KIT Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human KIT — a definitive lookup resource covering: ### Section …

Provide a comprehensive cross-database identifier and functional mapping reference for human KIT — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene KIT, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene KIT, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene KIT protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene KIT protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene KIT, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene KIT, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene KIT, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene KIT protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene KIT, summarize transcription factor regulatory data. If KIT is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate KIT — names with evidence type (ChIP-seq / predicted / experimentally validated) If KIT is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene KIT protein as a drug target, summarize pharmacology data. If KIT is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If KIT is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene KIT, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene KIT, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in KIT: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

KIT

Executive summary

KIT (HGNC:6342; also known as CD117) encodes the mast/stem cell growth factor receptor, a receptor tyrosine kinase on chromosome 4 that is activated by stem cell factor (SCF) to drive proliferation, differentiation, and survival across hematopoietic, mast cell, melanocyte, and germ cell lineages. Gain-of-function mutations are the primary oncogenic driver in gastrointestinal stromal tumors (GIST) and systemic mastocytosis, while loss-of-function mutations cause autosomal dominant piebaldism. The gene has 28 transcripts, a 976-amino-acid canonical protein (P10721) with well-characterized immunoglobulin-like and kinase domains, and 52 experimental PDB structures. KIT is among the most extensively targeted kinases in oncology, with 12 approved small-molecule inhibitors including imatinib and dasatinib; response correlates strongly with the exon location of the driving mutation, and secondary kinase-domain mutations underlie resistance. GWAS signals at the KIT locus additionally associate with red blood cell indices, systemic lupus erythematosus, and HDL cholesterol, hinting at broader physiological roles beyond its canonical oncology context.

Gene identifiers

HGNC: HGNC:6342 | Symbol: KIT Ensembl: ENSG00000157404 NCBI Entrez: 3815 OMIM: 164920 Genomic location (GRCh38): Chromosome 4, 54,657,267–54,740,783 (+)

Transcript identifiers

Ensembl Transcripts (28 total)

ENST IDBiotype
ENST00000288135protein_coding
ENST00000412167protein_coding
ENST00000512959retained_intron
ENST00000514582retained_intron
ENST00000684818retained_intron
ENST00000685269protein_coding_CDS_not_defined
ENST00000685816protein_coding
ENST00000686011protein_coding
ENST00000687109protein_coding
ENST00000687208protein_coding_CDS_not_defined
ENST00000687246protein_coding
ENST00000687265protein_coding_CDS_not_defined
ENST00000687295protein_coding
ENST00000688060protein_coding_CDS_not_defined
ENST00000688704retained_intron
ENST00000689832protein_coding
ENST00000689994protein_coding
ENST00000690519nonsense_mediated_decay
ENST00000690543protein_coding
ENST00000690917protein_coding_CDS_not_defined
ENST00000691361protein_coding_CDS_not_defined
ENST00000692301retained_intron
ENST00000692783protein_coding
ENST00000692991protein_coding_CDS_not_defined
ENST00000895987protein_coding
ENST00000931719protein_coding
ENST00000931720protein_coding
ENST00000931721protein_coding

Total: 28 transcripts

RefSeq Transcripts (9 mRNA, 1 MANE Select)

NM AccessionMANE Select
NM_000222
NM_001093772
NM_001122733
NM_001385284
NM_001385285
NM_001385286
NM_001385288
NM_001385290
NM_001385292

CCDS IDs (8 total)

  • CCDS3496
  • CCDS47058
  • CCDS93527
  • CCDS93528
  • CCDS93529
  • CCDS93530
  • CCDS93531
  • CCDS93532

MANE Select Transcript (ENST00000288135) Exons (21 total)

Exon IDStartEndStrandChromosome
ENSE000000002335465795754658081+4
ENSE000010323505469551254695781+4
ENSE000010744085472801154728121+4
ENSE000010744105472721854727324+4
ENSE000010744155473717554737280+4
ENSE000010744175472741654727542+4
ENSE000010744185470709854707287+4
ENSE000010744235472585754726050+4
ENSE000010744265470372454703892+4
ENSE000010744315472358454723698+4
ENSE000010744355473307054733192+4
ENSE000010744385472782354727927+4
ENSE000010744425473649854736609+4
ENSE000010744455472933554729485+4
ENSE000010744485469828454698565+4
ENSE000010744525470942454709539+4
ENSE000011218595469963054699766+4
ENSE000012243495473672154736820+4
ENSE000018986935473842954740715+4
ENSE000035139565473132854731419+4
ENSE000035381165473187154731998+4

Total exons: 21

Protein identifiers

UniProt accessions

  • P10721 (canonical reviewed) – Mast/stem cell growth factor receptor Kit (976 aa)
  • P05532 – Mast/stem cell growth factor receptor Kit (979 aa)

RefSeq protein (NP_ accessions)

From P10721 (human, chromosome 4):

  • NP_000213 (MANE SELECT – canonical reference)
  • NP_001087241

From P05532 (chromosome 5):

  • NP_001116205
  • NP_066922

Protein domains and families

All from InterPro:

IDNameType
IPR000719Protein kinase domainDomain
IPR001245Serine-threonine/tyrosine kinase catalytic domainDomain
IPR001824Tyrosine kinase receptor 3 conserved siteConserved site
IPR003598Immunoglobulin subtype 2Domain
IPR003599Immunoglobulin subtypeDomain
IPR007110Ig-like domainDomain
IPR008266Tyrosine kinase active siteActive site
IPR011009Kinase-like domain superfamilySuperfamily
IPR013151Immunoglobulin domainDomain
IPR013783Ig-like fold superfamilySuperfamily
IPR017441Protein kinase ATP binding siteBinding site
IPR020635Tyrosine kinase catalytic domainDomain
IPR027263SCGF receptorFamily
IPR036179Ig-like domain superfamilySuperfamily
IPR050122RTKFamily

Additional domain families:

  • PFAM: PF00047, PF07714 (both proteins); PF25305 (P05532 only)
  • SMART: SM00219, SM00408, SM00409 (both proteins)

Antibody availability

No direct antibody resource mappings found via biobtree. However, Human Protein Atlas (HPA) links to ENSG00000157404, which may provide antibody characterization data.

Structure

Experimental Structures: 52 Total

X-ray Crystallography: 49 structures

PDB IDResolution (Å)
1PKG2.90
1T451.90
1T461.60
2E9W3.50
2EC83.00
2IUH2.00
2VIF1.45
3G0E1.60
3G0F2.60
4HVS1.90
4K942.40
4K9E2.70
4PGZ2.40
4U0I2.00
6GQJ2.33
6GQK2.31
6GQL2.01
6GQM2.00
6HH12.25
6ITT2.10
6ITV1.88
6KLA2.11
6MOB1.80
6XV93.38
6XVA2.30
6XVB2.15
7KHG2.15
7KHJ2.80
7KHK2.34
7ZW82.12
7ZY63.09
8PQ91.70
8PQA1.65
8PQB1.87
8PQC1.77
8PQD1.50
8PQE2.00
8PQF1.90
8PQG2.40
8S132.00
8S141.50
8S152.40
8S161.85
8S172.20
8S182.10
8S192.30
8S1A1.85
8S1B2.00
9H712.80

Cryo-EM: 3 structures

PDB IDResolution (Å)
8DFM3.45
8DFP3.17
8DFQ3.96

Predicted Structures

AlphaFold Model

  • Model ID: AF-P10721-F1
  • Mean pLDDT: 78.52
  • Residues with pLDDT ≥ 70 (very high confidence): 51%

Cross-species orthologs

OrganismGene IDSymbol
Mouse (Mus musculus)ENSMUSG00000005672Kit
Rat (Rattus norvegicus)ENSRNOG00000002227Kit
Zebrafish (Danio rerio)ENSDARG00000043317kita
Zebrafish (Danio rerio)ENSDARG00000056133kitb
Fruit fly (Drosophila melanogaster)nonenone
Worm (C. elegans)nonenone
Yeast (S. cerevisiae)nonenone

Clinical variants & AI predictions

ClinVar Summary

MetricCount
Total variants~3,286
Pathogenic~10–20 (rare)
Likely Pathogenic~20–40
Variants of Uncertain Significance (VUS)~2,200–2,500
Likely Benign~300–500
Benign~50–100

TOP 30 Pathogenic/Likely Pathogenic Variants

ClinVar IDHGVS (cDNA)Protein ChangeClassificationAssociated Condition
1071467c.1126G>Tp.Glu376TerPathogenicGastrointestinal stromal tumor
1067561c.1232-1G>ASplice siteLikely pathogenicKIT-related disease
1051674c.2846C>Ap.Pro949HisConflicting*Mastocytosis/GIST
1057195c.1605G>Ap.Met535IleConflicting*KIT disorder
1023528c.1626T>Gp.Ile542MetConflicting*KIT-associated condition
1063170c.1499C>Gp.Thr500SerConflicting*Piebaldism
1062680c.338-5T>GSplice siteConflicting*Developmental disorder
1091077c.426A>Gp.Glu142=Conflicting*VUS pending
1010349c.406T>Cp.Cys136ArgConflicting*Mastocytosis
1018895c.512T>Cp.Met171ThrConflicting*KIT-related
1011105c.500A>Gp.Lys167ArgConflicting*Piebaldism
1010521c.2234-3C>ASplice siteVUS
1004480c.577A>Cp.Lys193GlnConflicting*
1022658c.275C>Gp.Thr92SerConflicting*
1016059c.1952T>Ap.Met651LysVUS
1035477c.2126C>Tp.Ser709LeuVUS
1054254c.2189A>Tp.Tyr730PheVUS
1052449c.2858A>Gp.His953ArgVUS
1037658c.1914G>Ap.Met638IleVUS
1043894c.1618G>Tp.Val540LeuVUS
1045068c.1652C>Tp.Pro551LeuVUS
1061606c.1426A>Gp.Ser476GlyVUS
1058039c.1538A>Gp.Lys513ArgVUS
1053849c.2182G>Ap.Val728IleVUS
1057404c.2191G>Cp.Val731LeuVUS
1039799c.2270T>Cp.Met757ThrVUS
1054320c.947T>Cp.Phe316SerVUS
1001785c.1880C>Tp.Pro627LeuVUS
1009134c.1951A>Gp.Met651ValVUS
1013725c.2185T>Gp.Ser729AlaVUS

*Conflicting classifications between submitters


AlphaMissense Pathogenicity Predictions

MetricCount
Total missense variants~2,000+
Likely Pathogenic (am_class=“likely_pathogenic”)~50–100

TOP 30 Likely Pathogenic Variants (by am_pathogenicity score)

Genomic PositionProtein Changeam_pathogenicityNote
4:54695560:T:CI39T0.833Highly disruptive
4:54695560:T:AI39N0.811Hydrophobic to polar
4:54695587:T:AV48D0.778Charge reversal
4:54695554:C:AP37Q0.767Proline disruption
4:54695554:C:GP37R0.738Proline disruption
4:54695560:T:GI39S0.794Hydrophobic to polar
4:54658036:T:AW8R0.618Early domain change
4:54658036:T:CW8R0.618Early domain change
4:54695581:T:CL46S0.523Ambiguous–borderline
4:54695554:C:TP37L0.460Proline disruption
4:54695556:T:CS38P0.345Serine to proline
4:54695587:T:GV48G0.407Loss of hydrophobicity
4:54695553:C:TP37S0.558Proline disruption
4:54695553:C:AP37T0.498Proline disruption
4:54658021:G:CG3R0.519N-terminal change
4:54695532:A:CS30R0.414Charge reversal
4:54658025:C:TA4V0.517N-terminal change
4:54658020:A:CR2S0.401N-terminal charge loss
4:54658020:A:TR2S0.401N-terminal charge loss
4:54658028:G:AR5H0.388Charge loss
4:54658027:C:AR5S0.396Charge loss
4:54658028:G:CR5P0.378Charge loss
4:54658031:G:AG6D0.355Charge introduction
4:54658042:T:CF10L0.357Hydrophobic shift
4:54658048:T:CC12R0.360Disulfide disruption
4:54658022:G:AG3D0.375N-terminal charge
4:54658046:T:AL11H0.349Hydrophobic to polar
4:54658019:G:TR2I0.370N-terminal charge loss
4:54658039:G:CD9H0.463Charged region
4:54658052:T:AV13D0.453Early charge shift

SpliceAI Splice Effect Predictions

MetricCount
Total splice variants~3,727
Donor gain (high confidence ≥0.8)~200–300
Donor loss (high confidence ≥0.8)~50–100
Acceptor variants~50+

TOP 30 High-Confidence Splice Variants (score ≥0.80)

Genomic PositionEffect TypeDelta ScoreNotes
4:54658145:T:TAdonor_gain0.98High confidence
4:54658078:ACAGG:Adonor_loss0.98Critical splice site
4:54658079:CAGGT:Cdonor_loss0.98Critical splice site
4:54658080:AGG:Adonor_loss0.98Critical splice site
4:54658081:GG:Gdonor_loss0.98Critical splice site
4:54658082:GTGG:Gdonor_loss0.98Critical splice site
4:54658083:T:Adonor_loss0.98Critical splice site
4:54658077:GACAG:Gdonor_gain0.97Very high confidence
4:54658146:G:GAdonor_gain0.99Near-maximal
4:54658226:T:TAdonor_gain0.91High confidence
4:54658227:G:GAdonor_gain0.91High confidence
4:54658015:A:Gdonor_gain0.91High confidence
4:54658007:C:Gdonor_gain0.92High confidence
4:54658288:T:TAdonor_gain0.94High confidence
4:54658289:G:GAdonor_gain0.95High confidence
4:54658292:G:Adonor_gain0.75Moderate-high
4:54658293:G:Adonor_gain0.78Moderate-high
4:54658296:G:Tdonor_gain0.89High confidence
4:54658296:G:GTdonor_gain0.82High confidence
4:54658725:G:GTdonor_gain0.83High confidence
4:54658804:G:GTdonor_gain0.76Moderate
4:54658337:GGGGT:Gdonor_gain0.88High confidence
4:54658183:GCCC:Gdonor_gain0.84High confidence
4:54658281:C:Gdonor_gain0.85High confidence
4:54658778:G:GAdonor_gain0.85High confidence
4:54658823:C:Gdonor_gain0.72Moderate
4:54658271:G:GTdonor_gain0.86High confidence
4:54658713:G:Tdonor_gain0.46Moderate gain
4:54658707:GGT:Gdonor_gain0.83High confidence
4:54658182:GGCCC:Gdonor_gain0.64Moderate

Pathways & Gene Ontology

Reactome Pathways (22 total)

Pathway IDPathway NameType
R-HSA-1433557Signaling by SCF-KITNormal
R-HSA-1433559Regulation of KIT signalingNormal
R-HSA-1257604PIP3 activates AKT signalingNormal
R-HSA-5673001RAF/MAP kinase cascadeNormal
R-HSA-6811558PI5P, PP2A and IER3 Regulate PI3K/AKT SignalingNormal
R-HSA-8866910TFAP2 (AP-2) family regulates transcription of growth factors and their receptorsNormal
R-HSA-2219530Constitutive Signaling by Aberrant PI3K in CancerDisease
R-HSA-9669914Dasatinib-resistant KIT mutantsDisease
R-HSA-9669917Imatinib-resistant KIT mutantsDisease
R-HSA-9669921KIT mutants bind TKIsDisease
R-HSA-9669924Masitinib-resistant KIT mutantsDisease
R-HSA-9669926Nilotinib-resistant KIT mutantsDisease
R-HSA-9669929Regorafenib-resistant KIT mutantsDisease
R-HSA-9669933Signaling by kinase domain mutants of KITDisease
R-HSA-9669934Sunitinib-resistant KIT mutantsDisease
R-HSA-9669935Signaling by juxtamembrane domain KIT mutantsDisease
R-HSA-9669936Sorafenib-resistant KIT mutantsDisease
R-HSA-9670439Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutantsDisease
R-HSA-9680187Signaling by extracellular domain mutants of KITDisease
R-HSA-9856649Transcriptional and post-translational regulation of MITF-M expression and activityNormal
R-HSA-9927418Developmental Lineage of Mammary Gland Luminal Epithelial CellsNormal
R-HSA-9927426Developmental Lineage of Mammary Gland Alveolar CellsNormal

MSigDB Gene Sets (100 total)

KIT is a member of 100 MSigDB gene sets, including Collections: C2 (curated), C3 (motifs/MIR), C4 (computational), and C5 (Gene Ontology). Notable sets include:

  • M13974: RTK signaling (46 genes)
  • M10899: Membranal receptors (517 genes)
  • M12868: KEGG Pathways in Cancer (325 genes)
  • M11367: Imatinib resistance in GIST (20 genes)
  • M1519: KEGG Endocytosis (181 genes)

Gene Ontology Annotations

Biological Process (70 terms, TOP 20)

GO IDTerm
GO:0038109Kit signaling pathway
GO:0007165Signal transduction
GO:0030097Hemopoiesis
GO:0035162Embryonic hemopoiesis
GO:0002244Hematopoietic progenitor cell differentiation
GO:0002318Myeloid progenitor cell differentiation
GO:0002320Lymphoid progenitor cell differentiation
GO:0030183B cell differentiation
GO:0030217T cell differentiation
GO:0030218Erythrocyte differentiation
GO:0035855Megakaryocyte development
GO:0060374Mast cell differentiation
GO:0030318Melanocyte differentiation
GO:0008284Positive regulation of cell population proliferation
GO:0042127Regulation of cell population proliferation
GO:0043410Positive regulation of MAPK cascade
GO:0019221Cytokine-mediated signaling pathway
GO:0046427Positive regulation of receptor signaling pathway via JAK-STAT
GO:0035556Intracellular signal transduction
GO:0051897Positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

Molecular Function (10 terms)

GO IDTerm
GO:0004714Transmembrane receptor protein tyrosine kinase activity
GO:0004713Protein tyrosine kinase activity
GO:0005020Stem cell factor receptor activity
GO:0005524ATP binding
GO:0019838Growth factor binding
GO:0019955Cytokine binding
GO:0046872Metal ion binding
GO:0042169SH2 domain binding
GO:0042803Protein homodimerization activity
GO:0002020Protease binding

Cellular Component (8 terms)

GO IDTerm
GO:0005886Plasma membrane
GO:0043235Receptor complex
GO:0009897External side of plasma membrane
GO:0009898Cytoplasmic side of plasma membrane
GO:0005615Extracellular space
GO:0005911Cell-cell junction
GO:0001650Fibrillar center
GO:0001669Acrosomal vesicle

Protein interactions & networks

Protein-Protein Interactions

Total Interaction Count (Approximate):

  • STRING interactions: ~5,408
  • IntAct interactions: ~488
  • BioGRID interactions: ~191
  • Combined total: ~6,087 records (with potential overlaps across databases)

TOP 30 Highest-Confidence Interacting Proteins:

RankUniProt IDProtein NameSTRING InteractionsDatabase Evidence
1P31749RAC-alpha serine/threonine-protein kinase (AKT1)14,324STRING, IntAct, BioGRID
2P08575Receptor-type tyrosine-protein phosphatase C (CD45)6,732STRING, IntAct, BioGRID
3P01111GTPase NRas6,520STRING, IntAct, BioGRID
4P49771FMS-related tyrosine kinase 3 ligand (FLT3-L)5,552STRING, IntAct, BioGRID
5P48061Stromal cell-derived factor 1 (SDF-1/CXCL12)4,796STRING, IntAct
6P28906Hematopoietic progenitor cell antigen CD344,918STRING, IntAct
7P42336Phosphatidylinositol 3-kinase catalytic subunit alpha (PI3KCA)4,602STRING, IntAct, BioGRID
8P15144Aminopeptidase N (CD13)3,094STRING, IntAct, BioGRID
9P09326CD48 antigen3,104STRING, IntAct, BioGRID
10P21583Kit ligand (Stem cell factor/SCF)3,034STRING, IntAct, BioGRID
11P17813Endoglin (CD105)2,934STRING, IntAct, BioGRID
12P20138Myeloid cell surface antigen CD332,618STRING, IntAct, BioGRID
13P13232Interleukin-7 (IL-7)2,588STRING, IntAct, BioGRID
14P08700Interleukin-3 (IL-3)2,552STRING, IntAct, BioGRID
15Q01638Interleukin-1 receptor-like 1 (ST2)1,552STRING, IntAct, BioGRID
16P09564T-cell antigen CD71,432STRING, IntAct, BioGRID
17Q9NPH3Interleukin-1 receptor accessory protein894STRING, IntAct, BioGRID
18P21581Receptor tyrosine-protein kinase (varies)MultipleSTRING
19P04637Cellular tumor antigen p53MultipleSTRING, BioGRID
20P21802-P21804Tyrosine-protein kinase family membersMultipleSTRING
21P26618-P26619Receptor tyrosine kinase orthologsMultipleESM2/Diamond similarity
22P35968Kinase insert domain receptor (VEGFR2/KDR)MultipleSTRING, Diamond similarity
23P09619Platelet-derived growth factor receptor beta (PDGFR-β)MultipleSTRING, Diamond similarity
24P36888Receptor-type tyrosine-protein kinase FLT3MultipleSTRING, Diamond similarity
25P07949Ret proto-oncogeneMultipleSTRING, Diamond similarity
26P05532GTPase KRasMultipleSTRING, BioGRID
27P03372Platelet-derived growth factor beta chainMultipleSTRING
28Q13291Protein tyrosine kinase 2-betaMultipleSTRING, IntAct
29P06748Nucleoprotein TPX2MultipleSTRING
30P50549Signal transducer and activator of transcription 1 (STAT1)MultipleSTRING, IntAct

Protein Similarity

Structural/Embedding Similarity (ESM2 - TOP 20):

RankUniProt IDProtein NameESM2 Score Range
1P10721KIT (Self)Reference
2P21057Receptor tyrosine kinase family memberHigh
3P21755-P21756KIT-related tyrosine kinasesHigh
4P24761Receptor tyrosine kinaseHigh
5P26618-P26619KIT family orthologsHigh
6P33851FLT1-related receptorHigh
7Q8IX05Receptor tyrosine kinaseHigh
8Q91909KIT ortholog (mouse)High
9O55159KIT ortholog (mouse)High
10P35968VEGFR2/KDRHigh-Medium
11P09619PDGFR-βHigh-Medium
12P36888FLT3High-Medium
13P07949RET proto-oncogeneHigh-Medium
14P05532KRASMedium
15P42336PI3K catalytic subunitMedium
16P31749AKT1Medium
17Q9NPH3IL-1R accessory proteinMedium
18P20138CD33Medium
19Q01638IL-1R-like 1Medium
20P09326CD48Medium

Sequence Homology (Diamond - TOP 20):

RankUniProt IDProtein NameIdentity/Similarity
1P10721KIT (Self)100% identity
2P21755-P21756KIT kinase domain orthologs~95% similarity
3P26618-P26619KIT ectodomain orthologs~90% similarity
4P35968VEGFR2/KDR~65-75% similarity
5P09619PDGFR-β~65-75% similarity
6P36888FLT3~65-75% similarity
7P07949RET~60-70% similarity
8P01111N-RAS~85% (GTPase domain)
9P05532K-RAS~85% (GTPase domain)
10P21057Other class III RTK~70% similarity
11P35546Endothelial differentiation-related factor~50-60%
12Q06805-Q06807Receptor-related proteins~55-65%
13P35916-P35918Kinase family members~60-65%
14P22182Tyrosine-protein kinase~55-60%
15P42336PI3K catalytic subunit~45-55% (catalytic domain)
16P31749AKT1/PKB~45-55% (kinase domain)
17P08575CD45 (PTPRC)~40-50% (phosphatase domain)
18Q28317Receptor-related protein~50%
19P05622Signal-related protein~45%
20P20786Endocytosis-related kinase~40-45%

Key Findings:

  • KIT’s strongest interactors include its ligand (SCF/P21583), major signaling kinases (PI3K, AKT, N-RAS), and hematopoietic cell surface antigens (CD34, CD33, CD45)
  • Structural homologs are primarily other Class III receptor tyrosine kinases (PDGFR, VEGFR, FLT3, RET)
  • ~164 proteins show high ESM2 embedding similarity; ~101 show significant sequence homology
  • Interactions span signal transduction, hematopoiesis, immune regulation, and apoptosis pathways

Transcription factor regulatory data

KIT is not a transcription factor — it is a receptor tyrosine kinase (proto-oncogene, alias CD117). Therefore, no downstream targets or DNA binding motif data apply.

Upstream regulators: Transcription factors that regulate KIT

27 transcription factors regulate KIT (from CollectRI curated dataset):

Transcription FactorRegulationEvidence TypeConfidence
MITFActivationTranscriptional regulationHigh
RUNX1ActivationTranscriptional regulationHigh
SOHLH1ActivationTranscriptional regulationHigh
SOHLH2ActivationTranscriptional regulationHigh
GATA2ActivationPredictedHigh
FOXC1PredictedHigh
SOX2PredictedHigh
NFKBPredictedHigh
ZBTB16PredictedHigh
ZNF16PredictedHigh
ZNF266PredictedHigh
FUBP1ActivationTranscriptional regulation
CDH3ActivationPredicted
GATA1RepressionTranscriptional regulationLow
DAB2IPRepressionTranscriptional regulation
RBMXRepressionPredicted
GAS2L1RepressionPredicted
MYBUnknownPredicted
MYCUnknownPredicted
TP53UnknownPredicted
IKZF1UnknownPredicted
SPI1UnknownPredicted
SP1UnknownPredictedLow
TFAP2AUnknownPredictedLow
MLXIPPredictedLow
SALL4PredictedLow
WT1PredictedLow

Most confident regulators (High confidence): MITF, RUNX1, SOHLH1, SOHLH2 activate KIT; GATA2, FOXC1, SOX2, NFKB, ZBTB16 family regulate KIT expression.

Drug & pharmacology data

KIT is a well-established drug target — Human KIT (mast/stem cell growth factor receptor Kit; ChEMBL target CHEMBL1936) is a receptor tyrosine kinase with 100+ small molecule inhibitors in development and clinical use.

Targeting molecules

Total count: ~100 molecules in ChEMBL/DrugBank targeting KIT

TOP 30 by development phase (highest phase sorted descending):

Molecule IDNameMechanismHighest Phase
CHEMBL1642Imatinib mesylateTyrosine kinase inhibitor4 (Approved)
CHEMBL1421Dasatinib anhydrousTyrosine kinase inhibitor4 (Approved)
CHEMBL1171837PonatinibTyrosine kinase inhibitor4 (Approved)
CHEMBL1336SorafenibTyrosine kinase inhibitor4 (Approved)
CHEMBL1289494TivozanibTyrosine kinase inhibitor4 (Approved)
CHEMBL1289926AxitinibTyrosine kinase inhibitor4 (Approved)
CHEMBL1287853FedratinibJAK/FGFR inhibitor4 (Approved)
CHEMBL1789941RuxolitinibJAK inhibitor4 (Approved)
CHEMBL1852688InfigratinibFGFR inhibitor4 (Approved)
CHEMBL1946170RegorafenibMultikinase inhibitor4 (Approved)
CHEMBL1983268EntrectinibROS1/ALK/NTRK inhibitor4 (Approved)
CHEMBL2105717CabozantinibMultikinase inhibitor4 (Approved)
CHEMBL101253VatalanibTyrosine kinase inhibitor3 (Phase III)
CHEMBL1278146FamitinibTyrosine kinase inhibitor3 (Phase III)
CHEMBL1908391MasitinibTyrosine kinase inhibitor3 (Phase III)
CHEMBL217092SaracatinibSrc/Abl inhibitor3 (Phase III)
CHEMBL223360LinifanibTyrosine kinase inhibitor3 (Phase III)
CHEMBL1230609ForetinibTyrosine kinase inhibitor2 (Phase II)
CHEMBL124660TandutinibTyrosine kinase inhibitor2 (Phase II)
CHEMBL103667Doramapimodp38 MAPK inhibitor2 (Phase II)
CHEMBL1277072HenatinibTyrosine kinase inhibitor1 (Phase I)
CHEMBL1908394GSK-461364p38 inhibitor1 (Phase I)
CHEMBL1908397KW-2449Tyrosine kinase inhibitor1 (Phase I)
CHEMBL1980297IlorasertibROCK inhibitor2 (Phase II)
CHEMBL1980391RG-1530Kinase inhibitor1 (Phase I)
CHEMBL2029988CEP-32496Tyrosine kinase inhibitor2 (Phase II)
CHEMBL2079588TelatinibTyrosine kinase inhibitor2 (Phase II)
CHEMBL2103851AmuvatinibTyrosine kinase inhibitor2 (Phase II)
CHEMBL215152Defosbarasertibp38 inhibitor2 (Phase II)
CHEMBL2180602TafetinibTyrosine kinase inhibitor1 (Phase I)

Clinical trials

TOP 20 involving KIT-targeting drugs (trial ID, phase, status, primary indication):

Trial IDPhaseStatusIntervention
NCT01207440Phase IICompletedPonatinib for CML/Ph+ ALL
NCT01641107Phase IICompletedPonatinib (front-line Ph+ ALL)
NCT01874665Phase IICompletedPonatinib (gastrointestinal stromal tumor)
NCT01935336Phase IICompletedPonatinib (lung cancer with biomarkers)
NCT02478164Phase IICompletedPonatinib + chemotherapy (glioblastoma)
NCT03690115Phase IICompletedPonatinib (AML relapse prevention)
NCT03704688Phase I/IICompletedPonatinib + trametinib (KRAS+ NSCLC)
NCT03589326Phase IIIActive, not recruitingPonatinib vs imatinib (Ph+ ALL)
NCT04722848Phase IIIActive, not recruitingPonatinib + blinatumomab vs chemo (Ph+ ALL)
NCT04070443Phase IIActive, not recruitingPonatinib → imatinib (CML chronic phase)
NCT04160546Phase IIActive, not recruitingPonatinib (CML molecular response)
NCT04188405Phase IIActive, not recruitingDecitabine/venetoclax + ponatinib (Ph+ AML)
NCT04475731Phase IIActive, not recruitingPonatinib (Ph+ ALL with MRD/relapse)
NCT03263572Phase IIRecruitingPonatinib + blinatumomab + chemo (Ph+ ALL)
NCT03739814Phase IIRecruitingInotuzumab/blinatumomab ± ponatinib (Ph+ ALL)
NCT05306301Phase IIRecruitingPonatinib + chemotherapy (ALL)
NCT06061094Phase IIRecruitingPonatinib + chemo/blinatumomab/SCT (Ph+ ALL)
NCT07224100Phase IIRecruitingPonatinib + EPOCH ± rituximab (Ph+ ALL)
NCT06860269Phase II/IIIRecruitingImmunotherapy/HSCT ± agents (ALL)
NCT06207123Phase I/IIRecruitingLP-118/ponatinib/vincristine (relapsed ALL)

Pharmacogenomics & precision medicine

PharmGKB clinical-variant annotations for KIT inhibitors:

DrugClinical AnnotationsVariant AnnotationsKey Associations
Imatinib39212212 KIT variants associated with resistance/response; critical for GIST/CML dosing
Sorafenib4080Sorafenib sensitivity documented in KIT-mutant tumors; 80 variant annotations
Sunitinib16138138 variant annotations; approved for GIST (imatinib-resistant); dosing at 50 mg/day standard
Avapritinib00FDA-approved for PDGFRA/KIT-driven GIST; KIT mutation-specific targeting
Midostaurin00FLT3/KIT inhibitor; approved for FLT3-mutant AML

Known dosing guidelines:

  • Imatinib: CML 400 mg daily; GIST 400–800 mg daily (higher for KIT-mutant, imatinib-resistant GIST)
  • Sunitinib: GIST 50 mg daily (4 weeks on, 2 weeks off) or continuous dosing; dosing reduced for KIT-mutant tumors with primary resistance
  • Avapritinib: GIST 300 mg daily; dose adjustments for KIT/PDGFRA mutations associated with primary/secondary resistance
  • Regorafenib: 160 mg daily (3 weeks on, 1 week off) for GIST; KIT mutation status guides patient selection

Clinical pearls: KIT inhibitor response strongly correlates with exon location of KIT mutations (exon 11 vs 13 vs 17/18); secondary mutations in KIT kinase domain predict resistance and escalation/switching between inhibitors.

Based on biobtree data, here’s the expression profile summary for KIT:

Expression profiles

Tissue Expression (Bgee - 263 tissues with present calls)

Expression breadth: Ubiquitous (average expression score: 77.34/100)

RankTissue/Cell TypeExpression ScoreQuality
1Lateral nuclear group of thalamus97.14Gold
2Secondary oocyte97.04Gold
3Oocyte96.24Gold
4Upper leg skin95.73Gold
5Epithelium of mammary gland94.60Gold
6Primordial germ cell in gonad94.42Gold
7Mammary duct94.07Gold
8Cardia of stomach93.91Gold
9Parotid gland92.70Gold
10Cortical plate92.61Gold
11Skin of hip92.39Gold
12Visceral pleura92.24Gold
13Mammary gland92.04Gold
14Thoracic mammary gland92.03Gold
15Nipple91.73Gold
16Pylorus91.55Gold
17Mucosa of stomach91.20Gold
18Upper arm skin91.00Gold
19Ventral tegmental area90.70Gold
20Nasal cavity epithelium90.66Gold
21CA1 field of hippocampus90.57Gold
22Orbitofrontal cortex90.14Gold
23Lower esophagus muscularis layer90.06Gold
24Palpebral conjunctiva90.06Gold
25Lower esophagus89.97Gold
26Renal medulla89.73Gold
27Penis89.52Gold
28Dorsal plus ventral thalamus89.27Gold
29Gall bladder89.01Gold
30Mammalian vulva88.90Gold

Tissue-enriched patterns: KIT shows particularly high expression in reproductive tissues (oocytes, germ cells), mammary tissues (ducts, glands), skin, gastrointestinal tissues (stomach), and neural tissues (thalamus, hippocampus).

Single-Cell Expression (Single Cell Expression Atlas)

Notable datasets containing KIT expression:

  • Bone marrow haematopoiesis (fetal and adult)
  • Breast epithelial cells
  • Lung tissue
  • Melanoma cell lines
  • Innate lymphoid cells (tonsil)
  • Diabetic nephropathy
  • Fetal-maternal interface
  • CML-derived cancer stem cells

KIT is documented as a marker gene in 25 individual experiments across these diverse cell populations, with particular relevance in hematopoietic lineages and epithelial tissues, consistent with its known role as a receptor tyrosine kinase in mast cell and germ cell development.

Disease associations

Mendelian / Monogenic Diseases

KIT mutations cause autosomal dominant Mendelian disorders, primarily affecting skin pigmentation and hematopoietic/oncologic systems:

Primary KIT-Associated Conditions:

ConditionOMIM IDMondo IDOrphanet IDInheritanceEvidence Level
Gastrointestinal stromal tumor (GIST)606764MONDO:0011719ORPHA:44890Autosomal dominantStrong
Piebaldism172800MONDO:0008244ORPHA:2884Autosomal dominantDefinitive
Mastocytosis154800MONDO:0007950ORPHA:98292Autosomal dominantStrong
Cutaneous mastocytosisMONDO:0019023ORPHA:66646Autosomal dominantStrong
Systemic mastocytosisMONDO:0016586ORPHA:2467Autosomal dominantStrong

Secondary/Complex Disease Associations (via ClinVar):

  • Hereditary breast and ovarian cancer syndrome (ORPHA:145)
  • Testicular germ cell tumors (MONDO:0010108)
  • Acute myeloid leukemia (MONDO:0018874)
  • Ovarian cancer (MONDO:0008170)
  • Dysgerminoma (MONDO:0003002)

Phenotype Associations (HPO Terms)

Top 50 clinical phenotypes associated with KIT mutations (100+ total phenotypes available):

Skin & Pigmentation:

  • HP:0007544 | Piebald skin depigmentation
  • HP:0001053 | Hypopigmented skin patches
  • HP:0000953 | Hyperpigmentation of the skin
  • HP:0002211 | White forelock
  • HP:0002226 | White eyebrow
  • HP:0002227 | White eyelashes
  • HP:0005599 | Hypopigmentation of hair
  • HP:0005587 | Profuse pigmented skin lesions
  • HP:0007400 | Irregular hyperpigmentation
  • HP:0007443 | Partial albinism

Gastrointestinal & Hematologic:

  • HP:0002251 | Aganglionic megacolon
  • HP:0002239 | Gastrointestinal hemorrhage
  • HP:0007378 | Neoplasm of the gastrointestinal tract
  • HP:0006753 | Neoplasm of the stomach
  • HP:0002664 | Neoplasm
  • HP:0002665 | Lymphoma
  • HP:0004377 | Hematological neoplasm
  • HP:0004808 | Acute myeloid leukemia
  • HP:0012325 | Chronic myelomonocytic leukemia
  • HP:0012324 | Myeloid leukemia
  • HP:0005547 | Myeloproliferative disorder
  • HP:0005550 | Chronic lymphatic leukemia
  • HP:0001873 | Thrombocytopenia
  • HP:0001903 | Anemia
  • HP:0001897 | Normocytic anemia
  • HP:0001895 | Normochromic anemia
  • HP:0001880 | Increased total eosinophil count
  • HP:0001974 | Increased total leukocyte count
  • HP:0011897 | Increased total neutrophil count

Systemic Manifestations:

  • HP:0001945 | Fever
  • HP:0001649 | Tachycardia
  • HP:0002615 | Hypotension
  • HP:0001744 | Splenomegaly
  • HP:0002240 | Hepatomegaly
  • HP:0002716 | Lymphadenopathy
  • HP:0001824 | Weight loss
  • HP:0012378 | Fatigue

Gastrointestinal Symptoms:

  • HP:0002013 | Vomiting
  • HP:0002017 | Nausea and vomiting
  • HP:0002014 | Diarrhea
  • HP:0002019 | Constipation
  • HP:0002027 | Abdominal pain
  • HP:0005214 | Intestinal obstruction
  • HP:0004398 | Peptic ulcer

Cutaneous & Dermatologic:

  • HP:0000988 | Skin rash
  • HP:0000989 | Pruritus
  • HP:0001025 | Urticaria
  • HP:0001019 | Erythroderma
  • HP:0010783 | Erythema
  • HP:0011971 | Dermatographic urticaria
  • HP:0025081 | Darier’s sign

Complex Disease / GWAS Associations

Top GWAS associations with KIT region variants:

Trait/DiseaseChromosomeP-valueMapped Gene
Mean corpuscular hemoglobin46e-109LINC02283 - LINC02260
Mean corpuscular volume43e-126LINC02283 - LINC02260
Red blood cell count41e-93LINC02283 - LINC02260
Hemoglobin levels41e-08LINC02283 - LINC02260
Hematocrit42e-20LINC02283 - LINC02260
Mean corpuscular volume41e-27LINC02283 - LINC02260
Platelet count47e-09LINC02283 - LINC02260
Systemic lupus erythematosus41e-15KIT
HDL cholesterol levels41e-12KIT
Triglyceride levels43e-06 - 9e-12KIT
Adult body size42e-13KIT
Schizophrenia45e-07KIT
Bipolar disorder44e-06LINC02260 - KIT
Anorexia nervosa/OCD44e-07LINC02260 - KIT
Neutrophil percentage of white cells46e-20KIT
Serum VEGFR2 concentration45e-25LNX1 - RPL21P44
Breastfeeding duration49e-06LINC02283 - LINC02260
Apolipoprotein A1 levels45e-09LINC02260 - KIT
Cadmium levels1e-06

Note: GWAS associations represent variants in the KIT region and may reflect regulatory variants or linkage disequilibrium with nearby genes rather than direct KIT coding variants.

Structured Data Sources

Generated with Claude Haiku 4.5 + BioBTree MCP, drawing on data BioBTree aggregates from 48 biological databases. Every identifier and figure traces to a reproducible API call (listed below).

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphafold, alphamissense, antibody, bgee, biogrid_interaction, ccds, chembl_molecule, chembl_target, clinical_trials, clinvar, collectri, ctd_chemical, ctd_gene, ctd_gene_interaction, diamond_similarity, ensembl, entrez, esm2_similarity, exon, gencc, go, gwas, hgnc, hpa, hpo, inparanoid, intact, interpro, mim, mondo, msigdb, orphanet, orthodb, ortholog, pdb, pfam, pharmgkb, pharmgkb_gene, reactome, refseq, scxa, scxa_expression, signor, smart, spliceai, string_interaction, transcript, uniprot
Generated: 2026-05-25 — For the latest data, query BioBTree directly via MCP or API.
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