FOXE1

forkhead box E1, the group of Forkhead boxes

Basic information

Region (hg38): 9:97853226-97856717

Previous symbols: [ "FKHL15", "TITF2", "FOXE2" ]

Links

ENSG00000178919 ∙ NCBI:2304 ∙ OMIM:602617 ∙ HGNC:3806 ∙ Uniprot:O00358 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bamforth-Lazarus syndrome (Definitive), mode of inheritance: AR
• Bamforth-Lazarus syndrome (Moderate), mode of inheritance: AR
• Bamforth-Lazarus syndrome (Limited), mode of inheritance: AR
• Bamforth-Lazarus syndrome (Supportive), mode of inheritance: AR
• Bamforth-Lazarus syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thyroid cancer, nonmedullary 4; Hypothyroidism, thyroidal, with spiky hair and cleft palate (Bamforth-Lazarus syndrome)	AD/AR	Endocrine; Oncologic	For Thyroid cancer, nonmedullary 4, individuals have been described as being susceptible to nonmedullary thyroid cancer, and awareness may allow early surveillance, diagnosis, and management; For Hypothyroidism, thyroidal, with spiky hair and cleft palate (Bamforth-Lazarus syndrome), the condition may be clinically recognizable, but recognition and prompt treatment of hypothyroidism can be beneficial	Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Oncologic	2918525; 8320710; 9697705; 12165566; 16882747; 17717707; 17318017; 19779022; 20484477; 20453517; 20094846; 21981779; 21311165; 25381600

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXE1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXE1 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				6	7	13
missense			20		1	21
nonsense			1			1
start loss						0
frameshift						0
inframe indel			1	3	2	6
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					10	10
Total	0	0	22	9	20

Variants in FOXE1

This is a list of pathogenic ClinVar variants found in the FOXE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-97853271-A-G			Benign (Nov 11, 2018)
9-97853378-G-C			Benign (Nov 11, 2018)
9-97853632-A-G			Benign (Nov 11, 2018)
9-97853667-C-A			Benign (Nov 11, 2018)
9-97853759-T-C			Benign (Nov 11, 2018)
9-97853784-G-C			Benign (Nov 11, 2018)
9-97853927-A-G		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
9-97853988-C-A		Inborn genetic diseases	Uncertain significance (Oct 03, 2024)
9-97854027-G-A		Inborn genetic diseases	Uncertain significance (Nov 30, 2021)
9-97854032-G-A		Inborn genetic diseases	Uncertain significance (May 04, 2023)
9-97854054-G-GC		Bamforth-Lazarus syndrome	Pathogenic (Jan 30, 2023)
9-97854065-C-G		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
9-97854084-G-A		Bamforth-Lazarus syndrome	Pathogenic (Mar 01, 2011)
9-97854108-C-T		Bamforth-Lazarus syndrome	Pathogenic (Mar 01, 2011)
9-97854140-C-G		not specified	Uncertain significance (Sep 23, 2024)
9-97854167-G-T		Bamforth-Lazarus syndrome	Uncertain significance (Dec 27, 2021)
9-97854193-C-T			Likely benign (Nov 01, 2022)
9-97854199-A-G		not specified • Bamforth-Lazarus syndrome	Benign/Likely benign (Dec 01, 2023)
9-97854218-C-T		Bamforth-Lazarus syndrome	Pathogenic (Mar 01, 2011)
9-97854240-A-T		congenital hypothyreodism	Likely pathogenic (Jun 03, 2024)
9-97854260-C-A		Thyroid cancer, nonmedullary, 4	Likely pathogenic (Sep 22, 2024)
9-97854267-C-T		Bamforth-Lazarus syndrome	Uncertain significance (Feb 03, 2021)
9-97854301-T-C		not specified • Bamforth-Lazarus syndrome	Benign (Nov 11, 2018)
9-97854375-T-C		Inborn genetic diseases	Uncertain significance (May 05, 2023)
9-97854385-C-T			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXE1	protein_coding	protein_coding	ENST00000375123	1	3451

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.792	0.203	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.315	149	160	0.930	0.00000739	2256
Missense in Polyphen		55	63.26	0.86943		738
Synonymous	0.328	70	73.6	0.951	0.00000363	840
Loss of Function	2.11	0	5.20	0.00	2.21e-7	84

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 binds consensus sites on a variety of gene promoters and activate their transcription. Involved in proper palate formation, most probably through the expression of MSX1 and TGFB3 genes which are direct targets of this transcription factor. Also implicated in thyroid gland morphogenesis. May indirectly play a role in cell growth and migration through the regulation of WNT5A expression. {ECO:0000269|PubMed:12165566, ECO:0000269|PubMed:16882747, ECO:0000269|PubMed:20094846, ECO:0000269|PubMed:20484477, ECO:0000269|PubMed:21177256, ECO:0000269|PubMed:24219130, ECO:0000269|PubMed:25381600, ECO:0000269|PubMed:9697705}.
• Disease: DISEASE: Bamforth-Lazarus syndrome (BLS) [MIM:241850]: A disease characterized by thyroid agenesis, cleft palate and choanal atresia. {ECO:0000269|PubMed:12165566, ECO:0000269|PubMed:21177256, ECO:0000269|PubMed:24219130, ECO:0000269|PubMed:9697705}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Thyroid cancer, non-medullary, 4 (NMTC4) [MIM:616534]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269|PubMed:25381600}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.106

Haploinsufficiency Scores

• ghis: 0.654

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.325

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Foxe1
• Phenotype: endocrine/exocrine gland 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; craniofacial phenotype; homeostasis/metabolism 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); digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: foxe1
• Affected structure: ceratobranchial cartilage
• Phenotype tag: abnormal
• Phenotype quality: deformed

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription by RNA polymerase II;thyroid hormone generation;anatomical structure morphogenesis;cell migration;cell differentiation;thyroid gland development;hair follicle morphogenesis;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;thymus development;embryonic organ morphogenesis;hard palate development;soft palate development;pharynx development;cranial skeletal system development
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;sequence-specific DNA binding