FOXA1

forkhead box A1, the group of Forkhead boxes

Basic information

Region (hg38): 14:37589552-37596059

Previous symbols: [ "HNF3A" ]

Links

ENSG00000129514 ∙ NCBI:3169 ∙ OMIM:602294 ∙ HGNC:5021 ∙ Uniprot:P55317 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXA1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXA1 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				1	2	3
missense			35	1		36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	35	2	2

Variants in FOXA1

This is a list of pathogenic ClinVar variants found in the FOXA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-37591369-G-C		not specified	Uncertain significance (Mar 06, 2025)
14-37591373-T-C		not specified	Uncertain significance (Dec 20, 2023)
14-37591423-G-A		not specified	Uncertain significance (Nov 07, 2022)
14-37591452-C-T			Benign (Mar 13, 2018)
14-37591563-G-A			Benign (Jun 20, 2018)
14-37591593-G-T		not specified	Uncertain significance (Feb 14, 2023)
14-37591708-G-A		not specified	Uncertain significance (Sep 25, 2023)
14-37591718-T-A		not specified	Likely benign (Feb 16, 2023)
14-37591724-A-G		not specified	Uncertain significance (Mar 04, 2025)
14-37591804-C-A		not specified	Uncertain significance (Jan 17, 2025)
14-37591804-C-T		not specified	Uncertain significance (Aug 01, 2024)
14-37591805-C-A		not specified	Uncertain significance (Nov 26, 2024)
14-37591808-G-A		not specified	Uncertain significance (Jun 18, 2021)
14-37591820-C-T		not specified	Uncertain significance (Aug 10, 2021)
14-37591822-T-A		not specified	Uncertain significance (May 26, 2024)
14-37591826-G-T		not specified	Uncertain significance (Dec 07, 2024)
14-37591841-C-T		not specified	Uncertain significance (Feb 03, 2022)
14-37591849-C-G		not specified	Uncertain significance (Jul 09, 2021)
14-37591854-A-C		not specified	Uncertain significance (Jul 26, 2024)
14-37591859-G-A		not specified	Uncertain significance (Jul 20, 2021)
14-37591896-G-T		not specified	Uncertain significance (Mar 20, 2024)
14-37591928-C-A		not specified	Uncertain significance (Feb 01, 2025)
14-37591930-C-T		not specified	Uncertain significance (Sep 26, 2023)
14-37591933-C-G		not specified	Uncertain significance (Feb 12, 2025)
14-37591966-C-T		not specified	Uncertain significance (Jan 07, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXA1	protein_coding	protein_coding	ENST00000250448	2	10057

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.222	0.770	125724	0	7	125731	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.439	243	263	0.924	0.0000122	3040
Missense in Polyphen		59	86.317	0.68353		1020
Synonymous	-1.01	130	116	1.12	0.00000584	974
Loss of Function	2.31	3	11.5	0.262	4.92e-7	134

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000115	0.0000924
European (Non-Finnish)	0.0000353	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). Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Its differential recruitment to chromatin is dependent on distribution of histone H3 methylated at 'Lys-5' (H3K4me2) in estrogen-regulated genes. Involved in the development of multiple endoderm-derived organ systems such as liver, pancreas, lung and prostate; FOXA1 and FOXA2 seem to have at least in part redundant roles (By similarity). Modulates the transcriptional activity of nuclear hormone receptors. Is involved in ESR1-mediated transcription; required for ESR1 binding to the NKX2-1 promoter in breast cancer cells; binds to the RPRM promoter and is required for the estrogen-induced repression of RPRM. Involved in regulation of apoptosis by inhibiting the expression of BCL2. Involved in cell cycle regulation by activating expression of CDKN1B, alone or in conjunction with BRCA1. 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. {ECO:0000250, ECO:0000269|PubMed:16087863, ECO:0000269|PubMed:16331276, ECO:0000269|PubMed:18358809, ECO:0000269|PubMed:19127412, ECO:0000269|PubMed:19917725}.
• Pathway: Androgen Receptor Network in Prostate Cancer;Endoderm Differentiation;Mesodermal Commitment Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Signal Transduction;AndrogenReceptor;FOXA1 transcription factor network;Signaling by Nuclear Receptors;Direct p53 effectors;Estrogen-dependent gene expression;ESR-mediated signaling;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.432

Intolerance Scores

• loftool: 0.0959
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.14

Haploinsufficiency Scores

• pHI: 0.812

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: Foxa1
• 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; 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); neoplasm; immune system phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: foxa1
• Affected structure: goblet cell
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin remodeling;regulation of transcription by RNA polymerase II;Notch signaling pathway;anatomical structure morphogenesis;negative regulation of epithelial to mesenchymal transition;dorsal/ventral neural tube patterning;cell differentiation;response to estradiol;positive regulation of intracellular estrogen receptor signaling pathway;hormone metabolic process;glucose homeostasis;positive regulation of apoptotic process;positive regulation of neuron differentiation;positive regulation of smoothened signaling pathway;positive regulation of mitotic cell cycle;positive regulation of transcription by RNA polymerase II;anatomical structure formation involved in morphogenesis;neuron fate specification;positive regulation of DNA-binding transcription factor activity;epithelial tube branching involved in lung morphogenesis;lung epithelial cell differentiation;secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development;epithelial-mesenchymal signaling involved in prostate gland development;prostate gland epithelium morphogenesis;prostate gland stromal morphogenesis;epithelial cell maturation involved in prostate gland development;alveolar secondary septum development;dopaminergic neuron differentiation;respiratory basal cell differentiation;positive regulation of cell-cell adhesion mediated by cadherin
• Cellular component: fibrillar center;nucleus;nucleoplasm;microvillus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;protein domain specific binding;sequence-specific DNA binding;transcription regulatory region DNA binding