Beginning August 1, 2023, the University of Utah Department of Pathology and ARUP Laboratories will no longer host this mutation database. Our clinical variant data will be consolidated and shared with free publicly accessible databases such as ClinVar. For any questions or concerns related to the removal of this database from our website, please click here and one of our molecular genetics medical directors will review your submission and get back to you.

Juvenile Polyposis Syndrome and SMAD4  Genetics Home Reference

Initial release: January 2010
Last update: May 2015

Mutations in the SMAD4 gene have been found in patients with Juvenile Polyposis Syndrome (JPS) (~20 percent), patients with combined Juvenile Polyposis/Hereditary Hemorrhagic Telangiectasia (JP/HHT) (100 percent, based on small numbers) or patients with HHT, but without reported symptoms of JPS (2-3 percent, based on small numbers).

JPS is an autosomal dominant condition characterized by the presence of more than five hamartomatuous polyps in the rectum, colon, or GI tract. Affected individuals may experience abdominal pain, diarrhea, rectal bleeding, anemia, and have an increased risk of developing gastrointestinal cancers. HHT is characterized by recurrent nosebleeds, telangiectases (mouth, face, hands, GI tract), and arteriovenous malformations (lung, brain, liver, spine). Arteriovenous malformations (AVMs) are usually congenital, while nosebleeds and external telangiectases often do not present until the second or third decade of life. JP/HHT is characterized by symptoms of both diseases in one or more family members of the same family.

The purpose of this database is to document all known SMAD4 mutations or gene variants including sequence based changes and large deletion/duplications that have been linked to JPS, JP/HHT or HHT, as well as any available associated clinical information or significant literature related to the disorder. The Genbank sequences NC_000018.9, NM_005359.5, and NP_005350.1 were used as reference sequences.

A collaboration between ARUP Laboratories and Ambry Genetics, analyzing a total of 4672 clinical cases for SMAD4 copy number analysis, found evidence of a SMAD4 processed pseudogene in 0.26% of the cases.

ARUP Laboratories offers the following testing:
  • HHT PANEL: Sequencing and Deletion/Duplication (test 2009337)

Database Information

The SMAD4 database currently has 87 total entries.


When citing in publications please use:

Wooderchak WL, Spencer Z, Crockett DK, McDonald J, Bayrak-Toydemir P. Repository of SMAD4 Mutations: Reference for Genotype/Phenotype Correlation. J Data Mining in Genom Proteomics 2010. 1:101 doi:10.4172/2155-0602.1000101.

Database URL: