Posterior polymorphous corneal dystrophy 3

Summary

Posterior polymorphous corneal dystrophy 3 (MONDO:0012200) is a disease caused by ZEB1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ZEB1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	posterior polymorphous corneal dystrophy 3
Mondo ID	MONDO:0012200
MeSH	C563788
OMIM	609141
DOID	DOID:0110857
UMLS	C1836724
MedGen	322978
GARD	0018214
Is cancer (heuristic)	no

Also known as: corneal dystrophy, POSTERIOR polymorphous, 3 · corneal dystrophy, posterior polymorphous, type 3 · posterior polymorphous corneal dystrophy caused by mutation in ZEB1 · posterior polymorphous corneal dystrophy type 3 · PPCD3 · Ppcd3 · ZEB1 posterior polymorphous corneal dystrophy

Data availability: 11 ClinVar variants · 3 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 › posterior polymorphous corneal dystrophy › posterior polymorphous corneal dystrophy 3

Related subtypes (3): posterior polymorphous corneal dystrophy 1, posterior polymorphous corneal dystrophy 2, corneal dystrophy, posterior polymorphous, 4

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

11 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
2443790	NM_001174096.2(ZEB1):c.1A>C (p.Met1Leu)	LOC130003630	Pathogenic	no assertion criteria provided
488897	NM_001174096.2(ZEB1):c.3G>A (p.Met1Ile)	LOC130003630	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12631	NM_001174096.2(ZEB1):c.2919_2920del (p.Gly974fs)	ZEB1	Pathogenic	no assertion criteria provided
12632	NM_001174096.2(ZEB1):c.1351C>T (p.Gln451Ter)	ZEB1	Pathogenic	no assertion criteria provided
2443789	NM_001174096.2(ZEB1):c.2252C>A (p.Ser751Ter)	ZEB1	Pathogenic	no assertion criteria provided
2664719	NM_001174096.2(ZEB1):c.692_693del (p.His231fs)	ZEB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4292343	NM_001174096.2(ZEB1):c.1448del (p.Pro483fs)	ZEB1	Likely pathogenic	criteria provided, single submitter
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
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.