FOXN1 (forkhead box N1)

Gene

• Entrez ID: 8456
• Gene name: Forkhead box N1
• Gene symbol: FOXN1
• Synonyms (NCBI Gene): FKHL20, RONU, TIDAND, TLIND, WHN
• Chromosome: 17
• Chromosome location: 17q11.2
• Summary: Mutations in the winged-helix transcription factor gene at the nude locus in mice and rats produce the pleiotropic phenotype of hairlessness and athymia, resulting in a severely compromised immune system. This gene is orthologous to the mouse and rat gene

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs34814444	T>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Genic downstream transcript variant, downstream transcript variant, coding sequence variant, intron variant, missense variant
rs104894562	C>T	Pathogenic	Stop gained, coding sequence variant
rs797046135	C>T	Likely-pathogenic	Genic upstream transcript variant, missense variant, upstream transcript variant, coding sequence variant, intron variant
rs886043619	TGTCCGCCCCCTGGGCTGTCCGGCTCAGGCC>-	Likely-pathogenic	Frameshift variant, coding sequence variant, intron variant
rs1064793129	CCCCCTGGGCTGTCCG>-	Likely-pathogenic, pathogenic, uncertain-significance	Frameshift variant, coding sequence variant, intron variant
rs1064795660	GT>AG	Likely-pathogenic	Splice donor variant
rs1064796115	G>-	Pathogenic, uncertain-significance	Frameshift variant, coding sequence variant
rs1288977950	C>T	Pathogenic	Missense variant, coding sequence variant
rs1438890364	C>G,T	Pathogenic	Stop gained, intron variant, missense variant, coding sequence variant
rs1555609768	G>T	Likely-pathogenic	Splice donor variant
rs1567886959	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant, intron variant
rs1567887558	GGGCC>CCA	Pathogenic	Frameshift variant, coding sequence variant, intron variant, 3 prime UTR variant
rs1597552140	A>-	Pathogenic	Frameshift variant, coding sequence variant, intron variant, genic upstream transcript variant, upstream transcript variant
rs1597558200	->TA	Pathogenic	Frameshift variant, coding sequence variant
rs1597566356	->ACCC	Pathogenic	Frameshift variant, coding sequence variant
rs1597566413	C>A	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs1597566699	->A	Pathogenic	Frameshift variant, coding sequence variant
rs1597566726	GAAGAGGAAAGATCC>-	Pathogenic	Coding sequence variant, inframe indel
rs1597567985	TCCTGGACCC>-	Uncertain-significance, pathogenic	Frameshift variant, coding sequence variant, intron variant
rs1597568117	C>-	Pathogenic	Frameshift variant, coding sequence variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT438125	hsa-miR-18b-5p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	24383669
MIRT438125	hsa-miR-18b-5p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	24383669
MIRT438123	hsa-miR-518b	Flow, Luciferase reporter assay, qRT-PCR, Western blot	24383669
MIRT438123	hsa-miR-518b	Flow, Luciferase reporter assay, qRT-PCR, Western blot	24383669
MIRT438125	hsa-miR-18b-5p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	24383669
MIRT438125	hsa-miR-18b-5p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	24383669
MIRT438123	hsa-miR-518b	Flow, Luciferase reporter assay, qRT-PCR, Western blot	24383669
MIRT438123	hsa-miR-518b	Flow, Luciferase reporter assay, qRT-PCR, Western blot	24383669
MIRT1997211	hsa-miR-1306	CLIP-seq
MIRT1997212	hsa-miR-3189-5p	CLIP-seq
MIRT1997213	hsa-miR-3677-5p	CLIP-seq
MIRT1997214	hsa-miR-4460	CLIP-seq
MIRT1997215	hsa-miR-4727-3p	CLIP-seq
MIRT1997216	hsa-miR-4758-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription cis-regulatory region binding	IBA
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	IEA
GO:0001942	Process	Hair follicle development	IEA
GO:0002260	Process	Lymphocyte homeostasis	IEA
GO:0002360	Process	T cell lineage commitment	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	TAS	10767081
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	TAS	10767081
GO:0006952	Process	Defense response	TAS	7969402
GO:0008544	Process	Epidermis development	IEA
GO:0008544	Process	Epidermis development	TAS	10767081
GO:0009887	Process	Animal organ morphogenesis	TAS	7969402
GO:0010468	Process	Regulation of gene expression	IEA
GO:0030097	Process	Hemopoiesis	IEA
GO:0030154	Process	Cell differentiation	IEA
GO:0030216	Process	Keratinocyte differentiation	IEA
GO:0030216	Process	Keratinocyte differentiation	IEA
GO:0030858	Process	Positive regulation of epithelial cell differentiation	IDA	24383669
GO:0033081	Process	Regulation of T cell differentiation in thymus	IEA
GO:0035878	Process	Nail development	IEA
GO:0043029	Process	T cell homeostasis	IEA
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0048514	Process	Blood vessel morphogenesis	IEA
GO:0048538	Process	Thymus development	IEA
GO:0048538	Process	Thymus development	IEA
GO:0051798	Process	Positive regulation of hair follicle development	IEA
GO:0097535	Process	Lymphoid lineage cell migration into thymus	IEA
GO:0097536	Process	Thymus epithelium morphogenesis	IEA
GO:1902232	Process	Regulation of positive thymic T cell selection	IEA

Other IDs

• MIM: 600838
• HGNC: 12765
• e!Ensembl: ENSG00000109101

Protein

• UniProt ID: O15353
• Protein name: Forkhead box protein N1 (Winged-helix transcription factor nude)
• Protein function: Transcriptional regulator which regulates the development, differentiation, and function of thymic epithelial cells (TECs) both in the prenatal and postnatal thymus. Acts as a master regulator of the TECs lineage development and is required from
• PDB: 5OCN, 6EL8
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00250	Forkhead	270 → 357	Forkhead domain	Domain

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

  MVSLPPPQSDVTLPGPTRLEGERQGDLMQAPGLPGSPAPQSKHAGFSCSSFVSDGPPERT
  PSLPPHSPRIASPGPEQVQGHCPAGPGPGPFRLSPSDKYPGFGFEEAAASSPGRFLKGSH
  APFHPYKRPFHEDVFPEAETTLALKGHSFKTPGPLEAFEEIPVDVAEAEAFLPGFSAEAW
  CNGLPYPSQEHGPQVLGSEVKVKPPVLESGAGMFCYQPPLQHMYCSSQPPFHQYSPGGGS
  YPIPYLGSSHYQYQRMAPQASTDGHQPLFPKPIYSYSILIFMALKNSKTGSLPVSEIYNF
  MTEHFPYFKTAPDGWKNSVRHNLSLNKCFEKVENKSGSSSRKGCLWALNPAKIDKMQEEL
  QKWKRKDPIAVRKSMAKPEELDSLIGDKREKLGSPLLGCPPPGLSGSGPIRPLAPPAGLS
  PPLHSLHPAPGPIPGKNPLQDLLMGHTPSCYGQTYLHLSPGLAPPGPPQPLFPQPDGHLE
  LRAQPGTPQDSPLPAHTPPSHSAKLLAEPSPARTMHDTLLPDGDLGTDLDAINPSLTDFD
  FQGNLWEQLKDDSLALDPLVLVTSSPTSSSMPPPQPPPHCFPPGPCLTETGSGAGDLAAP
  GSGGSGALGDLHLTTLYSAFMELEPTPPTAPAGPSVYLSPSSKPVALA

• Sequence length: 648

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
Severe combined immunodeficiency disease	Pathogenic	rs1223585973, rs104894562, rs2508427451	RCV005239597 RCV004799737 RCV004587812	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
T-cell immunodeficiency, congenital alopecia, and nail dystrophy	Pathogenic; Likely pathogenic	rs2151499042, rs2151498964, rs2151491863, rs2151492087, rs2151498933, rs2151499024, rs2151487481, rs545707585, rs2151490072, rs2151497970, rs2151499311, rs771407322, rs2508431005, rs762643472, rs1223585973, rs2508429713, rs104894562, rs2508348872, rs2508346463, rs2508429181, rs2508348438, rs2508354964, rs2508423710, rs2508427515, rs2508426674, rs2508347728, rs1064796227, rs1057524466, rs1064796115, rs1064795660, rs1064793129, rs1567887558, rs1161194345, rs1597558200, rs1406320425, rs1597566470, rs1597566699, rs1597567692, rs1597567985, rs1438890364, rs1288977950, rs1597552140, rs1597566356, rs1597566726, rs1597568117, rs2069719445, rs2069729948, rs2070018439, rs745708044, rs1169577591, rs2070011218	RCV004774422 RCV001378326 RCV001383306 RCV001389564 RCV001387604 RCV001859402 RCV001824253 RCV001865072 RCV001938176 RCV001941989 RCV001951067 RCV001972744 RCV002745540 RCV002834975 RCV003017934 RCV003000196 RCV003029583 RCV000009300 RCV003510612 RCV003510608 RCV003510889 RCV003509455 RCV003619918 RCV003620780 RCV003620843 RCV003620872 RCV003620998 RCV003621391 RCV004772907 RCV004772933 RCV002526627 RCV000555732 RCV001046946 RCV000699596 RCV000768224 RCV000821088 RCV000798236 RCV000813095 RCV000792460 RCV000810199 RCV000824264 RCV000818184 RCV001027390 RCV001027392 RCV001078466 RCV001078467 RCV004773238 RCV001059519 RCV001041286 RCV001068832 RCV001038501 RCV001078468 RCV001228694	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant	Pathogenic; Likely pathogenic	rs2151499042, rs2151499024, rs2508429713, rs104894562, rs1064796115, rs1064793129, rs1064796227, rs1161194345, rs1597566699, rs1597567985, rs1288977950, rs1597568117, rs1169577591	RCV001678593 RCV001564041 RCV003138449 RCV001027389 RCV001027399 RCV001027396 RCV005055361 RCV003227853 RCV005021193 RCV001027398 RCV004761884 RCV001027397 RCV003147589	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
T-CELL LYMPHOPENIA, INFANTILE, WITHOUT NAIL DYSTROPHY, AUTOSOMAL DOMINANT	Pathogenic	rs1288977950	RCV001027391	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
T-lymphocyte deficiency	Pathogenic	rs1597566356, rs1597566726	RCV001027393 RCV001027394	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Autism	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED IMMUNODEFICIENCY DUE TO FOXN1 HAPLOINSUFFICIENCY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISORDER OF PHARYNX	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FOXN1-related disorder	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE COMBINED IMMUNODEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE COMBINED IMMUNODEFICIENCY DUE TO FOXN1 DEFICIENCY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alopecia	Alopecia	BEFREE	10483588, 15180707, 25774666, 29672877		★☆☆☆☆ Found in Text Mining only
Alopecia	Alopecia	LHGDN	15180707		★☆☆☆☆ Found in Text Mining only
Alopecia	Alopecia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Alopecia universalis	Alopecia	BEFREE	22590644		★☆☆☆☆ Found in Text Mining only
Alopecia universalis	Alopecia universalis	Pubtator	22590644	Associate	★☆☆☆☆ Found in Text Mining only
Anencephaly	Anencephaly	BEFREE	18339010		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	26352270		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	30755392	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	28662289	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	39628682	Stimulate	★☆☆☆☆ Found in Text Mining only
CHARGE Syndrome	CHARGE Syndrome	BEFREE	29353058		★☆☆☆☆ Found in Text Mining only
Congenital absence of thymus	Aplasia of the thymus	BEFREE	10483588, 25774666, 31447097		★☆☆☆☆ Found in Text Mining only
Congenital absence of thymus	Aplasia of the thymus	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Congenital alopecia totalis	Congenital alopecia totalis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of thymus	Congenital Hypoplasia Of Thymus	BEFREE	28819138, 31566583		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	30755392	Associate	★☆☆☆☆ Found in Text Mining only
DiGeorge Syndrome	DiGeorge Syndrome	BEFREE	28819138, 31566583, 31600545		★☆☆☆☆ Found in Text Mining only
Ductal Carcinoma	Ductal Carcinoma	BEFREE	17465194		★☆☆☆☆ Found in Text Mining only
Dystrophia unguium	Nail dystrophy	BEFREE	20429426, 25774666, 31447097		★☆☆☆☆ Found in Text Mining only
Dystrophia unguium	Nail dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Eosinophilia, Tropical	Eosinophilia	BEFREE	28754914		★☆☆☆☆ Found in Text Mining only
Epithelioma	Epithelioma	BEFREE	10483588, 28606930		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	26671631		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	26671631		★☆☆☆☆ Found in Text Mining only
Hepatitis B	Hepatitis b	Pubtator	28662289	Associate	★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	29620247		★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune system disease	Pubtator	30755392	Associate	★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Keratosis Seborrheic	Seborrheic keratosis	Pubtator	28410231	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, T-Cell	T-cell leukemia	BEFREE	30256907		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	28662289		★☆☆☆☆ Found in Text Mining only
Lymphopenia	Lymphopenia	BEFREE	31447097		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of skin	Skin cancer	BEFREE	19729838		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24432845, 28006926, 28740671, 29725441		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	17465194		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10483588, 17465194, 19729838, 28740671, 29725441		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	18339010		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	29725441		★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	BEFREE	30256907		★☆☆☆☆ Found in Text Mining only
Relative macrocephaly	Macrocephaly	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Seborrheic keratosis	Seborrheic keratosis	BEFREE	19729838		★☆☆☆☆ Found in Text Mining only
Severe Combined Immunodeficiency	Severe combined immunodeficiency disease	BEFREE	15180707, 18339010, 20429426, 20864124, 21507891, 28077132, 31151968, 31566583		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency	Severe combined immunodeficiency disease	LHGDN	15180707		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency	Severe combined immunodeficiency	Pubtator	31151968, 33464451, 35303369	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe combined immunodeficiency due to FOXN1 deficiency	Severe combined immunodeficiency disease	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe T-cell immunodeficiency	Immunodeficiency	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Severe T-cell immunodeficiency	Immunodeficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Shprintzen-Goldberg syndrome	Shprintzen-Goldberg Syndrome	BEFREE	31600545		★☆☆☆☆ Found in Text Mining only
Spina Bifida	Spina Bifida	BEFREE	18339010		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	19729838, 21070984		★☆☆☆☆ Found in Text Mining only
T-cell immunodeficiency, congenital alopecia and nail dystrophy	T-Cell Immunodeficiency, Congenital Alopecia And Nail Dystrophy	ORPHANET_DG	10206641		★☆☆☆☆ Found in Text Mining only
T-cell immunodeficiency, congenital alopecia and nail dystrophy	T-Cell Immunodeficiency, Congenital Alopecia And Nail Dystrophy	CLINVAR_DG	10206641, 15180707		★☆☆☆☆ Found in Text Mining only
T-cell immunodeficiency, congenital alopecia and nail dystrophy	T-Cell Immunodeficiency, Congenital Alopecia And Nail Dystrophy	GENOMICS_ENGLAND_DG	11159512, 8911612		★☆☆☆☆ Found in Text Mining only
T-cell immunodeficiency, congenital alopecia and nail dystrophy	T-Cell Immunodeficiency, Congenital Alopecia And Nail Dystrophy	BEFREE	24432845		★☆☆☆☆ Found in Text Mining only
T-cell immunodeficiency, congenital alopecia and nail dystrophy	T-Cell Immunodeficiency, Congenital Alopecia And Nail Dystrophy	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Thymoma	Thymoma	BEFREE	10483588, 21070984, 28740671		★☆☆☆☆ Found in Text Mining only
Thymoma	Thymoma	LHGDN	17592270		★☆☆☆☆ Found in Text Mining only