GeneBe

FOXF1

protein-coding

forkhead box F1, the group of Forkhead boxes

Gene summary

This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the regulation of pulmonary genes as well as embryonic development. [provided by RefSeq, Jul 2008]

Previous symbols:
  • FKHL5

MANE transcript

NM_001451.3

Inheritance

AD

ClinVar variants

P:71U:96B:57

Top phenotype

Alveolar capillary dysplasia with misalignment of pulmonary veins

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr16:86,510,527-86,515,422

External References & Databases

Ensembl (ENSG00000103241)NCBI Gene (2294)OMIM (601089)HGNC:3809GenCCUniProt (Q12946)AlphaFoldClinVar (FOXF1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~4.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

alveolar capillary dysplasia with misalignment of pulmonary veinsSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0009934

Submitter: PanelApp Australia

alveolar capillary dysplasia with misalignment of pulmonary veinsSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0009934

Submitter: Orphanet

alveolar capillary dysplasia with misalignment of pulmonary veinsDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0009934

Submitter: G2P

alveolar capillary dysplasia with misalignment of pulmonary veinsSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0009934

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Alveolar capillary dysplasia with misalignment of pulmonary veinsAD

Manifestation: Cardiovascular; Genitourinary; Gastrointestinal; Musculoskeletal; Pulmonary

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 15520767; 19500772; 20425831; 22990143; 23407133; 23444129; 23505205; 24842713Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FOXF1 variants in ClinVar

13 Conditions Cataloged
not providedTotal: 95
Alveolar capillary dysplasia with pulmonary venous misalignmentTotal: 78
Inborn genetic diseasesTotal: 57
not specifiedTotal: 32
FOXF1-related disorderTotal: 21
FOXF1-related disordersTotal: 4
See casesTotal: 2
Fetal megacystisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001451.3. 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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
36
clinvar
5
clinvar
 45
missense
11
clinvar
20
clinvar
91
clinvar
13
clinvar
3
clinvar
 138
nonsense
14
clinvar
 14
start loss
0
frameshift
20
clinvar
6
clinvar
1
clinvar
 27
splice donor/acceptor (+/-2bp)
0
Total452696498224
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001451.3RefSeqNP_001442.22MANE Select
ENST00000262426.6EnsemblENSP00000262426.42MANE Select
ENST00001122298.1EnsemblENSP00000792103.12Standard
ENST00001122299.1EnsemblENSP00000792104.12Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
foxf1Danio rerio

Structure: vascular lymphangioblast

Quality: absent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • FOXA2 and FOXA3 transcription factor networks

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • blood vessel development
  • vasculogenesis
  • in utero embryonic development
  • somitogenesis

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
  • sequence-specific DNA binding

Cellular Component

  • nucleus
  • transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000262426
Coding exons
2
Length
3944
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.091612050.7860.000009782406
Missense (PolyPhen)2663.5870.40889775
Synonymous-2.1511992.71.280.00000469764
Loss of Function2.9209.910.004.49e-7115

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Probable transcription activator for a number of lung- specific genes.;
Disease
DISEASE: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) [MIM:265380]: A rare developmental disorder characterized by abnormal development of the capillary vascular system in the lungs. Histological features include failure of formation and ingrowth of alveolar capillaries, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. Affected infants present with respiratory distress and the disease is fatal within the newborn period. Additional features include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs. ACDMPV is a rare cause of persistent pulmonary hypertension of the newborn, an abnormal physiologic state caused by failure of transition of the pulmonary circulation from the high pulmonary vascular resistance of the fetus to the low pulmonary vascular resistance of the newborn. {ECO:0000269|PubMed:19500772, ECO:0000269|PubMed:23505205, ECO:0000269|PubMed:27145217}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.203

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.849

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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