Gene:
KIT
v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.


Annotated Labels

  1. Annotation of FDA Label for imatinib and ABL1,BCR,KIT
  2. Annotation of EMA Label for imatinib and ABL1,BCR,FIP1L1,KIT,PDGFRB
  3. Annotation of HCSC Label for imatinib and ABI1,BCR,FIP1L1,KIT,PDGFRA,PDGFRB


last updated 10/25/2013

2. Annotation of EMA Label for imatinib and ABL1,BCR,FIP1L1,KIT,PDGFRB

Testing required

Summary

The EMA European Public Assessment Report (EPAR) for imatinib (Glivec) contains pharmacogenetic information regarding the indication of the drug in patients with tumors positive for biomarkers including KIT (CD117), BCR-ABL (Philadelphia chromosome), PDGFR and FIP1L1-PDGFRalpha rearrangements.

There's more of this label. Read more.



PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

List of all variant annotations for KIT

Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs121913512 NC_000004.11:g.55594221A>G, NC_000004.12:g.54728055A>G, NG_007456.1:g.75061A>G, NM_000222.2:c.1924A>G, NM_001093772.1:c.1912A>G, NP_000213.1:p.Lys642Glu, NP_001087241.1:p.Lys638Glu, XM_005265740.1:c.1927A>G, XM_005265741.1:c.1927A>G, XM_005265742.1:c.1915A>G, XP_005265797.1:p.Lys643Glu, XP_005265798.1:p.Lys643Glu, XP_005265799.1:p.Lys639Glu, rs121913691
A > G
SNP
K642E
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Alternate Names:  PBT
Alternate Symbols:  C-Kit; CD117; SCFR
PharmGKB Accession Id: PA30128

Details

Cytogenetic Location: chr4 : q11 - q12
GP mRNA Boundary: chr4 : 55524095 - 55606881
GP Gene Boundary: chr4 : 55514095 - 55609881
Strand: plus

Visualization

UCSC has a Genome Browser that you can use to view PharmGKB annotations for this gene in context with many other sources of information.

View on UCSC Browser
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

The KIT gene is an important diagnostic pharmacogene for cancer PGx (see drug label annotations for imatinib).

KIT codes for a receptor tyrosine kinase that is expressed on stem cells such as hematopoietic stem cells that are necessary to form all red and white blood cell types [Article:17253940]. The interaction of KIT with its ligand stem cell factor plays a key role in hematopoietic stem cell survival, mitogenesis, proliferation, differentiation, adhesion, homing, migration, and functional activation [Article:17253940]. KIT dimerization activates downstream signaling pathways, including the PI3K-AKT-mTOR pathway, the RAS-RAF-MEK-ERK pathway, and the signal transducer and activator of transcription 3 (acute-phase response factor), or STAT3, pathway [Article:17253940].

KIT variants can occur in up to 85 % of GISTs [Article:24531699]. KIT variants have also been shown to be relevant for melanoma and leukemias such as AML [Article:24531699] [Article:25932436].

Although imatinib was originally approved for the treatment of BCR-ABL positive CML, this tyrosine kinase inhibitor was shown to be effective against variant KIT in GIST [Article:11526490] [Article:24531699].

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
History

Submitted by Caroline F Thorn

Key Publications
  1. Incidences and Prognostic Impact of c-KIT, WT1, CEBPA, and CBL Mutations, and Mutations Associated With Epigenetic Modification in Core Binding Factor Acute Myeloid Leukemia: A Multicenter Study in a Korean Population. Annals of laboratory medicine. 2015. Park Sang Hyuk, Lee Hyun Ji, Kim In-Suk, Kang Jeong-Eun, Lee Eun Yup, Kim Hyeoung-Joon, Kim Yeo-Kyeoung, Won Jong-Ho, Bang Soo Mee, Kim Hawk, Song Moo-Kon, Chung Joo Seop, Shin Ho-Jin. PubMed
  2. The GIST of targeted therapy for malignant melanoma. Annals of surgical oncology. 2014. Bello Danielle M, Dematteo Ronald P, Ariyan Charlotte E. PubMed
  3. Stem cell c-KIT and HOXB4 genes: critical roles and mechanisms in self-renewal, proliferation, and differentiation. Stem cells and development. 2006. Sharma Shilpa, Gurudutta Gangenahalli U, Satija Neeraj Kumar, Pati Soumya, Afrin Farhat, Gupta Pallavi, Verma Yogesh Kumar, Singh Vimal Kishor, Tripathi R P. PubMed
  4. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene. 2001. Tuveson D A, Willis N A, Jacks T, Griffin J D, Singer S, Fletcher C D, Fletcher J A, Demetri G D. PubMed
Drugs
Drug (1)
Diseases
Pathways

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Pazopanib Pathway, Pharmacokinetics
    Stylized representation of pazopanib transport and metabolism in the liver.
  1. Sorafenib Pharmacodynamics
    Mechanism of action of sorafenib

Curated Information ?

Evidence Gene
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
HOXB4
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
HRAS
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
KRAS
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
NRAS
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PDGFRA

Curated Information ?

Curated Information ?

Publications related to KIT: 27

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The SHIVA01 trial: what have we learned?. Pharmacogenomics. 2017. Le Tourneau Christophe, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The pharmacogenomics of drug resistance to protein kinase inhibitors. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy. 2016. Gillis Nancy K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Incidences and Prognostic Impact of c-KIT, WT1, CEBPA, and CBL Mutations, and Mutations Associated With Epigenetic Modification in Core Binding Factor Acute Myeloid Leukemia: A Multicenter Study in a Korean Population. Annals of laboratory medicine. 2015. Park Sang Hyuk, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The GIST of targeted therapy for malignant melanoma. Annals of surgical oncology. 2014. Bello Danielle M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors. Pharmacogenomics. 2013. Spraggs Colin F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Off-target effects of BCR-ABL1 inhibitors and their potential long-term implications in patients with chronic myeloid leukemia. Leukemia & lymphoma. 2012. Steegmann Juan Luis, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy. The pharmacogenomics journal. 2012. Savonarola A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research. 2012. Mross Klaus, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pazopanib for the treatment of metastatic renal cell carcinoma. Clinical therapeutics. 2012. Pick Amy M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Rho Kinase Regulates the Survival and Transformation of Cells Bearing Oncogenic Forms of KIT, FLT3, and BCR-ABL. Cancer cell. 2011. Mali Raghuveer Singh, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clinical pharmacology and therapeutics. 2010. Stegmeier F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Evolving novel anti-HER2 strategies. The lancet oncology. 2009. Jones Kellie L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gastrointestinal stromal tumor: a clinical overview. Hematology/oncology clinics of North America. 2009. Quek Richard, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proceedings of the National Academy of Sciences of the United States of America. 2009. Gajiwala Ketan S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008. Heinrich Michael C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Tumor suppressor FUS1 signaling pathway. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2008. Ji Lin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. Expert opinion on investigational drugs. 2008. Sonpavde Guru, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Molecular cancer therapeutics. 2007. Kumar Rakesh, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Stem cell c-KIT and HOXB4 genes: critical roles and mechanisms in self-renewal, proliferation, and differentiation. Stem cells and development. 2006. Sharma Shilpa, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cancer and leukemia group B gastrointestinal cancer committee. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Goldberg Richard M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gain-of-Function Mutations of Receptor Tyrosine Kinases in Gastrointestinal Stromal Tumors. Current genomics. 2006. Isozaki K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. The Journal of biological chemistry. 2004. Mol Clifford D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Imatinib mesylate--a new oral targeted therapy. The New England journal of medicine. 2002. Savage David G, et al. PubMed
STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene. 2001. Tuveson D A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science (New York, N.Y.). 1998. Hirota S, et al. PubMed

LinkOuts

NCBI Gene:
3815
OMIM:
164920
172800
273300
601626
606764
UCSC Genome Browser:
NM_000222
RefSeq RNA:
NM_000222
NM_001093772
RefSeq Protein:
NP_000213
NP_001087241
RefSeq DNA:
NG_007456
NT_022853
UniProtKB:
KIT_HUMAN (P10721)
Q6IQ28_HUMAN (Q6IQ28)
Ensembl:
ENSG00000157404
GenAtlas:
KIT
GeneCard:
KIT
MutDB:
KIT
ALFRED:
LO017051O
HuGE:
KIT
Comparative Toxicogenomics Database:
3815
ModBase:
P10721
HumanCyc Gene:
HS08211
HGNC:
6342

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