KLF4

Chr 9

KLF transcription factor 4

Also known as: EZF, GKLF

NCBI Gene: 9314ENSG00000136826UniProt: O43474OMIM: 602253

KLF4 encodes a zinc finger transcription factor that regulates embryonic development, maintains stem cell pluripotency, and is required for establishing the skin barrier function and ocular surface development. Mutations cause autosomal dominant epithelial dysplasia and genitourinary malformations, affecting epithelial tissues, kidneys, and genitourinary structures. This gene is highly constrained against loss-of-function variants (pLI = 0.997), indicating that heterozygous loss-of-function mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.17
Clinical Summary— KLF4
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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.17LOEUF
pLI 0.997
Z-score 3.84
OE 0.00 (0.00–0.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.10Z-score
OE missense 0.98 (0.89–1.09)
275 obs / 279.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.17)
0≤0.351.4
Missense OE0.98 (0.89–1.09)
0≤0.61.4
Synonymous OE1.27
0≤1.21.6
LoF obs/exp: 0 / 17.2Missense obs/exp: 275 / 279.7Syn Z: -2.43
DN
0.3793th %ile
GOF
0.3094th %ile
LOF
0.86top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

KLF4 · 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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients