FOXA3
protein-codingforkhead box A3, the group of Forkhead boxes
Gene summary
This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. The crystal structure of a similar protein in rat has been resolved. [provided by RefSeq, Jul 2008]
- HNF3G
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FOXA3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004497.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 45 | 2 | 47 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 45 | 4 | 1 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004488.2 | 2 | MANE Select | |
| Ensembl | ENSP00000304004.1 | 2 | MANE Select | |
| Ensembl | ENSP00000470816.1 | 1 | Standard | |
| Ensembl | ENSP00000546823.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| foxa3 | Danio rerio | Structure: goblet cell Quality: disrupted abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Maturity onset diabetes of the young - Homo sapiens (human)
- FOXA1 transcription factor network
- FOXA2 and FOXA3 transcription factor networks
Biological Process
- cellular glucose homeostasis
- chromatin organization
- regulation of transcription by RNA polymerase II
- multicellular organism development
- spermatogenesis
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- transcription factor binding
- protein domain specific binding
- sequence-specific DNA binding
Cellular Component
- nucleus
- nucleoplasm
- actin cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000302177
- Coding exons
- 2
- Length
- 9809
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125748
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.243 | 207 | 217 | 0.954 | 0.0000136 | 2209 |
| Missense (PolyPhen) | 33 | 53.51 | 0.61671 | 515 | ||
| Synonymous | -0.751 | 107 | 97.6 | 1.10 | 0.00000658 | 774 |
| Loss of Function | 2.42 | 1 | 8.68 | 0.115 | 3.71e-7 | 116 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000074 | 0.000070 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor that 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 (By similarity). 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; binds to and activates transcription from the G6PC promoter. Binds to the CYP3A4 promoter and activates its transcription in cooperation with CEBPA. Binds to the CYP3A7 promoter together with members of the CTF/NF-I family. Involved in regulation of neuronal-specific transcription. May be involved in regulation of spermatogenesis. {ECO:0000250, ECO:0000269|PubMed:12695546}.;
Recessive Scores
- pRec
- 0.245
Intolerance Scores
- LoFtool
- 0.0307
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.919
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |