FOXI3
protein-codingforkhead box I3, the group of Forkhead boxes
Gene summary
Enables DNA-binding transcription factor activity, RNA polymerase II-specific. Involved in pharyngeal system development. Is active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0800085
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0958194
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0958194
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0003780
Submitter: ClinGen
*FOXI3* was first reported in relation to autosomal dominant T-cell immunodeficiency in 2022 (Ghosh et al., PMID: 35987349). T-cell immunodeficiency is a broad classification of disorders that affect the cell-mediated aspects of the immune response, wherein circulating numbers of T lymphocytes are decreased or ineffective. At least 2 variants (nonsense) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in *FOXI3* have been reported in individuals with the following disease entities: T-cell immunodeficiency and Craniofacial microsomia 2. Per criteria outlined by the Clingen Lumping and Splitting Working Group, we found a difference in phenotypic variability. Therefore, the following disease entities have been split into multiple disease entities, T-cell immunodeficiency (MONDO:0003780) and Craniofacial microsomia 2 (MONDO:0958194). The split curation for Craniofacial microsomia 2 will be assessed separately. Variants in this gene have been reported in at least 2 probands in 1 publication (PMID: 35987349). The mechanism for disease is haploinsufficiency (PMID: 35987349). This gene-disease relationship is supported by knockout and variant mouse models presenting with absence or decreased weight of thymus (. PMID: 31600545, PMID: 37041148). In summary, there is limited evidence to support the relationship between *FOXI3* and T-cell immunodeficiency. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen SCID-CID GCEP on the meeting date August 21st 2025 (SOP Version 11).
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Craniofacial
Intervention: Audiologic/Otolaryngologic
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FOXI3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001135649.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 113 | 1 | 115 | ||
| missense | 7 | 209 | 8 | 1 | 225 | |
| nonsense | 5 | 5 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 3 | 20 | 1 | 24 | ||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 10 | 237 | 121 | 3 | 371 |
Highest pathogenic variant AF is 0.000008625101
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001129121.1 | 2 | MANE Select | |
| Ensembl | ENSP00000478384.2 | 2 | MANE Select | |
| Ensembl | ENSP00000814595.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| foxi3b | Danio rerio | Structure: epidermis Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Hair Follicle Development- Induction (Part 1 of 3)
Biological Process
- regulation of transcription by RNA polymerase II
- anatomical structure morphogenesis
- cell differentiation
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- sequence-specific DNA binding
Cellular Component
- nucleus
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Possible transcriptional factor. {ECO:0000250}.;