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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FOXC1
forkhead box C1
Chromosome 6 Β· 6p25.3
NCBI Gene: 2296Ensembl: ENSG00000054598.9HGNC: HGNC:3800UniProt: Q12948
249PubMed Papers
22Diseases
0Drugs
152Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of epithelial to mesenchymal transitionprotein bindingcell migrationDNA binding, bendingRieger anomalyAxenfeld-Rieger syndromeAxenfeld-Rieger syndrome type 3Axenfeld anomaly
✦AI Summary

FOXC1 is a forkhead box transcription factor that functions as a DNA-binding regulator acting either as a transcriptional activator or repressor 1. It binds consensus sequences in target gene promoters and promotes DNA bending upon binding 1. FOXC1 plays essential roles in multiple developmental processes including eye, bone, cardiovascular, kidney, and skin development 1. Mechanistically, FOXC1 regulates endochondral ossification through cooperation with GLI2 in hedgehog signaling and maintains cell viability through FOXO1 regulation 1. It also promotes epithelial-mesenchymal transition and induces cell cycle arrest in the G1 phase via TGFB1-mediated signals, suggesting tumor suppressor potential 1. In disease contexts, FOXC1 mutations cause anterior segment dysgenesis and Axenfeld-Rieger syndrome 1. FOXC1 is significantly overexpressed in triple-negative breast cancer (TNBC) and serves as a highly specific diagnostic marker for the triple-negative phenotype 2. In TNBC, FOXC1 expression associates with aggressive tumor phenotypes and is regulated by TNBC-specific super-enhancers 3. Additionally, FOXC1 loss in valvular endothelial cells causes myxomatous mitral valve degeneration through disrupted junctions and lymphatic vessel dysfunction 4. Recent evidence demonstrates FOXC1 regulates insulin signaling genes (Insr, Irs1) in skeletal muscle, contributing to metabolic health 5. FOXC1 functions as a conserved oncogenic driver in TNBC parallel to FOXA1 in estrogen receptor-positive breast cancer, cooperating with nuclear receptor NR2F2 6.

Sources cited
1
FOXC1 is a forkhead box DNA-binding transcription factor acting as activator or repressor in development; mutations cause congenital disorders
PMID: 15492844
2
FOXC1 is highly expressed in triple-negative breast cancer and is a specific diagnostic marker for the triple-negative phenotype with aggressive phenotype associations
PMID: 34784418
3
FOXC1 is specifically regulated by TNBC-specific super-enhancers and is an overexpressed key oncogene in triple-negative breast cancer
PMID: 33854062
4
FOXC1 and FOXC2 are required in valvular endothelial cells for maintaining mitral valve integrity, junctions, ECM organization, and lymphatic vessel function
PMID: 38989578
5
FOXC1 acts as transcriptional activator of insulin signaling genes (Insr and Irs1) in skeletal muscle and contributes to metabolic health
PMID: 40632872
6
FOXC1 is a conserved oncogenic driver in TNBC functioning in parallel to FOXA1 in ER+ breast cancer, cooperating with nuclear receptor NR2F2
PMID: 39171293
Disease Associationsβ“˜22
Rieger anomalyOpen Targets
0.81Strong
Axenfeld-Rieger syndromeOpen Targets
0.78Strong
Axenfeld-Rieger syndrome type 3Open Targets
0.65Moderate
Axenfeld anomalyOpen Targets
0.64Moderate
Peters anomalyOpen Targets
0.56Moderate
hypertensionOpen Targets
0.52Moderate
coronary artery diseaseOpen Targets
0.46Moderate
Ocular anterior segment dysgenesisOpen Targets
0.46Moderate
anterior segment dysgenesisOpen Targets
0.46Moderate
glaucomaOpen Targets
0.45Moderate
Axenfeld-Rieger anomaly with partially absent eye muscles, distinctive face, hydrocephaly, and skeletal abnormalitiesOpen Targets
0.43Moderate
open-angle glaucomaOpen Targets
0.43Moderate
Increased blood pressureOpen Targets
0.42Moderate
cardiovascular diseaseOpen Targets
0.42Moderate
congenital hydronephrosisOpen Targets
0.41Moderate
congenital anomaly of kidney and urinary tractOpen Targets
0.39Weak
aniridiaOpen Targets
0.39Weak
isolated aniridiaOpen Targets
0.38Weak
hearing lossOpen Targets
0.37Weak
Hearing impairmentOpen Targets
0.37Weak
Anterior segment dysgenesis 3UniProt
Axenfeld-Rieger syndrome 3UniProt
Pathogenic Variants152
NM_001453.3(FOXC1):c.141C>G (p.Tyr47Ter)Pathogenic
not provided|Axenfeld-Rieger syndrome type 3|Axenfeld-Rieger syndrome type 3;Anterior segment dysgenesis 3
β˜…β˜…β˜†β˜†2026β†’ Residue 47
NM_001453.3(FOXC1):c.599_617del (p.Gln200fs)Pathogenic
Axenfeld-Rieger syndrome type 3|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 200
NM_001453.3(FOXC1):c.274C>T (p.Gln92Ter)Pathogenic
Axenfeld-Rieger syndrome type 3
β˜…β˜…β˜†β˜†2025β†’ Residue 92
NM_001453.3(FOXC1):c.392C>T (p.Ser131Leu)Pathogenic
Anterior segment dysgenesis 3|Axenfeld-Rieger syndrome type 3|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 131
NM_001453.3(FOXC1):c.718_719del (p.Leu240fs)Pathogenic
Axenfeld-Rieger syndrome type 3|Anterior segment dysgenesis 3
β˜…β˜…β˜†β˜†2025β†’ Residue 240
NM_001453.3(FOXC1):c.1179C>G (p.Tyr393Ter)Pathogenic
Axenfeld-Rieger syndrome type 3|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 393
NM_001453.3(FOXC1):c.772G>T (p.Glu258Ter)Pathogenic
not provided|Axenfeld-Rieger syndrome type 3
β˜…β˜…β˜†β˜†2025β†’ Residue 258
NM_001453.3(FOXC1):c.821del (p.Pro274fs)Pathogenic
Axenfeld-Rieger syndrome type 3|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 274
NM_001453.3(FOXC1):c.208C>T (p.Gln70Ter)Pathogenic
Axenfeld-Rieger syndrome type 3|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 70
NM_001453.3(FOXC1):c.752_759del (p.Ala251fs)Pathogenic
Axenfeld-Rieger syndrome type 3|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 251
NM_001453.3(FOXC1):c.821dup (p.Ser276fs)Pathogenic
Axenfeld-Rieger syndrome type 3|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 276
NM_001453.3(FOXC1):c.256C>T (p.Leu86Phe)Pathogenic
not provided|Axenfeld-Rieger syndrome type 3
β˜…β˜…β˜†β˜†2024β†’ Residue 86
NM_001453.3(FOXC1):c.366G>A (p.Trp122Ter)Pathogenic
Axenfeld-Rieger syndrome type 3
β˜…β˜…β˜†β˜†2024β†’ Residue 122
NM_001453.3(FOXC1):c.404G>A (p.Cys135Tyr)Likely pathogenic
FOXC1-related disorder|Anterior segment dysgenesis 3;Axenfeld-Rieger syndrome type 3
β˜…β˜…β˜†β˜†2024β†’ Residue 135
NM_001453.3(FOXC1):c.508C>T (p.Arg170Trp)Pathogenic
Axenfeld-Rieger syndrome type 3
β˜…β˜…β˜†β˜†2024β†’ Residue 170
NM_001453.3(FOXC1):c.380G>T (p.Arg127Leu)Pathogenic
not provided|Axenfeld-Rieger syndrome type 3
β˜…β˜…β˜†β˜†2024β†’ Residue 127
NM_001453.3(FOXC1):c.316C>T (p.Gln106Ter)Pathogenic
Axenfeld-Rieger syndrome type 3|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 106
NM_001453.3(FOXC1):c.1297_1298del (p.Leu433fs)Pathogenic
not provided|Axenfeld-Rieger syndrome type 3
β˜…β˜…β˜†β˜†2023β†’ Residue 433
NM_001453.3(FOXC1):c.81_100del (p.Ala28fs)Pathogenic
Axenfeld-Rieger syndrome type 3|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 28
NM_001453.3(FOXC1):c.380G>A (p.Arg127His)Pathogenic
Axenfeld-Rieger syndrome type 3|FOXC1-related disorder
β˜…β˜…β˜†β˜†2022β†’ Residue 127
View on ClinVar β†—
Related Genes
PAX6Protein interaction98%GMDSProtein interaction89%PBX1Protein interaction87%PITX2Protein interaction83%GLI2Protein interaction48%FOXC2Shared pathway16%
Tissue Expression6 tissues
Heart
100%
Brain
86%
Ovary
51%
Lung
29%
Bone Marrow
17%
Liver
7%
Gene Interaction Network
Click a node to explore
FOXC1PAX6GMDSPBX1PITX2GLI2FOXC2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q12948
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.28LoF Tolerant
pLIβ“˜
0.05Tolerant
Observed/Expected LoF0.61 [0.32–1.28]
RankingsWhere FOXC1 stands among ~20K protein-coding genes
  • #1,548of 20,598
    Most Researched249 Β· top 10%
  • #501of 5,498
    Most Pathogenic Variants152 Β· top 10%
  • #13,445of 17,882
    Most Constrained (LOEUF)1.28
Genes detectedFOXC1
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
Human FOX gene family (Review).
PMID: 15492844
Int J Oncol Β· 2004
1.00
2
FOXC1.
PMID: 34784418
Arch Pathol Lab Med Β· 2022
0.90
3
Prognostic Significance of FOXC1 in Various Cancers: A Systematic Review and Meta-Analysis.
PMID: 31372939
Mol Diagn Ther Β· 2019
0.88
4
Molecular Subtyping of Triple-Negative Breast Cancers by Immunohistochemistry: Molecular Basis and Clinical Relevance.
PMID: 32406563
Oncologist Β· 2020
0.80
5
The human genetic variant rs6190 unveils Foxc1 and Arid5a as novel prometabolic targets of the glucocorticoid receptor in muscle.
PMID: 40632872
Sci Adv Β· 2025
0.70