KIT - dismech genes

Normal function · from ai-gene-review (P10721, commit 79fe13b38970) · AI-generated, not KB evidence

KIT (CD117, SCFR, c-Kit) is a single-pass type I transmembrane class III receptor tyrosine kinase and the cell-surface receptor for stem cell factor (SCF, encoded by KITLG). Its extracellular region comprises five immunoglobulin-like domains (D1-D5) that bind SCF and mediate receptor-receptor contacts; a single transmembrane helix connects to a cytoplasmic juxtamembrane autoinhibitory segment and a split (kinase-insert-interrupted) tyrosine-protein kinase domain (EC 2.7.10.1). Binding of dimeric SCF brings two KIT molecules together and drives receptor homodimerization, relieving juxtamembrane autoinhibition and triggering reciprocal trans-autophosphorylation on cytoplasmic tyrosines. The resulting phosphotyrosines both increase catalytic activity and serve as docking sites that recruit SH2/PTB-domain effectors, activating the RAS-RAF-MEK-ERK (MAPK), PI3K-AKT, PLCgamma-PKC, SRC-family kinase and JAK-STAT pathways to promote cell survival, proliferation, adhesion, and migration. KIT acts principally at the plasma membrane. Signaling is terminated by protein tyrosine phosphatases (SHP-1/PTPN6, SHP-2/PTPN11) and by CBL-mediated ubiquitination followed by receptor internalization and degradation. KIT-SCF signaling is essential for hematopoietic stem/progenitor cells, mast cells, melanocytes, germ cells/gametogenesis, and gastrointestinal interstitial cells of Cajal. Loss-of-function variants cause piebaldism, whereas gain-of-function/constitutively activating mutations (e.g. D816V, juxtamembrane in-frame deletions/duplications) drive gastrointestinal stromal tumors, systemic mastocytosis, and subsets of acute myeloid leukemia and germ-cell tumors.

Cell-surface receptor for stem cell factor (SCF/KITLG). The five Ig-like ectodomains bind dimeric SCF, which brings two KIT molecules together to form the active receptor dimer at the plasma membrane.

molecular function: stem cell factor receptor activity · directly involved in: Kit signaling pathway · locations: plasma membrane · in complex: receptor complex

SCF-induced dimerization relieves juxtamembrane autoinhibition and triggers reciprocal trans-autophosphorylation of the split cytoplasmic tyrosine kinase domain (EC 2.7.10.1); the resulting phosphotyrosines increase catalytic activity and recruit SH2/PTB effectors, initiating MAPK, PI3K-AKT and JAK-STAT signaling.

molecular function: transmembrane receptor protein tyrosine kinase activity · directly involved in: Kit signaling pathway; protein autophosphorylation; cell surface receptor protein tyrosine kinase signaling pathway · locations: plasma membrane

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Malignant Germ Cell Tumor of Ovary	somatic driver somatic	mechanism: KIT and RAS-PI3K Oncogenic Signaling Activation scoped to subtype: Dysgerminoma
Monoclonal Mast Cell Activation Syndrome	somatic driver somatic gain of function	mechanism: Somatic Activating KIT Mutation in a Small Mast Cell Clone
Piebaldism	causative
Yolk Sac Tumor	somatic driver somatic	scoped to subtype: Ovarian YST
Acute Myeloid Leukemia, Core Binding Factor	untyped Cooperating Mutation
Central Nervous System Germ Cell Tumor	untyped Recurrent germinoma-enriched somatic mutation somatic	mechanism: Recurrent KIT-RAS Signaling Alterations
Gastrointestinal Stromal Tumor	untyped Somatic Activating Mutations
Maculopapular Cutaneous Mastocytosis	untyped Somatic Driver Mutation	mechanism: Constitutive KIT Activation in Skin Mast Cells
Mixed Germ Cell Tumor	untyped Activating mutations in ~18-25% of cases, chiefly seminomatous components
Sinonasal Undifferentiated Carcinoma	untyped Co-occurring somatic activating mutation
Systemic Mastocytosis	untyped Somatic Driver Mutation	mechanism: Constitutive KIT D816V Signaling
Testicular Germ Cell Tumor	untyped Activating mutations in ~18-25% of TGCTs, primarily seminomas
Testicular Seminoma	untyped Activating mutations and focal amplification; mutations enriched in seminoma
Thymic Carcinoma	untyped Recurrent somatic oncogenic activation	mechanism: Receptor tyrosine kinase pathway activation

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
gastrointestinal stromal tumor MONDO:0011719	AD	Definitive 2020-01-14	Gastrointestinal Stromal Tumor untyped

Mechanism modules · computed from kb/

sustaining_proliferative_signaling via Malignant Germ Cell Tumor of Ovary