FOXK2

Chr 17

forkhead box K2

Also known as: ILF, ILF-1, ILF1, nGTBP

The protein functions as a transcriptional regulator that binds to specific DNA sequences and controls glucose metabolism, aerobic glycolysis, autophagy, and WNT/beta-catenin signaling pathways. Based on the provided information, no specific diseases or inheritance patterns associated with FOXK2 mutations are documented, and the low pLI score (0.025) suggests the gene is relatively tolerant to loss-of-function variants.

Summary from RefSeq, UniProt
0
Active trials
21
Pubs (1 yr)
22
P/LP submissions
0%
P/LP missense
0.58
LOEUF
DN
Mechanism· predicted
Clinical SummaryFOXK2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 142 VUS of 231 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.025
Z-score 3.05
OE 0.31 (0.170.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.40Z-score
OE missense 0.94 (0.861.03)
364 obs / 385.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.170.58)
00.351.4
Missense OE0.94 (0.861.03)
00.61.4
Synonymous OE1.25
01.21.6
LoF obs/exp: 7 / 22.7Missense obs/exp: 364 / 385.9Syn Z: -2.65
DN
0.7130th %ile
GOF
0.5465th %ile
LOF
0.49top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.

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

ClinVar Variant Classifications

231 submitted variants in ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic4
VUS142
Likely Benign21
Benign14
18
Pathogenic
4
Likely Pathogenic
142
VUS
21
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
4
0
4
VUS
0
116
26
0
142
Likely Benign
2
6
5
8
21
Benign
1
2
3
8
14
Total31245616199

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

View in ClinVar →

Protein Context — Lollipop Plot

FOXK2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗