FOXI1

forkhead box I1, the group of Forkhead boxes

Basic information

Region (hg38): 5:170105896-170109734

Previous symbols: [ "FKHL10" ]

Links

ENSG00000168269 ∙ NCBI:2299 ∙ OMIM:601093 ∙ HGNC:3815 ∙ Uniprot:Q12951 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 4 (Strong), mode of inheritance: AR
• Pendred syndrome (Supportive), mode of inheritance: AR
• autosomal recessive distal renal tubular acidosis (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 4 (Limited), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 4 (Limited), mode of inheritance: Unknown
• hearing loss disorder (Limited), mode of inheritance: AR
• enlarged vestibular aqueduct syndrome (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 4, with enlarged vestibular aqueduct	AR	Audiologic/Otolaryngologic; Endocrine	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Pendred syndrome, awareness of the potential for thyroid abnormalities may be beneficial to allow early detection and appropriate management	Audiologic/Otolaryngologic; Endocrine	17503324
Digenic inheritance (with SLC26A4) has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXI1 gene.

• not provided (90 variants)
• Autosomal recessive nonsyndromic hearing loss 4 (52 variants)
• Pendred syndrome;Autosomal recessive nonsyndromic hearing loss 4 (9 variants)
• Inborn genetic diseases (9 variants)
• not specified (7 variants)
• Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome (2 variants)
• Hearing impairment (2 variants)
• Nonsyndromic Hearing Loss, Mixed (2 variants)
• Pendred syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXI1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	20	3	25
missense		1	56	2		59
nonsense			1			1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			14	6	6	26
Total	0	1	74	28	9

Highest pathogenic variant AF is 0.000112

Variants in FOXI1

This is a list of pathogenic ClinVar variants found in the FOXI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-170105940-G-A		Autosomal recessive nonsyndromic hearing loss 4 • Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome	Uncertain significance (May 23, 2022)
5-170105965-C-T		not specified	Uncertain significance (Jan 23, 2024)
5-170105966-C-A			Likely benign (Mar 04, 2022)
5-170105968-T-A			Uncertain significance (Feb 24, 2022)
5-170105987-C-T		Autosomal recessive nonsyndromic hearing loss 4 • FOXI1-related disorder	Conflicting classifications of pathogenicity (Jan 25, 2024)
5-170106000-A-C		not specified	Uncertain significance (Aug 12, 2021)
5-170106020-C-T		Autosomal recessive nonsyndromic hearing loss 4	Uncertain significance (Jan 12, 2018)
5-170106029-G-T			Uncertain significance (Jul 05, 2022)
5-170106034-C-A		not specified	Uncertain significance (Sep 29, 2023)
5-170106034-C-G			Uncertain significance (Feb 09, 2022)
5-170106035-C-T		FOXI1-related disorder	Likely benign (May 23, 2023)
5-170106037-A-C		Autosomal recessive nonsyndromic hearing loss 4	Uncertain significance (Jun 21, 2021)
5-170106049-A-G		Hearing impairment	Likely pathogenic (Apr 12, 2021)
5-170106088-C-T		FOXI1-related disorder	Likely benign (Jan 18, 2024)
5-170106098-C-G			Likely benign (Nov 27, 2021)
5-170106100-C-T			Uncertain significance (Apr 02, 2021)
5-170106116-C-T			Uncertain significance (May 25, 2022)
5-170106118-A-G		Autosomal recessive nonsyndromic hearing loss 4	Uncertain significance (Jan 12, 2018)
5-170106134-C-G			Likely benign (Apr 08, 2022)
5-170106157-G-A			Uncertain significance (Dec 23, 2021)
5-170106158-G-A			Likely benign (May 12, 2022)
5-170106159-C-T			Uncertain significance (Oct 13, 2023)
5-170106182-C-T			Likely benign (Nov 16, 2023)
5-170106188-C-G		Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome	Likely benign (Aug 04, 2023)
5-170106189-G-A			Uncertain significance (Jan 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXI1	protein_coding	protein_coding	ENST00000306268	2	3827

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.773	0.226	125738	0	2	125740	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.728	201	232	0.866	0.0000144	2449
Missense in Polyphen		51	82.107	0.62114		876
Synonymous	0.0661	106	107	0.992	0.00000787	757
Loss of Function	2.51	1	9.25	0.108	3.97e-7	117

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator required for the development of normal hearing, sense of balance and kidney function. Required for the expression of SLC26A4/PDS, JAG1 and COCH in a subset of epithelial cells and the development of the endolymphatic system in the inner ear. Also required for the expression of SLC4A1/AE1, SLC4A9/AE4, ATP6V1B1 and the differentiation of intercalated cells in the epithelium of distal renal tubules (By similarity). {ECO:0000250}.

Recessive Scores

• pRec: 0.200

Intolerance Scores

• loftool: 0.0345
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24.33

Haploinsufficiency Scores

• pHI: 0.210
• hipred: N
• hipred_score: 0.292
• ghis: 0.447

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.650

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Foxi1
• Phenotype: craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: foxi1
• Affected structure: radial glial cell
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;anatomical structure morphogenesis;embryo development ending in birth or egg hatching;cell differentiation;inner ear morphogenesis;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleolus;intracellular membrane-bounded organelle
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;DNA binding, bending;sequence-specific DNA binding;transcription regulatory region DNA binding