FOXB1

Summary

FOXB1 (forkhead box B1, HGNC:3799) is a protein-coding gene on chromosome 15q22.2, encoding Forkhead box protein B1 (Q99853). Transcription factor expressed by neural progenitor cells in specific regions of the embryonic neuroepithelium.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including mammary gland development; nervous system development; and visual learning. Predicted to be located in chromatin and nucleus.

Source: NCBI Gene 27023 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_012182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3799
Approved symbol	FOXB1
Name	forkhead box B1
Location	15q22.2
Locus type	gene with protein product
Status	Approved
Aliases	HFKH-5, FKH5
Ensembl gene	ENSG00000171956
Ensembl biotype	protein_coding
OMIM	619961
Entrez	27023

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000396057, ENST00000558693, ENST00000560857

RefSeq mRNA: 1 — MANE Select: NM_012182 NM_012182

CCDS: CCDS32255

Canonical transcript exons

ENST00000396057 — 2 exons

Exon	Start	End
ENSE00001523708	60004907	60007444
ENSE00001523709	60004311	60004643

Expression profiles

Bgee: expression breadth broad, 56 present calls, max score 73.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6192 / max 59.0120, expressed in 171 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147015	0.4762	155
147016	0.0735	30
147014	0.0695	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hypothalamus	UBERON:0001898	73.02	gold quality
substantia nigra	UBERON:0002038	71.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.53	gold quality
left testis	UBERON:0004533	62.69	gold quality
testis	UBERON:0000473	62.36	gold quality
right testis	UBERON:0004534	60.84	gold quality
placenta	UBERON:0001987	56.53	gold quality
right uterine tube	UBERON:0001302	54.44	gold quality
lymph node	UBERON:0000029	49.19	gold quality
endometrium	UBERON:0001295	49.17	gold quality
sural nerve	UBERON:0015488	44.16	gold quality
bone marrow cell	CL:0002092	43.99	gold quality
ventricular zone	UBERON:0003053	40.24	gold quality
granulocyte	CL:0000094	39.32	gold quality
vermiform appendix	UBERON:0001154	38.80	silver quality
left ovary	UBERON:0002119	38.75	gold quality
amygdala	UBERON:0001876	38.54	gold quality
temporal lobe	UBERON:0001871	38.43	gold quality
ovary	UBERON:0000992	38.02	gold quality
bone marrow	UBERON:0002371	37.99	gold quality
leukocyte	CL:0000738	37.68	silver quality
skeletal muscle tissue	UBERON:0001134	37.34	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ganglionic eminence	UBERON:0004023	37.17	gold quality
lower esophagus mucosa	UBERON:0035834	37.11	gold quality
nucleus accumbens	UBERON:0001882	36.90	gold quality
monocyte	CL:0000576	36.89	silver quality
muscle tissue	UBERON:0002385	36.50	gold quality
cortical plate	UBERON:0005343	36.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.43

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
XIST

JASPAR motifs

Motif	Name	Family
MA0845.1	FOXB1	FOX

JASPAR matrix evidence (PMIDs): PMID:7739038

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxb1b	ENSDARG00000053650
danio_rerio	foxb1a	ENSDARG00000089042
mus_musculus	Foxb1	ENSMUSG00000059246
rattus_norvegicus	Foxb1	ENSRNOG00000089953
drosophila_melanogaster	fd96Cb	FBGN0004898

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), 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), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein B1 — Q99853 (reviewed: Q99853)

Alternative names: Transcription factor FKH-5

All UniProt accessions (1): Q99853

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor expressed by neural progenitor cells in specific regions of the embryonic neuroepithelium. Essential for the mammillary nuclei maintenance. Negatively regulates the proliferation of oligodendrocyte progenitors and promotes oligodendrocyte maturation. Also expressed in mammary glands, plays a role in lactation, controls development of mammary glands and the inferior colliculi of the midbrain in the central nervous system that regulates the milk-ejection reflex.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_036314* (*=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): sequence conflict 4, chain 1, DNA-binding region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99853-F1	66.60	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, HNF3ALPHA_Q6, GOBP_BEHAVIOR, GOBP_ASSOCIATIVE_LEARNING, GOBP_MAMMARY_GLAND_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT, CHX10_01

GO Biological Process (22): urogenital system development (GO:0001655), somitogenesis (GO:0001756), regulation of transcription by RNA polymerase II (GO:0006357), axon target recognition (GO:0007412), lactation (GO:0007595), visual learning (GO:0008542), anatomical structure morphogenesis (GO:0009653), spinal cord development (GO:0021510), mammillary body development (GO:0021767), thalamus development (GO:0021794), hypothalamus cell migration (GO:0021855), telencephalon cell migration (GO:0022029), cell differentiation (GO:0030154), midbrain development (GO:0030901), floor plate development (GO:0033504), negative regulation of neuron apoptotic process (GO:0043524), epithelial cell differentiation involved in mammary gland alveolus development (GO:0061030), mammillothalamic axonal tract development (GO:0061374), mammary gland lobule development (GO:0061377), inferior colliculus development (GO:0061379), cell migration in diencephalon (GO:0061381), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	9
regulation of DNA-templated transcription	2
mammary gland development	2
diencephalon development	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
system development	1
renal system development	1
anterior/posterior pattern specification	1
segmentation	1
chordate embryonic development	1
anatomical structure formation involved in morphogenesis	1
somite development	1
transcription by RNA polymerase II	1
cell communication	1
axonogenesis	1
body fluid secretion	1
milk ejection reflex	1
visual behavior	1
associative learning	1
developmental process	1
central nervous system development	1
limbic system development	1
cell migration	1
hypothalamus development	1
telencephalon development	1
forebrain cell migration	1
cellular developmental process	1
brain development	1
neural tube development	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
mammary gland epithelial cell differentiation	1
mammary gland alveolus development	1
mammillary axonal complex development	1
corpora quadrigemina development	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

Protein interactions and networks

STRING

952 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXB1	OTP	Q5XKR4	511
FOXB1	LHX5	Q9H2C1	473
FOXB1	SOX5	P35711	441
FOXB1	FOXC2	Q99958	433
FOXB1	IRX1	P78414	431
FOXB1	LHX1	P48742	425
FOXB1	LHX9	Q9NQ69	421
FOXB1	CFAP36	Q96G28	411
FOXB1	HOMEZ	Q8IX15	408
FOXB1	SIM1	P81133	404
FOXB1	FOXR2	Q6PJQ5	399
FOXB1	FAM81B	Q96LP2	380
FOXB1	TOMM40	O96008	378
FOXB1	DLX2	Q07687	372
FOXB1	LHX6	Q9UPM6	361

IntAct

23 interactions, top by confidence:

A	B	Type	Score
	FOXB1	psi-mi:“MI:0915”(physical association)	0.560
FOXB1	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	FOXB1	psi-mi:“MI:0915”(physical association)	0.560
KRT31	FOXB1	psi-mi:“MI:0915”(physical association)	0.560
FOXB1	KRT40	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	FOXB1	psi-mi:“MI:0915”(physical association)	0.560
FOXB1		psi-mi:“MI:0915”(physical association)	0.560
TRIM27	FOXB1	psi-mi:“MI:0915”(physical association)	0.560
FOXB1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
KRT40	FOXB1	psi-mi:“MI:0915”(physical association)	0.560
FOXB1	COPB1	psi-mi:“MI:0915”(physical association)	0.370
PHF5A	FOXB1	psi-mi:“MI:0915”(physical association)	0.370
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXB1	MACROH2A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (133): FOXB1 (Two-hybrid), FOXB1 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), YARS (Affinity Capture-MS), DDX39A (Affinity Capture-MS), SCRIB (Affinity Capture-MS), SMPD4 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), ARID3A (Affinity Capture-MS), GTF3C1 (Affinity Capture-MS), KPNA1 (Affinity Capture-MS), PDS5A (Affinity Capture-MS)

ESM2 similar proteins: A8WFJ9, A8XJD0, A8XJN7, A8XSQ8, B7ZQA9, F1R8Z9, G5EDS1, G5EGC9, O00409, O18214, O93529, P13528, P32029, P32030, P34683, P34766, P41934, Q02360, Q10902, Q18694, Q21187, Q22510, Q22910, Q23045, Q23175, Q28D67, Q28G71, Q33BP8, Q3BJS3, Q4VYR7, Q5M7L9, Q5W1J5, Q5WM45, Q64732, Q6P2Z3, Q6P8A3, Q7ZYQ0, Q90481, Q90WN4, Q91904

Diamond homologs: A0A078BQN7, A0A1W2PRP0, A0A8V0YY16, A1L1S5, A3KNJ3, A8MTJ6, A8XJN7, B5RHS5, D3Z120, F1R8Z9, O00358, O17617, O43638, O54743, O60129, O88470, P32027, P32028, P32030, P32315, P42128, P55316, P56260, P58012, P79772, P85037, P91278, Q00939, Q01167, Q02360, Q12946, Q12947, Q12948, Q12950, Q12951, Q12952, Q13461, Q19802, Q1A1A1, Q1A1A2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

41 predictions. Top by Δscore:

Variant	Effect	Δscore
15:60004640:TAAGG:T	donor_loss	0.9600
15:60004641:AAGGT:A	donor_loss	0.9600
15:60004642:AGG:A	donor_loss	0.9600
15:60004643:GGTGA:G	donor_loss	0.9600
15:60004644:G:A	donor_loss	0.9600
15:60004645:T:A	donor_loss	0.9600
15:60004903:CCA:C	acceptor_loss	0.9600
15:60004904:CAG:C	acceptor_loss	0.9600
15:60004906:GATCC:G	acceptor_gain	0.9500
15:60004905:A:AG	acceptor_gain	0.9300
15:60004906:G:GG	acceptor_gain	0.9300
15:60004644:G:GG	donor_gain	0.9200
15:60004906:GATC:G	acceptor_gain	0.7700
15:60004646:GAGCA:G	donor_loss	0.7100
15:60004906:GA:G	acceptor_gain	0.6900
15:60004823:G:GT	donor_gain	0.6000
15:60004895:C:G	acceptor_gain	0.5700
15:60004906:GAT:G	acceptor_gain	0.5700
15:60004903:CCAGA:C	acceptor_gain	0.5400
15:60004894:A:AG	acceptor_gain	0.5300
15:60004904:CAGAT:C	acceptor_gain	0.5000
15:60004642:AG:A	donor_gain	0.4800
15:60004643:GG:G	donor_gain	0.4800
15:60004908:TCCG:T	acceptor_gain	0.4800
15:60004902:CCCAG:C	acceptor_gain	0.4700
15:60004905:AGATC:A	acceptor_gain	0.4700
15:60004901:TCCCA:T	acceptor_gain	0.4400
15:60004906:G:T	acceptor_gain	0.4400
15:60004907:ATCCG:A	acceptor_gain	0.4400
15:60004639:TTAAG:T	donor_gain	0.4100

AlphaMissense

2112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:60005000:A:G	K13E	1.000
15:60005002:G:C	K13N	1.000
15:60005002:G:T	K13N	1.000
15:60005003:C:A	P14T	1.000
15:60005003:C:T	P14S	1.000
15:60005004:C:A	P14Q	1.000
15:60005004:C:G	P14R	1.000
15:60005007:C:A	P15H	1.000
15:60005009:T:A	Y16N	1.000
15:60005009:T:C	Y16H	1.000
15:60005009:T:G	Y16D	1.000
15:60005012:T:C	S17P	1.000
15:60005013:C:T	S17L	1.000
15:60005015:T:C	Y18H	1.000
15:60005016:A:G	Y18C	1.000
15:60005018:A:T	I19F	1.000
15:60005019:T:A	I19N	1.000
15:60005019:T:C	I19T	1.000
15:60005019:T:G	I19S	1.000
15:60005025:T:A	L21Q	1.000
15:60005025:T:C	L21P	1.000
15:60005025:T:G	L21R	1.000
15:60005030:G:C	A23P	1.000
15:60005031:C:A	A23D	1.000
15:60005035:G:A	M24I	1.000
15:60005035:G:C	M24I	1.000
15:60005035:G:T	M24I	1.000
15:60005036:G:C	A25P	1.000
15:60005037:C:A	A25D	1.000
15:60005040:T:A	I26N	1.000

dbSNP variants (sampled 300 via entrez): RS1000437452 (15:60004590 G>T), RS1000888710 (15:60006155 T>C), RS1001502824 (15:60003940 G>T), RS1002586828 (15:60006951 T>A), RS1002710625 (15:60006429 A>G), RS1002856261 (15:60003313 G>A), RS1003168805 (15:60002680 C>A), RS1003234638 (15:60006655 C>T), RS1004389196 (15:60002487 T>G), RS1004465594 (15:60002706 T>C), RS1004753677 (15:60002472 C>A), RS1005911803 (15:60006717 A>G), RS1006325030 (15:60003310 T>A,G), RS1006575700 (15:60004268 G>A), RS1006735729 (15:60006266 C>T)

Disease associations

OMIM: gene MIM:619961 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003542_185	Night sleep phenotypes	2.000000e-06
GCST009798_17	Asthma	2.000000e-19

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
trichostatin A	decreases reaction, affects expression	1
arsenite	increases methylation	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
ferrous chloride	decreases expression	1
bisphenol S	decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Fonofos	increases methylation	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Nickel	affects expression, decreases reaction	1
Parathion	increases methylation	1
Tobacco Smoke Pollution	increases methylation	1
Triclosan	increases expression	1
Zinc	increases expression	1
Genistein	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1W8	SEES3-1V human FOXB1, clone1	Embryonic stem cell	Male
CVCL_A1W9	SEES3-1V human FOXB1, clone2	Embryonic stem cell	Male
CVCL_A1X0	SEES3-1V human FOXB1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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