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liver","onset_id":null,"reference":"ORPHA:44890","source_release":"2026-06-23"},"sourceGroups":["orphanet"]}],"referenceLabels":{},"references":{"causeHtml":"<ul><li><a href=\"https://medlineplus.gov/genetics/condition/gastrointestinal-stromal-tumor\">Gastrointestinal stromal tumor</a></li></ul>","identityNote":"MONDO cross-references identify native condition entries. Ancestor membership does not transfer phenotype values between groups.","importantHtml":""},"sections":[{"bodyHtml":"<p>Genetic changes in one of several genes are involved in the formation of GISTs. About 80 percent of cases are associated with a mutation in the KIT gene, and about 10 percent of cases are associated with a mutation in the PDGFRA gene. Mutations in the KIT and PDGFRA genes are associated with both familial and sporadic GISTs. Less than 10 percent of cases are SDH-deficient GISTs, which are associated with mutations or other changes in the SDHA, SDHB, SDHC, or SDHD gene. SDH-deficient GIST can be familial or sporadic. A small number of people with a GIST have mutations in other genes.</p><p>The KIT and PDGFRA genes provide instructions for making receptor proteins that are found in the cell membrane of certain cell types. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. When a ligand attaches (binds), the KIT or PDGFRA receptor protein is turned on (activated), which leads to activation of a series of proteins in multiple signaling pathways. These signaling pathways control many important cellular processes, such as cell growth and division (proliferation) and survival.</p><p>Mutations in the KIT and PDGFRA genes lead to proteins that no longer require ligand binding to be activated. As a result, the proteins and the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of cells and leads to the formation of tumors.</p><p>The SDHA, SDHB, SDHC, and SDHD genes provide instructions for making proteins that come together to form the succinate dehydrogenase (SDH) enzyme. The SDH enzyme is involved in cellular pathways that are critical for converting the energy from food into a form that cells can use. Specifically, the SDH enzyme converts a compound called succinate to another compound called fumarate. Succinate acts as an oxygen sensor in the cell and can help turn on specific pathways that stimulate cells to grow in a low-oxygen environment (hypoxia).</p><p class=\"section-source\"><a href=\"https://medlineplus.gov/genetics/condition/gastrointestinal-stromal-tumor/#causes\">MedlinePlus Genetics: Causes</a></p>","key":"forms","title":"What causes Gastrointestinal stromal tumor?"},{"bodyHtml":"<p>Small tumors may cause no signs or symptoms. However, some people with GISTs may experience pain or swelling in the belly area (abdomen), nausea, vomiting, loss of appetite, or weight loss. Sometimes, tumors cause bleeding into the gastrointestinal tract, which may lead to low red blood cell counts (anemia) and, consequently, weakness and tiredness. Bleeding into the intestines may cause black and tarry stools, and bleeding into the throat or stomach may cause vomiting of blood.</p><p>Affected individuals with no family history of GIST typically have only one tumor (called a sporadic GIST). People with a family history of GISTs (called familial GISTs) often have multiple tumors and additional signs or symptoms, including noncancerous overgrowth (hyperplasia) of other cells in the gastrointestinal tract and patches of dark skin on various areas of the body. Some affected individuals have a skin condition called urticaria pigmentosa (also known as maculopapular cutaneous mastocytosis), which is characterized by raised patches of brownish skin that sting or itch when touched.</p><p>A rare form of GIST, called succinate dehydrogenase (SDH)-deficient GIST, tends to occur in childhood or young adulthood and affects females more commonly than males. In this form, tumors are almost always in the stomach. Individuals with an SDH-deficient GIST have a high risk of developing other types of tumors, particularly noncancerous tumors in the nervous system called paragangliomas and noncancerous lung tumors called pulmonary chondromas. When GISTs occur in combination with paragangliomas, the condition is known as Carney-Stratakis syndrome; the combination of GISTs, paragangliomas, and pulmonary chondromas is known as Carney triad; and the combination of GISTs and pulmonary chondroma is known as incomplete Carney triad.</p><p class=\"section-source\">Source: <a href=\"https://medlineplus.gov/genetics/condition/gastrointestinal-stromal-tumor\">MedlinePlus Genetics</a></p>","key":"overview","title":"Condition overview"}],"sharedSources":[],"slug":"gastrointestinal-stromal-tumor","sourceDocuments":[{"name":"Gastrointestinal stromal tumor","reviewed":"2014-09","sections":{"causes":{"fetchedAt":"2026-10-20T20:21:41.844986+00:00","label":"Causes","pageSha256":"cdd473981fdaa12aebfdb8201e909ece56445a168ac4824ebbe0e198568884fe","sourceUrl":"https://medlineplus.gov/genetics/condition/gastrointestinal-stromal-tumor/#causes","status":"available"}},"source_release":"2026-10-01","url":"https://medlineplus.gov/genetics/condition/gastrointestinal-stromal-tumor"}],"sourceNote":"MedlinePlus descriptions and Causes; original HPO annotations.","takeawayHtml":"Cause explanations are from MedlinePlus Genetics. 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