FOXK1

Chr 7

forkhead box K1

Also known as: FOXK1L

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).

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.40
Clinical SummaryFOXK1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 104 VUS of 163 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.805
Z-score 3.67
OE 0.17 (0.090.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.49Z-score
OE missense 0.66 (0.600.73)
288 obs / 434.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.090.40)
00.351.4
Missense OE0.66 (0.600.73)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 4 / 23.0Missense obs/exp: 288 / 434.3Syn Z: -0.39
DN
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.

ClinVar Variant Classifications

163 submitted variants in ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic1
VUS104
Likely Benign7
Benign6
Conflicting1
33
Pathogenic
1
Likely Pathogenic
104
VUS
7
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
1
0
1
VUS
0
91
13
0
104
Likely Benign
0
4
0
3
7
Benign
0
1
1
4
6
Conflicting
1
Total096487152

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

View in ClinVar →

Protein Context — Lollipop Plot

FOXK1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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