FOXF2

protein-coding

forkhead box F2, the group of Forkhead boxes

Gene summary

FOXF2 encodes forkhead box F2, one of many human homologues of the Drosophila melanogaster transcription factor forkhead. FOXF2 is expressed in lung and placenta, and has been shown to transcriptionally activate several lung-specific genes. [provided by RefSeq, Jul 2008]

Previous symbols:

FKHL6

MANE transcript

NM_001452.2

Inheritance

ClinVar variants

U:75B:12

Top phenotype

FOXF2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr6:1,389,576-1,395,603

External References & Databases

Ensembl (ENSG00000137273)

Transcript & Mutation Effects

hg38 • Region Span ~6.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

sensorineural hearing loss disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0020678

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FOXF2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 73

FOXF2-related disorderTotal: 20

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001452.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar	2 clinvar	9
missense			75 clinvar	3 clinvar		78
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	75	10	2	87

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001452.2	RefSeq	NP_001443.1	2	MANE Select
ENST00000645481.2	Ensembl	ENSP00000496415.1	2	MANE Select
ENST00001136688.1	Ensembl	ENSP00000815094.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
foxf2b	Danio rerio	Structure: pericyte Quality: decreased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

foxf2b

Danio rerio

Structure: pericyte

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

epithelial to mesenchymal transition
extracellular matrix organization
establishment of planar polarity of embryonic epithelium
negative regulation of transcription, DNA-templated
positive regulation of transcription, DNA-templated

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
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

Cellular Component

nucleus
transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259806
Coding exons: 2
Length: 5764
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.853	172	206	0.833	0.00000990	2807
Missense (PolyPhen)		21	56.901	0.36906		587
Synonymous	-1.57	115	95.5	1.20	0.00000480	919
Loss of Function	2.72	1	10.5	0.0949	4.52e-7	130

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00010	0.000092	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable transcription activator for a number of lung- specific genes.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.909

Gene Damage Prediction

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