FOXE3

forkhead box E3, the group of Forkhead boxes

Basic information

Region (hg38): 1:47416285-47418052

Previous symbols: [ "FKHL12" ]

Links

ENSG00000186790 ∙ NCBI:2301 ∙ OMIM:601094 ∙ HGNC:3808 ∙ Uniprot:Q13461 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital primary aphakia (Definitive), mode of inheritance: AR
• aortic aneurysm, familial thoracic 11, susceptibility to (Moderate), mode of inheritance: AD
• congenital primary aphakia (Strong), mode of inheritance: AR
• Peters anomaly (Supportive), mode of inheritance: AD
• congenital primary aphakia (Supportive), mode of inheritance: AR
• anterior segment dysgenesis (Supportive), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
• congenital primary aphakia (Strong), mode of inheritance: AR
• anterior segment dysgenesis 1 (Strong), mode of inheritance: AD
• aortic aneurysm, familial thoracic 11, susceptibility to (Strong), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Moderate), mode of inheritance: AD
• cataract (Definitive), mode of inheritance: AR
• cataract (Definitive), mode of inheritance: AD
• congenital primary aphakia (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aortic aneurysm, familial thoracic 11, susceptibility to; Anterior segment dysgenesis 2	AD/AR	Cardiovascular; Ophthalmologic	Individuals with Anterior segment dysgenesis have been described with glaucoma, and surveillance and early treatment may be beneficial, and agents that may contribute to glaucoma should be avoided; Individuals with Aortic aneurysm, familial thoracic 11 have been described as presenting with acute ascending aortic dissection and dilatation, and awareness may allow surveillance and early medical and surgical management	Cardiovascular; Ophthalmologic	3550563; 11159941; 16826526; 21150893; 26854927; 27218149

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXE3 gene.

• Congenital_primary_aphakia (345 variants)
• Anterior_segment_dysgenesis (333 variants)
• Cardiovascular_phenotype (318 variants)
• not_provided (56 variants)
• FOXE3-related_disorder (24 variants)
• not_specified (17 variants)
• Familial_thoracic_aortic_aneurysm_and_aortic_dissection (9 variants)
• Acute_aortic_dissection (6 variants)
• Congenital_aneurysm_of_ascending_aorta (6 variants)
• Cataract_34_multiple_types (5 variants)
• Aortic_aneurysm,_familial_thoracic_11,_susceptibility_to (5 variants)
• Anterior_segment_dysgenesis_1 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXE3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000012186.3. 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			17	151	2	170
missense	4	11	288	12	1	316
nonsense	4	2	1			7
start loss			7			7
frameshift	10	5	6			21
splice donor/acceptor (+/-2bp)						0
Total	18	18	319	163	3

Highest pathogenic variant AF is 0.0000971385

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXE3	protein_coding	protein_coding	ENST00000335071	1	1980

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.181	0.657	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.568	76	91.3	0.833	0.00000422	1920
Missense in Polyphen		38	55.707	0.68214		640
Synonymous	-0.947	51	43.1	1.18	0.00000204	750
Loss of Function	0.886	1	2.52	0.397	1.07e-7	52

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	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that controls lens epithelial cell growth through regulation of proliferation, apoptosis and cell cycle (PubMed:22527307, PubMed:25504734). During lens development, controls the ratio of the lens fiber cells to the cells of the anterior lens epithelium by regulating the rate of proliferation and differentiation (By similarity). Controls lens vesicle closure and subsequent separation of the lens vesicle from ectoderm (By similarity). Controls the expression of DNAJB1 in a pathway that is crucial for the development of the anterior segment of the eye (PubMed:27218149). {ECO:0000250|UniProtKB:Q9QY14, ECO:0000269|PubMed:22527307, ECO:0000269|PubMed:25504734, ECO:0000269|PubMed:27218149}.
• Disease: DISEASE: Anterior segment dysgenesis 2 (ASGD2) [MIM:610256]: A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. Some ASGD2 patients show congenital primary aphakia, a defect caused by eye development arrest around the 4th-5th week of gestation. This prevents the formation of any lens structure and leads to severe secondary ocular anomalies, including a complete aplasia of the anterior segment of the eye. In contrast, in secondary aphakic eyes, lens induction has occurred, and the lens vesicle has developed to some degree but finally has progressively resorbed perinatally, leading, therefore, to less severe ocular defects. ASGD2 inheritance is autosomal recessive. {ECO:0000269|PubMed:11159941, ECO:0000269|PubMed:11980846, ECO:0000269|PubMed:16826526, ECO:0000269|PubMed:19708017, ECO:0000269|PubMed:25504734}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cataract 34, multiple types (CTRCT34) [MIM:612968]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. {ECO:0000269|PubMed:27218149}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Aortic aneurysm, familial thoracic 11 (AAT11) [MIM:617349]: A form of thoracic aortic aneurysm, a disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. {ECO:0000269|PubMed:26854927}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Haploinsufficiency Scores

• pHI: 0.0749
• ghis: 0.466

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0598

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Foxe3
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); vision/eye phenotype

Zebrafish Information Network

• Gene name: foxe3
• Affected structure: aortic arch
• Phenotype tag: abnormal
• Phenotype quality: incomplete structure

Gene ontology

• Biological process: eye development;lens development in camera-type eye;trabecular meshwork development;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;anatomical structure morphogenesis;cell differentiation;mRNA transcription by RNA polymerase II;negative regulation of apoptotic process;cell development;iris morphogenesis;ciliary body morphogenesis;cornea development in camera-type eye;negative regulation of cell cycle arrest;negative regulation of lens fiber cell differentiation;positive regulation of lens epithelial cell proliferation
• Cellular component: nucleus;transcription factor complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;sequence-specific DNA binding