KIT
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
KIT (HGNC:6342) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
KIT proto-oncogene, receptor tyrosine kinase
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
PBT
Alias symbols
CD117, SCFR, C-Kit
%HI
8.78(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.24(Read more about gnomAD LOEUF score)
Cytoband
4q12
Genomic Coordinates
GRCh37/hg19: chr4:55524124-55606881 NCBI Ensembl UCSC
GRCh38/hg38: chr4:54657957-54740715 NCBI Ensembl UCSC
MANE Select Transcript
NM_000222.3 ENST00000288135.6 (Read more about MANE Select)
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulator... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-29633
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
05/08/2024

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 15194144
    Murakami et al [2004] sequenced the KIT gene in six families or individuals with piebaldism, a autosomal dominantly inherited disorder characterized by congenital leukoderma, typically on the forehead, abdomen, and knees. Missense, nonsense, frameshift, splice site, in-frame mutations and various complete and partial large deletions of the KIT gene have been reported in human piebaldism. The authors mention that the relatively mild form of the piebaldism phenotype is associated with KIT haploinsufficiency, and is consistent with the relatively mild piebaldism phenotype previously noted for proximal truncating mutations of the KIT gene.
  • PUBMED: 11174389
    Richards et al [2001] describe a missense mutation in a proband and her affected mother within the tyrosine kinase domain of KIT. The authors review the types and locations of mutations and assert "The severity of the clinical phenotype in patients with piebaldism correlates with the site of the mutation within the KIT gene. The most severe mutations, as in our patients, tend to be dominant negative missense mutations involving the intracellular tyrosine kinase domain. Mutations leading to an intermediate severity phenotype have largely been located at or near the transmembrane region, regardless of whether they occur by missense substitution, nonsense substitution, or frameshift mutation. The mildest phenotypes are those that occur in the amino terminal extracellular ligand binding domain with resultant haploinsufficiency."
  • PUBMED: 25355368
    Hemati et al [2015] describe a proband with a large deletion of 4q encompassing KIT with piebaldism and other congenital anomalies. The authors propose haploinsuffciency of KIT as causal for the piebald trait.
  • PUBMED: 36438053
    Wang et al [2022] report three families with piebaldism in which the phenotype was caused by novel heterozygous KIT variants including a sequence-level deletion, insertion and missense mutation classified as pathogenic/likely pathogenic variants according to the interpretation guidelines of American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
HI Evidence Comments:
Missense, nonsense, frameshift, splice site, in-frame mutations and various complete and partial large deletions of the KIT gene have been reported in human piebaldism, a rare autosomal dominant disorder of congenital depigmentation characterized by patches of white skin and hair in a distinct ventral midline pattern. Genetic studies involving the KIT gene have identified distinct genotype–phenotype relationships i.e. a dominant-negative effect for the severe form, and haploinsufficiency for the mild form of piebaldism. Of note, rare germline mutations of KIT, primarily via a gain-of-function mechanism, have been associated with cases of familial gastrointestinal stromal tumor (GIST) [PMID: 33212994] and mastocytosis [PMID: 24745672]. The role of haploinsufficiency in GIST and mastocytosis has not been documented.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000004.11) (NC_000004.12)