis , Spondylysis , Spondylolisthesis, Hip osteoarthritis , Protrusio acetabuli, Long bone overgrowth (dolichostenomelia) ,Osteochondritis dissecans , Knee osteoarthritis , Meniscal lesions , Wrist osteoarthritis , Ankle osteoarthritis, Joint laxity, Hand osteoarthritis , Arachnodactyly , Camptodactyly, Foot osteoarthritis , Pes planus, Skin velvety, Striae , Easy bruisability , Atrophic scarring

Incomplete penetrance


Variable expressivity


Animal model

Mouse study

MGI: No CHD in knockout mice


Variant info


Selected variant

The Clinvar variants presented in the below IGV track were selected based on the following criteria.

  1. Variant types are single nucleotide variant or Indel
  2. Clinical significance for the variant was assessed to be Pathogenic or Likely Pathogenic
  3. ClinVar review status for the variant is criteria provided

Download annotation file for SMAD3: BED file

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Selected References

  1. Li, F.-F., Zhou, J., Zhao, D.-D., Yan, P., Li, X., Han, Y., Li, X.-S., Wang, G.-Y., Yu, K.-J., & Liu, S.-L. (2015). Characterization of SMAD3 Gene Variants for Possible Roles in Ventricular Septal Defects and Other Congenital Heart Diseases. PLOS ONE, 10(6), e0131542. DOI:10.1371/journal.pone.0131542 PMID:26110764
  2. van de Laar, I. M. B. H., Oldenburg, R. A., Pals, G., Roos-Hesselink, J. W., de Graaf, B. M., Verhagen, J. M. A., Hoedemaekers, Y. M., Willemsen, R., Severijnen, L.-A., Venselaar, H., Vriend, G., Pattynama, P. M., Collée, M., Majoor-Krakauer, D., Poldermans, D., Frohn-Mulder, I. M. E., Micha, D., Timmermans, J., Hilhorst-Hofstee, Y., … Bertoli-Avella, A. M. (2011). Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis. Nature Genetics, 43(2), 121–126. DOI:10.1038/ng.744 PMID:21217753
  3. Fitzgerald, K. K., Bhat, A. M., Conard, K., Hyland, J., & Pizarro, C. (2014). NovelSMAD3Mutation in a Patient with Hypoplastic Left Heart Syndrome with Significant Aortic Aneurysm. Case Reports in Genetics, 2014, 1–4. DOI:10.1155/2014/591516 PMID:24711937