KITLG

Chr 12ADAR

KIT ligand

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

NCBI Gene: 4254ENSG00000049130UniProt: P21583

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]

Primary Disease Associations & Inheritance

[Skin/hair/eye pigmentation 7, blond/brown hair]MIM #611664
Deafness, autosomal dominant 69, unilateral or asymmetricMIM #616697
AD
Hyperpigmentation with or without hypopigmentationMIM #145250
AD
Waardenburg syndrome, type 2FMIM #619947
AR
UniProtDeafness, congenital, unilateral or asymmetric
149
ClinVar variants
21
Pathogenic / LP
0.85
pLI score
1
Active trials
Clinical Summary— KITLG
🧬
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.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 71 VUS of 149 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.42LOEUF
pLI 0.850
Z-score 3.11
OE 0.13 (0.05–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.81Z-score
OE missense 0.81 (0.69–0.94)
114 obs / 141.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.05–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.69–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 2 / 15.0Missense obs/exp: 114 / 141.1Syn Z: 0.11

ClinVar Variant Classifications

149 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic4
VUS71
Likely Benign37
Benign18
Conflicting2
17
Pathogenic
4
Likely Pathogenic
71
VUS
37
Likely Benign
18
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
7
9
0
17
Likely Pathogenic
1
2
1
0
4
VUS
9
48
10
4
71
Likely Benign
0
1
21
15
37
Benign
0
2
15
1
18
Conflicting
—2
Total11605620149

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

KITLG-related Waardenburg syndrome

limited
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
KIT LIGAND; KITLG
MIM #184745 · *

[Skin/hair/eye pigmentation 7, blond/brown hair]

MIM #611664

Molecular basis of disorder known

Deafness, autosomal dominant 69, unilateral or asymmetric

MIM #616697

Molecular basis of disorder known

Autosomal dominant

Hyperpigmentation with or without hypopigmentation

MIM #145250

Molecular basis of disorder known

Autosomal dominant

Waardenburg syndrome, type 2F

MIM #619947

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PGR-KITLG signaling drives a tumor-mast cell regulatory feedback to modulate apoptosis of breast cancer cells.
Yang Z et al.·Cancer Lett
2024
Unilateral, bilateral symmetric or asymmetric isolated hearing loss in patients with heterozygous KITLG variants.
Serey-Gaut M et al.·Hum Genet
2025Cohort
Overexpression of KITLG predicts unfavorable clinical outcomes and promotes lymph node metastasis via the JAK/STAT pathway in nasopharyngeal carcinoma.
Ling J et al.·Lab Invest
2022
Genetic association between inflammatory factors and abdominal aortic calcification: Insights from a genome-wide association study.
Li C et al.·Int J Cardiol
2025
Interleukin-30 subverts prostate cancer-endothelium crosstalk by fostering angiogenesis and activating immunoregulatory and oncogenic signaling pathways.
Ciummo SL et al.·J Exp Clin Cancer Res
2023
KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect.
Huang JC et al.·Int J Mol Sci
2022
Predicted plasma proteomics from genetic scores and treatment outcomes in major depression: a meta-analysis.
Oliva V et al.·Eur Neuropsychopharmacol
2025Meta-analysis
Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss.
Vona B et al.·J Eur Acad Dermatol Venereol
2022
De novo mutation in KITLG gene causes a variant of Familial Progressive Hyper- and Hypo-pigmentation (FPHH).
Gorenjak M et al.·Mol Genet Genomic Med
2021
Genome-wide association studies of cancer predisposition.
Stadler ZK et al.·Hematol Oncol Clin North Am
2010Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Lung CancerTKI ResistanceEGFR Sensitive Mutation

A Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations and Failed EGFR TKIs With the Combination of Enrotinib and Paclitaxel Monoclonal Antibody

NOT YET RECRUITING
NCT06048315Phase PHASE3Degan LuStarted 2023-09
AnlotinibPenpulimab

External Resources

Links to major genomics databases and tools