FOXB2

Summary

FOXB2 (forkhead box B2, HGNC:23315) is a protein-coding gene on chromosome 9q21.2, encoding Forkhead box protein B2 (Q5VYV0). Transcription factor.

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 anatomical structure morphogenesis; cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be located in chromatin.

Source: NCBI Gene 442425 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_001013735

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23315
Approved symbol	FOXB2
Name	forkhead box B2
Location	9q21.2
Locus type	gene with protein product
Status	Approved
Aliases	bA159H20.4
Ensembl gene	ENSG00000204612
Ensembl biotype	protein_coding
OMIM	619962
Entrez	442425

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000376708, ENST00000850987

RefSeq mRNA: 1 — MANE Select: NM_001013735 NM_001013735

CCDS: CCDS35045

Canonical transcript exons

ENST00000376708 — 1 exons

Exon	Start	End
ENSE00004283158	77019655	77020953

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 62.46.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	62.46	gold quality
right uterine tube	UBERON:0001302	41.83	silver quality
bone marrow cell	CL:0002092	40.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	38.55	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow	UBERON:0002371	36.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.67	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
hypothalamus	UBERON:0001898	34.96	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
calcaneal tendon	UBERON:0003701	31.13	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
liver	UBERON:0002107	30.40	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.73	gold quality
blood	UBERON:0000178	29.09	gold quality
lymph node	UBERON:0000029	28.84	gold quality
endometrium	UBERON:0001295	28.14	gold quality
duodenum	UBERON:0002114	28.14	gold quality
tonsil	UBERON:0002372	27.05	gold quality
superior frontal gyrus	UBERON:0002661	26.93	gold quality
leukocyte	CL:0000738	26.90	gold quality
monocyte	CL:0000576	26.84	gold quality
urinary bladder	UBERON:0001255	26.71	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
muscle of leg	UBERON:0001383	26.27	gold quality
gall bladder	UBERON:0002110	25.98	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• FOXB2 strongly activates Wnt signaling via the neurogenic ligand WNT7B and imposes a neuronal differentiation program on prostate cancer cells. (PMID:31611391)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxb2	ENSDARG00000037475
mus_musculus	Foxb2	ENSMUSG00000056829
rattus_norvegicus	Foxb2	ENSRNOG00000032137
drosophila_melanogaster	fd96Ca	FBGN0004897
caenorhabditis_elegans		WBGENE00003017

Paralogs (41): FOXP3 (ENSG00000049768), FOXC1 (ENSG00000054598), FOXJ2 (ENSG00000065970), FOXF1 (ENSG00000103241), FOXN1 (ENSG00000109101), FOXM1 (ENSG00000111206), FOXP1 (ENSG00000114861), FOXO3 (ENSG00000118689), FOXA2 (ENSG00000125798), FOXA1 (ENSG00000129514), FOXJ1 (ENSG00000129654), FOXK2 (ENSG00000141568), FOXO1 (ENSG00000150907), FOXH1 (ENSG00000160973), FOXQ1 (ENSG00000164379), FOXK1 (ENSG00000164916), FOXD4 (ENSG00000170122), FOXA3 (ENSG00000170608), FOXB1 (ENSG00000171956), FOXR1 (ENSG00000176302), FOXL1 (ENSG00000176678), FOXC2 (ENSG00000176692), FOXE1 (ENSG00000178919), FOXS1 (ENSG00000179772), FOXL2 (ENSG00000183770), FOXO4 (ENSG00000184481), FOXD4L1 (ENSG00000184492), FOXD4L4 (ENSG00000184659), FOXD2 (ENSG00000186564), FOXI2 (ENSG00000186766), FOXE3 (ENSG00000186790), FOXD3 (ENSG00000187140), FOXD4L3 (ENSG00000187559), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein B2 — Q5VYV0 (reviewed: Q5VYV0)

All UniProt accessions (1): Q5VYV0

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_001013757* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001766	Fork_head_dom	Domain
IPR018122	TF_fork_head_CS_1	Conserved_site
IPR030456	TF_fork_head_CS_2	Conserved_site
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR047389	FOXB1_B2_FH	Domain
IPR050211	FOX_domain-containing	Family

Pfam: PF00250

UniProt features (8 total): compositionally biased region 4, region of interest 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VYV0-F1	61.07	0.19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, chr9q21, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_BRAIN_HCP_WITH_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K27ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, IGLV5_37_TARGET_GENES, GSE15324_ELF4_KO_VS_WT_NAIVE_CD8_TCELL_DN, GSE17721_PAM3CSK4_VS_GADIQUIMOD_1H_BMDC_UP, ZNF547_TARGET_GENES, PRDM4_TARGET_GENES, GSE9946_IMMATURE_VS_MATURE_STIMULATORY_DC_DN

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), anatomical structure morphogenesis (GO:0009653), cell differentiation (GO:0030154), 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 (2): chromatin (GO:0000785), nucleus (GO:0005634)

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
transcription by RNA polymerase II	1
developmental process	1
anatomical structure development	1
cellular developmental process	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
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXB2	FOXR2	Q6PJQ5	461
FOXB2	PKNOX2	Q96KN3	373
FOXB2	NKX2-4	Q9H2Z4	367
FOXB2	SOX5	P35711	335
FOXB2	POU4F3	Q15319	331
FOXB2	POU4F2	Q12837	325
FOXB2	G3V325	G3V325	324
FOXB2	PRDM16	Q9HAZ2	322
FOXB2	ZMAT1	Q5H9K5	321
FOXB2	LHX1	P48742	311
FOXB2	SOX14	O95416	310
FOXB2	NKX3-2	P78367	308
FOXB2	IRX4	P78413	302
FOXB2	NKX3-1	Q99801	299
FOXB2	LRTM1	Q9HBL6	298

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: E7FBS9, O02754, O08789, O35449, O88470, P02831, P18111, P42128, P43241, P47902, P51179, P55318, P58012, P85037, Q01167, Q04649, Q08DG7, Q2THW0, Q2THW8, Q2THX0, Q3UCQ1, Q3Y598, Q4VUF1, Q5I1X5, Q5VYV0, Q5Y5T5, Q61850, Q63246, Q64733, Q6MG82, Q6NSM8, Q6P4S6, Q6VFT6, Q6VFT7, Q7TQ40, Q8WUF5, Q92570, Q96NZ1, Q96T25, Q99583

Diamond homologs: A0A8V0YY16, A1L1S5, A2BGM5, A8MTJ6, B5RHS5, D3Z120, O00358, O00409, O15353, O54743, O60129, O70220, O88470, O93529, P32027, P32028, P32030, P32314, P42128, P55316, P56260, P58012, Q00939, Q12946, Q12947, Q12948, Q12951, Q13461, Q1A1A1, Q1A1A2, Q1A1A3, Q1A1A4, Q1A1A5, Q1A1A6, Q28BS5, Q28D67, Q28F43, Q28G71, Q28H65, Q28HT3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

50 predictions. Top by Δscore:

Variant	Effect	Δscore
9:77020309:G:GT	donor_gain	0.6000
9:77020299:C:T	donor_gain	0.5400
9:77020471:G:GC	acceptor_gain	0.4700
9:77020663:G:GG	donor_gain	0.4300
9:77020498:G:GT	donor_gain	0.3900
9:77020662:T:TG	donor_gain	0.3900
9:77020362:C:T	donor_gain	0.3800
9:77020359:G:A	donor_gain	0.3700
9:77020355:C:CA	donor_gain	0.3600
9:77020697:TC:T	donor_gain	0.3600
9:77020358:T:TA	donor_gain	0.3500
9:77019906:T:TA	donor_gain	0.3300
9:77019907:A:AA	donor_gain	0.3300
9:77019988:C:CG	donor_gain	0.3300
9:77020360:G:A	donor_gain	0.3200
9:77019900:C:T	donor_gain	0.3100
9:77020019:G:GT	donor_gain	0.3000
9:77020445:C:A	donor_gain	0.3000
9:77020718:C:T	donor_gain	0.3000
9:77020019:G:T	donor_gain	0.2900
9:77020361:G:GT	donor_gain	0.2900
9:77020364:GC:G	donor_gain	0.2900
9:77020370:G:GT	donor_gain	0.2900
9:77020469:T:TG	donor_gain	0.2900
9:77020623:G:GA	donor_gain	0.2800
9:77019909:C:G	donor_gain	0.2700
9:77020655:G:GT	donor_gain	0.2700
9:77020671:G:GT	donor_gain	0.2700
9:77020698:C:A	donor_gain	0.2600
9:77020666:G:A	donor_gain	0.2500

AlphaMissense

2799 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:77019691:A:G	K13E	1.000
9:77019693:A:C	K13N	1.000
9:77019693:A:T	K13N	1.000
9:77019694:C:A	P14T	1.000
9:77019694:C:T	P14S	1.000
9:77019695:C:A	P14Q	1.000
9:77019695:C:G	P14R	1.000
9:77019700:T:C	Y16H	1.000
9:77019700:T:G	Y16D	1.000
9:77019704:C:A	S17Y	1.000
9:77019704:C:T	S17F	1.000
9:77019706:T:C	Y18H	1.000
9:77019707:A:G	Y18C	1.000
9:77019709:A:T	I19F	1.000
9:77019710:T:A	I19N	1.000
9:77019710:T:C	I19T	1.000
9:77019710:T:G	I19S	1.000
9:77019712:T:C	S20P	1.000
9:77019716:T:A	L21Q	1.000
9:77019716:T:C	L21P	1.000
9:77019716:T:G	L21R	1.000
9:77019721:G:C	A23P	1.000
9:77019722:C:A	A23D	1.000
9:77019725:T:C	M24T	1.000
9:77019725:T:G	M24R	1.000
9:77019726:G:A	M24I	1.000
9:77019726:G:C	M24I	1.000
9:77019726:G:T	M24I	1.000
9:77019727:G:C	A25P	1.000
9:77019728:C:A	A25E	1.000

dbSNP variants (sampled 300 via entrez): RS1000768752 (9:77018059 T>C), RS1000832934 (9:77019254 G>C), RS1001222334 (9:77017691 C>G,T), RS1001448810 (9:77018491 A>C), RS1002597769 (9:77020857 C>G,T), RS1005130555 (9:77018689 G>A,T), RS1005444202 (9:77018459 G>A), RS1005519950 (9:77019766 G>A,T), RS1007052125 (9:77017766 A>G), RS1007455003 (9:77020104 C>T), RS1008235109 (9:77020322 T>TGGCGTC), RS1008573450 (9:77019010 A>G), RS1009240593 (9:77021126 C>T), RS1009962562 (9:77021063 G>A,T), RS1010243697 (9:77017672 G>A)

Disease associations

OMIM: gene MIM:619962 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008395_6	End-stage kidney disease	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ferrous chloride	decreases expression	1
Fulvestrant	increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Endosulfan	decreases expression	1
Phthalic Acids	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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