FOXC1-related anterior segment dysgenesis

Summary

FOXC1-related anterior segment dysgenesis (MONDO:0100235) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	FOXC1-related anterior segment dysgenesis
Mondo ID	MONDO:0100235
GARD	0026091
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › anterior segment dysgenesis › iridogoniodysgenesis › FOXC1-related anterior segment dysgenesis

Related subtypes (6): congenital microcoria, aniridia-cerebellar ataxia-intellectual disability syndrome, chromosome 6pter-p24 deletion syndrome, bilateral acute depigmentation of the iris, Rieger anomaly, congenital ectropion uveae

Subtypes (2): Axenfeld-Rieger syndrome type 3, anterior segment dysgenesis 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
4532023	NM_001453.3(FOXC1):c.247T>C (p.Tyr83His)	FOXC1	Likely pathogenic	criteria provided, single submitter
4532024	NM_001453.3(FOXC1):c.1405C>A (p.Arg469Ser)	FOXC1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FOXC1	Orphanet:250923	Isolated aniridia
FOXC1	Orphanet:708	Peters anomaly
FOXC1	Orphanet:782	Axenfeld-Rieger syndrome
FOXC1	Orphanet:91483	Rieger anomaly
FOXC1	Orphanet:98978	Axenfeld anomaly

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FOXC1	HGNC:3800	ENSG00000054598	Q12948	Forkhead box protein C1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FOXC1	Forkhead box protein C1	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.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FOXC1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
parotid gland	1
trigeminal ganglion	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FOXC1	267	ubiquitous	marker	parotid gland, vena cava, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FOXC1	2,896

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FOXC1	Q12948	56.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of intermediate mesoderm	1	1427.5×	0.001	FOXC1
Formation of the ureteric bud	1	496.5×	0.002	FOXC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glomerular epithelium development	1	16852.0×	0.001	FOXC1
positive regulation of hematopoietic stem cell differentiation	1	16852.0×	0.001	FOXC1
apoptotic process involved in outflow tract morphogenesis	1	8426.0×	0.001	FOXC1
negative regulation of apoptotic process involved in outflow tract morphogenesis	1	8426.0×	0.001	FOXC1
positive regulation of core promoter binding	1	8426.0×	0.001	FOXC1
negative regulation of lymphangiogenesis	1	5617.3×	0.001	FOXC1
positive regulation of hematopoietic progenitor cell differentiation	1	5617.3×	0.001	FOXC1
paraxial mesoderm formation	1	3370.4×	0.002	FOXC1
mesenchymal cell development	1	2407.4×	0.002	FOXC1
glycosaminoglycan metabolic process	1	2407.4×	0.002	FOXC1
lacrimal gland development	1	2106.5×	0.002	FOXC1
maintenance of lens transparency	1	2106.5×	0.002	FOXC1
regulation of organ growth	1	2106.5×	0.002	FOXC1
lymph vessel development	1	1872.4×	0.002	FOXC1
primordial germ cell migration	1	1872.4×	0.002	FOXC1
positive regulation of DNA binding	1	1203.7×	0.003	FOXC1
vascular endothelial growth factor signaling pathway	1	1053.2×	0.003	FOXC1
cellular response to chemokine	1	991.3×	0.003	FOXC1
neural crest cell development	1	802.5×	0.003	FOXC1
positive regulation of keratinocyte differentiation	1	802.5×	0.003	FOXC1
negative regulation of mitotic cell cycle	1	802.5×	0.003	FOXC1
embryonic heart tube development	1	766.0×	0.003	FOXC1
ventricular cardiac muscle tissue morphogenesis	1	702.2×	0.003	FOXC1
artery morphogenesis	1	674.1×	0.003	FOXC1
blood vessel diameter maintenance	1	624.1×	0.004	FOXC1
cardiac muscle cell proliferation	1	581.1×	0.004	FOXC1
endochondral ossification	1	543.6×	0.004	FOXC1
vascular endothelial growth factor receptor signaling pathway	1	481.5×	0.004	FOXC1
ureteric bud development	1	455.5×	0.004	FOXC1
ovarian follicle development	1	391.9×	0.005	FOXC1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FOXC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FOXC1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FOXC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.