FOXA2

forkhead box A2, the group of Forkhead boxes

Basic information

Region (hg38): 20:22580997-22585455

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 (63 variants)
• Inborn genetic diseases (19 variants)
• not specified (8 variants)
• FOXA2-related condition (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.

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				18	6	24
missense		1	36	5	6	48
nonsense			1			1
start loss						0
frameshift			4			4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	1	41	24	12

Variants in FOXA2

This is a list of pathogenic ClinVar variants found in the FOXA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-22581844-G-A		not specified • FOXA2-related disorder	Likely benign (Jan 01, 2023)
20-22581855-A-G		Inborn genetic diseases	Uncertain significance (Jun 10, 2022)
20-22581870-G-T			Uncertain significance (Jun 04, 2022)
20-22581872-C-T			Uncertain significance (Nov 08, 2022)
20-22581893-T-A			Uncertain significance (Oct 24, 2023)
20-22581905-G-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 23, 2024)
20-22581932-G-A			Uncertain significance (Jul 14, 2022)
20-22581940-C-G			Likely benign (Sep 10, 2022)
20-22581949-G-T			Likely benign (Dec 02, 2021)
20-22581969-G-T		FOXA2-related disorder	Benign (Jan 29, 2024)
20-22581995-T-G		Inborn genetic diseases	Uncertain significance (Jan 22, 2024)
20-22582013-G-A		Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
20-22582036-T-C			Benign (Feb 01, 2024)
20-22582123-T-G			Uncertain significance (Jun 29, 2021)
20-22582124-T-A			Uncertain significance (Feb 04, 2022)
20-22582134-G-T		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
20-22582142-T-G		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
20-22582169-G-T		Inborn genetic diseases	Uncertain significance (Jul 20, 2021)
20-22582189-G-C		FOXA2-related disorder	Likely benign (Apr 05, 2019)
20-22582206-C-G			Uncertain significance (Jun 27, 2022)
20-22582217-G-A			Benign (Mar 27, 2023)
20-22582219-C-G			Likely benign (Oct 13, 2022)
20-22582234-C-T			Likely benign (Nov 25, 2023)
20-22582238-G-C			Uncertain significance (Jan 13, 2024)
20-22582241-G-A		not specified	Conflicting classifications of pathogenicity (Dec 22, 2022)

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
0.742	0.257	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

Haploinsufficiency Scores

• pHI: 0.531
• ghis: 0.550

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

Mouse Genome Informatics

• Gene name: Foxa2
• Phenotype: immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; vision/eye phenotype; reproductive system phenotype; normal 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); 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; neoplasm; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; craniofacial 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; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

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