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FOXI1
forkhead box I1
The FOXI1 gene provides instructions for making a protein that acts as a transcription factor, playing a vital role in regulating gene expression critical for the proper development of the inner ear and kidneys. FOXI1, or forkhead box I1, is a gene whose protein product is a transcription factor, meaning it controls when other genes are turned on or off.
FOXI1 is located on the long (q) arm of chromosome 5, at band 5q35.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The FOXI1 gene encodes a protein that belongs to the forkhead family of transcription factors, characterised by a distinct DNA-binding domain. This protein is essential for various developmental processes, particularly in the inner ear, where it influences cell differentiation and ion transport. Defects in the FOXI1 gene can lead to conditions affecting hearing and renal function.
What the gene does
The FOXI1 protein functions as a transcription factor, which means it binds to specific DNA sequences to regulate the activity of other genes. This regulatory role is crucial for embryonic development, especially in the formation of the inner ear structures responsible for hearing and balance, such as the endolymphatic sac epithelium. It is also involved in the development and proper functioning of the kidneys, influencing water and electrolyte balance. By controlling the expression of target genes, FOXI1 directs cellular processes that are fundamental for organogenesis and homeostasis.
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Chromosome location
The FOXI1 gene is situated on the long arm of chromosome 5, specifically at position 5q35.1. This genomic location indicates its precise address within the human genome. The gene spans a region of DNA that contains the instructions for synthesising the FOXI1 protein.
Protein structure
The FOXI1 protein is composed of 378 amino acids. It features a key Fork-head (DNA binding) domain spanning amino acids 123-217, which is responsible for its ability to bind to DNA and regulate gene transcription. Additionally, the protein contains two Disordered (Region) segments: one at the N-terminus from amino acids 1-26, and another longer region from amino acids 208-278, which may contribute to its flexibility and interactions with other proteins.
Key variants
Variations in the FOXI1 gene can alter the protein's structure and function, potentially affecting its role in gene regulation. These changes may include single nucleotide substitutions, small insertions, or deletions that can modify the protein's stability, DNA-binding affinity, or regulatory capacity. The clinical significance of these variants can range from benign to pathogenic, depending on their impact on protein function and the specific effect they have on downstream biological pathways.
Sample of pathogenic variants
1 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.748dup | p.Asp250fs | Pathogenic | ★☆☆☆ | Autosomal recessive nonsyndromic hearing loss 4 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Changes in the FOXI1 gene have been associated with developmental disorders, particularly those affecting the inner ear and kidneys. Dysfunction of the FOXI1 protein can lead to impairments in hearing, linked to its critical role in inner ear development and function. Further research continues to elucidate the full spectrum of conditions associated with FOXI1 variants.
No disease links recorded for this gene in our reference set.
UK clinical status
In the UK, the FOXI1 gene is included on the Monogenic hearing loss panel (R67) within the NHS Genomic Medicine Service, indicated by its green status, affirming its clinical relevance in this context.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the FOXI1 gene?
The FOXI1 gene produces a protein that acts as a transcription factor, controlling the expression of other genes. It is crucial for the proper development of the inner ear and kidneys, influencing cell differentiation and ion transport.
What types of health conditions are associated with FOXI1 gene variations?
Variations in the FOXI1 gene are primarily linked to conditions affecting the inner ear, including monogenic hearing loss, due to its role in the development and function of auditory structures. It may also have implications for kidney function.
Is the FOXI1 gene considered in UK genetic testing?
Yes, the FOXI1 gene is part of the Monogenic hearing loss panel (R67) within the NHS Genomic Medicine Service in the UK, indicating its importance in diagnosing inherited causes of hearing impairment.