Gastrointestinal stromal tumor: genes and variants
Gastrointestinal stromal tumor is linked to 11 analyzed proteins (SDHB, KIT, SDHC, PDGFRA, SDHA, ABL1, BCR, CSF1R and 3 more). 93 DNA variants are known to cause it; 3,420 more are uncertain, and 22 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Gastrointestinal stromal tumor
SDHB: Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial
It transfers electrons from succinate oxidation through iron-sulfur centers toward ubiquinone in mitochondrial complex II. Heterozygous loss-of-function variants strongly predispose to paraganglioma and pheochromocytoma and can also increase renal-tumor and gastrointestinal-stromal-tumor risk.
53 disease-causing and 447 uncertain variants in SDHB are linked to Gastrointestinal stromal tumor.
KIT: Mast/stem cell growth factor receptor Kit
Stem-cell-factor signaling through this pathway supports hematopoietic progenitors, mast cells, melanocytes, and germ cells. Activating variants drive gastrointestinal stromal tumors, systemic mastocytosis, and other malignancies, whereas loss-of-function variants can cause piebaldism.
23 disease-causing and 1,281 uncertain variants in KIT are linked to Gastrointestinal stromal tumor.
SDHC: Succinate dehydrogenase cytochrome b560 subunit, mitochondrial
It anchors succinate dehydrogenase to the inner mitochondrial membrane and helps transfer electrons from the catalytic subunits to ubiquinone. Heterozygous loss-of-function variants predispose to paraganglioma, pheochromocytoma, and some gastrointestinal stromal tumors.
16 disease-causing and 261 uncertain variants in SDHC are linked to Gastrointestinal stromal tumor.
PDGFRA: Platelet-derived growth factor receptor alpha
PDGF signaling through this pathway promotes proliferation, survival, and migration of mesenchymal progenitors. Activating mutations or fusions drive gastrointestinal stromal tumors and selected hematologic and solid malignancies and can create kinase-inhibitor sensitivity.
1 disease-causing and 1,427 uncertain variants in PDGFRA are linked to Gastrointestinal stromal tumor.
SDHA: Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
It catalyzes oxidation of succinate to fumarate while transferring electrons into respiratory-chain complex II, directly linking the TCA cycle with oxidative phosphorylation. Biallelic deficiency can cause mitochondrial disease, while heterozygous loss-of-function variants predispose to paraganglioma, pheochromocytoma, and selected gastrointestinal stromal tumors.
0 disease-causing and 4 uncertain variants in SDHA are linked to Gastrointestinal stromal tumor.
ABL1: Tyrosine-protein kinase ABL1
It coordinates cytoskeletal remodeling, adhesion, DNA-damage responses, and growth signaling through tightly regulated tyrosine phosphorylation. Fusion with BCR removes normal control and creates the constitutively active kinase that drives chronic myeloid leukemia and subsets of acute lymphoblastic leukemia.
0 disease-causing and 0 uncertain variants in ABL1 are linked to Gastrointestinal stromal tumor.
BCR: Breakpoint cluster region protein
It has serine/threonine kinase and GTPase-regulatory functions involved in cytoskeletal and signaling control. Chromosomal fusion with ABL1 creates the constitutively active BCR::ABL1 kinase that drives chronic myeloid leukemia and subsets of acute leukemia.
0 disease-causing and 0 uncertain variants in BCR are linked to Gastrointestinal stromal tumor.
CSF1R: Macrophage colony-stimulating factor 1 receptor
Signals from CSF1 and IL-34 through this pathway are required for development, survival, and function of macrophages and microglia. Pathogenic variants can cause adult-onset leukoencephalopathy with cognitive, psychiatric, and motor deterioration.
0 disease-causing and 0 uncertain variants in CSF1R are linked to Gastrointestinal stromal tumor.
FLT3: Receptor-type tyrosine-protein kinase FLT3
Its signaling supports survival and expansion of early hematopoietic progenitors. Internal tandem duplications and kinase-domain mutations produce constitutive activity in acute myeloid leukemia and are important prognostic markers and therapeutic targets.
0 disease-causing and 0 uncertain variants in FLT3 are linked to Gastrointestinal stromal tumor.
PDGFRB: Platelet-derived growth factor receptor beta
Its signaling supports pericytes, vascular smooth-muscle cells, and other mesenchymal lineages during growth and tissue repair. Oncogenic fusions drive myeloid neoplasms, while germline activating or loss-of-function variants can cause developmental and vascular disorders.
0 disease-causing and 0 uncertain variants in PDGFRB are linked to Gastrointestinal stromal tumor.
RET: Proto-oncogene tyrosine-protein kinase receptor Ret
Its activation by GDNF-family ligands guides development of the enteric nervous system, kidney, and other tissues. Activating variants cause multiple endocrine neoplasia type 2 and can drive cancer, whereas loss-of-function variants are an important cause of Hirschsprung disease.
0 disease-causing and 0 uncertain variants in RET are linked to Gastrointestinal stromal tumor.
Where Gastrointestinal stromal tumor variants cluster
- KIT Cytoplasmic (positions 546–976): 22 of 23 disease-causing changes, 2.2× more than its size predicts.
- SDHB 4Fe-4S ferredoxin-type (positions 176–206): 12 of 53 disease-causing changes, 2.0× more than its size predicts.
- SDHC Transmembrane (positions 66–90): 5 of 16 disease-causing changes, 2.1× more than its size predicts.
Known disease-causing variants in Gastrointestinal stromal tumor
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SDHB R46L | 46 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB G96S | 96 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB G96D | 96 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB C192R | 192 | 4Fe-4S ferredoxin-type | Disease-causing (★★) |
| SDHB C196Y | 196 | 4Fe-4S ferredoxin-type | Disease-causing (★★) |
| SDHB W200C | 200 | 4Fe-4S ferredoxin-type | Disease-causing (★★) |
| SDHB W200R | 200 | 4Fe-4S ferredoxin-type | Disease-causing (★★) |
| SDHB R217C | 217 | Interaction with SDHAF1 | Disease-causing (★★) |
| SDHB R217G | 217 | Interaction with SDHAF1 | Disease-causing (★★) |
| SDHB R217L | 217 | Interaction with SDHAF1 | Disease-causing (★★) |
| SDHB R230L | 230 | Disease-causing (★★) | |
| SDHB R242C | 242 | Disease-causing (★★) | |
| SDHB R242S | 242 | Disease-causing (★★) | |
| KIT V559A | 559 | Cytoplasmic | Disease-causing (★★) |
| SDHB R46G | 46 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB R46Q | 46 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB D74A | 74 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB C98Y | 98 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB D138Y | 138 | Disease-causing (★★) | |
| SDHB C189F | 189 | 4Fe-4S ferredoxin-type | Disease-causing (★★) |
| SDHB C189Y | 189 | 4Fe-4S ferredoxin-type | Disease-causing (★★) |
| SDHB C192Y | 192 | 4Fe-4S ferredoxin-type | Disease-causing (★★) |
| SDHB R217S | 217 | Interaction with SDHAF1 | Disease-causing (★★) |
| SDHB R230C | 230 | Disease-causing (★★) | |
| SDHB R230H | 230 | Disease-causing (★★) | |
| SDHB R242H | 242 | Disease-causing (★★) | |
| SDHC R72H | 72 | Transmembrane | Disease-causing (★★) |
| SDHC R72C | 72 | Transmembrane | Disease-causing (★★) |
| SDHC H127R | 127 | Transmembrane | Disease-causing (★★) |
| SDHC H127Y | 127 | Transmembrane | Disease-causing (★★) |
| SDHC H127N | 127 | Transmembrane | Disease-causing (★★) |
| KIT V560A | 560 | Cytoplasmic | Disease-causing (★★) |
| SDHB M1I | 1 | Disease-causing (★★) | |
| SDHB M1L | 1 | Disease-causing (★★) | |
| SDHB M1V | 1 | Disease-causing (★★) | |
| SDHB C98R | 98 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB I127S | 127 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB P197R | 197 | 4Fe-4S ferredoxin-type | Disease-causing (★★) |
| SDHB C253Y | 253 | Disease-causing (★★) | |
| SDHC R72L | 72 | Transmembrane | Disease-causing (★★) |
| SDHC R72G | 72 | Transmembrane | Disease-causing (★★) |
| SDHB C93R | 93 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB G99D | 99 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB H132P | 132 | 2Fe-2S ferredoxin-type | Disease-causing (★★) |
| SDHB V140F | 140 | Disease-causing (★★) | |
| SDHB C191Y | 191 | 4Fe-4S ferredoxin-type | Disease-causing (★★) |
| SDHB G208E | 208 | Interaction with SDHAF1 | Disease-causing (★★) |
| SDHB Q214R | 214 | Interaction with SDHAF1 | Disease-causing (★★) |
| SDHB C243W | 243 | Disease-causing (★★) | |
| SDHC M1R | 1 | Disease-causing (★★) | |
| SDHC M1I | 1 | Disease-causing (★★) | |
| SDHC M1L | 1 | Disease-causing (★★) | |
| SDHC M1V | 1 | Disease-causing (★★) | |
| SDHC R50C | 50 | Mitochondrial matrix | Disease-causing (★★) |
| SDHC G75D | 75 | Transmembrane | Disease-causing (★★) |
| SDHC Y126C | 126 | Transmembrane | Disease-causing (★★) |
| KIT W557R | 557 | Cytoplasmic | Disease-causing (★★) |
| SDHB G208R | 208 | Interaction with SDHAF1 | Disease-causing (★★) |
| SDHB N248K | 248 | Disease-causing (★★) | |
| KIT N819K | 819 | Protein kinase | Disease-causing (★★) |
Showing 60 of 93.
Uncertain variants in Gastrointestinal stromal tumor that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| SDHB Q214H | 214 | Interaction with SDHAF1 | Conflicting reports (★) | +7: 5 other pathogenic changes within 3 positions; Q214R at the same position is pathogenic; seen in 6.9e-07 of gnomAD DNA copies; REVEL 0.891 |
| SDHB H132R | 132 | 2Fe-2S ferredoxin-type | Uncertain (★★) | +7: in a 3D region that tolerates change poorly (1R); H132P at the same position is pathogenic; seen in 3.4e-06 of gnomAD DNA copies; REVEL 0.896 |
| SDHB L65F | 65 | 2Fe-2S ferredoxin-type | Uncertain (★★) | +7: 2 other pathogenic changes within 3 positions; L65P at the same position is pathogenic; seen in 3.4e-06 of gnomAD DNA copies; REVEL 0.775 |
| SDHB C192S | 192 | 4Fe-4S ferredoxin-type | Conflicting reports (★) | +6: 6 other pathogenic changes within 3 positions; C192Y at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| SDHB C113G | 113 | 2Fe-2S ferredoxin-type | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; C113S at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
| SDHB C93F | 93 | 2Fe-2S ferredoxin-type | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; C93R at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| SDHB C189R | 189 | 4Fe-4S ferredoxin-type | Conflicting reports (★) | +6: 7 other pathogenic changes within 3 positions; C189W at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| SDHB G96C | 96 | 2Fe-2S ferredoxin-type | Conflicting reports (★) | +6: 6 other pathogenic changes within 3 positions; G96S at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| SDHB G96V | 96 | 2Fe-2S ferredoxin-type | Conflicting reports (★) | +6: 6 other pathogenic changes within 3 positions; G96S at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| SDHB R217H | 217 | Interaction with SDHAF1 | Conflicting reports (★) | +6: 5 other pathogenic changes within 3 positions; R217S at the same position is pathogenic; REVEL 0.957 |
| SDHB C68R | 68 | 2Fe-2S ferredoxin-type | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; C68Y at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.98 |
| SDHB C186S | 186 | 4Fe-4S ferredoxin-type | Uncertain (★) | +6: 4 other pathogenic changes within 3 positions; C186Y at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| SDHB P197L | 197 | 4Fe-4S ferredoxin-type | Uncertain (★) | +6: 5 other pathogenic changes within 3 positions; P197R at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.98 |
| SDHB G99S | 99 | 2Fe-2S ferredoxin-type | Uncertain (★★) | +6: 5 other pathogenic changes within 3 positions; G99D at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.98 |
| SDHB G96R | 96 | 2Fe-2S ferredoxin-type | Uncertain (★) | +6: 6 other pathogenic changes within 3 positions; G96S at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| SDHB W200G | 200 | 4Fe-4S ferredoxin-type | Uncertain (★) | +6: 3 other pathogenic changes within 3 positions; W200C at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| SDHC R50L | 50 | Mitochondrial matrix | Uncertain (★★) | +6: R50C at the same position is pathogenic; REVEL 0.956 |
| SDHC R50H | 50 | Mitochondrial matrix | Uncertain (★★) | +6: R50C at the same position is pathogenic; REVEL 0.945 |
| SDHB D74N | 74 | 2Fe-2S ferredoxin-type | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; D74G at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.98 |
| KIT D816V | 816 | Protein kinase | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; D816Y at the same position is pathogenic; REVEL 0.890 |
| KIT V559F | 559 | Cytoplasmic | Uncertain (★★) | +6: 5 other pathogenic changes within 3 positions; V559D at the same position is pathogenic; REVEL 0.774 |
| SDHB I127L | 127 | 2Fe-2S ferredoxin-type | Uncertain (★★) | +6: in a 3D region that tolerates change poorly (1R); I127S at the same position is pathogenic; seen in 1.4e-06 of gnomAD DNA copies; REVEL 0.724 |
Which prediction tools work for Gastrointestinal stromal tumor
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 98 out of 100
- EVE: 97 out of 100
- CADD: 96 out of 100
- MutPred2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 88 out of 100
- phyloP: 84 out of 100
Same protein, different disease
- Piebaldism is also caused by KIT variants; they fall mostly in different places as the Gastrointestinal stromal tumor variants (8 disease-causing).
- Cutaneous mastocytosis is also caused by KIT variants; they fall partly in the same places as the Gastrointestinal stromal tumor variants (3 disease-causing).
Diseases related to Gastrointestinal stromal tumor
- Renal cell carcinoma, also linked to CSF1R, FLT3, KIT, PDGFRA and 2 more
- Colorectal cancer, also linked to ABL1, KIT, PDGFRA, PDGFRB and 1 more
- Acute myeloid leukemia, also linked to FLT3, KIT, PDGFRA and PDGFRB
- Hepatocellular carcinoma, also linked to FLT3, KIT, PDGFRB and RET
- Pheochromocytoma/paraganglioma syndrome 5, also linked to SDHA, SDHB and SDHC
- Ovarian cancer, also linked to KIT, PDGFRA and RET
- Non-small cell lung carcinoma, also linked to PDGFRA, PDGFRB and RET
- Inherited phaeochromocytoma and paraganglioma excluding NF1, also linked to SDHA, SDHB and SDHC
- Hereditary pheochromocytoma and paraganglioma, also linked to SDHA, SDHB and SDHC
- Pheochromocytoma, also linked to RET and SDHB
- Carney-Stratakis syndrome, also linked to SDHB and SDHC
- Idiopathic pulmonary fibrosis, also linked to PDGFRA and PDGFRB
Frequently asked questions
Which genes are linked to Gastrointestinal stromal tumor?
In CATVariant, Gastrointestinal stromal tumor is linked to 11 analyzed proteins: SDHB (Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial), KIT (Mast/stem cell growth factor receptor Kit), SDHC (Succinate dehydrogenase cytochrome b560 subunit, mitochondrial), PDGFRA (Platelet-derived growth factor receptor alpha), SDHA (Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial), ABL1 (Tyrosine-protein kinase ABL1) and 5 more.
How many genetic variants are linked to Gastrointestinal stromal tumor?
3,560 variants: 93 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 3,420 are of uncertain significance or have conflicting reports.
Which uncertain variants in Gastrointestinal stromal tumor look disease-causing?
22 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example SDHB Q214H, SDHB H132R, SDHB L65F, SDHB C192S and SDHB C113G. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Gastrointestinal stromal tumor?
Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.97, based on 52 disease-causing and 50 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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