Gene: KIT

Alternate names for this Gene: C-Kit|CD117|MASTC|PBT|SCFR

Gene Summary: This gene encodes a receptor tyrosine kinase. This gene was initially identified as a homolog of the feline sarcoma viral oncogene v-kit and is often referred to as proto-oncogene c-Kit. The canonical form of this glycosylated transmembrane protein has an N-terminal extracellular region with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain at the C-terminus. Upon activation by its cytokine ligand, stem cell factor (SCF), this protein phosphorylates multiple intracellular proteins that play a role in in the proliferation, differentiation, migration and apoptosis of many cell types and thereby plays an important role in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and in mast cell development, migration and function. This protein can be a membrane-bound or soluble protein. Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous leukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene.

Gene is located in Chromosome: 4

Location in Chromosome : 4q12

Description of this Gene: KIT proto-oncogene, receptor tyrosine kinase

Type of Gene: protein-coding

rs121913520 in KIT gene and Chronic myeloproliferative disorder PMID 19175693 2009 Molecular drug targets in myeloproliferative neoplasms: mutant ABL1, JAK2, MPL, KIT, PDGFRA, PDGFRB and FGFR1.

PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

rs121913506 in KIT gene and Cutaneous Mastocytosis PMID 19865100 2010 Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations.

PMID 24289326 2014 A new germline mutation in KIT associated with diffuse cutaneous mastocytosis in a Chinese family.

PMID 9990072 1999 Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis.

PMID 15173254 2004 A germline mutation in KIT in familial diffuse cutaneous mastocytosis.

PMID 21689725 2011 Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis.

rs1057519907 in KIT gene and Cutaneous Melanoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs13135792 in KIT gene and Eosinophil count procedure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs60334317 in KIT gene and Finding of Mean Corpuscular Hemoglobin PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1057519907 in KIT gene and Gastric Adenocarcinoma PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

rs1057519708 in KIT gene and Gastrointestinal Stromal Tumors PMID 17489795 2007 Characterization of tyrosine kinase I domain c-kit gene mutation Asn655Lys newly found in primary jejunal gastrointestinal stromal tumor.

PMID 21569090 2011 KIT amplification and gene mutations in acral/mucosal melanoma in Korea.

PMID 21689725 2011 Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis.

PMID 17259998 2007 Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation.

PMID 23582185 2013 Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells.

PMID 16731599 2006 An update on molecular genetics of gastrointestinal stromal tumours.

PMID 17001171 2006 A new familial GIST identified.

PMID 25504284 2015 Familial gastrointestinal stromal tumor syndrome: report of 2 cases with KIT exon 11 mutation.

PMID 15897563 2005 Analysis of KIT mutations in sporadic and familial gastrointestinal stromal tumors: therapeutic implications through protein modeling.

PMID 17943734 2008 Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor.

PMID 9797363 1998 A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumors.

PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

PMID 10224103 1999 Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region.

PMID 10680913 2000 Cause of familial and multiple gastrointestinal autonomic nerve tumors with hyperplasia of interstitial cells of Cajal is germline mutation of the c-kit gene.

PMID 14977822 2004 Pleomorphic characteristics of a germ-line KIT mutation in a large kindred with gastrointestinal stromal tumors, hyperpigmentation, and dysphagia.

PMID 16226710 2005 Structure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor.

PMID 15790786 2005 Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412.

PMID 19164557 2009 KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients.

PMID 20147452 2010 Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance.

PMID 11526490 2001 To investigate the function of activated c-KIT in GIST, we established a human GIST cell line, GIST882, which expresses an activating KIT mutation (K642E) in the first part of the cytoplasmic split tyrosine kinase domain.

PMID 17824795 2007 We present a case in which a germline KIT exon 13 mutation (K642E) was discovered in a patient with multiple GISTs of rectum, small intestine, and esophagus, as well as diffuse hyperplasia of the interstitial cells of Cajal.

PMID 15685537 2005 Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants.

PMID 17699867 2007 Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor.

PMID 15685537 2005 GIST cells carrying KIT -del557-558/T670I or KIT -InsAY502-503/V654A mutations were resistant to imatinib, while PKC412 significantly inhibited autophosporylation of these mutants.

PMID 15236194 2004 A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient.

PMID 24687822 2015 KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT Dysregulation.

PMID 9697690 1998 Familial gastrointestinal stromal tumours with germline mutation of the KIT gene.

PMID 22685257 2012 The UK NEQAS for Molecular Genetics scheme for gastrointestinal stromal tumour: findings and recommendations following four rounds of circulation.

PMID 11505412 2001 Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa.

PMID 15824741 2005 A mutation-created novel intra-exonic pre-mRNA splice site causes constitutive activation of KIT in human gastrointestinal stromal tumors.

PMID 9438854 1998 Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.

PMID 25394175 2015 A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

PMID 17259998 2007 Ligand-independent autophosphorylation was observed in the mutant KIT with Val559Ile as well as that with Val559Asp, as found in GISTs.

PMID 23852704 2014 Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.

PMID 17259998 2007 These results suggest that different mutations, even at the same codon, in juxtamembrane domain of the c-kit gene show different inhibitory effects of imatinib, and that patients with GISTs or mast cell neoplasms possessing this Val559Ile mutation are resistant to imatinib therapy.

PMID 19737976 2009 The aberrant localization of oncogenic kit tyrosine kinase receptor mutants is reversed on specific inhibitory treatment.

PMID 15685537 2005 GIST cells carrying KIT -del557-558/T670I or KIT -InsAY502-503/V654A mutations were resistant to imatinib, while PKC412 significantly inhibited autophosporylation of these mutants.

PMID 17363509 2007 We expressed c-KIT cDNA constructs encoding the V654A substitution alone and in combination with a typical activating exon 11 mutation characteristic of GIST, V560G, in factor-dependent FDC-P1 cells.

PMID 16751810 2006 Functional analyses and molecular modeling of two c-Kit mutations responsible for imatinib secondary resistance in GIST patients.

PMID 16638875 2006 These studies suggest that SU11248 may be a useful therapeutic agent to treat gastrointestinal stromal tumors harboring the imatinib-resistant KIT-V654A or KIT-T670I mutations, but it has no effect on the activity of the PDGFRA-D842V mutant.

PMID 16954519 2006 Molecular correlates of imatinib resistance in gastrointestinal stromal tumors.

PMID 7529964 1995 Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism.

PMID 17107413 2006 New mutations of KIT gene in two Chinese patients with piebaldism.

PMID 17124503 2007 Piebald trait: implication of kit mutation on in vitro melanocyte survival and on the clinical application of cultured epidermal autografts.

rs121913506 in KIT gene and Hematologic Neoplasms PMID 16731599 2006 An update on molecular genetics of gastrointestinal stromal tumours.

PMID 11526490 2001 STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications.

rs1057519709 in KIT gene and Leukemia, Myelocytic, Acute PMID 23714533 2013 The role of kinase inhibitors in the treatment of patients with acute myeloid leukemia.

PMID 19164557 2009 KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients.

PMID 23149070 2013 Dasatinib inhibits proliferation and induces apoptosis in the KASUMI-1 cell line bearing the t(8;21)(q22;q22) and the N822K c-kit mutation.

rs2855772 in KIT gene and Lupus Erythematosus, Systemic PMID 29494758 2018 Genome-wide association study identifies three novel susceptibility loci for systemic lupus erythematosus in Han Chinese.

rs121913682 in KIT gene and Mastocytosis, Systemic PMID 18559612 2008 Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis.

rs121913679 in KIT gene and Piebaldism PMID 9450866 1998 Piebaldism with deafness: molecular evidence for an expanded syndrome.

PMID 9699740 1998 A novel KIT gene missense mutation in a Japanese family with piebaldism.

PMID 8680409 1995 A 12-bp deletion (7818del12) in the c-kit protooncogene in a large Italian kindred with piebaldism.

PMID 1717985 1991 Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene in human piebaldism.

PMID 7687267 1993 Novel mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism.

PMID 1370874 1992 Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism.

PMID 11074500 2000 Three novel mutations of the proto-oncogene KIT cause human piebaldism.

PMID 1376329 1992 Human piebald trait resulting from a dominant negative mutant allele of the c-kit membrane receptor gene.

PMID 9450866 1998 In a South African girl of Xhosa stock with severe piebaldism and profound congenital sensorineural deafness we identified a novel missense substitution at a highly conserved residue in the intracellular kinase domain of the KIT proto-oncogene, R796G.

rs11345859 in KIT gene and Schizophrenia PMID 26198764 2015 Genome-wide association study of schizophrenia in Ashkenazi Jews.

rs1057519701 in KIT gene and Thymoma PMID 22357254 2012 Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors.

PMID 21325067 2011 Large-scale analysis of KIT aberrations in Chinese patients with melanoma.

PMID 23375402 2013 "When a thymic carcinoma ""becomes"" a GIST."

PMID 21969494 2011 Impressive response with imatinib in a heavily pretreated patient with metastatic c-KIT mutated thymic carcinoma.

PMID 17699867 2007 Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor.

PMID 19461405 2009 Long lasting response to the multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated metastatic thymic carcinoma.

PMID 20970876 2011 Promising efficacy of sorafenib in a relapsed thymic carcinoma with C-KIT exon 11 deletion mutation.

PMID 12960119 2003 Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors.

PMID 17372901 2007 L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition.

PMID 18448188 2008 Mutational status of EGFR and KIT in thymoma and thymic carcinoma.

PMID 20736294 2010 Imatinib upregulates compensatory integrin signaling in a mouse model of gastrointestinal stromal tumor and is more effective when combined with dasatinib.

PMID 19861435 2009 Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas.

PMID 15930355 2005 Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation.

PMID 15201427 2004 Thymic carcinoma with overexpression of mutated KIT and the response to imatinib.

rs1057519702 in KIT gene and melanoma PMID 21131919 2011 Genetic aberrations in primary esophageal melanomas: molecular analysis of c-KIT, PDGFR, KRAS, NRAS and BRAF in a series of 10 cases.

PMID 24661573 2014 Transcriptome sequencing of melanocytic nevi and melanomas from Grm1 transgenic mice to determine melanoma driver mutations.

PMID 24531699 2014 The GIST of targeted therapy for malignant melanoma.

PMID 21969494 2011 Impressive response with imatinib in a heavily pretreated patient with metastatic c-KIT mutated thymic carcinoma.

PMID 22357254 2012 Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors.

PMID 21569090 2011 KIT amplification and gene mutations in acral/mucosal melanoma in Korea.

PMID 11276010 2001 Gain-of-function mutation at the extracellular domain of KIT in gastrointestinal stromal tumours.

PMID 18955458 2008 Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor.

PMID 15790786 2005 Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412.

PMID 21690468 2011 Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification.

PMID 9438854 1998 Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.

PMID 20088873 2010 Mutations in KIT occur at low frequency in melanomas arising from anatomical sites associated with chronic and intermittent sun exposure.

PMID 23775962 2013 Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin.

PMID 7530509 1995 Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines.

PMID 21642685 2011 KIT as a therapeutic target in metastatic melanoma.

PMID 23582185 2013 Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells.

PMID 22261812 2012 Sunitinib therapy for melanoma patients with KIT mutations.

PMID 19812602 2010 Response to imatinib mesylate depends on the presence of the V559A-mutated KIT oncogene.

PMID 17372901 2007 L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition.

PMID 18980976 2008 KIT gene mutations and copy number in melanoma subtypes.

PMID 18510589 2008 Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation.

PMID 18936790 2008 Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib.

PMID 18421059 2008 Major response to imatinib mesylate in KIT-mutated melanoma.

PMID 19671763 2009 Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates.

PMID 16741525 2006 Detection of c-kit exons 11- and 17-activating mutations in testicular seminomas by high-resolution melting amplicon analysis.

PMID 16908931 2006 Somatic activation of KIT in distinct subtypes of melanoma.

PMID 20545949 2011 Marked response to imatinib mesylate in metastatic acral lentiginous melanoma on the thumb.

PMID 19671763 2009 We have identified the first human melanoma cell line with an endogenous L576P mutation, the most common KIT mutation in melanoma ( approximately 30-40%).

PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

PMID 19996579 2010 Anal mucosal melanoma with KIT-activating mutation and response to imatinib therapy--case report and review of the literature.

PMID 17372901 2007 L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition.

PMID 22932406 2012 [Secondary mutation of c-kit/PDGFRα genotypes after imatinib mesylate therapy and its relationship with efficacy of sunitinib].

PMID 16046538 2005 Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases.

PMID 24755198 2014 A meta-analysis of somatic mutations from next generation sequencing of 241 melanomas: a road map for the study of genes with potential clinical relevance.

PMID 21159146 2011 V559A and N822I double KIT mutant melanoma with predictable response to imatinib?

PMID 22355224 2011 "Study of the role of ""gatekeeper"" mutations V654A and T670I of c-kit kinase in the interaction with inhibitors by means mixed molecular dynamics/docking approach."

PMID 22160160 2012 High KIT and PDGFRA are associated with shorter patients survival in gastroenteropancreatic neuroendocrine tumors, but mutations are a rare event.

PMID 21159146 2011 V559A and N822I double KIT mutant melanoma with predictable response to imatinib?