Posterior polymorphous corneal dystrophy 1

Summary

Posterior polymorphous corneal dystrophy 1 (MONDO:0007378) is a disease caused by OVOL2 (GenCC Definitive), with 4 cohort genes.

At a glance

• Causal gene: OVOL2 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	posterior polymorphous corneal dystrophy 1
Mondo ID	MONDO:0007378
OMIM	122000
DOID	DOID:0110855
SNOMED CT	29504002
UMLS	C1852555
MedGen	343836
GARD	0018212
Is cancer (heuristic)	no

Also known as: corneal dystrophy, POSTERIOR polymorphous, 1 · corneal dystrophy, posterior polymorphous, type 1 · Maumenee corneal dystrophy · posterior polymorphous corneal dystrophy type 1 · PPCD1 · Ppcd1

Data availability: 10 ClinVar variants · 5 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 1

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

10 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
224837	NM_001303461.1(OVOL2):c.-297+895_-297+916dup	OVOL2	Pathogenic	no assertion criteria provided
224838	NM_001303461.1(OVOL2):c.-297+886T>C	OVOL2	Pathogenic	no assertion criteria provided
224839	NM_001303461.1(OVOL2):c.-297+949T>C	OVOL2	Pathogenic	no assertion criteria provided
224840	NM_021220.4(OVOL2):c.-274T>G	OVOL2	Pathogenic	no assertion criteria provided
1300211	NM_001174096.2(ZEB1):c.688-1G>A	ZEB1	Likely pathogenic	criteria provided, single submitter
769067	NM_001174089.2(SLC4A11):c.2496G>A (p.Met832Ile)	SLC4A11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5248	NM_014588.6(VSX1):c.479G>A (p.Gly160Asp)	VSX1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2223174	NM_021220.4(OVOL2):c.253G>C (p.Gly85Arg)	OVOL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1178384	NM_021220.4(OVOL2):c.511+7G>A	OVOL2	Benign	criteria provided, multiple submitters, no conflicts
1326982	NM_021220.4(OVOL2):c.512-4T>G	OVOL2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 7 · 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
OVOL2	Definitive	Autosomal dominant	posterior polymorphous corneal dystrophy 1	6
VSX1	Supportive	Autosomal dominant	posterior polymorphous corneal dystrophy	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VSX1	Orphanet:98973	Posterior polymorphous corneal dystrophy
OVOL2	Orphanet:98973	Posterior polymorphous corneal dystrophy
ZEB1	Orphanet:98973	Posterior polymorphous corneal dystrophy
ZEB1	Orphanet:98974	Fuchs endothelial corneal dystrophy
SLC4A11	Orphanet:1490	Corneal dystrophy-perceptive deafness syndrome
SLC4A11	Orphanet:293603	Congenital hereditary endothelial dystrophy type II
SLC4A11	Orphanet:98974	Fuchs endothelial corneal dystrophy

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
VSX1	HGNC:12723	ENSG00000100987	Q9NZR4	Visual system homeobox 1	gencc,clinvar
OVOL2	HGNC:15804	ENSG00000125850	Q9BRP0	Transcription factor Ovo-like 2	gencc,clinvar
ZEB1	HGNC:11642	ENSG00000148516	P37275	Zinc finger E-box-binding homeobox 1	clinvar
SLC4A11	HGNC:16438	ENSG00000088836	Q8NBS3	Solute carrier family 4 member 11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VSX1	Visual system homeobox 1	Binds to the 37-bp core of the locus control region (LCR) of the red/green visual pigment gene cluster.
OVOL2	Transcription factor Ovo-like 2	Zinc-finger transcription repressor factor.
ZEB1	Zinc finger E-box-binding homeobox 1	Acts as a transcriptional repressor.
SLC4A11	Solute carrier family 4 member 11	Multifunctional transporter with an impact in cell morphology and differentiation.

Protein-family classification

Druggable: 0 · Difficult: 3 · Unknown: 1 · 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	3	6.2×	0.013
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VSX1	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
OVOL2	Transcription factor	no		Znf_C2H2_type, Ovo-like, Znf_C2H2_sf
ZEB1	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf
SLC4A11	Other/Unknown	no		HCO3_transpt_euk, HCO3_transpt-like_TM_dom, PTrfase/Anion_transptr

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
olfactory segment of nasal mucosa	2
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
mucosa of transverse colon	1
pancreatic ductal cell	1
calcaneal tendon	1
colonic epithelium	1
tendon	1
metanephros cortex	1
nasal cavity epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VSX1	110	tissue_specific	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
OVOL2	190	broad	yes	pancreatic ductal cell, mucosa of transverse colon, olfactory segment of nasal mucosa
ZEB1	287	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
SLC4A11	197	broad	marker	nasal cavity epithelium, olfactory segment of nasal mucosa, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZEB1	4,171
VSX1	1,133
OVOL2	860
SLC4A11	846

Intra-cohort edges

A	B	Sources
OVOL2	ZEB1	string_interaction
SLC4A11	VSX1	string_interaction
SLC4A11	ZEB1	string_interaction
VSX1	ZEB1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC4A11	Q8NBS3	4
ZEB1	P37275	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
VSX1	Q9NZR4	61.61
OVOL2	Q9BRP0	61.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 4 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 4 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	4213.0×	0.005	ZEB1
borate transport	1	4213.0×	0.005	SLC4A11
negative regulation of white fat cell proliferation	1	4213.0×	0.005	OVOL2
fluid transport	1	1404.3×	0.008	SLC4A11
neural fold formation	1	1053.2×	0.008	OVOL2
endocardium formation	1	1053.2×	0.008	OVOL2
regulation of mesenchymal stem cell differentiation	1	1053.2×	0.008	SLC4A11
negative regulation of endothelial cell differentiation	1	842.6×	0.008	ZEB1
regulation of smooth muscle cell differentiation	1	842.6×	0.008	ZEB1
retinal bipolar neuron differentiation	1	702.2×	0.008	VSX1
regulation of T cell differentiation in thymus	1	601.9×	0.008	ZEB1
semicircular canal morphogenesis	1	601.9×	0.008	ZEB1
monoatomic ion homeostasis	1	601.9×	0.008	SLC4A11
epidermal cell differentiation	1	421.3×	0.010	OVOL2
negative regulation of keratinocyte differentiation	1	421.3×	0.010	OVOL2
regulation of keratinocyte proliferation	1	383.0×	0.010	OVOL2
monoatomic anion transport	1	351.1×	0.010	SLC4A11
cellular hypotonic response	1	351.1×	0.010	SLC4A11
obsolete negative regulation of transcription by competitive promoter binding	1	324.1×	0.010	OVOL2
intracellular monoatomic cation homeostasis	1	280.9×	0.010	SLC4A11
embryonic camera-type eye morphogenesis	1	280.9×	0.010	ZEB1
heart trabecula formation	1	280.9×	0.010	OVOL2
embryonic digestive tract morphogenesis	1	234.1×	0.011	OVOL2
negative regulation of stem cell proliferation	1	210.7×	0.011	OVOL2
bicarbonate transport	1	200.6×	0.011	SLC4A11
regulation of transforming growth factor beta receptor signaling pathway	1	200.6×	0.011	ZEB1
neuron maturation	1	200.6×	0.011	VSX1
positive regulation of keratinocyte differentiation	1	200.6×	0.011	OVOL2
labyrinthine layer blood vessel development	1	200.6×	0.011	OVOL2
negative regulation of keratinocyte proliferation	1	175.5×	0.012	ZEB1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
VSX1	0	0
OVOL2	0	0
ZEB1	0	0
SLC4A11	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	VSX1, OVOL2, ZEB1, SLC4A11

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
VSX1	0	—
OVOL2	0	—
ZEB1	0	—
SLC4A11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.