corneal dystrophy, Fuchs endothelial, 6

Summary

corneal dystrophy, Fuchs endothelial, 6 (MONDO:0013206) is a disease caused by ZEB1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ZEB1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	corneal dystrophy, Fuchs endothelial, 6
Mondo ID	MONDO:0013206
MeSH	C567675
OMIM	613270
UMLS	C2750448
MedGen	442478
GARD	0018221
Is cancer (heuristic)	no

Also known as: corneal dystrophy, Fuchs endothelial, 6 · corneal dystrophy, Fuchs endothelial, type 6 · FECD6 · Fuchs’ endothelial dystrophy caused by mutation in ZEB1 · ZEB1 Fuchs’ endothelial dystrophy

Data availability: 12 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › corneal disorder › corneal dystrophy › corneal endothelial dystrophy › Fuchs’ endothelial dystrophy › corneal dystrophy, Fuchs endothelial, 6

Related subtypes (7): corneal dystrophy, Fuchs endothelial, 1, corneal dystrophy, fuchs endothelial, 2, corneal dystrophy, Fuchs endothelial, 3, corneal dystrophy, Fuchs endothelial, 4, corneal dystrophy, fuchs endothelial, 5, corneal dystrophy, fuchs endothelial, 7, corneal dystrophy, Fuchs endothelial, 8

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

12 retrieved; paginated sample, class counts are floors:

3 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 benign/likely benign, 2 pathogenic/likely pathogenic, 1 benign, 1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
488897	NM_001174096.2(ZEB1):c.3G>A (p.Met1Ile)	LOC130003630	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691711	NM_001174096.2(ZEB1):c.1093dup (p.Ile365fs)	ZEB1	Pathogenic/Likely pathogenic	criteria provided, single submitter
2443788	NM_001174096.2(ZEB1):c.1923G>T (p.Gln641His)	ZEB1	Pathogenic	no assertion criteria provided
1032236	NM_001174096.2(ZEB1):c.504del (p.Gln169fs)	ZEB1	Likely pathogenic	criteria provided, single submitter
2444117	NM_001174096.2(ZEB1):c.831del (p.Ser279fs)	ZEB1	Likely pathogenic	criteria provided, single submitter
4532235	NM_001174096.2(ZEB1):c.361C>T (p.Gln121Ter)	ZEB1	Likely pathogenic	criteria provided, single submitter
12634	NM_001174096.2(ZEB1):c.2522A>C (p.Gln841Pro)	ZEB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3610325	NM_001174096.2(ZEB1):c.1691C>A (p.Ala564Glu)	ZEB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3382620	NM_001174096.2(ZEB1):c.593A>C (p.Glu198Ala)	ZEB1	Uncertain significance	criteria provided, single submitter
12633	NM_001174096.2(ZEB1):c.233A>C (p.Asn78Thr)	ZEB1	Benign	criteria provided, multiple submitters, no conflicts
1536748	NM_001174096.2(ZEB1):c.699G>A (p.Thr233=)	ZEB1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
709250	NM_001174096.2(ZEB1):c.2414T>C (p.Ile805Thr)	ZEB1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ZEB1	Definitive	Autosomal dominant	posterior polymorphous corneal dystrophy 3	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZEB1	Orphanet:98973	Posterior polymorphous corneal dystrophy
ZEB1	Orphanet:98974	Fuchs endothelial corneal dystrophy

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
ZEB1	HGNC:11642	ENSG00000148516	P37275	Zinc finger E-box-binding homeobox 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZEB1	Zinc finger E-box-binding homeobox 1	Acts as a transcriptional repressor.

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)
ZEB1	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf

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
calcaneal tendon	1
colonic epithelium	1
tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZEB1	287	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZEB1	4,171

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ZEB1	P37275	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	878.5×	0.003	ZEB1
Negative Regulation of CDH1 Gene Transcription	1	120.2×	0.010	ZEB1
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.010	ZEB1

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
regulation of mesenchymal cell proliferation	1	16852.0×	0.001	ZEB1
negative regulation of endothelial cell differentiation	1	3370.4×	0.002	ZEB1
regulation of smooth muscle cell differentiation	1	3370.4×	0.002	ZEB1
regulation of T cell differentiation in thymus	1	2407.4×	0.002	ZEB1
semicircular canal morphogenesis	1	2407.4×	0.002	ZEB1
embryonic camera-type eye morphogenesis	1	1123.5×	0.003	ZEB1
regulation of transforming growth factor beta receptor signaling pathway	1	802.5×	0.004	ZEB1
negative regulation of keratinocyte proliferation	1	702.2×	0.004	ZEB1
keratinocyte proliferation	1	581.1×	0.004	ZEB1
cochlea morphogenesis	1	581.1×	0.004	ZEB1
pattern specification process	1	468.1×	0.004	ZEB1
embryonic skeletal system morphogenesis	1	391.9×	0.004	ZEB1
cellular response to amino acid stimulus	1	306.4×	0.005	ZEB1
cartilage development	1	251.5×	0.006	ZEB1
positive regulation of neuron differentiation	1	198.3×	0.007	ZEB1
central nervous system development	1	115.4×	0.011	ZEB1
negative regulation of DNA-templated transcription	1	31.6×	0.039	ZEB1
cell differentiation	1	29.1×	0.040	ZEB1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.062	ZEB1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.071	ZEB1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ZEB1

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
ZEB1	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	ZEB1

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)
ZEB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.