FOXK1

Chr 7

forkhead box K1

Also known as: FOXK1L

NCBI Gene: 221937 ENSG00000164916 UniProt: P85037 OMIM: 616302

FOXK1 encodes a forkhead transcription factor that regulates glucose metabolism, autophagy, and muscle cell differentiation by binding to specific DNA sequences and either activating or repressing target genes. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and variable features including seizures and muscular abnormalities. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants (pLI=0.81, LOEUF=0.40).

OMIM ResearchSummary from RefSeq, UniProt

Enables 14-3-3 protein binding activity; DNA-binding transcription repressor activity, RNA polymerase II-specific; and transcription cis-regulatory region binding activity. Involved in several processes, including intracellular glucose homeostasis; negative regulation of autophagy; and regulation of DNA-templated transcription. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.40

Clinical Summary— FOXK1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.805

Z-score 3.67

OE 0.17 (0.09–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.49Z-score

OE missense 0.66 (0.60–0.73)

288 obs / 434.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.09–0.40)

0≤0.351.4

Missense OE?0.66 (0.60–0.73)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 4 / 23.0Missense obs/exp: 288 / 434.3Syn Z: -0.39

This gene — mechanism propensity

0.5082th %ile

GOF

0.4085th %ile

LOF

0.74top 10%

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

LOFprediction above median · LOEUF 0.40

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