KITLG

Chr 12ADAR

KIT ligand

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

This gene encodes the ligand of the tyrosine-kinase receptor encoded by the KIT locus. This ligand is a pleiotropic factor that acts in utero in germ cell and neural cell development, and hematopoiesis, all believed to reflect a role in cell migration. In adults, it functions pleiotropically, while mostly noted for its continued requirement in hematopoiesis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
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 OE?0.13 (0.050.42)
00.351.4
Missense OE?0.81 (0.690.94)
00.61.4
Synonymous OE?0.98
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

This gene — mechanism propensity

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 hyperpigmentation1

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

References

  1. 1.PMID 19375057

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.