FOXO4

forkhead box O4, the group of Forkhead boxes

Basic information

Region (hg38): X:71095851-71103535

Previous symbols: [ "MLLT7" ]

Links

ENSG00000184481 ∙ NCBI:4303 ∙ OMIM:300033 ∙ HGNC:7139 ∙ Uniprot:P98177 ∙ 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 FOXO4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXO4 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				2	1	3
missense			17			17
nonsense			2			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	19	2	1

Variants in FOXO4

This is a list of pathogenic ClinVar variants found in the FOXO4 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-71096539-G-T		not specified	Uncertain significance (Nov 23, 2024)
X-71096557-C-G		not specified	Uncertain significance (Jul 14, 2024)
X-71096571-A-T		not specified	Uncertain significance (Mar 29, 2024)
X-71096676-G-A		not specified	Uncertain significance (Oct 01, 2024)
X-71096725-C-G		not specified	Uncertain significance (Dec 27, 2023)
X-71096776-G-A		not specified	Uncertain significance (Feb 28, 2023)
X-71096787-G-T		not specified	Uncertain significance (Nov 26, 2024)
X-71096877-G-T		not specified	Uncertain significance (Jul 14, 2024)
X-71096913-G-T			Uncertain significance (Oct 30, 2019)
X-71096977-G-A		Clinodactyly;Intellectual disability, moderate;Macrocephaly;Abnormality of the face;Short 5th metacarpal	Uncertain significance (Jun 20, 2023)
X-71100738-G-A		not specified	Uncertain significance (Jan 04, 2022)
X-71100790-G-C		not specified	Uncertain significance (Sep 28, 2022)
X-71100792-G-A		not specified	Uncertain significance (Sep 03, 2024)
X-71100874-A-G		not specified	Uncertain significance (Oct 01, 2024)
X-71100896-A-C			Likely benign (Sep 01, 2022)
X-71100900-G-A		not specified	Uncertain significance (May 24, 2023)
X-71100916-C-T		not specified	Uncertain significance (Aug 16, 2022)
X-71100917-G-A			Benign (Apr 16, 2018)
X-71100927-G-A		not specified	Uncertain significance (May 26, 2023)
X-71101060-A-C		Intellectual disability	Uncertain significance (-)
X-71101176-C-T		not specified	Uncertain significance (Apr 13, 2023)
X-71101180-C-T		not specified	Uncertain significance (Dec 21, 2023)
X-71101258-G-C		not specified	Likely benign (Aug 10, 2024)
X-71101342-C-T		not specified	Uncertain significance (May 08, 2024)
X-71101351-C-T		not specified	Uncertain significance (Oct 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXO4	protein_coding	protein_coding	ENST00000374259	3	7339

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.813	0.186	123635	0	2	123637	0.00000809

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	140	207	0.677	0.0000159	3246
Missense in Polyphen		26	65.349	0.39786		1023
Synonymous	1.35	72	88.1	0.817	0.00000689	1122
Loss of Function	2.62	1	9.91	0.101	7.70e-7	156

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)	0.0000253	0.0000178
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity. {ECO:0000269|PubMed:10217147, ECO:0000269|PubMed:10783894, ECO:0000269|PubMed:12761217, ECO:0000269|PubMed:15126506, ECO:0000269|PubMed:16054032, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:22972301}.
• Disease: DISEASE: Note=A chromosomal aberration involving FOXO4 is found in acute leukemias. Translocation t(X;11)(q13;q23) with KMT2A/MLL1. The result is a rogue activator protein.
• Pathway: FoxO signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);IGF-Core;Signaling Pathways in Glioblastoma;AGE-RAGE pathway;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;VEGFA-VEGFR2 Signaling Pathway;Ras Signaling;EGF-EGFR Signaling Pathway;Disease;Signal Transduction;akt signaling pathway;ras signaling pathway;Post-translational protein modification;Metabolism of proteins;AKT phosphorylates targets in the nucleus;insulin Mam;TGF_beta_Receptor;EGFR1;Ub-specific processing proteases;PIP3 activates AKT signaling;Deubiquitination;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;IL6;Intracellular signaling by second messengers;Diseases of signal transduction;Signaling events mediated by HDAC Class III;FoxO family signaling;Class I PI3K signaling events mediated by Akt;Regulation of nuclear SMAD2/3 signaling;insulin (Consensus)

Recessive Scores

• pRec: 0.231

Intolerance Scores

• loftool: 0.118
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.832
• hipred: Y
• hipred_score: 0.771
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.959

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Foxo4
• Phenotype: neoplasm; 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); normal phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;transcription by RNA polymerase II;cell cycle arrest;mitotic G2 DNA damage checkpoint;muscle organ development;aging;negative regulation of cell population proliferation;insulin receptor signaling pathway;positive regulation of smooth muscle cell migration;negative regulation of angiogenesis;protein deubiquitination;response to nutrient levels;glucose homeostasis;positive regulation of transcription by RNA polymerase II;stem cell differentiation;negative regulation of smooth muscle cell differentiation;negative regulation of G0 to G1 transition;positive regulation of cell cycle arrest;response to water-immersion restraint stress
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;nuclear speck
• 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;beta-catenin binding;transcription factor binding;enzyme binding;identical protein binding;sequence-specific DNA binding;promoter-specific chromatin binding