FOXO1

forkhead box O1, the group of Forkhead boxes

Basic information

Region (hg38): 13:40555666-40666641

Previous symbols: [ "FKHR", "FOXO1A" ]

Links

ENSG00000150907 ∙ NCBI:2308 ∙ OMIM:136533 ∙ HGNC:3819 ∙ Uniprot:Q12778 ∙ 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 FOXO1 gene.

• Inborn genetic diseases (25 variants)
• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXO1 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				3	2	5
missense			24	1		25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	24	4	3

Variants in FOXO1

This is a list of pathogenic ClinVar variants found in the FOXO1 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-40557795-C-T			Benign (Oct 29, 2020)
13-40559613-A-T		not specified	Uncertain significance (Mar 27, 2023)
13-40559710-T-C		not specified	Uncertain significance (Oct 20, 2023)
13-40559734-C-T		not specified	Uncertain significance (Nov 17, 2022)
13-40559783-T-C		not specified	Uncertain significance (Jul 20, 2022)
13-40559867-T-C		not specified	Likely benign (Dec 11, 2023)
13-40559912-G-A		not specified	Uncertain significance (Jun 29, 2023)
13-40559917-G-C		not specified	Uncertain significance (Jan 07, 2022)
13-40559954-G-A		not specified	Uncertain significance (Jun 02, 2023)
13-40559974-G-A		not specified	Uncertain significance (Sep 17, 2021)
13-40559985-C-T		FOXO1-related disorder	Benign (Dec 31, 2019)
13-40560005-C-T		not specified	Uncertain significance (Jan 27, 2022)
13-40560023-G-A		not specified	Uncertain significance (Jan 04, 2022)
13-40560077-G-A		not specified	Uncertain significance (May 11, 2022)
13-40560133-C-T		not specified	Likely benign (Aug 15, 2023)
13-40560145-T-C		not specified	Uncertain significance (May 17, 2023)
13-40560310-G-A		not specified	Uncertain significance (Jan 09, 2024)
13-40560394-C-T		not specified	Uncertain significance (Dec 19, 2023)
13-40560395-T-C		not specified	Uncertain significance (Aug 22, 2023)
13-40560425-C-T		not specified	Uncertain significance (Feb 06, 2024)
13-40560492-G-A			Benign/Likely benign (Nov 01, 2023)
13-40560526-C-G		not specified	Uncertain significance (Aug 02, 2022)
13-40560570-A-G			Benign (Dec 31, 2019)
13-40560727-G-A		not specified	Uncertain significance (Feb 22, 2023)
13-40665731-C-T		Malignant lymphoma, large B-cell, diffuse	Pathogenic (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXO1	protein_coding	protein_coding	ENST00000379561	2	110931

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00275	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.71	221	305	0.725	0.0000167	4301
Missense in Polyphen		82	148.53	0.55208		1864
Synonymous	-0.624	126	117	1.07	0.00000685	1327
Loss of Function	3.86	0	17.3	0.00	9.88e-7	210

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)	0.00	0.00
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 the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'- TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity. Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP. In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC and PCK1. Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1. Promotes neural cell death. Mediates insulin action on adipose tissue. Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake. Regulates the transcriptional activity of GADD45A and repair of nitric oxide- damaged DNA in beta-cells. Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner. Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). {ECO:0000250|UniProtKB:G3V7R4, ECO:0000250|UniProtKB:Q9R1E0, ECO:0000269|PubMed:10358076, ECO:0000269|PubMed:12228231, ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:15890677, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:19221179, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:21245099}.
• Disease: DISEASE: Rhabdomyosarcoma 2 (RMS2) [MIM:268220]: A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas. Note=The gene represented in this entry may be involved in disease pathogenesis. Chromosomal aberrations involving FOXO1 are found in rhabdomyosarcoma. Translocation (2;13)(q35;q14) with PAX3 and translocation t(1;13)(p36;q14) with PAX7. The resulting protein is a transcriptional activator.
• Pathway: Insulin resistance - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);IGF-Core;Androgen receptor signaling pathway;Energy Metabolism;Integrated Breast Cancer Pathway;Leptin signaling pathway;Follicle Stimulating Hormone (FSH) signaling pathway;Signaling Pathways in Glioblastoma;White fat cell differentiation;B Cell Receptor Signaling Pathway;AGE-RAGE pathway;Adipogenesis;JAK-STAT;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Vitamin D Receptor Pathway;Nuclear Receptors Meta-Pathway;Copper homeostasis;Melatonin metabolism and effects;Rac1-Pak1-p38-MMP-2 pathway;Transcription factor regulation in adipogenesis;NAD metabolism, sirtuins and aging;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;BMP2-WNT4-FOXO1 Pathway in Human Primary Endometrial Stromal Cell Differentiation;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;miRNA regulation of prostate cancer signaling pathways;Liver steatosis AOP;Interleukin-4 and 13 signaling;White fat cell differentiation;Somatroph axis (GH) and its relationship to dietary restriction and aging;EGF-EGFR Signaling Pathway;Insulin Signaling;ErbB Signaling Pathway;Developmental Biology;Disease;Signal Transduction;akt signaling pathway;MAPK6/MAPK4 signaling;AKT phosphorylates targets in the nucleus;insulin Mam;BCR;TGF_beta_Receptor;EGFR1;CXCR4-mediated signaling events;MAPK family signaling cascades;PIP3 activates AKT signaling;IL3;Angiopoietin receptor Tie2-mediated signaling;Leptin;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;IL6;TNFalpha;IL-7;Intracellular signaling by second messengers;Diseases of signal transduction;Regulation of beta-cell development;Regulation of Androgen receptor activity;Signaling events mediated by HDAC Class III;FoxO family signaling;Class I PI3K signaling events mediated by Akt;Regulation of nuclear SMAD2/3 signaling;IL6-mediated signaling events;AKT-mediated inactivation of FOXO1A;Regulation of gene expression in beta cells;insulin;FSH (Consensus)

Recessive Scores

• pRec: 0.829

Intolerance Scores

• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

• pHI: 0.976
• hipred: Y
• hipred_score: 0.825
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Foxo1
• Phenotype: muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism 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; neoplasm; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; immune system phenotype; embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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

Zebrafish Information Network

• Gene name: foxo1a
• Affected structure: intestine
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;blood vessel development;temperature homeostasis;cellular glucose homeostasis;protein acetylation;autophagy;apoptotic process;cellular response to DNA damage stimulus;insulin receptor signaling pathway;cellular response to starvation;positive regulation of autophagy;cytokine-mediated signaling pathway;endocrine pancreas development;cellular response to insulin stimulus;negative regulation of stress-activated MAPK cascade;cellular response to oxidative stress;regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter;glucose homeostasis;positive regulation of apoptotic process;negative regulation of apoptotic process;fat cell differentiation;negative regulation of fat cell differentiation;positive regulation of gluconeogenesis;positive regulation of protein catabolic process;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;enamel mineralization;cellular response to hydrogen peroxide;cellular response to cold;cellular response to hyperoxia;cellular response to dexamethasone stimulus;cellular response to nitric oxide;negative regulation of canonical Wnt signaling pathway;energy homeostasis;neuronal stem cell population maintenance;response to fluoride;negative regulation of cardiac muscle hypertrophy in response to stress;regulation of neural precursor cell proliferation;regulation of reactive oxygen species metabolic process
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;transcription coactivator binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;protein binding;beta-catenin binding;transcription factor binding;ubiquitin protein ligase binding;sequence-specific DNA binding;protein phosphatase 2A binding