FOXI1

Chr 5AR

forkhead box I1

Also known as: FKH10, FKHL10, FREAC-6, FREAC6, HFH-3, HFH3

NCBI Gene: 2299ENSG00000168269UniProt: Q12951OMIM: 601093

FOXI1 encodes a forkhead transcription factor that activates expression of ion transporters and pumps essential for inner ear endolymphatic development and kidney intercalated cell differentiation. Mutations cause autosomal recessive deafness-4, affecting hearing and balance, and the gene shows high constraint against loss-of-function variants (pLI 0.77, LOEUF 0.51). FOXI1 is also required for normal kidney function through regulation of distal tubule epithelial cell development.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 0.511 OMIM phenotype
Clinical Summary— FOXI1
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Gene-Disease Validity (ClinGen)
enlarged vestibular aqueduct syndrome · ARDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
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ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 75 VUS of 151 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — FOXI1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.773
Z-score 2.51
OE 0.11 (0.04–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.73Z-score
OE missense 0.87 (0.77–0.97)
201 obs / 232.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.04–0.51)
0≤0.351.4
Missense OE0.87 (0.77–0.97)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 1 / 9.2Missense obs/exp: 201 / 232.2Syn Z: 0.07
DN
0.4884th %ile
GOF
0.3491th %ile
LOF
0.73top 10%

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

LOFprediction above median

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

ClinVar Variant Classifications

151 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic2
VUS75
Likely Benign31
Benign11
Conflicting16
16
Pathogenic
2
Likely Pathogenic
75
VUS
31
Likely Benign
11
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
1
1
0
2
VUS
1
56
16
2
75
Likely Benign
0
2
8
21
31
Benign
0
0
8
3
11
Conflicting
—16
Total1594926151

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

View in ClinVar →

Protein Context — Lollipop Plot

FOXI1 · 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

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
Foxi1 regulates multiple steps of mucociliary development and ionocyte specification through transcriptional and epigenetic mechanisms
Bowden S et al.·bioRxiv
2024Functional
Kidney intercalated cells and the transcription factor FOXi1 drive cystogenesis in tuberous sclerosis complex
Barone S et al.·Proc Natl Acad Sci U S A
2021
Identifying key genes associated with recurrence in non-small cell lung cancer through TCGA and single-cell analysis
Li W et al.·Front Med (Lausanne)
2025
FOXI1 inhibits gastric cancer cell proliferation by activating miR-590/ATF3 axis via integrating ChIP-seq and RNA-seq data.
Sun R et al.·Prog Biophys Mol Biol
2021
FOXI1 expression in chromophobe renal cell carcinoma and renal oncocytoma: a study of The Cancer Genome Atlas transcriptome-based outlier mining and immunohistochemistry.
Tong K et al.·Virchows Arch
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
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