FOXA2

forkhead box A2, the group of Forkhead boxes

Basic information

Region (hg38): 20:22580998-22585455

Previous symbols: [ "HNF3B" ]

Links

ENSG00000125798 ∙ NCBI:3170 ∙ OMIM:600288 ∙ HGNC:5022 ∙ Uniprot:Q9Y261 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined pituitary hormone deficiencies, genetic form (Supportive), mode of inheritance: AD
• combined pituitary hormone deficiencies, genetic form (Moderate), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXA2 gene.

• not_provided (97 variants)
• Inborn_genetic_diseases (69 variants)
• FOXA2-related_disorder (10 variants)
• not_specified (7 variants)
• Non-acquired_combined_pituitary_hormone_deficiency (1 variants)
• Congenital_syndromic_hypopituitarism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXA2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021784.5. 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				28	4	32
missense		1	92	17	6	116
nonsense		1	5			6
start loss						0
frameshift			7			7
splice donor/acceptor (+/-2bp)						0
Total	0	2	104	45	10

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXA2	protein_coding	protein_coding	ENST00000419308	2	4451

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125701	0	4	125705	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.378	248	265	0.935	0.0000120	3000
Missense in Polyphen		75	111.36	0.67351		1280
Synonymous	-1.80	143	118	1.21	0.00000575	922
Loss of Function	2.86	2	13.2	0.151	5.70e-7	141

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)	0.0000387	0.0000352
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 is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; FOXA1 and FOXA2 seem to have at least in part redundant roles. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis. Involved in regulation of fat metabolism. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation. {ECO:0000250}.
• Pathway: Longevity regulating pathway - multiple species - Homo sapiens (human);Maturity onset diabetes of the young - Homo sapiens (human);Heart Development;Cardiac Progenitor Differentiation;Endoderm Differentiation;Dopaminergic Neurogenesis;Mesodermal Commitment Pathway;Ectoderm Differentiation;Liver steatosis AOP;FOXA1 transcription factor network;FOXA2 and FOXA3 transcription factor networks;Hedgehog signaling events mediated by Gli proteins (Consensus)

Recessive Scores

• pRec: 0.659

Intolerance Scores

• loftool: 0.0183
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: foxa2
• Affected structure: exocrine pancreas
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: positive regulation of transcription from RNA polymerase II promoter by glucose;cell fate specification;chromatin organization;regulation of transcription by RNA polymerase II;adult locomotory behavior;anatomical structure morphogenesis;negative regulation of epithelial to mesenchymal transition;cell differentiation;regulation of blood coagulation;endocrine pancreas development;negative regulation of glucokinase activity;positive regulation of embryonic development;negative regulation of DNA-binding transcription factor activity;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of insulin secretion involved in cellular response to glucose stimulus;negative regulation of transcription from RNA polymerase II promoter by glucose;response to interleukin-6;dopaminergic neuron differentiation;primitive streak formation;positive regulation of cell-cell adhesion mediated by cadherin;positive regulation of gastrulation;negative regulation of detection of glucose
• Cellular component: nucleus;nucleoplasm;cytoplasm;cell junction
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription factor binding;protein domain specific binding;transcription regulatory region DNA binding