FOXA2
forkhead box A2, the group of Forkhead boxes
Basic information
Region (hg38): 20:22580998-22585455
Previous symbols: [ "HNF3B" ]
Links
Phenotypes
GenCC
Source:
- 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
- not_provided (84 variants)
- Inborn_genetic_diseases (61 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 26 | 30 | ||||
| missense | 79 | 15 | 101 | |||
| nonsense | 5 | |||||
| start loss | 0 | |||||
| frameshift | 6 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 2 | 89 | 41 | 10 |
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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
- hipred
- hipred_score
- 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