Posterior polymorphous corneal dystrophy 2

Summary

Posterior polymorphous corneal dystrophy 2 (MONDO:0012199) is a disease caused by COL8A2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: COL8A2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	posterior polymorphous corneal dystrophy 2
Mondo ID	MONDO:0012199
MeSH	C565176
OMIM	609140
DOID	DOID:0110856
UMLS	C1852795
MedGen	377757
GARD	0018213
Is cancer (heuristic)	no

Also known as: COL8A2 posterior polymorphous corneal dystrophy · corneal dystrophy, posterior polymorphous 2 · corneal dystrophy, POSTERIOR polymorphous, 2 · corneal dystrophy, posterior polymorphous, type 2 · posterior polymorphous corneal dystrophy caused by mutation in COL8A2 · posterior polymorphous corneal dystrophy type 2 · PPCD2 · Ppcd2

Data availability: 6 ClinVar variants · 1 GenCC gene-disease record.

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 2

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

6 retrieved; paginated sample, class counts are floors:

2 benign, 2 pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
17147	NM_005202.4(COL8A2):c.1363C>A (p.Gln455Lys)	COL8A2	Pathogenic	no assertion criteria provided
17148	NM_005202.4(COL8A2):c.1349T>G (p.Leu450Trp)	COL8A2	Pathogenic	no assertion criteria provided
3495812	NM_005202.4(COL8A2):c.872C>A (p.Pro291Gln)	COL8A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779152	NM_005202.4(COL8A2):c.1576_1583del (p.Pro526fs)	COL8A2	Uncertain significance	criteria provided, single submitter
1238973	NM_005202.4(COL8A2):c.*12G>T	COL8A2	Benign	criteria provided, multiple submitters, no conflicts
1255398	NM_005202.4(COL8A2):c.193+34C>T	COL8A2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
COL8A2	Strong	Autosomal dominant	posterior polymorphous corneal dystrophy 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL8A2	Orphanet:98973	Posterior polymorphous corneal dystrophy
COL8A2	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
COL8A2	HGNC:2216	ENSG00000171812	P25067	Collagen alpha-2(VIII) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL8A2	Collagen alpha-2(VIII) chain	Macromolecular component of the subendothelium.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL8A2	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom

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
ascending aorta	1
periodontal ligament	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL8A2	230	broad	marker	periodontal ligament, tendon of biceps brachii, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL8A2	1,544

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL8A2	P25067	58.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Collagen chain trimerization	1	259.6×	0.007	COL8A2
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL8A2
Collagen degradation	1	175.7×	0.007	COL8A2
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL8A2
Integrin cell surface interactions	1	134.3×	0.007	COL8A2

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
basement membrane assembly	1	1872.4×	0.003	COL8A2
camera-type eye morphogenesis	1	766.0×	0.004	COL8A2
endothelial cell proliferation	1	543.6×	0.004	COL8A2
extracellular matrix organization	1	122.1×	0.012	COL8A2
cell-cell adhesion	1	101.5×	0.012	COL8A2
angiogenesis	1	62.4×	0.016	COL8A2

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
COL8A2	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	COL8A2

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)
COL8A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.