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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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FOXI3
forkhead box I3
Chromosome 2 Β· 2p11.2
NCBI Gene: 344167Ensembl: ENSG00000214336.5HGNC: HGNC:35123UniProt: A8MTJ6
12PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
pharyngeal system developmentDNA-binding transcription factor activity, RNA polymerase II-specificnucleusRNA polymerase II cis-regulatory region sequence-specific DNA bindingcraniofacial microsomia 2Abnormality of the earcraniofacial microsomiatooth agenesis
✦AI Summary

FOXI3 encodes a forkhead family transcription factor essential for pharyngeal arch development and craniofacial morphogenesis 1. The protein functions as a pioneer transcription factor regulating multiple developmental processes including otic placode formation, hair follicle stem cell specification, and pharyngeal pouch development 23. FOXI3 is required for pre-placodal ectoderm to respond to inductive signals and form the inner ear, with loss-of-function resulting in absence of otic placodes and associated structures 2. In hair development, FOXI3 controls stem cell specification and activation, with deficiency leading to impaired follicle downgrowth and progressive hair loss 3. The protein genetically interacts with TBX1 in pharyngeal pouch endoderm development, regulating thymus and parathyroid gland formation 4. Pathogenic FOXI3 variants cause craniofacial microsomia and oculo-auriculo-vertebral spectrum disorders, characterized by ear dysplasia, microtia, mandibular hypoplasia, and facial asymmetry 156. These conditions show autosomal dominant inheritance with reduced penetrance or autosomal recessive patterns 1. FOXI3 variants represent the second most frequent genetic cause of craniofacial microsomia, accounting for approximately 1% of all cases and 13% of familial cases 5.

Sources cited
1
FOXI3 is a transcription factor required for pharyngeal arch development and pathogenic variants cause craniofacial microsomia with autosomal dominant inheritance and reduced penetrance
PMID: 37041148
2
FOXI3 is necessary for otic placode development and pre-placodal ectoderm response to inductive signals
PMID: 26550799
3
FOXI3 regulates hair follicle stem cell specification and activation, with deficiency causing impaired hair development
PMID: 26992132
4
FOXI3 genetically interacts with TBX1 in pharyngeal pouch endoderm development for thymus and parathyroid gland formation
PMID: 31412026
5
FOXI3 variants cause microtia and craniofacial microsomia, representing the second most frequent genetic cause accounting for 1% of all cases
PMID: 36260083
6
FOXI3 variants cause oculo-auriculo-vertebral spectrum disorders with importance of nuclear localization signal integrity
PMID: 40128339
Disease Associationsβ“˜21
craniofacial microsomia 2Open Targets
0.53Moderate
Abnormality of the earOpen Targets
0.46Moderate
craniofacial microsomiaOpen Targets
0.41Moderate
tooth agenesisOpen Targets
0.38Weak
neurodegenerative diseaseOpen Targets
0.35Weak
genetic disorderOpen Targets
0.19Weak
Aplasia/Hypoplasia of the thymusOpen Targets
0.18Weak
pulmonary vascular congestionOpen Targets
0.16Weak
hair colorOpen Targets
0.14Weak
response to stimulusOpen Targets
0.10Weak
basal cell carcinomaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.05Suggestive
Branchio-otic syndromeOpen Targets
0.05Suggestive
Thickened earlobes - conductive deafnessOpen Targets
0.05Suggestive
thickened earlobes-conductive deafness syndromeOpen Targets
0.05Suggestive
auriculocondylar syndromeOpen Targets
0.05Suggestive
oculoauriculovertebral spectrum with radial defectsOpen Targets
0.04Suggestive
microtiaOpen Targets
0.04Suggestive
branchiootic syndromeOpen Targets
0.04Suggestive
branchiogenic deafness syndromeOpen Targets
0.04Suggestive
Craniofacial microsomia 2UniProt
Pathogenic Variants8
NM_001135649.3(FOXI3):c.706C>T (p.Arg236Trp)Likely pathogenic
Craniofacial microsomia 2|Craniofacial microsomia 1|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 236
NM_001135649.3(FOXI3):c.596T>G (p.Leu199Arg)Likely pathogenic
Craniofacial microsomia 2
β˜…β˜†β˜†β˜†2024β†’ Residue 199
NM_001135649.3(FOXI3):c.308del (p.Gly103fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 103
NM_001135649.3(FOXI3):c.702C>A (p.Phe234Leu)Pathogenic
Craniofacial microsomia 2|Craniofacial microsomia
β˜†β˜†β˜†β˜†2023β†’ Residue 234
NM_001135649.3(FOXI3):c.700T>G (p.Phe234Val)Pathogenic
Craniofacial microsomia|Craniofacial microsomia 2
β˜†β˜†β˜†β˜†2023β†’ Residue 234
NM_001135649.3(FOXI3):c.703C>T (p.Arg235Cys)Likely pathogenic
Craniofacial microsomia 1
β˜†β˜†β˜†β˜†2022β†’ Residue 235
NM_001135649.3(FOXI3):c.305T>A (p.Phe102Tyr)Likely pathogenic
Craniofacial microsomia
β˜†β˜†β˜†β˜†β†’ Residue 102
NM_001135649.3(FOXI3):c.673T>C (p.Cys225Arg)Likely pathogenic
Craniofacial microsomia
β˜†β˜†β˜†β˜†β†’ Residue 225
View on ClinVar β†—
Related Genes
FOXL3Shared pathway33%FOXD4L5Shared pathway33%FOXD4L6Shared pathway33%FOXB2Shared pathway33%FOXI2Shared pathway33%FOXD4L4Shared pathway33%
Tissue Expression6 tissues
Brain
100%
Lung
22%
Liver
15%
Ovary
15%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
FOXI3FOXL3FOXD4L5FOXD4L6FOXB2FOXI2FOXD4L4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt A8MTJ6
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.73LoF Tolerant
pLIβ“˜
0.65Intermediate
Observed/Expected LoF0.32 [0.16–0.73]
RankingsWhere FOXI3 stands among ~20K protein-coding genes
  • #16,451of 20,598
    Most Researched12
  • #3,142of 5,498
    Most Pathogenic Variants8
  • #5,685of 17,882
    Most Constrained (LOEUF)0.73
Genes detectedFOXI3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
FOXI3 pathogenic variants cause one form of craniofacial microsomia.
PMID: 37041148
Nat Commun Β· 2023
1.00
2
Thymic inborn errors of immunity.
PMID: 39428079
J Allergy Clin Immunol Β· 2025
0.90
3
Foxi3
PMID: 37543988
Dev Dyn Β· 2023
0.80
4
Novel variants in FOXI3 gene confirm its implication in Oculo-Auriculo-Vertebral spectrum.
PMID: 40128339
Eur J Hum Genet Β· 2025
0.70
5
Foxi3 Deficiency Compromises Hair Follicle Stem Cell Specification and Activation.
PMID: 26992132
Stem Cells Β· 2016
0.60