SMAD4 SMAD family member 4

Gene info

Synonyms

None

Previous symbol

MADH4

External ID

HGNC: 6770
Entrez Gene: 4089
Ensembl: ENSG00000141646
UCSC: uc060pfa.1
OMIM: 600993
UniProtKB: Q13485

Disease info

Disease

CHD Phenotype

  • Atrial septal defect
  • Ventricular septal defect
  • Patent ductus arteriosus
  • Pulmonic stenosis
  • Aortic stenosis
  • Coarctation of the aorta

Extra Cardiac Phenotype

Short stature , Obesity , Prenatal growth deficiency , Microcephaly , Incomplete jaw opening , Maxillary hypoplasia , Midface hypoplasia, Prognathism , Short philtrum, Small ears , Anomalous middle ear bones , Low-set ears, Deafness , Blepharophimosis , Narrow palpebral fissures , Hypertelorism , Microphthalmia , Hyperopia , Strabismus , Deep-set eyes , Bushy eyebrows , Prominent nasal root , Broad mid-nose , Narrow alar root, Small mouth , Thin upper lip , Cleft lip/palate, Short neck, Laryngotracheal stenosis, Respiratory failure , Cryptorchidism , menstrual abnormality, Decreased joint mobility , Thickened calvarium , Large, flattened vertebrae with large pedicles , Platyspondyly , Vertebral fusions, Hypoplastic iliac wings, Short long bones , Cone-shaped epiphyses, Brachydactyly , Clinodactyly , Camptodactyly , Dupuytren contractures, Toe syndactyly (2-3), Overlapping toes, Thickened skin , Stiff skin, Sparse, fine hair , Generalized muscle hypertrophy , Mental retardation , Seizures, Cerebellar ataxia, Cerebellar atrophy, Autism or autistic-like condition, Abnormal voice

Incomplete penetrance

Yes

Variable expressivity

Yes

Animal model

Mouse study

1

MGI ID

894293

Variant info

Clinvar

SMAD4

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 , Likely Pathogenic or Pathogenic/Likely Pathogenic
  3. ClinVar review status for the variant is criteria provided

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Selected References

  1. Le Goff, C., Mahaut, C., Abhyankar, A., Le Goff, W., Serre, V., Afenjar, A., Destrée, A., di Rocco, M., Héron, D., Jacquemont, S., Marlin, S., Simon, M., Tolmie, J., Verloes, A., Casanova, J.-L., Munnich, A., & Cormier-Daire, V. (2011). Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Nature Genetics, 44(1), 85–88. https://doi.org/10.1038/ng.1016 DOI:10.1038/ng.1016 PMID:22158539
  2. Lin, A. E., Michot, C., Cormier‐Daire, V., L’Ecuyer, T. J., Matherne, G. P., Barnes, B. H., Humberson, J. B., Edmondson, A. C., Zackai, E., O’Connor, M. J., Kaplan, J. D., Ebeid, M. R., Krier, J., Krieg, E., Ghoshhajra, B., & Lindsay, M. E. (2016). Gain‐of‐function mutations in SMAD4 cause a distinctive repertoire of cardiovascular phenotypes in patients with Myhre syndrome. American Journal of Medical Genetics Part A, 170(10), 2617–2631. Portico. https://doi.org/10.1002/ajmg.a.37739 DOI:10.1002/ajmg.a.37739 PMID:27302097