KITLG

Chr 12ADAR

KIT ligand

Also known as: DCUA, DFNA69, FPH2, FPHH, KL-1, Kitl, MGF, SCF

This gene encodes KIT ligand (also called stem cell factor), which binds to the KIT receptor and regulates cell survival, proliferation, hematopoiesis, stem cell maintenance, gametogenesis, and melanogenesis. Mutations cause piebaldism, characterized by congenital patches of depigmented skin and white hair, with autosomal dominant inheritance. The gene is highly constrained against loss-of-function mutations, indicating that complete loss of function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismAD/ARLOEUF 0.424 OMIM phenotypes
Clinical SummaryKITLG
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.850
Z-score 3.11
OE 0.13 (0.050.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.81Z-score
OE missense 0.81 (0.690.94)
114 obs / 141.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.050.42)
00.351.4
Missense OE0.81 (0.690.94)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 2 / 15.0Missense obs/exp: 114 / 141.1Syn Z: 0.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedKITLG-related Waardenburg syndromeDNAD
DN
0.4189th %ile
GOF
0.6053th %ile
LOF
0.52top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOF1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

GOFGain-of-function mutation of KIT ligand on melanin synthesis causes familial progressive hyperpigmentationPMID:19375057

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KITLG · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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