FOXN1

forkhead box N1, the group of Forkhead boxes

Basic information

Region (hg38): 17:28506243-28538900

Previous symbols: [ "WHN", "RONU" ]

Links

ENSG00000109101 ∙ NCBI:8456 ∙ OMIM:600838 ∙ HGNC:12765 ∙ Uniprot:O15353 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• T-cell immunodeficiency, congenital alopecia, and nail dystrophy (Definitive), mode of inheritance: AR
• T-cell immunodeficiency, congenital alopecia, and nail dystrophy (Supportive), mode of inheritance: AD
• T-cell immunodeficiency, congenital alopecia, and nail dystrophy (Strong), mode of inheritance: AR
• T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant (Strong), mode of inheritance: AD
• T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant (Moderate), mode of inheritance: AD
• T-cell immunodeficiency, congenital alopecia, and nail dystrophy (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
T-cell lymphopenia with or without nail dystrophy, autosomal dominant; T-cell immunodeficiency, congenital alopecia, and nail dystrophy; T-cell immunodeficiency with thymic aplasia	AD/AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported in cell immunodeficiency, congenital alopecia, and nail dystrophy, but has not been described as curative in T-cell lymphopenia with or without nail dystrophy, autosomal dominant; In T-cell immunodeficiency with thymic aplasia, thymus transplantation has been reported as curative	Allergy/Immunology/Infectious; Dermatologic	8911612; 10206641; 15180707; 18339010; 20429426; 20864124; 21507891; 31447097; 31566583

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXN1 gene.

• T-cell_immunodeficiency,_congenital_alopecia,_and_nail_dystrophy (720 variants)
• Inborn_genetic_diseases (92 variants)
• not_provided (56 variants)
• T-cell_lymphopenia,_infantile,_with_or_without_nail_dystrophy,_autosomal_dominant (30 variants)
• FOXN1-related_disorder (20 variants)
• not_specified (16 variants)
• Severe_combined_immunodeficiency_disease (4 variants)
• T-lymphocyte_deficiency (2 variants)
• Autism (1 variants)
• T-CELL_LYMPHOPENIA,_INFANTILE,_WITHOUT_NAIL_DYSTROPHY,_AUTOSOMAL_DOMINANT (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001369369.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	243	5	255
missense	3	5	311	17	1	337
nonsense	10	3				13
start loss						0
frameshift	35	15	6			56
splice donor/acceptor (+/-2bp)		4	2			6
Total	48	27	326	260	6

Highest pathogenic variant AF is 0.00000681554

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXN1	protein_coding	protein_coding	ENST00000226247	8	32654

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.942	0.0579	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.657	350	386	0.906	0.0000228	4147
Missense in Polyphen		63	98.636	0.63871		1218
Synonymous	0.353	172	178	0.966	0.0000121	1400
Loss of Function	3.78	3	22.2	0.135	0.00000104	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000431	0.000431
Ashkenazi Jewish	0.00149	0.00149
East Asian	0.0000544	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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 the onset of differentiation in progenitor TECs in the developing fetus to the final differentiation steps through which TECs mature to acquire their full functionality. Regulates, either directly or indirectly the expression of a variety of genes that mediate diverse aspects of thymus development and function, including MHC Class II, DLL4, CCL25, CTSL, CD40 and PAX1. Regulates the differentiation of the immature TECs into functional cortical TECs (cTECs) and medullary TECs (mTECs). Essential for maintenance of mTECs population in the postnatal thymus. Involved in the morphogenesis and maintenance of the three-dimensional thymic microstructure which is necessary for a fully functional thymus. Plays an important role in the maintenance of hematopoiesis and particularly T lineage progenitors within the bone marrow niche with age. Essential for the vascularization of the thymus anlage. Promotes the terminal differentiation of epithelial cells in the epidermis and hair follicles, partly by negatively regulating the activity of protein kinase C (By similarity). Plays a crucial role in the early prenatal stages of T-cell ontogeny (PubMed:21507891). {ECO:0000250|UniProtKB:Q61575, ECO:0000269|PubMed:21507891}.

Recessive Scores

• pRec: 0.245

Intolerance Scores

• loftool: 0.0592
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.7

Haploinsufficiency Scores

• pHI: 0.487
• hipred: Y
• hipred_score: 0.583
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0312

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Foxn1
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; neoplasm; endocrine/exocrine gland phenotype; pigmentation phenotype; hearing/vestibular/ear phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary 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); normal phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: foxn1
• Affected structure: thymus
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: hair follicle development;T cell lineage commitment;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;defense response;epidermis development;animal organ morphogenesis;keratinocyte differentiation;positive regulation of epithelial cell differentiation;nail development;T cell homeostasis;positive regulation of transcription by RNA polymerase II;blood vessel morphogenesis;epithelial cell proliferation;positive regulation of hair follicle development;lymphoid lineage cell migration into thymus;thymus epithelium morphogenesis;regulation of positive thymic T cell selection
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;sequence-specific DNA binding