FOXF1

forkhead box F1, the group of Forkhead boxes

Basic information

Region (hg38): 16:86510526-86515422

Previous symbols: [ "FKHL5" ]

Links

ENSG00000103241 ∙ NCBI:2294 ∙ OMIM:601089 ∙ HGNC:3809 ∙ Uniprot:Q12946 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• alveolar capillary dysplasia with misalignment of pulmonary veins (Definitive), mode of inheritance: AD
• alveolar capillary dysplasia with misalignment of pulmonary veins (Supportive), mode of inheritance: AD
• alveolar capillary dysplasia with misalignment of pulmonary veins (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alveolar capillary dysplasia with misalignment of pulmonary veins	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Genitourinary; Gastrointestinal; Musculoskeletal; Pulmonary	15520767; 19500772; 20425831; 22990143; 23407133; 23444129; 23505205; 24842713

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXF1 gene.

• not provided (48 variants)
• Alveolar capillary dysplasia with pulmonary venous misalignment (44 variants)
• Inborn genetic diseases (16 variants)
• FOXF1-related condition (3 variants)
• not specified (2 variants)
• VATER association (1 variants)
• Abnormal cardiac atrium morphology (1 variants)
• Atresia of urethra;Fetal megacystis;Ventricular septal defect (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	10	5	16
missense	2	7	25	4	3	41
nonsense	5					5
start loss						0
frameshift	9	3	1			13
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			5		9	14
Total	16	10	36	15	17

Variants in FOXF1

This is a list of pathogenic ClinVar variants found in the FOXF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-86510566-C-T		FOXF1-related disorder	Likely benign (Feb 25, 2020)
16-86510568-C-T		Alveolar capillary dysplasia with pulmonary venous misalignment	Uncertain significance (Oct 26, 2018)
16-86510585-G-C		Inborn genetic diseases	Uncertain significance (May 23, 2023)
16-86510589-AG-A		Alveolar capillary dysplasia with pulmonary venous misalignment	Pathogenic (May 07, 2021)
16-86510601-C-A			Uncertain significance (Dec 03, 2022)
16-86510604-ACGG-A			Likely benign (Sep 01, 2023)
16-86510604-ACGGCGG-A			Uncertain significance (Oct 25, 2022)
16-86510604-ACGGCGGCGG-A			Uncertain significance (Aug 28, 2023)
16-86510604-A-ACGG		Alveolar capillary dysplasia with pulmonary venous misalignment • FOXF1-related disorder	Conflicting classifications of pathogenicity (Jan 22, 2024)
16-86510607-G-T		Inborn genetic diseases	Uncertain significance (Jul 05, 2023)
16-86510608-C-CGGCGGA			Uncertain significance (Sep 27, 2022)
16-86510615-G-A		Inborn genetic diseases	Uncertain significance (Dec 14, 2021)
16-86510615-G-GGGCGGCGGCGGCGGGGGA		Alveolar capillary dysplasia with pulmonary venous misalignment	Uncertain significance (Mar 30, 2021)
16-86510623-CGGCG-C		Alveolar capillary dysplasia with pulmonary venous misalignment	Pathogenic (-)
16-86510623-C-CG			Pathogenic (Aug 04, 2020)
16-86510625-G-GCCC			Uncertain significance (Mar 10, 2023)
16-86510626-CGGG-C		Alveolar capillary dysplasia with pulmonary venous misalignment	Conflicting classifications of pathogenicity (Jan 29, 2024)
16-86510639-G-A		Inborn genetic diseases	Uncertain significance (Dec 26, 2023)
16-86510642-GC-G			Pathogenic (Jan 19, 2018)
16-86510654-G-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2023)
16-86510658-C-A		Alveolar capillary dysplasia with pulmonary venous misalignment	Pathogenic (Oct 01, 2019)
16-86510659-G-C			Likely benign (Jul 16, 2018)
16-86510664-G-A		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
16-86510667-C-A			Uncertain significance (Dec 02, 2021)
16-86510667-C-T		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXF1	protein_coding	protein_coding	ENST00000262426	2	3944

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.958	0.0420	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	161	205	0.786	0.00000978	2406
Missense in Polyphen		26	63.587	0.40889		775
Synonymous	-2.15	119	92.7	1.28	0.00000469	764
Loss of Function	2.92	0	9.91	0.00	4.49e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.203

Haploinsufficiency Scores

• pHI: 0.359
• hipred: Y
• hipred_score: 0.837
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.849

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Foxf1
• Phenotype: muscle phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; embryo phenotype; respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: foxf1
• Affected structure: vascular lymphangioblast
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;blood vessel development;vasculogenesis;in utero embryonic development;somitogenesis;morphogenesis of a branching structure;positive regulation of mesenchymal cell proliferation;endocardial cushion development;cardiac left ventricle morphogenesis;smoothened signaling pathway;determination of left/right symmetry;midgut development;heart development;positive regulation of cell-substrate adhesion;detection of wounding;extracellular matrix organization;respiratory tube development;lung development;positive regulation of cell migration;pancreas development;negative regulation of mast cell degranulation;establishment of epithelial cell apical/basal polarity;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;lung alveolus development;lateral mesodermal cell differentiation;embryonic digestive tract morphogenesis;digestive tract development;embryonic ectodermal digestive tract morphogenesis;embryonic foregut morphogenesis;negative regulation of inflammatory response;smooth muscle cell differentiation;regulation of smooth muscle cell differentiation;lung vasculature development;trachea development;epithelial tube branching involved in lung morphogenesis;right lung morphogenesis;lung lobe morphogenesis;venous blood vessel development;epithelial cell differentiation involved in mammary gland alveolus development;cellular response to cytokine stimulus;cellular response to organic cyclic compound;renal system development;ureter development;mesenchyme migration;ductus arteriosus closure;cell-cell adhesion
• Cellular component: nucleus;transcription factor complex
• 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