KITLG - dismech genes

Normal function · from ai-gene-review (P21583, commit 79fe13b38970) · AI-generated, not KB evidence

KITLG encodes Kit ligand (stem cell factor, SCF; also known as mast cell growth factor/MGF and Steel factor), the sole physiological ligand for the class III receptor tyrosine kinase KIT (CD117). It is a four-helix-bundle cytokine of the SCF family, synthesized as a single-pass type I transmembrane precursor that can either remain membrane-anchored to support juxtacrine signaling or be released as a soluble ectodomain (sKITLG) by regulated proteolytic shedding; alternative splicing of the protease-sensitive exon-6 region tunes the balance between the readily shed (SCF248) and predominantly membrane-bound (SCF220) forms. Biologically active as a non-covalent homodimer, KITLG binds two KIT ectodomains and brings the receptors together, driving KIT dimerization and trans-autophosphorylation and thereby activating PI3K-AKT, RAS-RAF-MAPK, PLCgamma and STAT signaling in the receiving cell. Through this receptor engagement KITLG functions as an essential niche and growth-factor signal controlling the survival, proliferation, migration and differentiation of KIT-expressing cells, including hematopoietic stem and progenitor cells, mast cells, melanocytes and germ cells. It is produced by supporting cells such as bone-marrow stromal and perivascular cells, keratinocytes, endothelial cells and gonadal Sertoli cells. Consistent with these roles, KITLG variants cause familial progressive hyperpigmentation, non-syndromic unilateral or asymmetric deafness and Waardenburg syndrome type 2F, and common variation at the locus underlies normal skin, hair and eye pigmentation variation.

Stem cell factor receptor binding: as a non-covalent homodimer, KITLG binds two molecules of the receptor tyrosine kinase KIT and brings them together, driving KIT dimerization and trans-autophosphorylation to initiate downstream signaling. Acts both as a membrane-anchored (juxtacrine) ligand and as a shed soluble ligand.

molecular function: stem cell factor receptor binding · directly involved in: positive regulation of cell population proliferation · locations: plasma membrane; extracellular region

Cytokine/growth-factor activity: KITLG acts as a hematopoietic cytokine that promotes the survival, proliferation and differentiation of KIT-expressing progenitor cells, augmenting myeloid and lymphoid progenitor proliferation and synergizing with colony-stimulating factors.

molecular function: cytokine activity · directly involved in: positive regulation of hematopoietic progenitor cell differentiation; positive regulation of cell population proliferation · locations: extracellular region; 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
Familial Progressive Hyperpigmentation With Or Without Hypopigmentation	causative germline gain of function	mechanism: KITLG Gain-of-Function Variant in the Receptor-Binding Motif animal model: K14-SCF transgenic mouse
Waardenburg Syndrome Type 2F	causative germline	mechanism: Biallelic KITLG Variants Reducing KIT Ligand Signalling

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
nonsyndromic genetic hearing loss MONDO:0019497	AD	Limited 2018-01-16	no dismech entry

Mechanism modules · computed from kb/

neural_crest_melanocyte_deficiency via Waardenburg Syndrome Type 2F