FOXO3B

Summary

FOXO3B (forkhead box O3B, HGNC:3822) is a protein-coding gene on chromosome 17p11.2, encoding Forkhead box protein O3B (A0A2Z4LIS9). Transcription factor. It is a selective cancer dependency (DepMap: 15.3% of cell lines).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in mitochondrial matrix. Predicted to be active in nucleus.

Source: NCBI Gene 2310 — RefSeq curated summary.

At a glance

• Cancer dependency (DepMap): dependent in 15.3% of screened cell lines
• MANE Select transcript: NM_001368135

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3822
Approved symbol	FOXO3B
Name	forkhead box O3B
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000240445
Ensembl biotype	protein_coding
OMIM	620471
Entrez	2310

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000395675, ENST00000442380, ENST00000443457, ENST00000454745

RefSeq mRNA: 2 — MANE Select: NM_001368135 NM_001368134, NM_001368135

CCDS: CCDS92269

Canonical transcript exons

ENST00000395675 — 4 exons

Exon	Start	End
ENSE00001522453	18667629	18673055
ENSE00002718958	18681615	18681846
ENSE00003877371	18682204	18682314
ENSE00003878725	18680741	18680829

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 84.73.

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	84.73	gold quality
cortical plate	UBERON:0005343	82.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.89	gold quality
ventricular zone	UBERON:0003053	79.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.43	gold quality
stromal cell of endometrium	CL:0002255	74.65	gold quality
endometrium	UBERON:0001295	68.75	gold quality
ovary	UBERON:0000992	68.67	gold quality
left ovary	UBERON:0002119	68.26	gold quality
islet of Langerhans	UBERON:0000006	68.03	gold quality
smooth muscle tissue	UBERON:0001135	67.55	gold quality
tonsil	UBERON:0002372	66.79	gold quality
placenta	UBERON:0001987	66.24	gold quality
lymph node	UBERON:0000029	66.21	gold quality
right ovary	UBERON:0002118	65.99	gold quality
urinary bladder	UBERON:0001255	65.47	gold quality
adrenal tissue	UBERON:0018303	65.32	gold quality
corpus callosum	UBERON:0002336	64.63	gold quality
vermiform appendix	UBERON:0001154	64.48	gold quality
body of uterus	UBERON:0009853	64.44	gold quality
uterine cervix	UBERON:0000002	64.36	gold quality
gall bladder	UBERON:0002110	63.84	gold quality
muscle tissue	UBERON:0002385	63.80	gold quality
right coronary artery	UBERON:0001625	63.58	gold quality
endocervix	UBERON:0000458	63.46	gold quality
skeletal muscle tissue	UBERON:0001134	63.44	gold quality
myometrium	UBERON:0001296	63.36	gold quality
fallopian tube	UBERON:0003889	62.72	gold quality
left uterine tube	UBERON:0001303	62.48	gold quality
prefrontal cortex	UBERON:0000451	62.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.52

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• our results clearly show that, for reliable genetic investigation of FOXO3A exonic regions, a special study design is mandatory accounting for the FOXO3B sequence homology (PMID:22588664)
• human FOXO3B locus encodes a bona fide human gene; unlike FOXO3A, FOXO3B is cytosolically localized in both the presence and absence of active Akt (PMID:29925039)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Forkhead box protein O3B — A0A2Z4LIS9 (reviewed: A0A2Z4LIS9)

All UniProt accessions (3): A0A2Z4LIS9, A0A590UJX0, I3L3U3

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor.

Subcellular location. Cytoplasm. Cytosol.

RefSeq proteins (2): NP_001355063, NP_001355064* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001766	Fork_head_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00250

UniProt features (8 total): compositionally biased region 3, region of interest 2, chain 1, DNA-binding region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A2Z4LIS9-F1	60.11	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 117

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 12 (showing top): GOBP_RESPONSE_TO_STARVATION, GOCC_MITOCHONDRIAL_MATRIX, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, HOFT_CD4_POSITIVE_ALPHA_BETA_MEMORY_T_CELL_BCG_VACCINE_AGE_18_45YO_ID_56D_TOP_100_DEG_AFTER_IN_VITRO_RE_STIMULATION_DN, CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_UP, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_RESPONSE_TO_NUTRIENT_LEVELS, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GOCC_MITOCHONDRION, chr17p11

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXO3B	TBC1D28	Q2M2D7	380
FOXO3B	ETV6	P41212	362
FOXO3B	HIF1A	Q16665	361
FOXO3B	ETV3	P41162	353
FOXO3B	NTM	Q9P121	350
FOXO3B	BHLHE41	Q9C0J9	348
FOXO3B	CDK2	P24941	345
FOXO3B	E2F1	Q01094	343
FOXO3B	CTNNB1	P35222	334
FOXO3B	PTK2	Q05397	323
FOXO3B	TVP23B	Q9NYZ1	322
FOXO3B	TP53	P04637	316
FOXO3B	ARL5C	A6NH57	314
FOXO3B	SESN3	P58005	307
FOXO3B	POU5F1B	Q06416	306

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2Z4LIS9, A2VE02, A4D1S0, A5PKC7, A5PL33, A6H7B4, A6NEL2, A6QP24, A6QPM6, A8MTW9, A8MYA2, D3ZAQ5, D4AAA5, E7EW31, O75474, O75638, O89113, O94850, P0C7X2, P14652, P50617, P70339, Q2KIS6, Q3UN58, Q5JPB2, Q5VZ46, Q6GQX2, Q6NZ36, Q6ZSJ8, Q6ZW13, Q76NI1, Q7TNS8, Q80TS7, Q86UU5, Q8IWN7, Q8N6K4, Q8N944

Diamond homologs: A0A2Z4LIS9, A3RK74, A3RK75, A4L7N3, A8MYZ6, B3LYS5, B3P0K6, B4G4S8, B4HF64, B4JSC2, B4KBF6, B4MB78, B4NFR1, B4PTD3, E1BPQ1, G3V7R4, O16850, O43524, P0CG31, P23512, P32182, P32183, P32315, P33205, P33206, P35582, P35583, P35584, P55317, P55318, P84961, P98177, Q07342, Q10924, Q12778, Q28EM1, Q298W7, Q3Y598, Q4VUF1, Q63248

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

0 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

615 predictions. Top by Δscore:

Variant	Effect	Δscore
17:18680737:TCA:T	donor_loss	1.0000
17:18680738:CA:C	donor_loss	1.0000
17:18680739:A:C	donor_loss	1.0000
17:18680825:CAGAA:C	acceptor_gain	1.0000
17:18673065:C:CT	acceptor_gain	0.9900
17:18680826:AGAA:A	acceptor_gain	0.9900
17:18680827:GAA:G	acceptor_gain	0.9900
17:18680830:C:CC	acceptor_gain	0.9900
17:18682196:CAACT:C	donor_loss	0.9900
17:18682197:AACTC:A	donor_loss	0.9900
17:18682198:ACTCA:A	donor_loss	0.9900
17:18682200:TCA:T	donor_loss	0.9900
17:18682201:CACCT:C	donor_loss	0.9900
17:18682202:A:AG	donor_loss	0.9900
17:18682202:ACCTC:A	donor_gain	0.9900
17:18682203:CCTCC:C	donor_gain	0.9900
17:18677326:T:TA	donor_gain	0.9800
17:18680736:CTCA:C	donor_gain	0.9800
17:18680739:A:AC	donor_gain	0.9800
17:18680740:C:CC	donor_gain	0.9800
17:18680828:AA:A	acceptor_gain	0.9800
17:18681616:T:TA	donor_gain	0.9800
17:18682202:A:AC	donor_gain	0.9800
17:18682202:ACCT:A	donor_gain	0.9800
17:18682203:C:CC	donor_gain	0.9800
17:18682203:CCT:C	donor_gain	0.9800
17:18682203:CCTC:C	donor_gain	0.9800
17:18673067:C:CT	acceptor_gain	0.9700
17:18673068:G:T	acceptor_gain	0.9700
17:18680735:A:AC	donor_gain	0.9600

AlphaMissense

1843 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:18672433:A:G	L250P	1.000
17:18672456:C:A	W242C	1.000
17:18672456:C:G	W242C	1.000
17:18672345:G:C	F279L	0.999
17:18672345:G:T	F279L	0.999
17:18672346:A:C	F279C	0.999
17:18672346:A:G	F279S	0.999
17:18672347:A:G	F279L	0.999
17:18672367:A:G	M272T	0.999
17:18672369:C:A	W271C	0.999
17:18672369:C:G	W271C	0.999
17:18672421:G:T	A254D	0.999
17:18672430:A:C	I251S	0.999
17:18672430:A:G	I251T	0.999
17:18672430:A:T	I251N	0.999
17:18672443:A:G	Y247H	0.999
17:18672458:A:G	W242R	0.999
17:18672458:A:T	W242R	0.999
17:18672828:C:A	W118C	0.999
17:18672828:C:G	W118C	0.999
17:18672830:A:G	W118R	0.999
17:18672830:A:T	W118R	0.999
17:18672388:A:T	L265Q	0.998
17:18672418:A:T	I255N	0.998
17:18672422:C:G	A254P	0.998
17:18672442:T:C	Y247C	0.998
17:18672454:C:T	G243E	0.998
17:18672347:A:C	F279V	0.997
17:18672347:A:T	F279I	0.997
17:18672367:A:C	M272R	0.997

dbSNP variants (sampled 300 via entrez): RS1000253512 (17:18678729 G>A), RS1000436850 (17:18672562 C>T), RS1000853660 (17:18677118 A>G,T), RS1001326773 (17:18676810 C>T), RS1001581449 (17:18672495 G>A,C,T), RS1001654905 (17:18672247 C>A,T), RS1002194599 (17:18677514 G>A), RS1002264293 (17:18683958 G>A), RS1002662638 (17:18670961 G>A,C), RS1002719216 (17:18679699 T>C,G), RS1002722353 (17:18676575 C>T), RS1003238767 (17:18682112 C>T), RS1003724626 (17:18675234 G>A), RS1004001445 (17:18669880 G>A), RS1004150882 (17:18683456 C>T)

Disease associations

OMIM: gene MIM:620471 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Smoke	decreases expression	1
T-2 Toxin	increases expression	1
Valproic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.