KIT

Summary

KIT (KIT proto-oncogene, receptor tyrosine kinase, HGNC:6342) is a protein-coding gene on chromosome 4q12, encoding Mast/stem cell growth factor receptor Kit (P10721). 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 me…. In precision oncology, KIT Exon 11 Mutation confers sensitivity to Imatinib in Gastrointestinal Stromal Tumor (CIViC Level A); 158 further curated variant–drug associations are listed below. It is haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 3815 — RefSeq curated summary.

At a glance

• Gene–disease (curated): gastrointestinal stromal tumor (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 32
• Clinical variants (ClinVar): 3,434 total — 77 pathogenic, 36 likely-pathogenic
• Phenotypes (HPO): 121
• Druggable target: yes — 99 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 159 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000222

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6342
Approved symbol	KIT
Name	KIT proto-oncogene, receptor tyrosine kinase
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	CD117, SCFR, C-Kit
Ensembl gene	ENSG00000157404
Ensembl biotype	protein_coding
OMIM	164920
Entrez	3815

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 15 protein_coding, 7 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000288135, ENST00000412167, ENST00000512959, ENST00000514582, ENST00000684818, ENST00000685269, ENST00000685816, ENST00000686011, ENST00000687109, ENST00000687208, ENST00000687246, ENST00000687265, ENST00000687295, ENST00000688060, ENST00000688704, ENST00000689832, ENST00000689994, ENST00000690519, ENST00000690543, ENST00000690917, ENST00000691361, ENST00000692301, ENST00000692783, ENST00000692991, ENST00000895987, ENST00000931719, ENST00000931720, ENST00000931721

RefSeq mRNA: 8 — MANE Select: NM_000222 NM_000222, NM_001093772, NM_001385284, NM_001385285, NM_001385286, NM_001385288, NM_001385290, NM_001385292

CCDS: CCDS3496, CCDS47058, CCDS93527, CCDS93528, CCDS93529, CCDS93530, CCDS93531, CCDS93532

Canonical transcript exons

ENST00000288135 — 21 exons

Exon	Start	End
ENSE00000000233	54657957	54658081
ENSE00001032350	54695512	54695781
ENSE00001074408	54728011	54728121
ENSE00001074410	54727218	54727324
ENSE00001074415	54737175	54737280
ENSE00001074417	54727416	54727542
ENSE00001074418	54707098	54707287
ENSE00001074423	54725857	54726050
ENSE00001074426	54703724	54703892
ENSE00001074431	54723584	54723698
ENSE00001074435	54733070	54733192
ENSE00001074438	54727823	54727927
ENSE00001074442	54736498	54736609
ENSE00001074445	54729335	54729485
ENSE00001074448	54698284	54698565
ENSE00001074452	54709424	54709539
ENSE00001121859	54699630	54699766
ENSE00001224349	54736721	54736820
ENSE00001898693	54738429	54740715
ENSE00003513956	54731328	54731419
ENSE00003538116	54731871	54731998

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 97.14.

FANTOM5 (CAGE): breadth broad, TPM avg 25.7152 / max 4613.4776, expressed in 846 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47659	23.6884	812
47658	1.9587	382
47657	0.0496	21
47675	0.0185	9

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	97.14	gold quality
secondary oocyte	CL:0000655	97.04	gold quality
oocyte	CL:0000023	96.24	gold quality
upper leg skin	UBERON:0004262	95.73	gold quality
epithelium of mammary gland	UBERON:0003244	94.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.42	gold quality
mammary duct	UBERON:0001765	94.07	gold quality
cardia of stomach	UBERON:0001162	93.91	gold quality
parotid gland	UBERON:0001831	92.70	gold quality
cortical plate	UBERON:0005343	92.61	gold quality
skin of hip	UBERON:0001554	92.39	gold quality
visceral pleura	UBERON:0002401	92.24	gold quality
mammary gland	UBERON:0001911	92.04	gold quality
thoracic mammary gland	UBERON:0005200	92.03	gold quality
nipple	UBERON:0002030	91.73	gold quality
pylorus	UBERON:0001166	91.55	gold quality
mucosa of stomach	UBERON:0001199	91.20	gold quality
upper arm skin	UBERON:0004263	91.00	gold quality
ventral tegmental area	UBERON:0002691	90.70	gold quality
nasal cavity epithelium	UBERON:0005384	90.66	gold quality
CA1 field of hippocampus	UBERON:0003881	90.57	gold quality
orbitofrontal cortex	UBERON:0004167	90.14	gold quality
palpebral conjunctiva	UBERON:0001812	90.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.06	gold quality
lower esophagus	UBERON:0013473	89.97	gold quality
renal medulla	UBERON:0000362	89.73	gold quality
penis	UBERON:0000989	89.52	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.27	gold quality
gall bladder	UBERON:0002110	89.01	gold quality
mammalian vulva	UBERON:0000997	88.90	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	8074.43
E-ANND-2	yes	3816.73
E-MTAB-6678	yes	2457.94
E-GEOD-70580	yes	1595.19
E-CURD-46	yes	1030.62
E-CURD-114	yes	644.49
E-CURD-7	yes	609.13
E-ENAD-21	yes	609.13
E-CURD-84	yes	311.41
E-HCAD-1	yes	54.69
E-CURD-88	yes	46.91
E-CURD-119	yes	40.29
E-CURD-122	yes	17.52
E-GEOD-130148	yes	17.30
E-MTAB-8410	yes	17.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDH3, DAB2IP, FOXC1, FUBP1, GAS2L1, GATA1, GATA2, IKZF1, MITF, MLXIP, MYB, MYC, NFKB, RBMX, RUNX1, SALL4, SOHLH1, SOHLH2, SOX2, SP1, SPI1, TFAP2A, TP53, WT1, ZBTB16, ZNF16, ZNF266

miRNA regulators (miRDB)

110 targeting KIT, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• a tumor marker for cardiac myxoma (PMID:11642722)
• The complexity of KIT gene mutations and chromosome rearrangements and their clinical correlation in gastrointestinal stromal (pacemaker cell) tumors. (PMID:11786393)
• Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling. (PMID:11825908)
• Mutations of c-KIT causing spontaneous activation of the KIT receptor kinase are associated with sporadic adult human mastocytosis (SAHM) and with human gastrointestinal stromal tumors. (PMID:11861291)
• role of c-KIT mutations in the biology of mast cell malignancies (PMID:11919394)
• We have shown for the 1st time that CD117 is expressed at a much higher level in AML myeloblasts than in normal myeloid precursors. (PMID:12008077)
• REVIEW: Signal transduction though the KIT pathway in mast cells and involvement in MC activation and mediator release. (PMID:12041664)
• all classes of interstitial cells of Cajal express CD117, thus it serves as a marker for gastrointestinal stromal tumors (GIST) derived from these cells; mutations in CD117 or aberrations of chromosome 4 are often found in GIST - review (PMID:12072198)
• Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene. (PMID:12091362)
• Asn(822)-Lys mutation affecting a highly conserved codon within the tyrosine kinase activation loop leading to constitutive ligand-independent activation of the KIT receptor was identified in the Kasumi-1 cell (PMID:12111653)
• essential role for c-Kit in KS tumorigenesis (PMID:12134042)
• c-Kit-expressing Ewing tumor cells are resistant to imatinib mesylate. (PMID:12172985)
• Mutations were not detected in over 100 normal individuals and are likely to be the cause of piebaldism in our subjects. (PMID:12204004)
• findings demonstrate a unique KIT sequence and expression pattern among mediastinal seminomas; KIT sequencing may assist in differentiating primary from metastatic MS (PMID:12379771)
• stem cell factor has “late” effects on fetal hemoglobin modulation during erythropoiesis, related to the expression pattern of CD117. (PMID:12393703)
• the SCF-c-kit system, possibly with the contribution of mast cells, may have a growth-regulating role in the normal pancreas, which is altered during malignant transformation. (PMID:12429808)
• Data show that the adapter protein APS preferentially associates with phosphorylated Tyr-568 and Tyr-936 of the receptor for stem-cell factor (c-Kit). (PMID:12444928)
• Fibroblat-like cells lacking this protein express SK3 in smooth gut muscle in health and dissease. (PMID:12457234)
• c-kit gene mutation may play a significant role in the pathogenesis of GIST and also may be a prognostic marker. (PMID:12485499)
• KIT isoforms have remarkable differences in their signaling capabilities (PMID:12511554)
• KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in gastrointestinal stromal tumors (PMID:12522257)
• KIT could be a useful marker for chromophobe renal cell carcinomas (PMID:12584564)
• Point mutations in c-Kit in core binding factor leukemias correlate with white blood cell count and the white blood cell index (PMID:12592353)
• Point mutation may be associated with urticaria pigmentosa in children. (PMID:12598308)
• c-kit+ cells were found in glomeruli and interstitium. Colocalization of CD34+ and c-kit+ was seen in some rounded interstitial and spindle-shaped cells. This shows potential involvement of SCF/c-kit in crescentic glomerulonephritis. (PMID:12666065)
• overexpression of the c-kit protein is associated with large cell neuroendocrine carcinoma of the lung (PMID:12711118)
• gain-of-function mutation in exon 11 of the c-kit gene is an important prognostic factor for gastrointestinal mesenchymal tumors, including myogenic and neurogenic tumors as well as GISTs (PMID:12759497)
• overexpression of c-KIT is associated with extensive-stage small-cell lung carcinoma (PMID:12796027)
• Mutations of the c-kit gene is associated with testicular germ cell tumors (PMID:12824871)
• types of mutations in sinonasal NK/T cell lymphoma in northeast district of China (PMID:12824925)
• c-Src phosphorylates the receptor KIT, thereby creating docking sites for SH2 domain containing proteins, leading to recruitment of Crk to the receptor. (PMID:12878163)
• Mutations and deletions in c-kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors (PMID:12918066)
• surface expression of c-Kit is regulated by TACE, which controls mast cell survival (PMID:14625290)
• the presence of c-Kit and VEGF overexpression is associated with the presence of second primary tumors in patients with melanoma; overexpression of c-Kit is more likely to be seen in the superficial spreading type (PMID:14634801)
• tr-kit promotes the formation of a multimolecular complex composed of Fyn, PLCgamma1 and Sam68, which allows phosphorylation of PLCgamma1 by Fyn, and may modulate RNA metabolism. (PMID:14647465)
• findings of co-expression of KIT and/or FMS with their respective ligands implies these receptors might contribute to leukemogenesis in some patients with AML through autocrine, paracrine, or intracrine interactive stimulation. (PMID:14654075)
• c-kit overexpression observed in a subset of colorectal neuroendocrine carcinomas may not be mediated via activating mutations, and does not appear to be an initiating event during tumorigenesis (PMID:14657715)
• This result suggests that the loss of expression of this protein might correlate with malignant breast cancer progression, but it is most likely involved at an early stage of human breast cancer development. (PMID:14669790)
• KIT expression is a rare event in multiple myeloma and not detectable in monoclonal gammopathy of undetermined significance and lymphoplasmacytic lymphoma (PMID:14677065)
• activating KIT mutations may contribute to tumorigenesis in a subset of seminomas, but are not involved in non-seminomatous germ cell tumors. (PMID:14695343)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kita	ENSDARG00000043317
danio_rerio	kitb	ENSDARG00000056133
mus_musculus	Kit	ENSMUSG00000005672
rattus_norvegicus	Kit	ENSRNOG00000002227

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Mast/stem cell growth factor receptor Kit — P10721 (reviewed: P10721)

Alternative names: Piebald trait protein, Proto-oncogene c-Kit, Tyrosine-protein kinase Kit, p145 c-kit, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

All UniProt accessions (11): P10721, A0A0U2N547, A0A8I5KPX7, A0A8I5KQZ6, A0A8I5KR87, A0A8I5KRE7, A0A8I5KS03, A0A8I5KXA4, A0A8I5QKL5, A0A8I5QKP7, A0A8J8Z860

UniProt curated annotations — full annotation on UniProt →

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 regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.

Subunit / interactions. Monomer in the absence of bound KITLG/SCF. Homodimer in the presence of bound KITLG/SCF, forming a heterotetramer with two KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues) with the adapter proteins GRB2 and GRB7 (via SH2 domain), and SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ domain). Interacts (via phosphorylated tyrosine residues) with PIK3R1 and PIK3 catalytic subunit. Interacts (via phosphorylated tyrosine) with CRK (isoform Crk-II), FYN, SHC1 and MATK/CHK (via SH2 domain). Interacts with LYN and FES/FPS. Interacts (via phosphorylated tyrosine residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with PLCG1. Interacts with DOK1 and TEC. Interacts (KITLG/SCF-bound) with IL1RL1. Interacts with IL1RAP (independent of stimulation with KITLG/SCF). A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex contains IL1RL1, IL1RAP, KIT and MYD88.

Subcellular location. Cell membrane Cell membrane Cytoplasm.

Tissue specificity. In testis, detected in spermatogonia in the basal layer and in interstitial Leydig cells but not in Sertoli cells or spermatocytes inside the seminiferous tubules (at protein level). Expression is maintained in ejaculated spermatozoa (at protein level).

Post-translational modifications. Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation. Autophosphorylated on tyrosine residues. KITLG/SCF binding enhances autophosphorylation. Isoform 1 shows low levels of tyrosine phosphorylation in the absence of added KITLG/SCF (in vitro). Kinase activity is down-regulated by phosphorylation on serine residues by protein kinase C family members. Phosphorylation at Tyr-568 is required for interaction with PTPN11/SHP-2, CRK (isoform Crk-II) and members of the SRC tyrosine-protein kinase family. Phosphorylation at Tyr-570 is required for interaction with PTPN6/SHP-1. Phosphorylation at Tyr-703, Tyr-823 and Tyr-936 is important for interaction with GRB2. Phosphorylation at Tyr-721 is important for interaction with PIK3R1. Phosphorylation at Tyr-823 and Tyr-936 is important for interaction with GRB7.

Disease relevance. Piebald trait (PBT) [MIM:172800] Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. The disease is caused by variants affecting the gene represented in this entry. Gastrointestinal stromal tumor (GIST) [MIM:606764] Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery. The gene represented in this entry is involved in disease pathogenesis. Testicular germ cell tumor (TGCT) [MIM:273300] A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. The gene represented in this entry may be involved in disease pathogenesis. Leukemia, acute myelogenous (AML) [MIM:601626] A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase. Mastocytosis, cutaneous (MASTC) [MIM:154800] A form of mastocytosis, a heterogeneous group of disorders associated with abnormal proliferation and accumulation of mast cells in various tissues, especially in the skin and hematopoietic organs. MASTC is an autosomal dominant form characterized by macules, papules, nodules, or diffuse infiltration of the skin, often associated with localized hyperpigmentation. Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed Darier sign. The disease is caused by variants affecting the gene represented in this entry. Mastocytosis, systemic (MASTSYS) [MIM:154800] A severe form of mastocytosis characterized by abnormal proliferation and accumulation of mast cells in several organs, resulting in a systemic disease that may affect bone, gastrointestinal tract, lymphatics, spleen, and liver. In some cases, it is associated with a clonal hematologic non-mast-cell lineage disease, such as a myelodysplastic or myeloproliferative disorder. It can also lead to mast cell leukemia, which carries a high risk of mortality. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Activity is down-regulated by PRKCA-mediated phosphorylation on serine residues. Inhibited by imatinib/STI-571 (Gleevec) and sunitinib; these compounds maintain the kinase in an inactive conformation.

Induction. Up-regulated by cis-retinoic acid in neuroblastoma cell lines.

Miscellaneous. Numerous proteins are phosphorylated in response to KIT signaling, but it is not evident to determine which are directly phosphorylated by KIT under in vivo conditions.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P10721-1	1, GNNK(+), KitA(+)	yes
P10721-2	2, GNNK(-), Kit(+)
P10721-4	3, TR-KIT

RefSeq proteins (8): NP_000213, NP_001087241, NP_001372213, NP_001372214, NP_001372215, NP_001372217, NP_001372219, NP_001372221 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001824	Tyr_kinase_rcpt_3_CS	Conserved_site
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR027263	SCGF_receptor	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF00047, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (194 total): strand 63, sequence variant 37, helix 26, modified residue 15, glycosylation site 10, mutagenesis site 8, binding site 7, domain 6, turn 5, disulfide bond 5, topological domain 2, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, active site 1, site 1, transmembrane region 1

Structure

Experimental structures (PDB)

52 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2VIF	X-RAY DIFFRACTION	1.45
8PQD	X-RAY DIFFRACTION	1.5
8S14	X-RAY DIFFRACTION	1.5
1T46	X-RAY DIFFRACTION	1.6
3G0E	X-RAY DIFFRACTION	1.6
8PQA	X-RAY DIFFRACTION	1.65
8PQ9	X-RAY DIFFRACTION	1.7
8PQC	X-RAY DIFFRACTION	1.77
6MOB	X-RAY DIFFRACTION	1.8
8S16	X-RAY DIFFRACTION	1.85
8S1A	X-RAY DIFFRACTION	1.85
8PQB	X-RAY DIFFRACTION	1.87
6ITV	X-RAY DIFFRACTION	1.88
1T45	X-RAY DIFFRACTION	1.9
4HVS	X-RAY DIFFRACTION	1.9
8PQF	X-RAY DIFFRACTION	1.9
2IUH	X-RAY DIFFRACTION	2
4U0I	X-RAY DIFFRACTION	2
6GQM	X-RAY DIFFRACTION	2
8PQE	X-RAY DIFFRACTION	2
8S13	X-RAY DIFFRACTION	2
8S1B	X-RAY DIFFRACTION	2
6GQL	X-RAY DIFFRACTION	2.01
8S18	X-RAY DIFFRACTION	2.1
6ITT	X-RAY DIFFRACTION	2.1
6KLA	X-RAY DIFFRACTION	2.11
7ZW8	X-RAY DIFFRACTION	2.12
6XVB	X-RAY DIFFRACTION	2.15
7KHG	X-RAY DIFFRACTION	2.15
8S17	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10721-F1	78.52	0.51

Antibody-complex structures (SAbDab): 2 — 4K94, 4K9E

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 792 (proton acceptor); 936 (important for interaction with phosphotyrosine-binding proteins)

Ligand- & substrate-binding residues (7): 568; 596–603; 623; 671–677; 796; 797; 810

Post-translational modifications (15): 547, 553, 568, 570, 703, 721, 730, 741, 746, 821, 823, 891, 900, 936, 959

Disulfide bonds (5): 58–97, 136–186, 151–183, 233–290, 428–491

Glycosylation sites (10): 130, 145, 283, 293, 300, 320, 352, 367, 463, 486

Mutagenesis-validated functional residues (8):

Position	Phenotype
381	reduces autophosphorylation in response to kitlg/scf.
386	reduces autophosphorylation in response to kitlg/scf.
571	reduction in sh2b2/aps binding. abolishes sh2b2/aps binding; when associated with a-939.
623	stronger interaction with mpdz.
741	abolishes down-regulation of kinase activity by pkc/prkca-mediated phosphorylation; when associated with a-746.
746	abolishes down-regulation of kinase activity by pkc/prkca-mediated phosphorylation; when associated with a-741.
823	no decrease in activity. leads to autophosphorylation at tyr-900.
939	reduction in sh2b2/aps binding. abolishes sh2b2/aps binding; when associated with a-571.

Function

Pathways and Gene Ontology

Reactome pathways

39 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-1433559	Regulation of KIT signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8866910	TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
R-HSA-9669914	Dasatinib-resistant KIT mutants
R-HSA-9669917	Imatinib-resistant KIT mutants
R-HSA-9669921	KIT mutants bind TKIs
R-HSA-9669924	Masitinib-resistant KIT mutants
R-HSA-9669926	Nilotinib-resistant KIT mutants
R-HSA-9669929	Regorafenib-resistant KIT mutants
R-HSA-9669933	Signaling by kinase domain mutants of KIT
R-HSA-9669934	Sunitinib-resistant KIT mutants
R-HSA-9669935	Signaling by juxtamembrane domain KIT mutants
R-HSA-9669936	Sorafenib-resistant KIT mutants
R-HSA-9670439	Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants
R-HSA-9680187	Signaling by extracellular domain mutants of KIT
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-199418	Negative regulation of the PI3K/AKT network
R-HSA-212436	Generic Transcription Pathway
R-HSA-2219528	PI3K/AKT Signaling in Cancer
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5683057	MAPK family signaling cascades

MSigDB gene sets: 846 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GCACCTT_MIR18A_MIR18B, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_EMBRYONIC_HEMOPOIESIS, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE

GO Biological Process (85): ovarian follicle development (GO:0001541), hematopoietic progenitor cell differentiation (GO:0002244), myeloid progenitor cell differentiation (GO:0002318), lymphoid progenitor cell differentiation (GO:0002320), immature B cell differentiation (GO:0002327), mast cell chemotaxis (GO:0002551), positive regulation of dendritic cell cytokine production (GO:0002732), glycosphingolipid metabolic process (GO:0006687), inflammatory response (GO:0006954), signal transduction (GO:0007165), spermatogenesis (GO:0007283), spermatid development (GO:0007286), positive regulation of cell population proliferation (GO:0008284), primordial germ cell migration (GO:0008354), regulation of cell shape (GO:0008360), visual learning (GO:0008542), male gonad development (GO:0008584), cell migration (GO:0016477), cytokine-mediated signaling pathway (GO:0019221), stem cell population maintenance (GO:0019827), lamellipodium assembly (GO:0030032), actin cytoskeleton organization (GO:0030036), hemopoiesis (GO:0030097), B cell differentiation (GO:0030183), T cell differentiation (GO:0030217), erythrocyte differentiation (GO:0030218), melanocyte differentiation (GO:0030318), positive regulation of cell migration (GO:0030335), positive regulation of pseudopodium assembly (GO:0031274), positive regulation of mast cell cytokine production (GO:0032765), somatic stem cell population maintenance (GO:0035019), embryonic hemopoiesis (GO:0035162), ectopic germ cell programmed cell death (GO:0035234), intracellular signal transduction (GO:0035556), hematopoietic stem cell migration (GO:0035701), megakaryocyte development (GO:0035855), Fc receptor signaling pathway (GO:0038093), Kit signaling pathway (GO:0038109), erythropoietin-mediated signaling pathway (GO:0038162), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (15): protease binding (GO:0002020), protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), stem cell factor receptor activity (GO:0005020), ATP binding (GO:0005524), growth factor binding (GO:0019838), cytokine binding (GO:0019955), SH2 domain binding (GO:0042169), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (11): fibrillar center (GO:0001650), acrosomal vesicle (GO:0001669), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), external side of plasma membrane (GO:0009897), cytoplasmic side of plasma membrane (GO:0009898), signaling receptor complex (GO:0043235), cytoplasm (GO:0005737), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Drug resistance of KIT mutants	7
Signaling by KIT in disease	5
Intracellular signaling by second messengers	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by SCF-KIT	1
PI3K/AKT Signaling in Cancer	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
hematopoietic progenitor cell differentiation	2
protein binding	2
plasma membrane	2
female gonad development	1
anatomical structure development	1
hemopoiesis	1
cell differentiation	1
B cell differentiation	1
leukocyte chemotaxis	1
mast cell migration	1
dendritic cell cytokine production	1
positive regulation of leukocyte mediated immunity	1
positive regulation of cytokine production involved in immune response	1
regulation of dendritic cell cytokine production	1
glycolipid metabolic process	1
sphingolipid metabolic process	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
developmental process involved in reproduction	1
male gamete generation	1
germ cell development	1
spermatid differentiation	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gamete generation	1
cell migration	1
regulation of cell morphogenesis	1
regulation of biological quality	1
visual behavior	1
associative learning	1
gonad development	1
development of primary male sexual characteristics	1
cell motility	1
cell surface receptor signaling pathway	1

Protein interactions and networks

STRING

5408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIT	KITLG	P21583	999
KIT	CLEC11A	Q9Y240	993
KIT	CXCL12	P48061	972
KIT	CD34	P28906	953
KIT	IL3	P08700	944
KIT	ANPEP	P15144	919
KIT	IL1RAP	Q9NPH3	919
KIT	CD33	P20138	897
KIT	ANO1	Q5XXA6	891
KIT	GRB2	P29354	887
KIT	PTPRC	P08575	881
KIT	FLT3LG	P49771	860
KIT	IL7	P13232	826
KIT	CXCR4	P30991	824
KIT	ENG	P17813	817

IntAct

488 interactions, top by confidence:

A	B	Type	Score
KIT	PIK3R1	psi-mi:“MI:2364”(proximity)	0.750
PIK3R1	KIT	psi-mi:“MI:0914”(association)	0.750
PIK3R1	KIT	psi-mi:“MI:0407”(direct interaction)	0.750
GRB2	KIT	psi-mi:“MI:0915”(physical association)	0.740
GRB2	KIT	psi-mi:“MI:0914”(association)	0.740
PLCG1	KIT	psi-mi:“MI:2364”(proximity)	0.670
PLCG1	KIT	psi-mi:“MI:0914”(association)	0.670
PLCG1	KIT	psi-mi:“MI:0407”(direct interaction)	0.670
CRK	KIT	psi-mi:“MI:0914”(association)	0.590
GRB7	KIT	psi-mi:“MI:0914”(association)	0.590
PIK3R2	KIT	psi-mi:“MI:0914”(association)	0.590
KIT	KITLG	psi-mi:“MI:0407”(direct interaction)	0.540
KITLG	KIT	psi-mi:“MI:0915”(physical association)	0.540
KIT	Ptpn11	psi-mi:“MI:0915”(physical association)	0.520
Ptpn11	KIT	psi-mi:“MI:0915”(physical association)	0.520
Mpdz	KIT	psi-mi:“MI:0915”(physical association)	0.510
KIT	Mpdz	psi-mi:“MI:0915”(physical association)	0.510
	KIT	psi-mi:“MI:0915”(physical association)	0.500
KIT	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
KIT	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (191): PIK3CG (Co-localization), BCR (Co-localization), CSF2RA (Co-localization), PIK3R1 (Co-localization), PLCG1 (Co-localization), KIT (Co-localization), KIT (Affinity Capture-MS), CBL (Affinity Capture-Western), HSP90B1 (Affinity Capture-Western), KIT (Affinity Capture-Western), RPS6KB1 (Negative Genetic), TP53 (Positive Genetic), SMO (Positive Genetic), ILKAP (Two-hybrid), PTPN20B (Two-hybrid)

ESM2 similar proteins: A0A7H0DND3, A1XRN2, A8WH72, A8WH74, A8WH75, A8WUV1, B1A4M7, B1A4N2, B1A4N8, B1A4P2, B1A4P6, B1A4P7, B1A4P8, B1A4P9, B1A4Q0, B1A4Q2, B1A4Q3, B1A4Q5, B1A4Q6, B1A4Q8, B1A4Q9, B1A4R0, B1A4R4, B2D1Y0, O55159, P0DQP8, P10721, P16234, P21057, P21755, P21756, P24761, P24765, P26618, P26619, P33851, Q16YE7, Q1L867, Q3T0L5, Q5FVR3

Diamond homologs: D2IYS2, G3V9H8, O08775, O42127, O73791, O73798, O97799, P00529, P00545, P04048, P05532, P05622, P07333, P07949, P09581, P09619, P10721, P11362, P13369, P16092, P16234, P17948, P18460, P18461, P20786, P21802, P21803, P21804, P22182, P22455, P22607, P23049, P26618, P26619, P33497, P35546, P35590, P35916, P35917, P35918

SIGNOR signaling

80 interactions.

A	Effect	B	Mechanism
KIT	“up-regulates activity”	KIT	phosphorylation
SRC	“up-regulates activity”	KIT	phosphorylation
GRB2	down-regulates	KIT
SOCS6	down-regulates	KIT	ubiquitination
axitinib	down-regulates	KIT	“chemical inhibition”
sunitinib	down-regulates	KIT	“chemical inhibition”
N-(1,3-benzodioxol-5-ylmethyl)-4-(4-benzofuro[3,2-d]pyrimidinyl)-1-piperazinecarbothioamide	down-regulates	KIT	“chemical inhibition”
4-amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydrobenzimidazol-2-ylidene]-2-quinolinone	down-regulates	KIT	“chemical inhibition”
“dovitinib; bis(lactic acid)”	down-regulates	KIT	“chemical inhibition”
imatinib	down-regulates	KIT	“chemical inhibition”
“imatinib methanesulfonate”	down-regulates	KIT	“chemical inhibition”
masitinib	down-regulates	KIT	“chemical inhibition”
motesanib	down-regulates	KIT	“chemical inhibition”
3-(4-quinolinylmethylamino)-N-[4-(trifluoromethoxy)phenyl]-2-thiophenecarboxamide	down-regulates	KIT	“chemical inhibition”
CHEK2	up-regulates	KIT	phosphorylation
“pazopanib hydrochloride”	down-regulates	KIT	“chemical inhibition”
regorafenib	down-regulates	KIT	“chemical inhibition”
tandutinib	down-regulates	KIT	“chemical inhibition”
Telatinib	down-regulates	KIT	“chemical inhibition”
vatalanib	down-regulates	KIT	“chemical inhibition”
KITLG	up-regulates	KIT	binding
KIT	“up-regulates activity”	GRB2	binding
KIT	“up-regulates activity”	GRB7	binding
DAB2IP	“down-regulates quantity by repression”	KIT	“transcriptional regulation”
GATA1	“down-regulates quantity by repression”	KIT	“transcriptional regulation”
KITLG	“up-regulates activity”	KIT	binding
KIT	“up-regulates activity”	ERK1/2
KIT	“up-regulates activity”	PI3K	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of KIT signaling	7	45.7×	9e-09
Downstream signal transduction	10	41.4×	5e-12
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	7	39.5×	2e-08
Signaling by SCF-KIT	13	35.1×	1e-14
Tie2 Signaling	5	32.7×	9e-06
Long-term potentiation	6	31.0×	1e-06
Signaling by ALK	5	31.0×	1e-05
Ras activation upon Ca2+ influx through NMDA receptor	5	31.0×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	46.9×	6e-12
protein localization to synapse	6	37.1×	3e-06
peptidyl-tyrosine dephosphorylation	5	35.8×	3e-05
receptor clustering	7	35.2×	4e-07
positive regulation of Rac protein signal transduction	5	26.1×	1e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	6	24.0×	3e-05
B cell receptor signaling pathway	5	16.2×	9e-04
establishment of cell polarity	5	15.4×	1e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

c-KIT activation has been shown to have oncogenic activity in gastrointestinal stromal tumors (GISTs), melanomas, lung cancer, and other tumor types. The targeted therapeutics nilotinib and sunitinib have shown efficacy in treating KIT overactive patients, and are in late-stage trials in melanoma and GIST. KIT overactivity can be the result of many genomic events from genomic amplification to overexpression to missense mutations. Missense mutations have been shown to be key players in mediating clinical response and acquired resistance in patients being treated with these targeted therapeutics.

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — AML, GIST, MEL, MGCT.

Clinical variants and AI predictions

ClinVar

3434 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	77
Likely pathogenic	36
Uncertain significance	1658
Likely benign	1330
Benign	48

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071467	NM_000222.3(KIT):c.1126G>T (p.Glu376Ter)	Pathogenic
1299653	NM_000222.3(KIT):c.2415_2422del (p.Thr806fs)	Pathogenic
1331512	NM_000222.3(KIT):c.21_22del (p.Trp8fs)	Pathogenic
1368363	NM_000222.3(KIT):c.1000_1003dup (p.Val335fs)	Pathogenic
13843	NM_000222.3(KIT):c.1990G>A (p.Gly664Arg)	Pathogenic
13844	NC_000004.12:g.(?54229292)(54740716_)del	Pathogenic
13846	NM_000222.3(KIT):c.1676_1681del (p.Val559_Val560del)	Pathogenic
13847	NM_000222.3(KIT):c.1925_1926del (p.Lys642fs)	Pathogenic
13848	NM_000222.3(KIT):c.1681dup (p.Glu561fs)	Pathogenic
13850	NM_000222.3(KIT):c.253del (p.Glu85fs)	Pathogenic
13851	NM_000222.3(KIT):c.1879+1G>A	Pathogenic
13854	NM_000222.3(KIT):c.1652_1666del (p.Pro551_Val555del)	Pathogenic
13855	NM_000222.3(KIT):c.1649_1663del (p.Lys550_Val555delinsIle)	Pathogenic
13856	NM_000222.3(KIT):c.1676T>A (p.Val559Asp)	Pathogenic
13857	NC_000004.12:g.54727416_54727442del	Pathogenic
13858	NM_000222.3(KIT):c.2386A>G (p.Arg796Gly)	Pathogenic
13861	NM_000222.3(KIT):c.2539A>C (p.Thr847Pro)	Pathogenic
13862	NM_000222.3(KIT):c.2515G>A (p.Glu839Lys)	Pathogenic
13863	NM_000222.3(KIT):c.2446G>C (p.Asp816His)	Pathogenic
13864	NM_000222.3(KIT):c.1751T>G (p.Phe584Cys)	Pathogenic
13866	NM_000222.3(KIT):c.1924A>G (p.Lys642Glu)	Pathogenic
1405140	NM_000222.3(KIT):c.364del (p.Arg122fs)	Pathogenic
1450203	NM_000222.3(KIT):c.2080C>T (p.Gln694Ter)	Pathogenic
1451251	NM_000222.3(KIT):c.1482C>A (p.Tyr494Ter)	Pathogenic
1451608	NM_000222.3(KIT):c.1666C>T (p.Gln556Ter)	Pathogenic
1452413	NM_000222.3(KIT):c.366_369del (p.Ser123fs)	Pathogenic
2033857	NM_000222.3(KIT):c.761_765del (p.Lys254fs)	Pathogenic
2043850	NM_000222.3(KIT):c.32_33insG (p.Cys12fs)	Pathogenic
2126350	NM_000222.3(KIT):c.828_832dup (p.Ser278fs)	Pathogenic
2203546	NM_000222.3(KIT):c.2139del (p.Cys714fs)	Pathogenic

SpliceAI

3727 predictions. Top by Δscore:

Variant	Effect	Δscore
4:54695723:C:T	donor_gain	1.0000
4:54695748:GGCT:G	donor_gain	1.0000
4:54695749:GCT:G	donor_gain	1.0000
4:54695751:T:G	donor_gain	1.0000
4:54703712:T:TA	acceptor_gain	1.0000
4:54703716:ACCAG:A	acceptor_loss	1.0000
4:54703717:CCAGC:C	acceptor_loss	1.0000
4:54703718:CAG:C	acceptor_loss	1.0000
4:54703719:A:AG	acceptor_gain	1.0000
4:54703719:AGCA:A	acceptor_loss	1.0000
4:54703720:G:A	acceptor_loss	1.0000
4:54703720:G:GT	acceptor_gain	1.0000
4:54703720:GC:G	acceptor_gain	1.0000
4:54703720:GCA:G	acceptor_gain	1.0000
4:54703720:GCAGA:G	acceptor_gain	1.0000
4:54703883:G:GT	donor_gain	1.0000
4:54703883:G:T	donor_gain	1.0000
4:54703886:GTA:G	donor_gain	1.0000
4:54703887:T:TA	donor_gain	1.0000
4:54703888:A:AA	donor_gain	1.0000
4:54703888:AGTAG:A	donor_loss	1.0000
4:54703889:GTAG:G	donor_gain	1.0000
4:54703892:GGTAA:G	donor_loss	1.0000
4:54703893:GT:G	donor_loss	1.0000
4:54703894:T:G	donor_loss	1.0000
4:54707087:A:AG	acceptor_gain	1.0000
4:54707092:A:AG	acceptor_gain	1.0000
4:54707093:A:G	acceptor_gain	1.0000
4:54707095:TAGAT:T	acceptor_loss	1.0000
4:54707096:A:AG	acceptor_gain	1.0000

AlphaMissense

6468 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:54727437:T:A	W557R	1.000
4:54727437:T:C	W557R	1.000
4:54727495:T:C	L576P	1.000
4:54727519:T:C	F584S	1.000
4:54727534:T:A	L589Q	1.000
4:54727534:T:C	L589P	1.000
4:54727832:T:A	L595Q	1.000
4:54727832:T:C	L595P	1.000
4:54727834:G:A	G596S	1.000
4:54727834:G:C	G596R	1.000
4:54727834:G:T	G596C	1.000
4:54727835:G:A	G596D	1.000
4:54727835:G:T	G596V	1.000
4:54727840:G:A	G598R	1.000
4:54727840:G:C	G598R	1.000
4:54727841:G:A	G598E	1.000
4:54727841:G:T	G598V	1.000
4:54727844:C:A	A599D	1.000
4:54727846:T:A	F600I	1.000
4:54727846:T:C	F600L	1.000
4:54727846:T:G	F600V	1.000
4:54727847:T:C	F600S	1.000
4:54727847:T:G	F600C	1.000
4:54727848:C:A	F600L	1.000
4:54727848:C:G	F600L	1.000
4:54727849:G:A	G601R	1.000
4:54727849:G:C	G601R	1.000
4:54727849:G:T	G601W	1.000
4:54727850:G:A	G601E	1.000
4:54727850:G:C	G601A	1.000

dbSNP variants (sampled 300 via entrez): RS1000008469 (4:54677781 C>T), RS1000029898 (4:54714708 C>T), RS1000045501 (4:54701244 C>A,T), RS1000093263 (4:54720059 T>A), RS1000138811 (4:54737249 T>C), RS1000158120 (4:54673049 G>A), RS1000164778 (4:54687309 G>C), RS1000193439 (4:54740657 T>C), RS1000221275 (4:54690208 G>A), RS1000224231 (4:54656277 T>G), RS1000234175 (4:54684203 G>A), RS1000335020 (4:54714460 T>C), RS1000338100 (4:54740311 C>T), RS1000384197 (4:54720422 A>G), RS1000426640 (4:54672826 C>T)

Disease associations

OMIM: gene MIM:164920 | disease phenotypes: MIM:606764, MIM:172800, MIM:273300, MIM:601626, MIM:154800, MIM:181500, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
piebaldism	Definitive	Autosomal dominant
mastocytosis	Strong	Autosomal dominant
gastrointestinal stromal tumor	Strong	Autosomal dominant
cutaneous mastocytosis	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
gastrointestinal stromal tumor	Definitive	AD

Mondo (16): gastrointestinal stromal tumor (MONDO:0011719), hereditary neoplastic syndrome (MONDO:0015356), piebaldism (MONDO:0008244), testicular germ cell tumor (MONDO:0010108), acute myeloid leukemia (MONDO:0018874), cutaneous mastocytosis (MONDO:0019023), mastocytosis (MONDO:0007950), dysgerminoma (MONDO:0003002), schizophrenia (MONDO:0005090), testicular cancer (MONDO:0005447), hereditary skin disorder (MONDO:0100118), ovarian cancer (MONDO:0008170), lip and oral cavity carcinoma (MONDO:0023644), hereditary breast ovarian cancer syndrome (MONDO:0003582), systemic mastocytosis (MONDO:0016586)

Orphanet (11): Inherited cancer-predisposing syndrome (Orphanet:140162), Gastrointestinal stromal tumor (Orphanet:44890), Piebaldism (Orphanet:2884), Germ cell tumor of testis (Orphanet:363504), Acute myeloid leukemia (Orphanet:519), Cutaneous mastocytosis (Orphanet:66646), Mastocytosis (Orphanet:98292), Rare ovarian cancer (Orphanet:213500), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Systemic mastocytosis (Orphanet:2467), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

121 total (30 of 121 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000027	Azoospermia
HP:0000252	Microcephaly
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000431	Wide nasal bridge
HP:0000598	Abnormality of the ear
HP:0000664	Synophrys
HP:0000939	Osteoporosis
HP:0000953	Hyperpigmentation of the skin
HP:0000969	Edema
HP:0000980	Pallor
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001025	Urticaria
HP:0001034	Hypermelanotic macule
HP:0001053	Hypopigmented skin patches
HP:0001067	Neurofibroma
HP:0001072	Thickened skin
HP:0001100	Heterochromia iridis
HP:0001176	Large hands
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001279	Syncope
HP:0001392	Abnormality of the liver
HP:0001442	Typified by somatic mosaicism
HP:0001649	Tachycardia
HP:0001744	Splenomegaly

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST000387_12	Bipolar disorder	4.000000e-06
GCST000503_6	Mean corpuscular volume	1.000000e-15
GCST000585_17	Mean corpuscular volume	1.000000e-27
GCST001765_43	Red blood cell traits	3.000000e-39
GCST002698_1	Serum VEGFR2 concentration	5.000000e-25
GCST002715_9	Breastfeeding duration	9.000000e-06
GCST002936_29	Cadmium levels	1.000000e-06
GCST003050_20	Schizophrenia	5.000000e-07
GCST004003_9	Hematocrit	1.000000e-08
GCST004004_32	Mean corpuscular volume	2.000000e-36
GCST004005_13	Hemoglobin levels	1.000000e-08
GCST004006_29	Mean corpuscular hemoglobin	1.000000e-08
GCST004008_14	Red blood cell count	4.000000e-16
GCST004008_19	Red blood cell count	2.000000e-28
GCST004332_3	Red blood cell count	4.000000e-10
GCST004334_6	Mean corpuscular hemoglobin	3.000000e-12
GCST004335_3	Mean corpuscular volume	9.000000e-13
GCST005754_1	Systemic lupus erythematosus	1.000000e-15
GCST005991_10	Platelet count	7.000000e-09
GCST005993_74	Mean corpuscular hemoglobin	6.000000e-109
GCST005994_20	Hematocrit	2.000000e-20
GCST005995_8	Hemoglobin	6.000000e-16
GCST005996_60	Red blood cell count	1.000000e-93
GCST006011_105	Mean corpuscular volume	3.000000e-126
GCST006576_1	Anorexia nervosa or obsessive-compulsive disorder	4.000000e-07
GCST010241_281	Apolipoprotein A1 levels	5.000000e-09
GCST010242_129	HDL cholesterol levels	1.000000e-12
GCST010244_311	Triglyceride levels	9.000000e-12
GCST010658_7	High density lipoprotein cholesterol levels	5.000000e-07
GCST010660_15	Triglyceride levels	3.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0006864	breastfeeding duration
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004309	platelet count
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D004407	Dysgerminoma	C04.557.465.330.300
D046152	Gastrointestinal Stromal Tumors	C04.557.450.565.370; C06.301.371.308; C06.405.249.308
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D008415	Mastocytosis	C04.557.450.565.465; C20.762.750
D034701	Mastocytosis, Cutaneous	C04.557.450.565.465.500; C04.588.805.309; C17.800.882.356; C20.762.750.563
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D016116	Piebaldism	C16.320.290.040.600; C16.320.565.100.102.600; C16.320.850.080.600; C17.800.621.440.102.600; C17.800.827.080.600; C18.452.648.100.102.600
D012873	Skin Diseases, Genetic	C16.320.850; C17.800.827
D013736	Testicular Neoplasms	C04.588.322.762; C04.588.945.440.915; C12.100.500.260.937; C12.200.294.260.937; C12.200.758.409.937; C12.900.619.937; C19.344.762; C19.391.829.782
C563236	Testicular Germ Cell Tumor (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1936 (SINGLE PROTEIN), CHEMBL2111428 (SELECTIVITY GROUP), CHEMBL4523731 (PROTEIN-PROTEIN INTERACTION), CHEMBL4630731 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

99 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 415,711 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL1642	IMATINIB MESYLATE	4	70,143
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL3813873	PEXIDARTINIB	4
CHEMBL4204794	AVAPRITINIB	4
CHEMBL4216467	RIPRETINIB	4
CHEMBL477772	PAZOPANIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL535	SUNITINIB	4
CHEMBL5416410	DASATINIB	4
CHEMBL553	ERLOTINIB	4
CHEMBL576982	QUIZARTINIB	4
CHEMBL601719	CRIZOTINIB	4

Clinical evidence (CIViC)

Drug × variant × indication: 159 predictive associations from 189 curated evidence items; also 8 oncogenic, 8 prognostic, 4 diagnostic, 1 functional.

Variant	Therapy	Indication	Effect	Level	CIViC
KIT Exon 11 Mutation	Imatinib	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC A	EID654 +2
KIT Exon 9 Mutation	Imatinib	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC A	EID1221 +1
KIT D816V	Avapritinib	Systemic Mastocytosis	Sensitivity/Response	CIViC A	EID11274
KIT Mutation	Imatinib	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC A	EID11282
KIT Mutation	Ripretinib	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC A	EID11284
KIT Mutation	Sunitinib	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC A	EID11285
KIT Exon 11 Mutation	Regorafenib Anhydrous	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC B	EID4599 +2
KIT Exon 9 Mutation	Sunitinib	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC B	EID1223 +2
KIT D816V	Midostaurin	Systemic Mastocytosis	Sensitivity/Response	CIViC B	EID1725
KIT EXPRESSION	Sunitinib	Glioblastoma	Sensitivity/Response	CIViC B	EID10180
KIT EXPRESSION	Imatinib	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC B	EID2480
KIT Exon 11 Mutation	Imatinib	Melanoma	Sensitivity/Response	CIViC B	EID58
KIT Exon 9 Mutation	Regorafenib Anhydrous	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC B	EID4628
KIT Mutation	Imatinib	Melanoma	Sensitivity/Response	CIViC B	EID1222
KIT Mutation	Nilotinib	Melanoma	Sensitivity/Response	CIViC B	EID7145
KIT Mutation	Dasatinib	Core Binding Factor Acute Myeloid Leukemia	Sensitivity/Response	CIViC B	EID8576
KIT RS3733542	Selumetinib	Acute Myeloid Leukemia	Sensitivity/Response	CIViC B	EID1136
KIT V654A	Sunitinib	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC B	EID304
KIT Wildtype	Regorafenib Anhydrous	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC B	EID4144
KIT Y503_F504insAY	Imatinib	Gastrointestinal Stromal Tumor	Sensitivity/Response	CIViC B	EID2394
NOT KIT D816V	Imatinib	Systemic Mastocytosis	Sensitivity/Response	CIViC B	EID11158
KIT Exon 9 Mutation	Regorafenib Anhydrous	Gastrointestinal Stromal Tumor	Reduced Sensitivity	CIViC B	EID4139 +1
KIT Exon 9 Mutation	Imatinib	Gastrointestinal Stromal Tumor	Reduced Sensitivity	CIViC B	EID2477
KIT P551_E554delPMYE	Sunitinib	Gastrointestinal Stromal Tumor	Resistance	CIViC B	EID4454 +2
KIT Amplification	Imatinib	Mucosal Melanoma	Resistance	CIViC B	EID1466
KIT Amplification	Nilotinib	Melanoma	Resistance	CIViC B	EID5907
KIT D816V	Imatinib	Systemic Mastocytosis	Resistance	CIViC B	EID11160
KIT EXPRESSION	Imatinib	Gastrointestinal Stromal Tumor	Resistance	CIViC B	EID2488
KIT Exon 11 Mutation	Sunitinib	Gastrointestinal Stromal Tumor	Resistance	CIViC B	EID4072
KIT EXPRESSION	Imatinib	Endometrial Cancer	Sensitivity/Response	CIViC C	EID1024 +1

+129 more predictive associations (showing top 30 by evidence level).

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs121913512	KIT		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family

Most potent curated ligand interactions (52 total), top 25:

Ligand	Action	Affinity	Parameter
stem cell factor	Agonist	9.82	pKd
AC710	Inhibition	9.0	pKd
BPR1R024	Inhibition	8.96	pIC50
dovitinib	Inhibition	8.7	pIC50
famitinib	Inhibition	8.7	pIC50
compound 6li [Chan et al., 2022]	Inhibition	8.59	pKd
cediranib	Inhibition	8.52	pIC50
CHMFL-KIT-64	Inhibition	8.4	pIC50
ibcasertib	Inhibition	8.4	pIC50
elenestinib	Inhibition	8.35	pIC50
quizartinib	Inhibition	8.32	pKd
compound 7k [PMID: 23521020]	Inhibition	8.31	pIC50
JNJ-28312141	Inhibition	8.3	pIC50
sitravatinib	Inhibition	8.22	pIC50
risvodetinib	Inhibition	8.11	pIC50
henatinib	Inhibition	8.1	pIC50
SU11652	Inhibition	8.0	pIC50
KBP-7018	Inhibition	8.0	pIC50
compound 8h [PMID: 22765894]	Inhibition	7.96	pIC50
sunitinib	Inhibition	7.88	pIC50
compound 8i [PMID: 22765894]	Inhibition	7.86	pIC50
linifanib	Inhibition	7.85	pIC50
SU-14813	Inhibition	7.82	pIC50
labuxtinib	Inhibition	7.7	pIC50
edicotinib	Inhibition	7.7	pIC50

Binding affinities (BindingDB)

1184 measured of 2024 human assays (2024 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
US20250360145, Example 119	IC50	0.73 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 87	IC50	0.83 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 83	IC50	1.2 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
Staurosporine	KD	1.7 nM
FORETINIB	IC50	1.9 nM
US20250360145, Example 101	IC50	1.9 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
3-methoxy-8-[[5-methoxy-6-[(5-methoxy-2-pyridinyl)methoxy]-3-pyridinyl]methyl]-1,5-naphthyridine	IC50	2.1 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 93	IC50	2.1 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 56	IC50	2.2 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 72	IC50	2.2 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 100	IC50	2.2 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
FIIN-1	KD	2.8 nM
N-[2-methyl-5-[5-[(2,2,3,3-tetrafluorocyclobutyl)oxymethyl]-1,2,4-oxadiazol-3-yl]phenyl]imidazo[1,2-a]pyridine-3-carboxamide	IC50	3 nM	US-9199981: Compounds and compositions as C-kit kinase inhibitors
US20250360145, Example 66	IC50	3 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 116	IC50	3 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
FRIN-1	KD	3.1 nM
US20250360145, Example 55	IC50	3.2 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
2-[[3-methoxy-5-[(7-methoxy-1,5-naphthyridin-4-yl)methyl]-2-pyridinyl]oxymethyl]-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine	IC50	3.3 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 74	IC50	3.3 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 79	IC50	3.6 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
(3R,4R)-3-methoxy-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	IC50	3.93 nM	US-10189849: CDK inhibitors
3-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-1-(3-methoxyphenyl)urea	IC50	4 nM
3-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-1-(4-methylphenyl)urea	IC50	4 nM
3-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-1-(4-fluorophenyl)urea	IC50	4 nM
US20250360145, Example 80	IC50	4 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 59	IC50	4.4 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 82	IC50	4.6 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 112	IC50	4.7 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 88	IC50	4.9 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
3-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-1-(3-nitrophenyl)urea	IC50	5 nM
3-[4-(3-amino-1,2-benzoxazol-4-yl)phenyl]-1-(4-methoxyphenyl)urea	IC50	5 nM
N-[4-[1-(3-amino-3-methylbutanoyl)piperidin-4-yl]-2-(cyclohexen-1-yl)phenyl]-5-cyano-1H-imidazole-2-carboxamide	IC50	5 nM	US-8697716: Method of inhibiting C-KIT kinase
US20250360145, Example 136	IC50	5 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
US20250360145, Example 81	IC50	5.1 nM	US-20250360145: CSF-1R INHIBITORS AND USES THEREOF
N-benzyl-1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
N-[(4-methylphenyl)methyl]-1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
N-[(4-methylphenyl)methyl]-1-(6-phenylpyrrolo[2,1-f][1,2,4]triazin-4-yl)azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
2-(4-methylphenyl)-N-[1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidin-3-yl]acetamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
N-[(4-methylphenyl)methyl]-1-[6-(2-methylpyrazol-3-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
1-[6-(1-methylimidazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]-N-[(4-methylphenyl)methyl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
(1S)-1-(4-methylphenyl)-N-[[1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidin-3-yl]methyl]ethanamine	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
(1R)-1-(4-methylphenyl)-N-[[1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidin-3-yl]methyl]ethanamine	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
N-[(4-fluorophenyl)methyl]-1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
N-(4-chlorophenyl)-1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
N-(4-cyanophenyl)-1-[6-(1,5-dimethylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
N-(4-cyano-2-methylphenyl)-1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
N-(4-cyanophenyl)-3-methyl-1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
3-methyl-N-[(4-methylphenyl)methyl]-1-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit
1-[6-(3,5-dimethylpyrazolidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]-N-[(4-methylphenyl)methyl]azetidine-3-carboxamide	IC50	5.5 nM	US-9688680: Compositions useful for treating disorders related to kit

ChEMBL bioactivities

5653 potent at pChembl≥5 of 5711 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL4448433
9.92	IC50	0.12	nM	CHEMBL4448433
9.80	Ki	0.1585	nM	CHEMBL404366
9.74	IC50	0.18	nM	CHEMBL3683258
9.74	IC50	0.18	nM	CHEMBL4448433
9.70	IC50	0.2	nM	AVAPRITINIB
9.70	Ki	0.1995	nM	CHEMBL273187
9.68	Kd	0.21	nM	SUNITINIB
9.62	IC50	0.24	nM	AVAPRITINIB
9.60	Kd	0.25	nM	SU-014813
9.60	Ki	0.2512	nM	CHEMBL373798
9.57	IC50	0.27	nM	AVAPRITINIB
9.57	Kd	0.27	nM	CEDIRANIB
9.55	Kd	0.28	nM	SUNITINIB
9.54	Kd	0.29	nM	SU-014813
9.51	Kd	0.31	nM	CEDIRANIB
9.50	Ki	0.3162	nM	CHEMBL402846
9.50	Ki	0.3162	nM	CHEMBL272938
9.49	Kd	0.32	nM	CEDIRANIB
9.43	Kd	0.37	nM	SUNITINIB
9.42	Kd	0.38	nM	CEDIRANIB
9.40	Kd	0.4	nM	CHEMBL4205999
9.39	Kd	0.41	nM	SUNITINIB
9.37	Kd	0.43	nM	STAUROSPORINE
9.34	Kd	0.46	nM	CHEMBL1908396
9.31	Kd	0.49	nM	AXITINIB
9.30	Ki	0.5012	nM	CHEMBL271441
9.29	Kd	0.51	nM	SU-014813
9.27	Kd	0.54	nM	CEDIRANIB
9.25	Kd	0.56	nM	SU-014813
9.24	Kd	0.57	nM	DASATINIB
9.22	Kd	0.6	nM	CHEMBL2203434
9.22	IC50	0.6	nM	CHEMBL6163448
9.22	Kd	0.6	nM	STAUROSPORINE
9.21	Kd	0.62	nM	DASATINIB
9.19	IC50	0.65	nM	CHEMBL5802203
9.19	IC50	0.65	nM	CHEMBL5864761
9.19	IC50	0.65	nM	CHEMBL5991236
9.19	IC50	0.65	nM	CHEMBL5912912
9.19	IC50	0.65	nM	CHEMBL5876826
9.19	Kd	0.64	nM	STAUROSPORINE
9.18	Kd	0.66	nM	DASATINIB
9.17	IC50	0.67	nM	CHEMBL4448433
9.17	Kd	0.68	nM	SU-014813
9.17	Kd	0.68	nM	DASATINIB
9.16	Kd	0.69	nM	CHEMBL1908396
9.15	IC50	0.7	nM	SUNITINIB
9.15	Kd	0.71	nM	SUNITINIB
9.15	Kd	0.7	nM	SUNITINIB
9.10	IC50	0.8	nM	SUNITINIB

PubChem BioAssay actives

2337 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-(5-ethyl-1,2-oxazol-3-yl)-3-[4-[2-[[6-(4-ethylpiperazin-1-yl)pyrimidin-4-yl]amino]-1,3-thiazol-5-yl]phenyl]urea	1587963: Inhibition of human c-KIT A loop exon 17 D820Y single mutant using poly (Glu,Tyr) 4:1 as substrate in presence of 33P-gamma-ATP by hotspot kinase assay	ic50	<0.0001	uM
3-N-[4-(1-methylpiperidin-4-yl)phenyl]-1-pyridin-2-yl-1,2,4-triazole-3,5-diamine	623446: Displacement of [33P]ATP from human recombinant c-KIT domain after 20 mins by scintillation counting	ki	<0.0001	uM
Avapritinib	2141013: Inhibition of KIT (unknown origin)	ic50	0.0002	uM
Sunitinib	435802: Binding constant for KIT(V559D,V654A) kinase domain	kd	0.0002	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435802: Binding constant for KIT(V559D,V654A) kinase domain	kd	0.0003	uM
4-[4-(5-benzylpyrimidin-2-yl)piperazin-1-yl]-6,7-bis(2-methoxyethoxy)quinazoline	1380500: Binding affinity to KIT D816V mutant (unknown origin)	kd	0.0004	uM
Dasatinib	1797044: Kinase Assay and Binding Constant Measurement from Article 10.1073/pnas.0504952102: “Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases.”	kd	0.0004	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	624788: Binding constant for KIT(D816H) kinase domain	kd	0.0004	uM
Axitinib	624791: Binding constant for KIT(V559D) kinase domain	kd	0.0005	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435410: Binding constant for KIT kinase domain	kd	0.0006	uM
N-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]-5-(1-ethylpiperidin-4-yl)oxypyridine-2-carboxamide	712316: Binding affinity to KIT expressed in HEK-293 cells	kd	0.0006	uM
1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-methoxyphenyl]-3-[1-(1,3-thiazol-2-yl)ethyl]urea	624786: Binding constant for KIT kinase domain	kd	0.0007	uM
N-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]-3-hydroxypyridine-2-carboxamide	469529: Binding affinity to KIT	kd	0.0010	uM
3-N-[4-(4-morpholin-4-ylcyclohexyl)phenyl]-1-pyridin-2-yl-1,2,4-triazole-3,5-diamine	623446: Displacement of [33P]ATP from human recombinant c-KIT domain after 20 mins by scintillation counting	ki	0.0010	uM
1-(3-bromophenyl)-3-[4-(quinazolin-4-ylamino)phenyl]urea	1254378: Inhibition of c-Kit (unknown origin) by radiometric protein kinase assay	ic50	0.0010	uM
1-(3-bromophenyl)-3-[4-(thieno[2,3-d]pyrimidin-4-ylamino)phenyl]urea	1254378: Inhibition of c-Kit (unknown origin) by radiometric protein kinase assay	ic50	0.0010	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	1431276: Inhibition of recombinant human N-terminal GST/His6-tagged c-KIT (544 to 976 residues) expressed in baculovirus infected sf9 cells using biotinylated peptide substrate GGLFDDPSYVNVQNL in presence of ATP incubated for 1 to 4 hrs by time resolved fluorescence assay	ic50	0.0010	uM
2-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-3-methyl-5-(2-morpholin-4-ylethyl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4-one	536879: Inhibition of c-Kit after 30 mins by ELISA	ic50	0.0010	uM
3-(2-aminoquinazolin-6-yl)-1-(2-cyclopentylethyl)-4-methylpyridin-2-one	407623: Inhibition of c-Kit by TR-FRET assay	ic50	0.0010	uM
N-(2-aminopyrimidin-5-yl)-6-chloro-3-[3-(trifluoromethyl)anilino]-1,2-benzoxazole-7-carboxamide	387174: Inhibition of c-kit	ic50	0.0010	uM
N-(6-acetamido-3-pyridinyl)-6-chloro-3-[3-(trifluoromethyl)anilino]-1,2-benzoxazole-7-carboxamide	387174: Inhibition of c-kit	ic50	0.0010	uM
2-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-5-[(2R)-2-hydroxy-3-morpholin-4-ylpropyl]-3-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4-one	536879: Inhibition of c-Kit after 30 mins by ELISA	ic50	0.0010	uM
2-[(2-amino-4-pyridinyl)methylamino]-N-(2,2-difluoro-1,3-benzodioxol-5-yl)benzamide	308523: Inhibition of human recombinant cKit by FRET assay	ic50	0.0010	uM
2-[(2-acetamido-4-pyridinyl)methylamino]-N-(2,2-difluoro-1,3-benzodioxol-5-yl)benzamide	308523: Inhibition of human recombinant cKit by FRET assay	ic50	0.0010	uM
5-[2-(dimethylamino)ethyl]-2-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-3-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4-one	536879: Inhibition of c-Kit after 30 mins by ELISA	ic50	0.0010	uM
6-(2,6-dichlorophenyl)-2-(4-fluoro-3-methylanilino)-8-methylpyrido[2,3-d]pyrimidin-7-one	1797044: Kinase Assay and Binding Constant Measurement from Article 10.1073/pnas.0504952102: “Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases.”	kd	0.0010	uM
N-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]-5-(1-ethyl-2,2,6,6-tetramethylpiperidin-4-yl)oxypyridine-2-carboxamide	712316: Binding affinity to KIT expressed in HEK-293 cells	kd	0.0010	uM
1-[4-[(6-aminoquinazolin-4-yl)amino]phenyl]-3-[4-chloro-3-(trifluoromethyl)phenyl]urea	759167: Inhibition of wild-type cKIT (unknown origin)-mediated phosphorylation of biotinylated poly-Glu-Tyr preincubated for 30 to 60 mins prior to substrate addition by TR-FRET assay	ic50	0.0010	uM
4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-N-methylpyridine-2-carboxamide	1779639: Inhibition of c-Kit (unknown origin)	ic50	0.0010	uM
1-[4-[7-(dimethylamino)quinazolin-4-yl]oxyphenyl]-3-[[6-(trifluoromethyl)-3-pyridinyl]methyl]urea	1785257: Inhibition of human c-Kit by Kinomescan method	ic50	0.0011	uM
2-[5-[(6-cyclopropyloxy-3-pyridinyl)amino]-4-methyl-3-pyridinyl]-N-methyl-1H-pyrrolo[2,3-c]pyridine-7-carboxamide	2141406: Inhibition of c-Kit (unknown origin) in presence of ATP	ic50	0.0011	uM
N-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]-5-(1,2,2,6,6-pentamethylpiperidin-4-yl)oxypyridine-2-carboxamide	712316: Binding affinity to KIT expressed in HEK-293 cells	kd	0.0011	uM
N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide	624790: Binding constant for KIT(L576P) kinase domain	kd	0.0013	uM
1-hexyl-3-[4-(3-methyl-2H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]urea	1444935: Inhibition of cKIT (unknown origin) using FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition in presence of ATP by mobility shift assay	ic50	0.0014	uM
(7Z)-7-(5-fluoro-2-oxo-1H-indol-3-ylidene)-N-(2-hydroxyethyl)-2-methyl-1,4,5,6-tetrahydroindole-3-carboxamide	773015: Inhibition of c-KIT (unknown origin)	ic50	0.0014	uM
2-[3-[6-[[4-(2-methyl-1,3-oxazol-4-yl)phenyl]methylamino]pyrimidin-4-yl]imidazo[1,2-a]pyridin-7-yl]oxyethanol	1766133: Inhibition of N-terminal GST-tagged human recombinant C-KIT V654A mutant (544 to end residues) using GGMEDIYEFMGGKKK as substrate measured after 40 mins in presence of [gamma-33P]ATP by scintillation counting analysis	ic50	0.0015	uM
1-(4-methoxyphenyl)-3-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-6-yl]urea	491752: Inhibition of cKIT	ic50	0.0015	uM
3-(2-imidazo[1,2-a]pyridin-7-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1465750: Inhibition of wild type KIT (unknown origin) using biotinylated poly-Glu-Tyr as substrate preincubated for 30 mins followed by substrate addition in presence of ATP by TR-FRET assay	ic50	0.0016	uM
Quizartinib	526665: Binding affinity to cKIT	kd	0.0016	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624791: Binding constant for KIT(V559D) kinase domain	kd	0.0016	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	435167: Binding constant for KIT(V559D) kinase domain	kd	0.0017	uM
1-[4-(3-methyl-2H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-(3-phenylpropyl)urea	1444935: Inhibition of cKIT (unknown origin) using FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition in presence of ATP by mobility shift assay	ic50	0.0017	uM
Ponatinib	1465750: Inhibition of wild type KIT (unknown origin) using biotinylated poly-Glu-Tyr as substrate preincubated for 30 mins followed by substrate addition in presence of ATP by TR-FRET assay	ic50	0.0017	uM
Pazopanib	624790: Binding constant for KIT(L576P) kinase domain	kd	0.0018	uM
N-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]isoquinoline-3-carboxamide	469529: Binding affinity to KIT	kd	0.0018	uM
1-[4-(3-methyl-2H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]-3-quinolin-3-ylurea	1444935: Inhibition of cKIT (unknown origin) using FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition in presence of ATP by mobility shift assay	ic50	0.0019	uM
3-[2-(2-aminopyrimidin-5-yl)ethynyl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1465750: Inhibition of wild type KIT (unknown origin) using biotinylated poly-Glu-Tyr as substrate preincubated for 30 mins followed by substrate addition in presence of ATP by TR-FRET assay	ic50	0.0019	uM
N-(3-methoxyphenyl)-4-methyl-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamide	732855: Inhibition of c-KIT (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr prior to substrate addition measured after 2 hrs by FRET assay	ic50	0.0019	uM
3-[2-(6-amino-3-pyridinyl)ethynyl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1465750: Inhibition of wild type KIT (unknown origin) using biotinylated poly-Glu-Tyr as substrate preincubated for 30 mins followed by substrate addition in presence of ATP by TR-FRET assay	ic50	0.0020	uM
5-[2-(diethylamino)ethyl]-2-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-3-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4-one	536879: Inhibition of c-Kit after 30 mins by ELISA	ic50	0.0020	uM

CTD chemical–gene interactions

109 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Arsenic Trioxide	increases reaction, decreases expression, decreases phosphorylation, increases expression, affects binding	6
Tretinoin	affects cotreatment, increases expression, decreases activity, decreases expression, affects expression	5
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Imatinib Mesylate	decreases reaction, increases expression, decreases activity	3
Cisplatin	affects cotreatment, increases expression, decreases response to substance	3
bisphenol A	decreases methylation, increases expression	2
potassium chromate(VI)	increases expression, affects cotreatment, decreases expression	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	2
tanespimycin	decreases expression, increases degradation	2
Semaxinib	decreases activity	2
entinostat	affects cotreatment, increases expression	2
ponatinib	decreases activity, decreases phosphorylation	2
Dasatinib	affects binding, decreases phosphorylation	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Aldrin	affects cotreatment, increases expression	2
Allergens	increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Chelating Agents	affects binding, decreases expression	2
Copper	affects binding, decreases expression	2
Dichlorodiphenyldichloroethane	affects cotreatment, increases expression	2
Dichlorodiphenyl Dichloroethylene	affects cotreatment, increases expression	2
Dieldrin	increases expression, affects cotreatment	2
Doxorubicin	increases expression	2
Estradiol	increases expression, affects cotreatment	2
Parathion	decreases reaction, increases expression, affects cotreatment	2
Cadmium Chloride	decreases expression, increases abundance	2
GSK-J4	decreases expression	1

ChEMBL screening assays

2305 unique, capped per target: 2242 binding, 32 admet, 22 functional, 9 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003893	Binding	Inhibition of c-Kit	Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities. — J Med Chem
CHEMBL1775383	Functional	Inhibition of c-Kit mRNA expression in human GIST882 cells after 24 hrs by qualitative RT-PCR analysis	Targeting the c-Kit Promoter G-quadruplexes with 6-Substituted Indenoisoquinolines. — ACS Med Chem Lett
CHEMBL4017684	ADMET	Inhibition of human c-Kit using poly[Glu:Tyr] (4:1) as substrate measured after 2 hrs in presence of [33gammaP]ATP by P18 ion exchange chromatographic method	Design, synthesis and optimization of bis-amide derivatives as CSF1R inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

106 cell lines: 76 cancer cell line, 17 factor-dependent cell line, 6 induced pluripotent stem cell, 5 transformed cell line, 2 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0003	HMC-1	Cancer cell line	Male
CVCL_0589	Kasumi-1	Cancer cell line	Male
CVCL_1236	GR-ST	Cancer cell line	Male
CVCL_1326	Karpas-45	Cancer cell line	Male
CVCL_1575	NCI-H650	Cancer cell line	Male
CVCL_1658	EW-8	Cancer cell line	Male
CVCL_1714	SUP-T1	Cancer cell line	Male
CVCL_1E03	BC7	Cancer cell line	Male
CVCL_1H35	Sup-T1 Nef-ER 31	Cancer cell line	Male
CVCL_2196	SKNO-1	Cancer cell line	Male

Clinical trials (associated diseases)

339 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01377077	PHASE4	UNKNOWN	Punchgrafting Techniques for Vitiligo
NCT01640678	PHASE4	UNKNOWN	Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients
NCT02458417	PHASE4	COMPLETED	Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients
NCT00171977	PHASE4	COMPLETED	Post-Marketing Clinical Study of Postoperative Adjuvant Therapy With Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors (GIST)
NCT00510354	PHASE4	COMPLETED	Treatment of Patients With Everolimus and Imatinib Mesylate Who Have Progressive Gastro Intestinal Stromal Tumors (GIST) and Are Resistant to Imatinib Mesylate
NCT00756509	PHASE4	COMPLETED	Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT02800330	PHASE4	COMPLETED	The Effects of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib
NCT04825574	PHASE4	COMPLETED	Study for Patients Previously Treated in Avapritinib Clinical Trials
NCT02156427	PHASE3	COMPLETED	Evaluation of Non-cultured Epidermal Cellular Grafting vs Hyaluronic Acid for Repigmenting Vitiligo and Piebaldism
NCT00009906	PHASE3	TERMINATED	Comparison of Two Different Doses of STI571 in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
NCT00041197	PHASE3	COMPLETED	Imatinib Mesylate in Treating Patients With Primary Gastrointestinal Stromal Tumor That Has Been Completely Removed By Surgery
NCT00075218	PHASE3	COMPLETED	A Study To Assess The Safety And Efficacy Of SU11248 In Patients With Gastrointestinal Stromal Tumor(GIST)
NCT00103168	PHASE3	COMPLETED	Imatinib Mesylate or Observation Only in Treating Patients Who Have Undergone Surgery for Localized Gastrointestinal Stromal Tumor
NCT00293124	PHASE3	COMPLETED	Open-label Trial of GlivecWith Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumors
NCT00324987	PHASE3	TERMINATED	Imatinib Mesylate With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
NCT00372567	PHASE3	TERMINATED	Safety And Effectiveness Of Daily Dosing With Sunitinib Or Imatinib In Patients With Gastrointestinal Stromal Tumors
NCT00471328	PHASE3	COMPLETED	Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib
NCT00685828	PHASE3	UNKNOWN	Imatinib Mesylate in Treating Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumor
NCT00688766	PHASE3	TERMINATED	Study Evaluating IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) Following Failure of at Least Imatinib and Sunitinib
NCT00751036	PHASE3	TERMINATED	Nilotinib 800 Mg And Imatinib 800 Mg For The Treatment Of Patients With Gastrointestinal Stromal Tumors (Gist) Refractory To Imatinib 400 Mg
NCT00785785	PHASE3	COMPLETED	A Study of Nilotinib Versus Imatinib in GIST Patients
NCT00812240	PHASE3	TERMINATED	Masitinib in First Line Treatment of Gastro-Intestinal Stromal Tumor (GIST)
NCT00956072	PHASE3	TERMINATED	Imatinib Mesylate With or Without Surgery in Treating Patients With Metastatic Gastrointestinal Stromal Tumor That is Responding to Imatinib Mesylate
NCT01031628	PHASE3	TERMINATED	Study of Dose Escalation Versus no Dose Escalation of Imatinib in Metastatic Gastrointestinal Stromal Tumors (GIST) Patients
NCT01151852	PHASE3	COMPLETED	Rechallenge of Imatinib in GIST Having no Effective Treatment: RIGHT
NCT01265810	PHASE3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01271712	PHASE3	COMPLETED	Study of Regorafenib as a 3rd-line or Beyond Treatment for Gastrointestinal Stromal Tumors (GIST)
NCT01289028	PHASE3	COMPLETED	Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib.
NCT01462994	PHASE3	COMPLETED	Detection of CF-DNA in Patients With Gastrointestinal Stromal Tumors (GIST)
NCT01694277	PHASE3	COMPLETED	Masitinib in Patients With Gastrointestinal Stromal Tumour After Progression With Imatinib
NCT02260505	PHASE3	COMPLETED	Efficiency of Imatinib Treatment Maintenance or Interruption After 3 Years of Adjuvant Treatment in Patients With Gastrointestinal Stromal Tumours (GIST)
NCT02576080	PHASE3	UNKNOWN	Efficacy of Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index
NCT02866045	PHASE3	UNKNOWN	EUS-FNB vs. Single-incision Needle-knife (SINK) Biopsy for Gastrointestinal SELs
NCT03353753	PHASE3	COMPLETED	Phase 3 Study of DCC-2618 vs Placebo in Advanced GIST Patients Who Have Been Treated With Prior Anticancer Therapies
NCT03426722	PHASE3	COMPLETED	L-carnitine vs Placebo for the Treatment of Muscle Cramps After Imatinib in Gastrointestinal Stromal Tumors
NCT03465722	PHASE3	COMPLETED	(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST
NCT03673501	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib
NCT04409223	PHASE3	TERMINATED	Efficacy and Safety of Famitinib Versus Sunitinib in the Treatment of Advanced Gastrointestinal Stromal Tumour Patients After Failure of Imatinib
NCT05208047	PHASE3	ACTIVE_NOT_RECRUITING	(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors