FOXC1
forkhead box C1, the group of Forkhead boxes
Basic information
Region (hg38): 6:1609914-1613897
Previous symbols: [ "FKHL7", "IRID1" ]
Links
Phenotypes
GenCC
Source:
- Axenfeld-Rieger syndrome type 3 (Definitive), mode of inheritance: AD
- Peters anomaly (Definitive), mode of inheritance: AD
- anterior segment dysgenesis 3 (Definitive), mode of inheritance: AD
- aniridia (Strong), mode of inheritance: AD
- Axenfeld-Rieger syndrome type 3 (Strong), mode of inheritance: AD
- Peters anomaly (Supportive), mode of inheritance: AD
- Axenfeld-Rieger syndrome (Supportive), mode of inheritance: AD
- Rieger anomaly (Supportive), mode of inheritance: AD
- Axenfeld anomaly (Supportive), mode of inheritance: AD
- isolated aniridia (Supportive), mode of inheritance: AD
- anterior segment dysgenesis 3 (Strong), mode of inheritance: AD
- Axenfeld-Rieger syndrome type 3 (Strong), mode of inheritance: AD
- anterior segment dysgenesis 3 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Axenfeld-Rieger syndrome, type 3; Anterior segment dysgenesis 3 | AD | Cardiovascular; Ophthalmologic; Pharmacogenomic | Individuals with Axenfeld-Rieger anomaly have a high risk of developing glaucoma, but treatment may not be effective in the majority of cases; Awareness of cardiac anomalies (eg, valvular anomalies leading to congestive heart failure have been described) may allow early detection and treatment; Agents that may contribute to glaucoma should be avoided | Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal; Ophthalmologic | 9445211; 9792859; 9620769; 11004268; 11007653; 10713890; 12036988; 11170889; 12036988; 12614756; 12614756; 17197537; 18498376; 19668217; 19793056; 23239455 |
ClinVar
This is a list of variants' phenotypes submitted to
- Axenfeld-Rieger syndrome type 3 (376 variants)
- not provided (103 variants)
- Inborn genetic diseases (34 variants)
- Axenfeld-Rieger syndrome type 3;Anterior segment dysgenesis 3 (19 variants)
- not specified (17 variants)
- Anterior segment dysgenesis 3 (11 variants)
- FOXC1-related condition (9 variants)
- Anterior segment dysgenesis 3;Axenfeld-Rieger syndrome type 3 (9 variants)
- Axenfeld-Rieger anomaly with partially absent eye muscles, distinctive face, hydrocephaly, and skeletal abnormalities (2 variants)
- Congenital anomaly of kidney and urinary tract (2 variants)
- Anterior segment dysgenesis (2 variants)
- Hypertelorism and tetralogy of fallot (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 FOXC1 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 | 101 | 117 | ||||
| missense | 10 | 11 | 171 | 197 | ||
| nonsense | 21 | 24 | ||||
| start loss | 0 | |||||
| frameshift | 38 | 13 | 52 | |||
| inframe indel | 34 | 53 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 10 | |||||
| Total | 71 | 29 | 215 | 114 | 24 |
Highest pathogenic variant AF is 0.0000137
Variants in FOXC1
This is a list of pathogenic ClinVar variants found in the FOXC1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FOXC1 | protein_coding | protein_coding | ENST00000380874 | 1 | 3447 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.953 | 0.0465 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.342 | 213 | 228 | 0.936 | 0.0000109 | 3504 |
| Missense in Polyphen | 58 | 92.546 | 0.62672 | 1311 | ||
| Synonymous | -4.90 | 167 | 104 | 1.61 | 0.00000542 | 1162 |
| Loss of Function | 2.88 | 0 | 9.63 | 0.00 | 4.16e-7 | 139 |
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:
- Function
- FUNCTION: DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development (PubMed:11782474, PubMed:15299087, PubMed:15684392, PubMed:16492674, PubMed:27907090, PubMed:14506133, PubMed:14578375, PubMed:15277473, PubMed:16449236, PubMed:17210863, PubMed:19793056, PubMed:19279310, PubMed:25786029, PubMed:27804176). Acts either as a transcriptional activator or repressor (PubMed:11782474). Binds to the consensus binding site 5'-[G/C][A/T]AAA[T/C]AA[A/C]-3' in promoter of target genes (PubMed:7957066, PubMed:11782474, PubMed:12533514, PubMed:14506133, PubMed:19793056, PubMed:27804176). Upon DNA-binding, promotes DNA bending (PubMed:7957066, PubMed:14506133). Acts as a transcriptional coactivator (PubMed:26565916). Stimulates Indian hedgehog (Ihh)- induced target gene expression mediated by the transcription factor GLI2, and hence regulates endochondral ossification (By similarity). Acts also as a transcriptional coregulator by increasing DNA-binding capacity of GLI2 in breast cancer cells (PubMed:26565916). Regulates FOXO1 through binding to a conserved element, 5'-GTAAACAAA-3' in its promoter region, implicating FOXC1 as an important regulator of cell viability and resistance to oxidative stress in the eye (PubMed:17993506). Cooperates with transcription factor FOXC2 in regulating expression of genes that maintain podocyte integrity (By similarity). Promotes cell growth inhibition by stopping the cell cycle in the G1 phase through TGFB1-mediated signals (PubMed:12408963). Involved in epithelial- mesenchymal transition (EMT) induction by increasing cell proliferation, migration and invasion (PubMed:20406990, PubMed:22991501). Involved in chemokine CXCL12-induced endothelial cell migration through the control of CXCR4 expression (By similarity). Plays a role in the gene regulatory network essential for epidermal keratinocyte terminal differentiation (PubMed:27907090). Essential developmental transcriptional factor required for mesoderm-derived tissues, such as the somites, skin, bone and cartilage. Positively regulates CXCL12 and stem cell factor expression in bone marrow mesenchymal progenitor cells, and hence plays a role in the development and maintenance of mesenchymal niches for haematopoietic stem and progenitor cells (HSPC). Plays a role in corneal transparency by preventing both blood vessel and lymphatic vessel growth during embryonic development in a VEGF-dependent manner. Involved in chemokine CXCL12-induced endothelial cell migration through the control of CXCR4 expression (By similarity). May function as a tumor suppressor (PubMed:12408963). {ECO:0000250|UniProtKB:Q61572, ECO:0000269|PubMed:11782474, ECO:0000269|PubMed:12408963, ECO:0000269|PubMed:12533514, ECO:0000269|PubMed:14506133, ECO:0000269|PubMed:14578375, ECO:0000269|PubMed:15277473, ECO:0000269|PubMed:15299087, ECO:0000269|PubMed:15684392, ECO:0000269|PubMed:16449236, ECO:0000269|PubMed:16492674, ECO:0000269|PubMed:17210863, ECO:0000269|PubMed:17993506, ECO:0000269|PubMed:19279310, ECO:0000269|PubMed:19793056, ECO:0000269|PubMed:20406990, ECO:0000269|PubMed:22991501, ECO:0000269|PubMed:25786029, ECO:0000269|PubMed:26565916, ECO:0000269|PubMed:27804176, ECO:0000269|PubMed:27907090, ECO:0000269|PubMed:7957066}.;
- Disease
- DISEASE: Axenfeld-Rieger syndrome 3 (RIEG3) [MIM:602482]: An autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals. Features include posterior corneal embryotoxon, prominent Schwalbe line and iris adhesion to the Schwalbe line, hypertelorism, hypodontia, sensorineural deafness, redundant periumbilical skin, and cardiovascular defects such as patent ductus arteriosus and atrial septal defect. When associated with tooth anomalies, the disorder is known as Rieger syndrome. {ECO:0000269|PubMed:11170889, ECO:0000269|PubMed:11179011, ECO:0000269|PubMed:11589884, ECO:0000269|PubMed:11740218, ECO:0000269|PubMed:12454026, ECO:0000269|PubMed:12592227, ECO:0000269|PubMed:14506133, ECO:0000269|PubMed:14578375, ECO:0000269|PubMed:15277473, ECO:0000269|PubMed:15477465, ECO:0000269|PubMed:16449236, ECO:0000269|PubMed:16936096, ECO:0000269|PubMed:17210863, ECO:0000269|PubMed:17653043, ECO:0000269|PubMed:19279310, ECO:0000269|PubMed:23239455, ECO:0000269|PubMed:24914578, ECO:0000269|PubMed:25786029, ECO:0000269|PubMed:27804176, ECO:0000269|PubMed:9792859}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Anterior segment dysgenesis 3 (ASGD3) [MIM:601631]: A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD3 inheritance is autosomal dominant. {ECO:0000269|PubMed:12614756, ECO:0000269|PubMed:18484311, ECO:0000269|PubMed:19279310, ECO:0000269|PubMed:19793056, ECO:0000269|PubMed:20881294, ECO:0000269|PubMed:9620769}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- HH-Core;Heart Development;Mesodermal Commitment Pathway;BMP Signaling Pathway in Eyelid Development
(Consensus)
Recessive Scores
- pRec
- 0.299
Haploinsufficiency Scores
- pHI
- 0.713
- hipred
- hipred_score
- ghis
- 0.601
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.323
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Foxc1
- Phenotype
- endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; pigmentation 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); normal phenotype; reproductive 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); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype;
Zebrafish Information Network
- Gene name
- foxc1b
- Affected structure
- blood vessel morphogenesis
- Phenotype tag
- abnormal
- Phenotype quality
- disrupted
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;angiogenesis;ovarian follicle development;eye development;ureteric bud development;in utero embryonic development;somitogenesis;kidney development;lymph vessel development;endochondral ossification;blood vessel remodeling;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;Notch signaling pathway;heart development;cell population proliferation;germ cell migration;anatomical structure morphogenesis;positive regulation of epithelial to mesenchymal transition;mesenchymal cell development;neural crest cell development;cell migration;negative regulation of angiogenesis;cerebellum development;cell differentiation;collagen fibril organization;glycosaminoglycan metabolic process;lacrimal gland development;embryonic heart tube development;maintenance of lens transparency;vascular endothelial growth factor signaling pathway;odontogenesis of dentin-containing tooth;camera-type eye development;positive regulation of DNA binding;positive regulation of keratinocyte differentiation;positive regulation of transcription, DNA-templated;negative regulation of mitotic cell cycle;positive regulation of transcription by RNA polymerase II;regulation of organ growth;vascular endothelial growth factor receptor signaling pathway;paraxial mesoderm formation;artery morphogenesis;regulation of blood vessel size;ventricular cardiac muscle tissue morphogenesis;cardiac muscle cell proliferation;chemokine-mediated signaling pathway;cellular response to epidermal growth factor stimulus;glomerular epithelium development;negative regulation of lymphangiogenesis;positive regulation of hematopoietic progenitor cell differentiation;positive regulation of hematopoietic stem cell differentiation;negative regulation of apoptotic process involved in outflow tract morphogenesis;positive regulation of core promoter binding;cellular response to chemokine
- Cellular component
- nucleus;nucleoplasm;nuclear heterochromatin;cytosol
- Molecular function
- RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;transcription coactivator binding;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;transcription factor binding;DNA binding, bending;sequence-specific DNA binding;transcription regulatory region DNA binding;promoter-specific chromatin binding