KIT KIT proto-oncogene, receptor tyrosine kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: KITprovided by HGNC
Official Full Name: KIT proto-oncogene, receptor tyrosine kinaseprovided by HGNC
Primary source: HGNC:HGNC:6342
See related: Ensembl:ENSG00000157404 MIM:164920
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PBT; SCFR; C-Kit; CD117; MASTC
Summary: This gene encodes the human homolog of the proto-oncogene c-kit. C-kit was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit. This protein is a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous lukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Broad expression in thyroid (RPKM 30.0), ovary (RPKM 23.0) and 21 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 4q12

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	4	NC_000004.12 (54657928..54740715)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (55524095..55606881)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Regardless of the high immunoexpression of C-KIT, there was no association with the MAPK mutations among primary oral and sinonasal melanoma samples
Title: CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway.
This is the first report that high-viremia Hepatitis C Virus-Infected patients resistant to the antiviral therapy most probably have mutated C-Kit gene and are likely to develop Hepatocellular Carcinoma.
Title: Role of TGF-β1 and C-Kit Mutations in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients: in vitro Study.
found that the binding capacity of RUNX1-ETO9a, a truncated RUNX1-ETO isoform, to the c-KIT promoter was stronger than that of RUNX1-ETO, suggesting RUNX1-ETO9a as another valuable therapeutic target in t(8;21) AML
Title: The RUNX1-ETO fusion protein trans-activates c-KIT expression by recruiting histone acetyltransferase P300 on its promoter.
Authors revealed that ICCs could promote hBSMC proliferation and contraction, and cyclic stretch could promote acetylcholine receptor M2 and M3 caused by c-kit in the ICCs, which promoted the contraction of hBSMCs
Title: Cyclic Stretch Promotes Proliferation and Contraction of Human Bladder Smooth Muscle Cells by Cajal-Mediated c-kit Expression in Interstitial Cells.
The KIT D816V mutation arises in early haematopoietic stem and progenitor cells and the mutation frequency is approaching 100% in mature mast cells, which express the aberrant marker CD45RA.
Title: Single-cell analysis reveals the KIT D816V mutation in haematopoietic stem and progenitor cells in systemic mastocytosis.
Bradykinin-mediated Ca(2+) signaling regulates cell growth and mobility in human cardiac c-Kit(+) progenitor cells.
Title: Bradykinin-mediated Ca<sup>2+</sup> signalling regulates cell growth and mobility in human cardiac c-Kit<sup>+</sup> progenitor cells.
Our results show that CD81 is an independent factor affecting the overall survival (OS) and progression free survival of plasma cell myeloma (PCM) patients, and CD117 is an independent factor affecting the OS of PCM patients. CD117-positive and CD81-negative patients with PCM have a better prognosis.
Title: Expression of CD81 and CD117 in plasma cell myeloma and the relationship to prognosis.
Study reports a four-generation Japanese family with progressive hyperpigmentation and lentigines due to a missense mutation near the C-terminus of KIT.
Title: Autosomal dominant progressive hyperpigmentation and lentigines in a Japanese pedigree due to a missense mutation near the C-terminus of KIT.
Longitudinal cohort study of 53 patients revealed that KIT mutation is not correlated with cutaneous features of pediatric mastocytosis and is not a predictor of clinical evolution.
Title: Paediatric mastocytosis: long-term follow-up of 53 patients with whole sequencing of KIT. A prospective study.
The preclinical findings suggest that the c-KIT-directed Antibody-Drug Conjugate may be a promising therapeutic for the treatment of mutant and wild-type c-KIT-positive cancers
Title: Preclinical Antitumor Activity of a Novel Anti-c-KIT Antibody-Drug Conjugate against Mutant and Wild-type c-KIT-Positive Solid Tumors.

Submit: New GeneRIF Correction See all GeneRIFs (881)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Acute myeloid leukemia MedGen: C0023467 OMIM: 601626 GeneReviews: CEBPA-Associated Familial Acute Myeloid Leukemia (AML)	Compare labs
Gastrointestinal stroma tumor MedGen: C0238198 OMIM: 606764 GeneReviews: Not available	Compare labs
Malignant tumor of testis MedGen: C0153594 OMIM: 273300 GeneReviews: Not available	Compare labs
Mastocytosis MedGen: C0024899 OMIM: 154800 GeneReviews: Not available	Compare labs
Partial albinism MedGen: C0080024 OMIM: 172800 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of hematological and biochemical traits in a Japanese population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Identification of a variant in KDR associated with serum VEGFR2 and pharmacodynamics of pazopanib. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Seventy-five genetic loci influencing the human red blood cell. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	The mechanism of HIV-1 induced apoptosis in astrocytes involves the upregulation of the receptor tyrosine kinase protooncogene c-Kit by the HIV-1 Nef protein	PubMed
Tat	tat	HIV-1 Tat downregulates the expression of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT; CD117) in human primary T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-67781 (e-PCR)
- UniSTS:853

GDB:512789 (e-PCR)
- UniSTS:157531

STS-N21003 (e-PCR)
- UniSTS:21855

GDB:181531 (e-PCR)
- UniSTS:155257

SHGC-12679 (e-PCR)
- UniSTS:62849

SHGC4-128 (e-PCR)
- UniSTS:79238

GDB:250632 (e-PCR)
- UniSTS:156301

GDB:626073 (e-PCR)
- UniSTS:158385

SHGC-50170 (e-PCR)
- UniSTS:72370

GDB:626077 (e-PCR)
- UniSTS:158386

GDB:626080 (e-PCR)
- UniSTS:158387

Kit (e-PCR), detects polymorphism
- UniSTS:527042

G15879 (e-PCR)
- UniSTS:79825

Homology

Homologs of the KIT gene: The KIT gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 288 organisms have orthologs with human gene KIT
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
SH2 domain binding	IEA Inferred from Electronic Annotation more info
cytokine binding	IDA Inferred from Direct Assay more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
protease binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed
stem cell factor receptor activity	IEA Inferred from Electronic Annotation more info
transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transmembrane receptor protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
B cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Fc receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
Kit signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Kit signaling pathway	IDA Inferred from Direct Assay more info	PubMed
MAPK cascade	TAS Traceable Author Statement more info
T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
actin cytoskeleton reorganization	IDA Inferred from Direct Assay more info	PubMed
activation of MAPK activity	IDA Inferred from Direct Assay more info	PubMed
cell chemotaxis	IDA Inferred from Direct Assay more info	PubMed
cellular response to thyroid hormone stimulus	IEA Inferred from Electronic Annotation more info
cytokine-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
dendritic cell cytokine production	ISS Inferred from Sequence or Structural Similarity more info
detection of mechanical stimulus involved in sensory perception of sound	ISS Inferred from Sequence or Structural Similarity more info
digestive tract development	ISS Inferred from Sequence or Structural Similarity more info
ectopic germ cell programmed cell death	IEA Inferred from Electronic Annotation more info
embryonic hemopoiesis	ISS Inferred from Sequence or Structural Similarity more info
epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
erythrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
erythropoietin-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
germ cell migration	IEA Inferred from Electronic Annotation more info
glycosphingolipid metabolic process	IEA Inferred from Electronic Annotation more info
hematopoietic progenitor cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
hematopoietic stem cell migration	IEA Inferred from Electronic Annotation more info
hemopoiesis	TAS Traceable Author Statement more info	PubMed
immature B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
lamellipodium assembly	ISS Inferred from Sequence or Structural Similarity more info
lymphoid progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
male gonad development	IEP Inferred from Expression Pattern more info	PubMed
mast cell chemotaxis	IDA Inferred from Direct Assay more info	PubMed
mast cell cytokine production	IDA Inferred from Direct Assay more info	PubMed
mast cell degranulation	IMP Inferred from Mutant Phenotype more info	PubMed
mast cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
mast cell differentiation	TAS Traceable Author Statement more info	PubMed
mast cell proliferation	TAS Traceable Author Statement more info	PubMed
megakaryocyte development	ISS Inferred from Sequence or Structural Similarity more info
melanocyte adhesion	ISS Inferred from Sequence or Structural Similarity more info
melanocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
melanocyte differentiation	TAS Traceable Author Statement more info	PubMed
melanocyte migration	ISS Inferred from Sequence or Structural Similarity more info
myeloid progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of programmed cell death	IEA Inferred from Electronic Annotation more info
ovarian follicle development	ISS Inferred from Sequence or Structural Similarity more info
peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
pigmentation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of JAK-STAT cascade	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of JAK-STAT cascade	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of MAP kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of Notch signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of cell migration	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of colon smooth muscle contraction	IEA Inferred from Electronic Annotation more info
positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
positive regulation of long-term neuronal synaptic plasticity	IEA Inferred from Electronic Annotation more info
positive regulation of phosphatidylinositol 3-kinase activity	TAS Traceable Author Statement more info	PubMed
positive regulation of phosphatidylinositol 3-kinase signaling	TAS Traceable Author Statement more info	PubMed
positive regulation of phospholipase C activity	TAS Traceable Author Statement more info	PubMed
positive regulation of protein kinase B signaling	TAS Traceable Author Statement more info
positive regulation of pseudopodium assembly	IEA Inferred from Electronic Annotation more info
positive regulation of pyloric antrum smooth muscle contraction	IEA Inferred from Electronic Annotation more info
positive regulation of small intestine smooth muscle contraction	IEA Inferred from Electronic Annotation more info
positive regulation of tyrosine phosphorylation of STAT protein	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of vascular smooth muscle cell differentiation	IDA Inferred from Direct Assay more info	PubMed
protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of bile acid metabolic process	IEA Inferred from Electronic Annotation more info
regulation of cell proliferation	TAS Traceable Author Statement more info	PubMed
regulation of cell shape	ISS Inferred from Sequence or Structural Similarity more info
regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info
response to cadmium ion	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed
somatic stem cell division	IEA Inferred from Electronic Annotation more info
somatic stem cell population maintenance	IEA Inferred from Electronic Annotation more info
spermatid development	IEA Inferred from Electronic Annotation more info
spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info
spermatogenesis	TAS Traceable Author Statement more info	PubMed
stem cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
stem cell population maintenance	TAS Traceable Author Statement more info	PubMed
tongue development	IEA Inferred from Electronic Annotation more info
transmembrane receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
visual learning	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
acrosomal vesicle	IEA Inferred from Electronic Annotation more info
cell-cell junction	IEA Inferred from Electronic Annotation more info
cytoplasmic side of plasma membrane	IEA Inferred from Electronic Annotation more info
external side of plasma membrane	IEA Inferred from Electronic Annotation more info
extracellular space	IDA Inferred from Direct Assay more info	PubMed
fibrillar center	IDA Inferred from Direct Assay more info
integral component of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mast cell granule	IEA Inferred from Electronic Annotation more info
plasma membrane	IDA Inferred from Direct Assay more info
plasma membrane	TAS Traceable Author Statement more info
receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: mast/stem cell growth factor receptor Kit

Names: c-Kit protooncogene; p145 c-kit; piebald trait protein; proto-oncogene c-Kit; proto-oncogene tyrosine-protein kinase Kit; soluble KIT variant 1; tyrosine-protein kinase Kit; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene-like protein

NP_000213.1

EC 2.7.10.1

NP_001087241.1

EC 2.7.10.1

XP_005265797.1

EC 2.7.10.1

XP_005265798.1

EC 2.7.10.1

XP_005265799.1

EC 2.7.10.1

XP_016863667.1

EC 2.7.10.1

XP_016863668.1

EC 2.7.10.1

XP_016863669.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007456.1 RefSeqGene

Range

4935..87721

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_307

mRNA and Protein(s)

NM_000222.3 → NP_000213.1 mast/stem cell growth factor receptor Kit isoform 1 precursor

See identical proteins and their annotated locations for NP_000213.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

BC071593, DC376760, X06182

Consensus CDS

CCDS3496.1

UniProtKB/Swiss-Prot

P10721

UniProtKB/TrEMBL

A0A024RDA0

Related

ENSP00000288135.5, ENST00000288135.5

Conserved Domains (6) summary

cd00096
Location:426 → 505

Ig; Immunoglobulin domain

cd05860
Location:311 → 411

Ig4_SCFR; Fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR)

smart00410
Location:220 → 307

IG_like; Immunoglobulin like

cd05104
Location:553 → 928

PTKc_Kit; Catalytic domain of the Protein Tyrosine Kinase, Kit

pfam00047
Location:216 → 305

ig; Immunoglobulin domain

pfam07714
Location:589 → 924

Pkinase_Tyr; Protein tyrosine kinase
NM_001093772.1 → NP_001087241.1 mast/stem cell growth factor receptor Kit isoform 2 precursor

See identical proteins and their annotated locations for NP_001087241.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the central coding region, compared to variant 1, resulting in a shorter protein (isoform 2).

Source sequence(s)

BC071593, CN414753, DC376760, X06182

Consensus CDS

CCDS47058.1

UniProtKB/Swiss-Prot

P10721

Related

ENSP00000390987.2, ENST00000412167.6

Conserved Domains (6) summary

cd00096
Location:426 → 505

Ig; Immunoglobulin domain

cd05860
Location:311 → 411

Ig4_SCFR; Fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR)

smart00410
Location:220 → 307

IG_like; Immunoglobulin like

cd05104
Location:549 → 924

PTKc_Kit; Catalytic domain of the Protein Tyrosine Kinase, Kit

pfam00047
Location:216 → 305

ig; Immunoglobulin domain

pfam07714
Location:585 → 920

Pkinase_Tyr; Protein tyrosine kinase

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p13 Primary Assembly

Range

54657928..54740715

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005265740.1 → XP_005265797.1 mast/stem cell growth factor receptor Kit isoform X1

Conserved Domains (6) summary

cd00096
Location:427 → 506

Ig; Immunoglobulin domain

cd05860
Location:312 → 412

Ig4_SCFR; Fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR)

smart00410
Location:220 → 308

IG_like; Immunoglobulin like

cd05104
Location:554 → 929

PTKc_Kit; Catalytic domain of the Protein Tyrosine Kinase, Kit

pfam00047
Location:216 → 306

ig; Immunoglobulin domain

pfam07714
Location:590 → 925

Pkinase_Tyr; Protein tyrosine kinase
XM_005265741.1 → XP_005265798.1 mast/stem cell growth factor receptor Kit isoform X2

Conserved Domains (6) summary

cd00096
Location:427 → 506

Ig; Immunoglobulin domain

cd05860
Location:312 → 412

Ig4_SCFR; Fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR)

smart00410
Location:220 → 308

IG_like; Immunoglobulin like

cd05104
Location:554 → 928

PTKc_Kit; Catalytic domain of the Protein Tyrosine Kinase, Kit

pfam00047
Location:216 → 306

ig; Immunoglobulin domain

pfam07714
Location:590 → 924

Pkinase_Tyr; Protein tyrosine kinase
XM_005265742.3 → XP_005265799.1 mast/stem cell growth factor receptor Kit isoform X4

Conserved Domains (6) summary

cd00096
Location:427 → 506

Ig; Immunoglobulin domain

cd05860
Location:312 → 412

Ig4_SCFR; Fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR)

smart00410
Location:220 → 308

IG_like; Immunoglobulin like

cd05104
Location:550 → 925

PTKc_Kit; Catalytic domain of the Protein Tyrosine Kinase, Kit

pfam00047
Location:216 → 306

ig; Immunoglobulin domain

pfam07714
Location:586 → 921

Pkinase_Tyr; Protein tyrosine kinase
XM_017008179.1 → XP_016863668.1 mast/stem cell growth factor receptor Kit isoform X5
XM_017008178.1 → XP_016863667.1 mast/stem cell growth factor receptor Kit isoform X3
XM_017008180.1 → XP_016863669.1 mast/stem cell growth factor receptor Kit isoform X6

UniProtKB/TrEMBL

A0A0U2N547

Conserved Domains (6) summary

cd00096
Location:426 → 505

Ig; Immunoglobulin domain

cd05860
Location:311 → 411

Ig4_SCFR; Fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR)

smart00410
Location:220 → 307

IG_like; Immunoglobulin like

cd05104
Location:549 → 923

PTKc_Kit; Catalytic domain of the Protein Tyrosine Kinase, Kit

pfam00047
Location:216 → 305

ig; Immunoglobulin domain

pfam07714
Location:585 → 919

Pkinase_Tyr; Protein tyrosine kinase