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); 157 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 (top 4% of genes corpus-wide)
• Clinical variants (ClinVar): 3,516 total — 79 pathogenic, 45 likely-pathogenic (top 1% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 7 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 5 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 121
• Drug target: yes — 32 curated mechanism-of-action drugs; 99 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 12 — Avapritinib, Dasatinib Anhydrous, Imatinib Mesylate, +9 more
• Precision-oncology evidence (CIViC): 158 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.24 (highly constrained)
• MANE Select transcript: NM_000222
• Interaction hub: 4,726 STRING partners (top 1% of genes corpus-wide)

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: 29 — 16 protein_coding, 7 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000288135

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 4: 1

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, ENST00001133481

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.

Highest expression (Bgee): lateral nuclear group of thalamus, secondary oocyte, oocyte, upper leg skin, epithelium of mammary gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

KIT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	2.6e-13	+0.16	4:54852968:A:G
Cells Cultured fibroblasts	eqtl	1.1e-06	+0.48	4:54498742:A:G
Brain Nucleus accumbens basal ganglia	eqtl	6.7e-03	-0.26	4:55311237:G:GC
Brain Cerebellum	eqtl	7.3e-03	-0.16	4:54735161:T:G
Breast Mammary Tissue	sqtl	8.4e-03	-1.12	4:55573976:C:T
Colon Transverse	sqtl	1.2e-02	-1.24	4:54797499:C:A
Skin Sun Exposed Lower leg	eqtl	2.4e-02	+0.46	4:54657574:G:A
Lung	sqtl	3.5e-02	+0.30	4:55592934:GTAC:G

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

showing 100 of 290 tissues 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
superior vestibular nucleus	UBERON:0007227	88.84	gold quality
choroid plexus epithelium	UBERON:0003911	88.31	gold quality
eye	UBERON:0000970	88.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.33	gold quality
inferior vagus X ganglion	UBERON:0005363	87.20	gold quality
medulla oblongata	UBERON:0001896	87.15	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.14	gold quality
urethra	UBERON:0000057	87.04	gold quality
middle temporal gyrus	UBERON:0002771	86.64	gold quality
pons	UBERON:0000988	86.49	gold quality
mucosa of urinary bladder	UBERON:0001259	86.25	gold quality
periodontal ligament	UBERON:0008266	86.02	gold quality
pleura	UBERON:0000977	85.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.69	gold quality
subthalamic nucleus	UBERON:0001906	85.64	gold quality
colonic epithelium	UBERON:0000397	85.54	gold quality
fundus of stomach	UBERON:0001160	85.48	gold quality
rectum	UBERON:0001052	85.43	gold quality
seminal vesicle	UBERON:0000998	85.39	gold quality
synovial joint	UBERON:0002217	85.37	gold quality
skin of leg	UBERON:0001511	85.32	gold quality
zone of skin	UBERON:0000014	85.30	gold quality
saliva-secreting gland	UBERON:0001044	85.23	gold quality
left ovary	UBERON:0002119	84.91	gold quality
Ammon’s horn	UBERON:0001954	84.86	gold quality
stomach	UBERON:0000945	84.75	gold quality
ovary	UBERON:0000992	84.61	gold quality
nephron tubule	UBERON:0001231	84.51	gold quality
amniotic fluid	UBERON:0000173	84.41	gold quality
lung	UBERON:0002048	84.33	gold quality
nasal cavity mucosa	UBERON:0001826	84.22	gold quality
body of stomach	UBERON:0001161	84.16	gold quality
parietal lobe	UBERON:0001872	84.13	gold quality
thyroid gland	UBERON:0002046	83.74	gold quality
minor salivary gland	UBERON:0001830	83.60	gold quality
postcentral gyrus	UBERON:0002581	83.57	gold quality
urinary bladder	UBERON:0001255	83.55	gold quality
right lobe of thyroid gland	UBERON:0001119	83.52	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	82.95	silver quality
right lung	UBERON:0002167	82.91	gold quality
parietal pleura	UBERON:0002400	82.90	gold quality
left lobe of thyroid gland	UBERON:0001120	82.82	gold quality
entorhinal cortex	UBERON:0002728	82.75	gold quality
skin of abdomen	UBERON:0001416	82.73	gold quality
mouth mucosa	UBERON:0003729	82.73	gold quality
trachea	UBERON:0003126	82.65	gold quality
bone marrow cell	CL:0002092	82.54	gold quality
right ovary	UBERON:0002118	82.35	gold quality
inferior olivary complex	UBERON:0002127	82.35	silver quality
superior surface of tongue	UBERON:0007371	82.32	silver quality
lateral globus pallidus	UBERON:0002476	82.28	silver quality
cerebellum	UBERON:0002037	82.25	gold quality
diaphragm	UBERON:0001103	82.22	gold quality
ganglionic eminence	UBERON:0004023	82.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.12	gold quality
pharyngeal mucosa	UBERON:0000355	81.93	silver quality
superior frontal gyrus	UBERON:0002661	81.82	gold quality
pigmented layer of retina	UBERON:0001782	81.72	gold quality
retina	UBERON:0000966	81.70	gold quality
cerebellar cortex	UBERON:0002129	81.70	gold quality
upper lobe of left lung	UBERON:0008952	81.70	gold quality
trabecular bone tissue	UBERON:0002483	81.63	gold quality
prefrontal cortex	UBERON:0000451	81.60	gold quality
esophagus	UBERON:0001043	81.55	gold quality
upper lobe of lung	UBERON:0008948	81.50	gold quality
cerebellar hemisphere	UBERON:0002245	81.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	81.40	gold quality
trigeminal ganglion	UBERON:0001675	81.39	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.38	gold quality
kidney	UBERON:0002113	81.37	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Breast	tissue	79.2	medium
Thyroid gland	tissue	36.5	not detected
Cerebellum	tissue	31.6	high
Midbrain	tissue	29.9
Superior colliculi	tissue	26.3
Hippocampus	tissue	25.2	not detected
Ovary	tissue	24.9	medium
Hippocampal formation	tissue	24.1
Cerebral cortex	tissue	23.9	not detected
Retrosplenial and cingulate cortex	tissue	23.9
Retrosplenial cortex	tissue	21.4
Motor cortex	tissue	20.6
Thalamus	tissue	20.3
Prefrontal cortex	tissue	18.7
Insular cortex	tissue	16.7
Pons	tissue	16.4
Amygdala	tissue	16.3
Lung	tissue	15.9	medium
Caudate putamen	tissue	15.3
Gallbladder	tissue	14.9	not detected
Salivary gland	tissue	14.8	not detected
Entorhinal cortex	tissue	14.6
Skin 1	tissue	13.7	medium
Temporal cortex	tissue	13.5
Basal ganglia	tissue	13.3	not detected
Cervix	tissue	13.2	not detected
Stomach 1	tissue	13.2	not detected
Frontal cortex	tissue	13.0
Ventral forebrain	tissue	12.7
Putamen	tissue	12.1
Medulla oblongata	tissue	11.7
Rectum	tissue	11.3	low
Somatosensory cortex	tissue	10.7
Small intestine	tissue	10.5	not detected
Esophagus	tissue	10.3	not detected
Urinary bladder	tissue	10.0	not detected
Colon	tissue	9.1	low
Occipital cortex	tissue	9.1
Septum	tissue	9.0
Locus coeruleus	tissue	8.8
Olfactory bulb	tissue	8.3
Smooth muscle	tissue	8.0	not detected
Kidney	tissue	8.0	low
Placenta	tissue	7.9	not detected
Nucleus accumbens	tissue	7.8
Hypothalamus	tissue	7.4
Postcentral gyrus	tissue	7.4
Endometrium 1	tissue	7.3	not detected
Duodenum	tissue	6.8	not detected
Choroid plexus	tissue	6.2
Seminal vesicle	tissue	5.6	not detected
Spinal cord	tissue	5.4
Tongue	tissue	4.9
Substantia nigra	tissue	4.5
Appendix	tissue	4.5	not detected
Periaqueductal gray	tissue	4.4
Testis	tissue	4.3	medium
Tonsil	tissue	4.3	not detected
Adipose tissue	tissue	3.9	not detected
Bone marrow	tissue	3.8	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Hippocampus, CA1 (35.6), Cerebellar cortex (30.2), Hippocampus, CA2 (29.3), Dentate gyrus (26.7), Ventral hippocampus (24.1).

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)

Targeting KIT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 110 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.24, missense Z 4.17 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000288135 splits into 7 regions with different missense tolerance; 1 is missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
4:54,658,015–54,695,537	46 / 38.8	1.19	no
4:54,695,538–54,727,228	401 / 601.0	0.67	no
4:54,727,229–54,727,506	78 / 77.6	1.01	no
4:54,727,507–54,727,881	7 / 36.9	0.19	yes (p 8.6e-07)
4:54,727,882–54,731,996	158 / 218.7	0.72	no
4:54,731,997–54,736,807	63 / 137.4	0.46	no
4:54,736,808–54,738,554	105 / 103.5	1.01	no
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), RET (ENSG00000165731), AXL (ENSG00000167601), ROR2 (ENSG00000169071), ALK (ENSG00000171094), INSR (ENSG00000171105), ERBB4 (ENSG00000178568), CSF1R (ENSG00000182578), EPHB3 (ENSG00000182580), EPHA10 (ENSG00000183317), ROR1 (ENSG00000185483), EPHB4 (ENSG00000196411), NTRK1 (ENSG00000198400), DDR1 (ENSG00000204580)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96677) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 204 distinct phenotype terms.

Mouse phenotype (MP)	Records
white spotting	21
absent coat pigmentation	16
belly spot	15
anemia	12
macrocytic anemia	11
male infertility	9
variable body spotting	9
decreased mast cell number	8
diluted coat color	8
abnormal coat/hair pigmentation	8
postnatal lethality, complete penetrance	6
postnatal lethality	5
infertility	4
female infertility	4
neonatal lethality, complete penetrance	4
prenatal lethality, incomplete penetrance	4
decreased hematocrit	3
increased mast cell number	3
irregular coat pigmentation	3
enlarged spleen	3
small ovary	3
arrest of spermatogenesis	3
reduced male fertility	3
reduced female fertility	3
premature death	3

+179 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q4VSN5	99.5%	Diamond
Bos taurus	P43481	99.4%	Diamond
Capra hircus	Q28317	99.4%	Diamond
Felis catus	Q28889	99.2%	Diamond
Macaca mulatta	Q20CR4	98.9%	Diamond
Canis lupus familiaris	O97799	98.4%	Diamond
Sus scrofa	Q2HWD6	98.1%	Diamond
Callithrix jacchus	Q76II0	94.6%	Diamond
Gallus gallus	P18461	92.7%	Diamond
Notophthalmus viridescens	Q91147	87.9%	Diamond
Pleurodeles waltl	Q91285	87.8%	Diamond
Coturnix coturnix	Q90330	81.0%	Diamond
Xenopus laevis	P22182	80.6%	Diamond
Takifugu rubripes	Q8AXC7	73.2%	Diamond
Coturnix japonica	P52583	73.1%	Diamond
Ciona intestinalis	Q4H3K6	60.1%	Diamond
Halocynthia roretzi	Q95YM9	59.9%	Diamond
Drosophila melanogaster	Q09147	55.0%	Diamond
Hydra vulgaris	Q86PM4	50.2%	Diamond
Caenorhabditis elegans	Q21038	49.5%	Diamond
Dugesia japonica	Q8MY85	46.6%	Diamond
Strongylocentrotus purpuratus	Q26614	46.4%	Diamond
Bombyx mori	D2IYS2	44.0%	Diamond
Dictyostelium discoideum	Q6XHA6	40.2%	Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 4)	P04048	99.2%	Diamond
Feline sarcoma virus (STRAIN MCDONOUGH)	P00545	99.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC02260	ncRNA	339978
PDGFRA	protein-coding	5156
LINC02358	ncRNA	107986226
LINC02283	ncRNA	105377656

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): A0A0U2N547, A0A8I5KPX7, A0A8I5KQZ6, A0A8I5KR87, A0A8I5KRE7, A0A8I5KS03, A0A8I5KXA4, A0A8I5QKL5, A0A8I5QKP7, P10721, 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)

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

UniProt features (200 total): strand 64, sequence variant 37, helix 31, 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)

showing 30 of 65 structures by resolution:

PDB	Title	Method	Resolution (Å)
2VIF	Crystal structure of SOCS6 SH2 domain in complex with a c-KIT phosphopeptide	X-RAY DIFFRACTION	1.45
8PQD	c-KIT kinase domain in complex with avapritinib derivative 10	X-RAY DIFFRACTION	1.5
8S14	c-KIT kinase domain in complex with sunitinib	X-RAY DIFFRACTION	1.5
1T46	STRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF C-KIT TYROSINE KINASE	X-RAY DIFFRACTION	1.6
3G0E	KIT kinase domain in complex with sunitinib	X-RAY DIFFRACTION	1.6
8PQA	c-KIT kinase domain in complex with avapritinib derivative 4	X-RAY DIFFRACTION	1.65
9TFD	KIT kinase domain in complex with a pyrrolotriazine-based compound (11)	X-RAY DIFFRACTION	1.65
8PQ9	c-KIT kinase domain in complex with avapritinib	X-RAY DIFFRACTION	1.7
9TFE	KIT kinase domain in complex with an aminopyrimidine-based compound (15)	X-RAY DIFFRACTION	1.7
9TFG	KIT kinase domain in complex with a 6-,7-dimethoxyquinoline-based compound (19)	X-RAY DIFFRACTION	1.7
9TFH	KIT kinase domain in complex with a 7-methylquinazoline-based compound (25)	X-RAY DIFFRACTION	1.7
9TFK	KIT kinase domain in complex with a quinoline-3-carbonitrile-based compound (38)	X-RAY DIFFRACTION	1.7
9TFJ	KIT kinase domain in complex with a 6,7-dimethoxyquinazoline-based compound (34)	X-RAY DIFFRACTION	1.75
8PQC	c-KIT kinase domain in complex with avapritinib derivative 9	X-RAY DIFFRACTION	1.77
6MOB	Crystal structure of KIT1 in complex with DP2976 via co-crystallization	X-RAY DIFFRACTION	1.8
9TFF	KIT kinase domain in complex with a pyrrolopyrimidine-based compound (17)	X-RAY DIFFRACTION	1.8
9TFL	KIT kinase domain in complex with a methyl quinazoline-7-carboxylate-based compound (41)	X-RAY DIFFRACTION	1.8
8S16	c-KIT kinase domain in complex with imatinib	X-RAY DIFFRACTION	1.85
8S1A	c-KIT kinase domain in complex with crenolanib	X-RAY DIFFRACTION	1.85
8PQB	c-KIT kinase domain in complex with avapritinib derivative 8	X-RAY DIFFRACTION	1.87
6ITV	Crystal structure of activated c-KIT in complex with compound	X-RAY DIFFRACTION	1.88
1T45	STRUCTURAL BASIS FOR THE AUTOINHIBITION AND STI-571 INHIBITION OF C-KIT TYROSINE KINASE	X-RAY DIFFRACTION	1.9
4HVS	Crystal structure of KIT kinase domain with a small molecule inhibitor, PLX647	X-RAY DIFFRACTION	1.9
8PQF	c-KIT kinase domain in complex with avapritinib derivative 12	X-RAY DIFFRACTION	1.9
9TFI	KIT kinase domain in complex with a 6,7-bis(2-methoxyethoxy)quinazoline-based compound …	X-RAY DIFFRACTION	1.9
2IUH	Crystal structure of the PI3-kinase p85 N-terminal SH2 domain in complex with c-Kit …	X-RAY DIFFRACTION	2
4U0I	Crystal structure of KIT in complex with ponatinib	X-RAY DIFFRACTION	2
6GQM	Crystal structure of human c-KIT kinase domain in complex with a small molecule …	X-RAY DIFFRACTION	2
8PQE	c-KIT kinase domain in complex with avapritinib derivative 11	X-RAY DIFFRACTION	2
8S13	apo c-KIT-wt kinase domain	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 4K94, 4K9E

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, CD markers, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Mutated cancer genes, Mutational cancer driver genes, Disease related genes, FDA approved drug targets, Biotech drugs, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of amino acid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; nucleoli fibrillar center

Antibody reliability (HPA): IH enhanced · IF supported

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)

Position	Role
792	proton acceptor
936	important for interaction with phosphotyrosine-binding proteins

Ligand- & substrate-binding residues (7)

Position	Role
568	Mg(2+)
596–603	ATP
623	ATP
671–677	ATP
796	ATP
797	Mg(2+)
810	Mg(2+)

Post-translational modifications (15)

Type	Positions
Phosphotyrosine	547, 553, 568, 570, 703, 721, 730, 823, 900, 936
Phosphoserine	741, 746, 821, 891, 959

Disulfide bonds (5)

Type	Positions
Disulfide bond	58–97, 136–186, 151–183, 233–290, 428–491

Glycosylation sites (10)

Type	Positions
N-linked (glcnac…) asparagine	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

20 curated (TAS) of 39; 18 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

39 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-9669914	Dasatinib-resistant KIT mutants ⚕	curated
R-HSA-9669917	Imatinib-resistant KIT mutants ⚕	curated
R-HSA-9669921	KIT mutants bind TKIs ⚕	curated
R-HSA-9669924	Masitinib-resistant KIT mutants ⚕	curated
R-HSA-9669926	Nilotinib-resistant KIT mutants ⚕	curated
R-HSA-9669929	Regorafenib-resistant KIT mutants ⚕	curated
R-HSA-9680187	Signaling by extracellular domain mutants of KIT ⚕	curated
R-HSA-9669935	Signaling by juxtamembrane domain KIT mutants ⚕	curated
R-HSA-9669933	Signaling by kinase domain mutants of KIT ⚕	curated
R-HSA-9670439	Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants ⚕	curated
R-HSA-9669936	Sorafenib-resistant KIT mutants ⚕	curated
R-HSA-9669934	Sunitinib-resistant KIT mutants ⚕	curated
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells	curated
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-8866910	TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	curated
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9669937	Drug resistance of KIT mutants ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-9669938	Signaling by KIT in disease ⚕	—
R-HSA-1266738	Developmental Biology	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-9730414	MITF-M-regulated melanocyte development	—
R-HSA-199418	Negative regulation of the PI3K/AKT network	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-1433559	Regulation of KIT signaling	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-1433557	Signaling by SCF-KIT	electronic
R-HSA-8864260	Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	—

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 (67): ovarian follicle development (GO:0001541), hematopoietic progenitor cell differentiation (GO:0002244), immature B cell differentiation (GO:0002327), mast cell chemotaxis (GO:0002551), positive regulation of dendritic cell cytokine production (GO:0002732), inflammatory response (GO:0006954), signal transduction (GO:0007165), spermatogenesis (GO:0007283), 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), 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), positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531), mast cell degranulation (GO:0043303), positive regulation of MAPK cascade (GO:0043410), pigmentation (GO:0043473), tongue development (GO:0043586), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), response to cadmium ion (GO:0046686), protein autophosphorylation (GO:0046777), positive regulation of long-term neuronal synaptic plasticity (GO:0048170), digestive tract development (GO:0048565), stem cell differentiation (GO:0048863), epithelial cell proliferation (GO:0050673), detection of mechanical stimulus involved in sensory perception of sound (GO:0050910), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cell chemotaxis (GO:0060326), mast cell differentiation (GO:0060374), mast cell proliferation (GO:0070662), melanocyte migration (GO:0097324), melanocyte adhesion (GO:0097326), positive regulation of pyloric antrum smooth muscle contraction (GO:0120072), positive regulation of colon smooth muscle contraction (GO:1904343), positive regulation of small intestine smooth muscle contraction (GO:1904349), positive regulation of vascular associated smooth muscle cell differentiation (GO:1905065), positive regulation of cytokine production involved in immune response (GO:0002720), protein phosphorylation (GO:0006468), chemotaxis (GO:0006935)

+7 more (showing top 60).

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 (9): acrosomal vesicle (GO:0001669), 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

10 top-level categories:

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

showing 60 of 75 GO namespaces:

Category	Terms
cellular anatomical structure	3
protein binding	2
plasma membrane	2
female gonad development	1
animal gross anatomical part developmental process	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
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
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
cellular response to cytokine stimulus	1
multicellular organismal process	1
maintenance of cell number	1
lamellipodium organization	1
plasma membrane bounded cell projection assembly	1
cytoskeleton organization	1
actin filament-based process	1
cell development	1
lymphocyte differentiation	1
B cell activation	1
enzyme binding	1
protein kinase activity	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1
transmembrane receptor protein tyrosine kinase activity	1
Kit signaling pathway	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein domain specific binding	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 18 of 92 annotations. The rest are phylogenetic / computational / electronic (IEA).

18 experimentally-supported GO terms:

GO term	NS	Evidence
Fc receptor signaling pathway	BP	direct assay
Kit signaling pathway	BP	direct assay
actin cytoskeleton organization	BP	direct assay
cell chemotaxis	BP	direct assay
cytokine-mediated signaling pathway	BP	direct assay
male gonad development	BP	expression pattern
mast cell chemotaxis	BP	direct assay
mast cell degranulation	BP	mutant phenotype
positive regulation of MAPK cascade	BP	mutant phenotype
positive regulation of mast cell cytokine production	BP	direct assay
positive regulation of receptor signaling pathway via JAK-STAT	BP	mutant phenotype
positive regulation of tyrosine phosphorylation of STAT protein	BP	mutant phenotype
positive regulation of vascular associated smooth muscle cell differentiation	BP	direct assay
protein autophosphorylation	BP	direct assay
plasma membrane	CC	direct assay
cytokine binding	MF	direct assay
protein homodimerization activity	MF	physical interaction
transmembrane receptor protein tyrosine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 4,726 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIT	KITLG	P21583	946
KIT	CD34	P28906	941
KIT	ANO1	Q5XXA6	898
KIT	PTPRC	P08575	881
KIT	IL3	P08700	863
KIT	CD48	P09326	806
KIT	NRAS	P01111	798
KIT	AKT1	P31749	797
KIT	SLAMF1	Q13291	789
KIT	TET2	Q6N021	789
KIT	ITGAM	P11215	778
KIT	CD19	P15391	774
KIT	CD33	P20138	770
KIT	FLT3LG	P49771	770
KIT	ANPEP	P15144	767

IntAct

Human interaction partners of KIT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 146 partners by confidence:

Partner	Interaction type	MIscore	Records
PIK3R1	proximity	0.750	19
GRB2	physical association	0.740	6
PLCG1	proximity	0.670	31
PIK3R2	association	0.590	19
CRK	association	0.590	4
GRB7	association	0.590	4
KITLG	direct interaction	0.540	2
PIK3R3	direct interaction	0.440	31
PTPN11	direct interaction	0.440	29
RASA1	direct interaction	0.440	16
SOCS6	direct interaction	0.440	12
SH2D2A	direct interaction	0.440	10
PATJ	direct interaction	0.440	9
LCK	direct interaction	0.440	8
PLCG2	direct interaction	0.440	8
SH2D1B	direct interaction	0.440	8
SHC1	direct interaction	0.440	8
LYN	direct interaction	0.440	7
YES1	direct interaction	0.440	7
BLK	direct interaction	0.440	5
GRIP1	direct interaction	0.440	5
GRIP2	direct interaction	0.440	5
HSH2D	direct interaction	0.440	5
MAGI2	direct interaction	0.440	5
SHC2	direct interaction	0.440	5
SRC	direct interaction	0.440	5
TNS3	direct interaction	0.440	5
PTK6	direct interaction	0.440	4
SH2D3C	direct interaction	0.440	4
SOCS2	direct interaction	0.440	4

BioGRID (191 interactions; top human partners by supporting records): GRB2 (Affinity Capture-Western; 9 records), PIK3R1 (Co-localization; 9 records), SOCS6 (Reconstituted Complex; 6 records), CBL (Affinity Capture-Western; 5 records), PLCG1 (Co-localization; 5 records), PTPN6 (Affinity Capture-Western; 5 records), STAT1 (Co-localization; 5 records), TEC (Affinity Capture-Western; 5 records), BMPR2 (Affinity Capture-MS; 4 records), LYN (Affinity Capture-Western; 4 records), PTPN11 (Reconstituted Complex; 4 records), CRK (Affinity Capture-MS; 3 records), GRB10 (Two-hybrid; 3 records), GRB7 (Reconstituted Complex; 3 records), KITLG (Reconstituted Complex; 3 records)

SIGNOR signaling

showing 53 of 80 signaling 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
KIT	“up-regulates activity”	JAK2	binding
KIT	up-regulates	SRC_kinase_family	phosphorylation
AML1-ETO	“up-regulates quantity by expression”	KIT	“transcriptional regulation”
pazopanib	“down-regulates activity”	KIT	“chemical inhibition”
sunitinib	“down-regulates activity”	KIT	“chemical inhibition”
lapatinib	“down-regulates activity”	KIT	“chemical inhibition”
FUBP1	“up-regulates quantity by expression”	KIT	“transcriptional regulation”
RUNX1	“up-regulates quantity by expression”	KIT	“transcriptional regulation”
ponatinib	“down-regulates activity”	KIT	“chemical inhibition”
CBL	“down-regulates activity”	KIT	ubiquitination
CBLB	“down-regulates activity”	KIT	ubiquitination
KIT	“up-regulates activity”	STAP1	phosphorylation
STAP1	“up-regulates activity”	KIT	binding
cabozantinib	“down-regulates activity”	KIT	“chemical inhibition”
SOHLH2	“up-regulates quantity by expression”	KIT	“transcriptional regulation”
KIT	“up-regulates activity”	CTNNB1	phosphorylation
KIT	“up-regulates activity”	PHB	phosphorylation
KIT	“up-regulates activity”	CBL	phosphorylation
PRKCA	down-regulates	KIT	phosphorylation
PTPN6	down-regulates	KIT	binding
KIT	up-regulates	KIT	phosphorylation
KIT	“up-regulates activity”	PI3K	binding
KIT	“up-regulates activity”	PTPN11	phosphorylation
PRKCA	“down-regulates activity”	KIT	phosphorylation
KIT	“up-regulates activity”	STAT1	phosphorylation

Protein complexes (CORUM) (8)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

8 complexes by size:

Complex	Subunits	Members
★ CBL-CRKL-KIT-PIK3R1 complex	4	CBL, CRKL, KIT, PIK3R1
★ IL1RAP-IL1RL1-KIT complex	3	IL1RAP, IL1RL1, KIT
★ CSK-KIT complex	2	CSK, KIT
★ GRB2-KIT complex	2	GRB2, KIT
★ GRB7-KIT complex	2	GRB7, KIT
★ KIT-SOCS6 complex	2	KIT, SOCS6
★ KIT-LYN complex	2	KIT, LYN
★ IL1RAP-KIT complex	2	IL1RAP, KIT

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
KITLG	receptor

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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	9	49.6×	3e-12
Regulation of signaling by CBL	10	45.5×	5e-13
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	9	42.9×	1e-11
Downstream signal transduction	12	41.9×	6e-15
Signaling by CSF3 (G-CSF)	8	41.9×	2e-10
Signaling by SCF-KIT	18	41.0×	1e-22
Negative regulation of FLT3	6	39.3×	1e-07
Interleukin-3, Interleukin-5 and GM-CSF signaling	12	34.9×	6e-14

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	40.6×	1e-11
Fc-gamma receptor signaling pathway involved in phagocytosis	8	39.3×	3e-09
peptidyl-tyrosine dephosphorylation	6	37.2×	8e-07
protein localization to synapse	6	32.1×	2e-06
B cell receptor signaling pathway	11	30.9×	1e-11
receptor clustering	7	30.6×	3e-07
peptidyl-tyrosine phosphorylation	10	29.5×	2e-10
negative regulation of inflammatory response to antigenic stimulus	7	29.5×	3e-07

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.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for KIT: 3,516 ClinVar records (124 pathogenic / likely pathogenic); 49 CIViC cancer variants; 32 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

3,516 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	79
Likely pathogenic	45
Uncertain significance	1640
Likely benign	1191
Benign	56

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 124 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
13866	NM_000222.3(KIT):c.1924A>G (p.Lys642Glu)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
13863	NM_000222.3(KIT):c.2446G>C (p.Asp816His)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
409664	NM_000222.3(KIT):c.2454del (p.Asn819fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
409725	NM_000222.3(KIT):c.1735_1737del (p.Asp579del)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
375928	NM_000222.3(KIT):c.2458G>T (p.Asp820Tyr)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
949598	NM_000222.3(KIT):c.568C>T (p.Gln190Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
375933	NM_000222.3(KIT):c.2485G>C (p.Ala829Pro)	Pathogenic	criteria provided, single submitter	3
13851	NM_000222.3(KIT):c.1879+1G>A	Pathogenic	criteria provided, single submitter	2
375923	NM_000222.3(KIT):c.1965T>A (p.Asn655Lys)	Pathogenic	criteria provided, single submitter	2
651292	NM_000222.3(KIT):c.1526A>T (p.Lys509Ile)	Pathogenic	criteria provided, single submitter	2
280912	NM_000222.3(KIT):c.2591_2594del (p.Phe863_Ser864insTer)	Pathogenic	criteria provided, single submitter	1
458850	NM_000222.3(KIT):c.108_109insT (p.Pro37fs)	Pathogenic	criteria provided, single submitter	1
569047	NM_000222.3(KIT):c.389del (p.Asn130fs)	Pathogenic	criteria provided, single submitter	1
580901	NM_000222.3(KIT):c.2152_2153del (p.Ser717_Thr718insTer)	Pathogenic	criteria provided, single submitter	1
648178	NM_000222.3(KIT):c.756+1G>A	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore KIT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 2,031):

Position(s)	Effect	Δscore	Sites
4:54695723	donor_gain	1.0000
4:54695751	donor_gain	1.0000
4:54703712	acceptor_gain	1.0000
4:54703719–54703720	acceptor_loss	1.0000	6
4:54703883	donor_gain	1.0000
4:54703893–54703894	donor_loss	1.0000	5
4:54707093	acceptor_gain	1.0000
4:54707096–54707097	acceptor_loss	1.0000	2
4:54707288–54707289	donor_loss	1.0000	4
4:54723699–54723700	donor_loss	1.0000	4

AlphaMissense

2,241 missense substitutions predicted likely pathogenic (of 6,468 scored), across 522 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M836	9	0.997	1.000
M624	9	0.986	0.998
M724	9	0.980	0.999
M780	9	0.964	0.999
M889	9	0.963	1.000
M903	9	0.934	0.999
M638	9	0.902	0.989
D792	8	1.000	1.000
N797	8	1.000	1.000
D810	8	1.000	1.000
H790	8	0.999	1.000
F811	8	0.999	1.000
D851	8	0.999	1.000
F600	8	0.998	1.000
D677	8	0.998	1.000
D816	8	0.997	0.999
F879	8	0.993	1.000
D820	8	0.991	0.998
F842	8	0.984	0.999
S850	8	0.983	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Chromophobe)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (validation)	favorable	6.08e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.36e-05
Rectum Adenocarcinoma (TCGA)	favorable	0.000333

Disease associations

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

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
piebaldism	Definitive	Autosomal dominant	6
mastocytosis	Strong	Autosomal dominant	2
gastrointestinal stromal tumor	Strong	Autosomal dominant	5
cutaneous mastocytosis	Strong	Autosomal dominant	2

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
gastrointestinal stromal tumor	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
Adult solid tumours cancer susceptibility	green
Adult solid tumours for rare disease	green
DDG2P	green
Inherited predisposition to GIST	green
Monogenic hearing loss	green
Paediatric disorders	green
Pigmentary skin disorders	green
Rare genetic inflammatory skin disorders	green
Sarcoma cancer susceptibility	amber
Sarcoma susceptibility	amber

Mondo (7): gastrointestinal stromal tumor (MONDO:0011719), piebaldism (MONDO:0008244), mastocytosis (MONDO:0007950), dysgerminoma (MONDO:0003002), testicular germ cell tumor (MONDO:0010108), hereditary neoplastic syndrome (MONDO:0015356), cutaneous mastocytosis (MONDO:0019023)

Orphanet (6): Gastrointestinal stromal tumor (Orphanet:44890), Piebaldism (Orphanet:2884), Mastocytosis (Orphanet:98292), Germ cell tumor of testis (Orphanet:363504), Inherited cancer-predisposing syndrome (Orphanet:140162), Cutaneous mastocytosis (Orphanet:66646)

HPO phenotypes

showing 60 of 121 phenotypes (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:0001000	Abnormal skin pigmentation
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
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001880	Increased total eosinophil count
HP:0001895	Normochromic anemia
HP:0001897	Normocytic anemia
HP:0001903	Anemia
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002017	Nausea and vomiting
HP:0002018	Nausea
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002086	Abnormality of the respiratory system
HP:0002094	Dyspnea
HP:0002211	White forelock
HP:0002226	White eyebrow
HP:0002227	White eyelashes
HP:0002239	Gastrointestinal hemorrhage
HP:0002240	Hepatomegaly
HP:0002251	Aganglionic megacolon
HP:0002315	Headache
HP:0002615	Hypotension
HP:0002653	Bone pain
HP:0002659	Increased susceptibility to fractures
HP:0002664	Neoplasm
HP:0002665	Lymphoma

GWAS associations

showing 30 of 32 associations:

Study	Trait	p-value
GCST006011_105	Mean corpuscular volume	3e-126
GCST005993_24	Mean corpuscular hemoglobin	6e-109
GCST005996_20	Red blood cell count	1e-93
GCST001765_23	Red blood cell traits	3e-39
GCST004004_32	Mean corpuscular volume	2e-36
GCST004008_19	Red blood cell count	2e-28
GCST000585_17	Mean corpuscular volume	1e-27
GCST002698_1	Serum VEGFR2 concentration	5e-25
GCST005994_20	Hematocrit	2e-20
GCST90002399_420	Neutrophil percentage of white cells	6e-20
GCST004008_14	Red blood cell count	4e-16
GCST005995_8	Hemoglobin	6e-16
GCST000503_6	Mean corpuscular volume	1e-15
GCST005754_1	Systemic lupus erythematosus	1e-15
GCST010988_369	Adult body size	2e-13
GCST004335_10	Mean corpuscular volume	9e-13
GCST010242_3	HDL cholesterol levels	1e-12
GCST004334_2	Mean corpuscular hemoglobin	3e-12
GCST010244_121	Triglyceride levels	9e-12
GCST004332_3	Red blood cell count	4e-10
GCST010241_277	Apolipoprotein A1 levels	5e-9
GCST005991_10	Platelet count	7e-9
GCST004003_9	Hematocrit	1e-8
GCST004005_13	Hemoglobin levels	1e-8
GCST004006_29	Mean corpuscular hemoglobin	1e-8
GCST006576_1	Anorexia nervosa or obsessive-compulsive disorder	4e-7
GCST003050_20	Schizophrenia	5e-7
GCST010658_7	High density lipoprotein cholesterol levels	5e-7
GCST002936_29	Cadmium levels	1e-6
GCST010660_6	Triglyceride levels	3e-6

EFO canonical traits (from GWAS)

10 canonical traits:

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

7 disease descriptors:

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
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
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
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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the KIT protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

32 curated-mechanism drugs:

Drug	Modality	Max phase
AVAPRITINIB	Small molecule	4
DASATINIB ANHYDROUS	Small molecule	4
IMATINIB MESYLATE	Small molecule	4
MIDOSTAURIN	Small molecule	4
PAZOPANIB HYDROCHLORIDE	Small molecule	4
PEXIDARTINIB	Small molecule	4
QUIZARTINIB	Small molecule	4
REGORAFENIB	Small molecule	4
RIPRETINIB	Small molecule	4
SORAFENIB TOSYLATE	Small molecule	4
SUNITINIB	Small molecule	4
TIVOZANIB HYDROCHLORIDE	Small molecule	4
CATEQUENTINIB	Small molecule	3
CEDIRANIB	Small molecule	3
CM-082	Unknown	3
DOVITINIB	Small molecule	3
FAMITINIB	Small molecule	3
MASITINIB	Small molecule	3
MOTESANIB	Small molecule	3
SEMAXANIB	Small molecule	3
SERALUTINIB	Small molecule	3
VATALANIB	Small molecule	3
AMUVATINIB	Small molecule	2
BRIQUILIMAB	Antibody	2
ENMD-2076	Small molecule	2
FORETINIB	Small molecule	2
SU-014813	Small molecule	2
TANDUTINIB	Small molecule	2
TELATINIB	Small molecule	2
XL-820	Unknown	2
XL-999	Small molecule	2
OSI-930	Small molecule	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 532,523 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 99 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL4204794	AVAPRITINIB	4	1,416
CHEMBL5416410	DASATINIB	4	674
CHEMBL1421	DASATINIB ANHYDROUS	4	55,947
CHEMBL941	IMATINIB	4	113,105
CHEMBL1642	IMATINIB MESYLATE	4	70,926
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL3813873	PEXIDARTINIB	4	3,751
CHEMBL576982	QUIZARTINIB	4	4,647
CHEMBL1946170	REGORAFENIB	4	13,318
CHEMBL4216467	RIPRETINIB	4	1,151
CHEMBL1336	SORAFENIB	4	87,476
CHEMBL535	SUNITINIB	4	80,232
CHEMBL1289494	TIVOZANIB	4	4,697
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL1983268	ENTRECTINIB	4
CHEMBL553	ERLOTINIB	4
CHEMBL1287853	FEDRATINIB	4
CHEMBL939	GEFITINIB	4
CHEMBL1852688	INFIGRATINIB	4
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4
CHEMBL1289601	LENVATINIB	4
CHEMBL1448	NICLOSAMIDE	4
CHEMBL255863	NILOTINIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL1171837	PONATINIB	4
CHEMBL1789941	RUXOLITINIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL1278146	FAMITINIB	3
CHEMBL1908391	MASITINIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL276711	SEMAXANIB	3
CHEMBL101253	VATALANIB	3
CHEMBL428690	ALVOCIDIB	3
CHEMBL415049	BARASERTIB	3
CHEMBL5095229	BEZUCLASTINIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL545315	CANERTINIB DIHYDROCHLORIDE	3
CHEMBL300138	ENZASTAURIN	3
CHEMBL3545413	FLUMATINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL5314535	PIMICOTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL217092	SARACATINIB	3
CHEMBL3989926	SITRAVATINIB	3
CHEMBL5095202	VIMSELTINIB	3
CHEMBL2103851	AMUVATINIB	2
CHEMBL482968	ENMD-2076	2
CHEMBL1230609	FORETINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL124660	TANDUTINIB	2

Clinical evidence (CIViC)

Drug × variant × indication, from 188 curated evidence items; also 8 prognostic, 7 oncogenic, 4 diagnostic, 2 functional. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

showing 30 of 158 predictive associations by evidence level:

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

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

Clinical-actionability assertions (CIViC AMP/ASCO/CAP)

Curated AMP/ASCO/CAP tier assertions — the clinical-actionability classification (Tier I highest) for this gene’s variants, distilling the CIViC evidence above into a tiered call.

2 CIViC assertions:

Molecular profile	Disease	Therapy	Type	AMP tier	Significance
KIT D816V	Systemic Mastocytosis	Imatinib †	Predictive	Tier I - Level A	Resistance
KIT D816V	Systemic Mastocytosis		Oncogenic		Oncogenic

† an FDA-approved companion diagnostic exists for this assertion.

CIViC curated variants (49)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

N822K (missense variant), C809G (missense variant), D820A (missense variant), D820G (missense variant), T670I (missense variant), P551_E554delPMYE (inframe deletion), K558delinsNP (delins), V560_L576del (inframe deletion), A502_Y503insAY (inframe insertion), D816E (missense variant), S628N (missense variant), M541L (missense variant), V560DEL (amino acid deletion,inframe deletion), rs17084733 (3 prime UTR variant), T417_D419delinsY, F506_F508DUP, K484_G487DEL, Exon 13 Mutation, Wildtype (wild type), V555_V559DEL, K550_K559DEL, Mutation (transcript variant), EXPRESSION, RS3733542 (synonymous variant), Exon 9 Mutation (exon variant), V560_Y578del, A502_Y503dup, Amplification (transcript amplification), D816V (missense variant), Exon 11 Mutation (coding sequence variant), Internal Duplication (inframe insertion), Exon 14 Mutation (exon variant), L576P (missense variant), V654A (missense variant), Y503_F504insAY (inframe insertion), K550_W557del (inframe deletion), K550_K558del (inframe deletion), W557_K558del (conservative inframe deletion), K558_V559del, V559D (missense variant), V560D (missense variant), V560G (missense variant), D579del (conservative inframe deletion), K642E (missense variant), D816H (missense variant), D820Y (missense variant), N822H (missense variant), Y823D (missense variant), A829P (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

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 (53 total), top 25:

Ligand	Action	Affinity	Parameter
stem cell factor	Agonist	9.82	pKd
BLU-808	Inhibition	9.52	pIC50
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

Binding affinities (BindingDB)

3298 measured of 5067 human assays (5079 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4448433	IC50	0.02 nM
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	EC50	0.05 nM
(S)-5-(3-cyclopropyl-1-(2-hydroxy-3-methoxypropyl)-1H-pyrazol-4-yl)-N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.1 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)phenyl)-5-(1-(2,3-dihydroxypropyl)-3,5-dimethyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.1 nM	US-20240262826: WILD TYPE KIT INHIBITORS
3-(2,6-Difluoro-3,5-dimethoxyphenyl)-1-methyl-1,3,4,7-tetrahydro-2H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2-one	IC50	0.12 nM
3-[3-[4-[dideuterio(methylamino)methyl]phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine	IC50	0.2 nM
N-[2-chloro-5-(2-cyclopropyl-2H-1,2,3,4-tetrazol-5-yl)phenyl]-5-[1-(2-hydroxyethyl)-3-methyl-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.2 nM	US-20240262826: WILD TYPE KIT INHIBITORS
5-(3-cyclopropyl-1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.2 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)phenyl)-5-(1-(2-hydroxy-3-methoxypropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.2 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluorophenyl)-5-(1-(2-hydroxypropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.2 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-[2-chloro-5-(2-ethyltetrazol-5-yl)-4-fluorophenyl]-5-[1-[(2S)-2-hydroxy-3-methoxypropyl]-3-methylpyrazol-4-yl]pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.2 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluoro-2-methylphenyl)-5-(1-(2-hydroxy-2-methylpropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.3 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(R)-N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluoro-2-methylphenyl)-5-(1-(2-hydroxypropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.3 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(R)-N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)phenyl)-5-(1-(2,3-dihydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.3 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-2-methylphenyl)-5-(1-((2R,3S)-3-hydroxybutan-2-yl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide or N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-2-methylphenyl)-5-(1-((2S,3R)-3-hydroxybutan-2-yl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.3 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(2-chloro-5-(5-((1R,2S)-2-fluorocyclopropyl)-2H-tetrazol-2-yl)phenyl)-5-(1-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide or N-(2-chloro-5-(5-((1S,2R)-2-fluorocyclopropyl)-2H-tetrazol-2-yl)phenyl)-5-(1-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.3 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)phenyl)-5-(1-(1,3-dihydroxypropan-2-yl)-3,5-dimethyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.3 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)phenyl)-5-(1-(2-hydroxypropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.3 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(R)-N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluorophenyl)-5-(1-(2-hydroxy-3-(2-methoxyethoxy)propyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.3 nM	US-20240262826: WILD TYPE KIT INHIBITORS
CHEMBL4784002	IC50	0.336 nM
(2R)-2-(4-fluorophenyl)-N-[4-(2-{[2-methoxy-4-(methylsulfonyl)phenyl]-amino}[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl]propanamide	IC50	0.34 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
AZD1152, 33	IC50	0.37 nM
CHEMBL3329684	IC50	0.4 nM
N-[1-(fluoromethyl)-2-oxo-3-pyridinyl]-2-[4-[[(2R)-2-hydroxypropanoyl]-methylamino]cyclohexyl]-6-methoxyindazole-5-carboxamide	IC50	0.4 nM	US-20240300923: IRAK4 Inhibitors
N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-2-methylphenyl)-5-(1-(2-hydroxyethyl)-3,5-dimethyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
5-(1-(2-hydroxy-2-methylpropyl)-3,5-dimethyl-1H-pyrazol-4-yl)-N-(2-methyl-5-(5-methyl-2H-tetrazol-2-yl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)phenyl)-5-(1-(2-hydroxy-2-methylpropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluorophenyl)-5-(1-(2-hydroxy-2-methylpropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-N-(2-chloro-5-(2-ethyl-2H-tetrazol-5-yl)phenyl)-5-(1-(2-hydroxypropyl)-3,5-dimethyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluoro-2-methylphenyl)-5-(1-(2-hydroxypropyl)-3,5-dimethyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-5-(3-cyclopropyl-1-(2,3-dihydroxy-3-methylbutyl)-1H-pyrazol-4-yl)-N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(R)-5-(3-cyclopropyl-1-(2,3-dihydroxy-3-methylbutyl)-1H-pyrazol-4-yl)-N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(R)-N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluorophenyl)-5-(1-(2-hydroxypropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluorophenyl)-5-(1-((2S,3S)-3-hydroxybutan-2-yl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide or N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluorophenyl)-5-(1-((2R,3R)-3-hydroxybutan-2-yl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.4 nM	US-20240262826: WILD TYPE KIT INHIBITORS
CHEMBL4084391	IC50	0.5 nM
6-methoxy-N-(1-methyl-2-oxo-3-pyridinyl)-2-[4-(2-oxo-1-pyridinyl)cyclohexyl]indazole-5-carboxamide	IC50	0.5 nM	US-20240300923: IRAK4 Inhibitors
N-(4-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)-2-methylphenyl)-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)phenyl)-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)phenyl)-5-(1-(2-hydroxy-3-methoxypropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-2-methylphenyl)-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluoro-2-methylphenyl)-6-fluoro-5-(1-(2-hydroxy-2-methylpropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluoro-2-methylphenyl)-5-(1-(2-hydroxypropyl)-3-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
(S)-N-(2-chloro-5-(2-cyclopropyl-2H-tetrazol-5-yl)-4-fluorophenyl)-5-(1-(2-hydroxypropyl)-5-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-2-methylphenyl)-5-(1-((2S,3S)-3-hydroxybutan-2-yl)-5-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide or N-(5-(2-cyclopropyl-2H-tetrazol-5-yl)-2-methylphenyl)-5-(1-((2R,3R)-3-hydroxybutan-2-yl)-5-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(2-chloro-5-(5-((1S,2R)-2-fluorocyclopropyl)-2H-tetrazol-2-yl)phenyl)-5-(1-((R)-2,3-dihydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide or N-(2-chloro-5-(5-((1R,2S)-2-fluorocyclopropyl)-2H-tetrazol-2-yl)phenyl)-5-(1-((R)-2,3-dihydroxy-2-methylpropyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
N-(5-(5-cyclopropyl-2H-tetrazol-2-yl)-2-methylphenyl)-4-fluoro-6-(1-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide	IC50	0.5 nM	US-20240262826: WILD TYPE KIT INHIBITORS
US20240300923, Example 28	IC50	0.5 nM	US-20240300923: IRAK4 Inhibitors
Alectinib	IC50	0.59 nM	US-9126931: Tetracyclic compound

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

2360 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
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-(prop-2-enoylamino)naphthalen-1-yl]benzamide	2267782: Inhibition of wild type His-tagged KIT (unknown origin) extracted from Escherichia coli BL21 (DE3) by HTRF analysis	ic50	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
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
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
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-N-[3-iodo-4-(prop-2-enoylamino)phenyl]-4-methylbenzamide	2267782: Inhibition of wild type His-tagged KIT (unknown origin) extracted from Escherichia coli BL21 (DE3) by HTRF analysis	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-cyclopropyl-4-(prop-2-enoylamino)phenyl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2267782: Inhibition of wild type His-tagged KIT (unknown origin) extracted from Escherichia coli BL21 (DE3) by HTRF analysis	ic50	0.0012	uM
Ponatinib	2267782: Inhibition of wild type His-tagged KIT (unknown origin) extracted from Escherichia coli BL21 (DE3) by HTRF analysis	ic50	0.0012	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
Ripretinib	2267782: Inhibition of wild type His-tagged KIT (unknown origin) extracted from Escherichia coli BL21 (DE3) by HTRF analysis	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-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylphenyl]-4-(prop-2-enoylamino)-3-(trifluoromethyl)benzamide	2267782: Inhibition of wild type His-tagged KIT (unknown origin) extracted from Escherichia coli BL21 (DE3) by HTRF analysis	ic50	0.0019	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	affects binding, increases reaction, decreases expression, decreases phosphorylation, increases expression	6
Tretinoin	affects expression, affects cotreatment, increases expression, decreases activity, decreases 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)	affects cotreatment, decreases expression, increases expression	2
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	2
tanespimycin	decreases expression, increases degradation	2
Semaxinib	decreases activity	2
entinostat	increases expression, affects cotreatment	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	decreases expression, affects binding	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	increases abundance, decreases expression	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

108 cell lines: 78 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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 339 trials:

NCT	Phase	Status	Title
NCT01377077	Phase 4	UNKNOWN	Punchgrafting Techniques for Vitiligo
NCT01640678	Phase 4	UNKNOWN	Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients
NCT02458417	Phase 4	COMPLETED	Autologous Cell Suspension Grafting Using ReCell in Vitiligo and Piebaldism Patients
NCT00171977	Phase 4	COMPLETED	Post-Marketing Clinical Study of Postoperative Adjuvant Therapy With Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors (GIST)
NCT00510354	Phase 4	COMPLETED	Treatment of Patients With Everolimus and Imatinib Mesylate Who Have Progressive Gastro Intestinal Stromal Tumors (GIST) and Are Resistant to Imatinib Mesylate
NCT00756509	Phase 4	COMPLETED	Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib
NCT00777504	Phase 4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT02800330	Phase 4	COMPLETED	The Effects of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib
NCT04825574	Phase 4	COMPLETED	Study for Patients Previously Treated in Avapritinib Clinical Trials
NCT02156427	Phase 3	COMPLETED	Evaluation of Non-cultured Epidermal Cellular Grafting vs Hyaluronic Acid for Repigmenting Vitiligo and Piebaldism
NCT00009906	Phase 3	TERMINATED	Comparison of Two Different Doses of STI571 in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
NCT00041197	Phase 3	COMPLETED	Imatinib Mesylate in Treating Patients With Primary Gastrointestinal Stromal Tumor That Has Been Completely Removed By Surgery
NCT00075218	Phase 3	COMPLETED	A Study To Assess The Safety And Efficacy Of SU11248 In Patients With Gastrointestinal Stromal Tumor(GIST)
NCT00103168	Phase 3	COMPLETED	Imatinib Mesylate or Observation Only in Treating Patients Who Have Undergone Surgery for Localized Gastrointestinal Stromal Tumor
NCT00293124	Phase 3	COMPLETED	Open-label Trial of GlivecWith Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumors
NCT00324987	Phase 3	TERMINATED	Imatinib Mesylate With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
NCT00372567	Phase 3	TERMINATED	Safety And Effectiveness Of Daily Dosing With Sunitinib Or Imatinib In Patients With Gastrointestinal Stromal Tumors
NCT00471328	Phase 3	COMPLETED	Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib
NCT00685828	Phase 3	UNKNOWN	Imatinib Mesylate in Treating Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumor
NCT00688766	Phase 3	TERMINATED	Study Evaluating IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) Following Failure of at Least Imatinib and Sunitinib
NCT00751036	Phase 3	TERMINATED	Nilotinib 800 Mg And Imatinib 800 Mg For The Treatment Of Patients With Gastrointestinal Stromal Tumors (Gist) Refractory To Imatinib 400 Mg
NCT00785785	Phase 3	COMPLETED	A Study of Nilotinib Versus Imatinib in GIST Patients
NCT00812240	Phase 3	TERMINATED	Masitinib in First Line Treatment of Gastro-Intestinal Stromal Tumor (GIST)
NCT00956072	Phase 3	TERMINATED	Imatinib Mesylate With or Without Surgery in Treating Patients With Metastatic Gastrointestinal Stromal Tumor That is Responding to Imatinib Mesylate
NCT01031628	Phase 3	TERMINATED	Study of Dose Escalation Versus no Dose Escalation of Imatinib in Metastatic Gastrointestinal Stromal Tumors (GIST) Patients
NCT01151852	Phase 3	COMPLETED	Rechallenge of Imatinib in GIST Having no Effective Treatment: RIGHT
NCT01265810	Phase 3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01271712	Phase 3	COMPLETED	Study of Regorafenib as a 3rd-line or Beyond Treatment for Gastrointestinal Stromal Tumors (GIST)
NCT01289028	Phase 3	COMPLETED	Efficacy of Nilotinib in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Imatinib and Sunitinib.
NCT01462994	Phase 3	COMPLETED	Detection of CF-DNA in Patients With Gastrointestinal Stromal Tumors (GIST)
NCT01694277	Phase 3	COMPLETED	Masitinib in Patients With Gastrointestinal Stromal Tumour After Progression With Imatinib
NCT02260505	Phase 3	COMPLETED	Efficiency of Imatinib Treatment Maintenance or Interruption After 3 Years of Adjuvant Treatment in Patients With Gastrointestinal Stromal Tumours (GIST)
NCT02576080	Phase 3	UNKNOWN	Efficacy of Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index
NCT02866045	Phase 3	UNKNOWN	EUS-FNB vs. Single-incision Needle-knife (SINK) Biopsy for Gastrointestinal SELs
NCT03353753	Phase 3	COMPLETED	Phase 3 Study of DCC-2618 vs Placebo in Advanced GIST Patients Who Have Been Treated With Prior Anticancer Therapies
NCT03426722	Phase 3	COMPLETED	L-carnitine vs Placebo for the Treatment of Muscle Cramps After Imatinib in Gastrointestinal Stromal Tumors
NCT03465722	Phase 3	COMPLETED	(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST
NCT03673501	Phase 3	ACTIVE_NOT_RECRUITING	A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib
NCT04409223	Phase 3	TERMINATED	Efficacy and Safety of Famitinib Versus Sunitinib in the Treatment of Advanced Gastrointestinal Stromal Tumour Patients After Failure of Imatinib
NCT05208047	Phase 3	RECRUITING	(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
NCT05734105	Phase 3	ACTIVE_NOT_RECRUITING	A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib
NCT06640361	Phase 3	RECRUITING	A Study of Olverembatinib in SDH-deficient GIST.
NCT07585266	Phase 3	RECRUITING	A Study to Investigate Velzatinib Compared With Imatinib in Adult Participants With Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (StrateGIST Frontline)
NCT00006413	Phase 2	COMPLETED	Stem Cell Transplantation to Treat Systemic Mastocytosis
NCT00255346	Phase 2	COMPLETED	Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)
NCT00831974	Phase 2	COMPLETED	Efficacy of AB1010 in Patients With Systemic Indolent Mastocytosis
NCT01266369	Phase 2	COMPLETED	Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation
NCT01384513	Phase 2	COMPLETED	A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies
NCT01701843	Phase 2	TERMINATED	Cromoglicate in Mastocytosis
NCT02478957	Phase 2	COMPLETED	Treatment of Indolent Systemic Mastocytosis With PA101
NCT05186753	Phase 2	ACTIVE_NOT_RECRUITING	(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis
NCT00003939	Phase 2	COMPLETED	Ecteinascidin 743 in Treating Patients With Advanced Soft Tissue Sarcoma
NCT00004895	Phase 2	COMPLETED	Octreotide as Palliative Therapy for Cancer-Related Bowel Obstruction That Cannot Be Removed by Surgery
NCT00005049	Phase 2	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III Ovarian Epithelial Cancer or Gastrointestinal Cancer
NCT00005597	Phase 2	COMPLETED	S9926 Temozolomide in Patients With Unresectable/Metastatic Gastrointestinal Stromal Tumors
NCT00005862	Phase 2	COMPLETED	SU5416 in Treating Patients With Advanced, Metastatic, or Recurrent Soft Tissue Sarcomas
NCT00005874	Phase 2	COMPLETED	Nitrocamptothecin in Treating Patients With Soft Tissue Sarcomas
NCT00025246	Phase 2	COMPLETED	Imatinib Mesylate in Treating Patients With Gastrointestinal Stromal Tumor That Has Been Completely Removed During Surgery
NCT00028002	Phase 2	COMPLETED	Neoadjuvant and Adjuvant Imatinib Mesylate in Treating Patients With Primary or Recurrent Malignant Gastrointestinal Stromal Tumor
NCT00030667	Phase 2	COMPLETED	Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for KIT across ~30M SureChEMBL compounds — explore on Sugi Predict.