FOXI1 (forkhead box I1)

Gene

• Entrez ID: 2299
• Gene name: Forkhead box I1
• Gene symbol: FOXI1
• Synonyms (NCBI Gene): FKH10, FKHL10, FREAC-6, FREAC6, HFH-3, HFH3
• Chromosome: 5
• Chromosome location: 5q35.1
• Summary: This gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain. This gene may play an important role in the development of the cochlea and vestibulum, as well as in embryogenesis. The encoded protei

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121909340	G>A	Pathogenic, uncertain-significance	Intron variant, missense variant, downstream transcript variant, coding sequence variant, genic downstream transcript variant
rs121909341	G>A,C	Pathogenic	Intron variant, missense variant, downstream transcript variant, coding sequence variant, genic downstream transcript variant
rs147596900	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Synonymous variant, downstream transcript variant, genic downstream transcript variant, coding sequence variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017392	hsa-miR-335-5p	Microarray	18185580
MIRT1001668	hsa-miR-1184	CLIP-seq
MIRT1001669	hsa-miR-1205	CLIP-seq
MIRT1001670	hsa-miR-1293	CLIP-seq
MIRT1001671	hsa-miR-3158-5p	CLIP-seq
MIRT1001672	hsa-miR-3194-3p	CLIP-seq
MIRT1001673	hsa-miR-342-5p	CLIP-seq
MIRT1001674	hsa-miR-3611	CLIP-seq
MIRT1001675	hsa-miR-4269	CLIP-seq
MIRT1001676	hsa-miR-4483	CLIP-seq
MIRT1001677	hsa-miR-4651	CLIP-seq
MIRT1001678	hsa-miR-4664-5p	CLIP-seq
MIRT1001679	hsa-miR-608	CLIP-seq
MIRT1001680	hsa-miR-758	CLIP-seq
MIRT1001681	hsa-miR-876-3p	CLIP-seq
MIRT1996834	hsa-miR-3680	CLIP-seq
MIRT1996835	hsa-miR-4428	CLIP-seq
MIRT1996836	hsa-miR-4719	CLIP-seq
MIRT1996837	hsa-miR-4798-3p	CLIP-seq
MIRT1996838	hsa-miR-539	CLIP-seq
MIRT1001668	hsa-miR-1184	CLIP-seq
MIRT1001669	hsa-miR-1205	CLIP-seq
MIRT1001671	hsa-miR-3158-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription cis-regulatory region binding	IEA
GO:0000976	Function	Transcription cis-regulatory region binding	ISS
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	19214237
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	19214237
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	19214237
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005634	Component	Nucleus	IC	19214237
GO:0005634	Component	Nucleus	IEA
GO:0005730	Component	Nucleolus	IDA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0008301	Function	DNA binding, bending	NAS	7957066
GO:0009653	Process	Anatomical structure morphogenesis	IBA
GO:0009792	Process	Embryo development ending in birth or egg hatching	NAS	7957066
GO:0030154	Process	Cell differentiation	IBA
GO:0042472	Process	Inner ear morphogenesis	IEA
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0043565	Function	Sequence-specific DNA binding	ISS
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	19214237
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 601093
• HGNC: 3815
• e!Ensembl: ENSG00000168269

Protein

• UniProt ID: Q12951
• Protein name: Forkhead box protein I1 (Forkhead-related protein FKHL10) (Forkhead-related transcription factor 6) (FREAC-6) (Hepatocyte nuclear factor 3 forkhead homolog 3) (HFH-3) (HNF-3/fork-head homolog 3)
• Protein 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 sy
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00250	Forkhead	122 → 208	Forkhead domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in kidney.
• Sequence:

  MSSFDLPAPSPPRCSPQFPSIGQEPPEMNLYYENFFHPQGVPSPQRPSFEGGGEYGATPN
  PYLWFNGPTMTPPPYLPGPNASPFLPQAYGVQRPLLPSVSGLGGSDLGWLPIPSQEELMK
  LVRPPYSYSALIAMAIHGAPDKRLTLSQIYQYVADNFPFYNKSKAGWQNSIRHNLSLNDC
  FKKVPRDEDDPGKGNYWTLDPNCEKMFDNGNFRRKRKRKSDVSSSTASLALEKTESSLPV
  DSPKTTEPQDILDGASPGGTTSSPEKRPSPPPSGAPCLNSFLSSMTAYVSGGSPTSHPLV
  TPGLSPEPSDKTGQNSLTFNSFSPLTNLSNHSGGGDWANPMPTNMLSYGGSVLSQFSPHF
  YNSVNTSGVLYPREGTEV

• Sequence length: 378

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hearing impairment	Likely pathogenic	rs777573595	RCV001375208	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOSOMAL RECESSIVE DISTAL RENAL TUBULAR ACIDOSIS	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal recessive nonsyndromic hearing loss 4	Uncertain significance; Likely benign; Conflicting classifications of pathogenicity; Benign	ClinVar ClinVar, GenCC	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRANIOFACIAL ABNORMALITIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FOXI1-related disorder	Likely benign; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEARING LOSS DISORDER	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUMINAL A BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonsyndromic Hearing Loss, Mixed	Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pendred syndrome	Uncertain significance; Likely benign	ClinVar CTD, ClinVar, Disgenet, HPO, Orphanet CTD, ClinVar, Disgenet, HPO, Orphanet CTD, ClinVar, Disgenet, HPO, Orphanet CTD, ClinVar, Disgenet, HPO, Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PENDREDS SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS OF BILATERAL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TRIPLE-NEGATIVE BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia, Hemolytic, Congenital	Anemia	BEFREE	31600869		★☆☆☆☆ Found in Text Mining only
Autosomal recessive distal renal tubular acidosis	Renal Tubular Acidosis	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma Large Cell	Large cell carcinoma	Pubtator	38168015	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	32299640, 36681680	Associate	★☆☆☆☆ Found in Text Mining only
Chromophobe Renal Cell Carcinoma	Chromophobe Carcinoma	BEFREE	31177114		★☆☆☆☆ Found in Text Mining only
Compensated hypothyroidism	Compensated hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital bilateral aplasia of vas deferens	Congenital bilateral absence of vas deferens	Pubtator	20972246	Associate	★☆☆☆☆ Found in Text Mining only
Congenital sensorineural hearing loss	Congenital Sensorineural Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	28793269		★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic Fibrosis	BEFREE	30069044, 30069046		★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL RECESSIVE (disorder)	Deafness	BEFREE	23824987		★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT	Deafness	GENOMICS_ENGLAND_DG	29242249		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT	Deafness	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT	Deafness	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Distal Renal Tubular Acidosis	Distal Renal Tubular Acidosis	BEFREE	31300090		★☆☆☆☆ Found in Text Mining only
Dystonic Disorders	Dystonia	Pubtator	37182269	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	36499699	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss Sensorineural	Hearing loss	Pubtator	29242249	Associate	★☆☆☆☆ Found in Text Mining only
Hyperparathyroidism	Hyperparathyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Kidney Neoplasms	Kidney neoplasm	Pubtator	36816543	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	28358374		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	28358374		★☆☆☆☆ Found in Text Mining only
Oncocytoma, renal	Oncocytoma of kidney	BEFREE	31177114		★☆☆☆☆ Found in Text Mining only
Pendred syndrome	Pendred Syndrome	Orphanet			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Pendred syndrome	Pendred syndrome	Pubtator	30268946	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Pendred`s syndrome	Pendred Syndrome	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Pendred`s syndrome	Pendred Syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	28793269		★☆☆☆☆ Found in Text Mining only
RENAL TUBULAR ACIDOSIS, DISTAL, AUTOSOMAL RECESSIVE	Renal Tubular Acidosis	ORPHANET_DG	29242249		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Speech Disorders	Speech Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	28358374		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	28358374	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid carcinoma	Thyroid Carcinoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tracheal Stenosis	Tracheal Stenosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Unilateral deafness	Deafness	BEFREE	20621367		★☆☆☆☆ Found in Text Mining only