Epithelial basement membrane dystrophy

Summary

Epithelial basement membrane dystrophy (MONDO:0007375) is a disease with 1 cohort gene and 5 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 8
• Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epithelial basement membrane dystrophy
Mondo ID	MONDO:0007375
MeSH	C535477
OMIM	121820
Orphanet	98956
DOID	DOID:0060447
SNOMED CT	373426005
UMLS	C0521723
MedGen	99275
GARD	0009732
Is cancer (heuristic)	no

Also known as: anterior basement membrane dystrophy · Cogan corneal dystrophy · Cogan microcystic epithelial dystrophy · corneal dystrophy, epithelial basement MEMBRANE · EBMD · epithelial basement membrane corneal dystrophy · Map-dot-fingerprint dystrophy · Map-dot-fingerprint dystrophy of cornea · microcystic dystrophy of the cornea

Data availability: 8 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 › epithelial and subepithelial corneal dystrophy › epithelial basement membrane dystrophy

Related subtypes (4): Meesmann corneal dystrophy, gelatinous drop-like corneal dystrophy, Lisch epithelial corneal dystrophy, subepithelial mucinous corneal dystrophy

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

8 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic, 2 uncertain significance, 2 pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3720657	NM_000358.3(TGFBI):c.1856T>A (p.Met619Lys)	TGFBI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7866	NM_000358.3(TGFBI):c.1663C>T (p.Arg555Trp)	TGFBI	Pathogenic	criteria provided, multiple submitters, no conflicts
7871	NM_000358.3(TGFBI):c.1501C>A (p.Pro501Thr)	TGFBI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7877	NM_000358.3(TGFBI):c.1526T>G (p.Leu509Arg)	TGFBI	Pathogenic	no assertion criteria provided
7878	NM_000358.3(TGFBI):c.1998G>C (p.Arg666Ser)	TGFBI	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904412	NM_000358.3(TGFBI):c.895G>A (p.Asp299Asn)	TGFBI	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4533224	NM_000358.3(TGFBI):c.459+6A>G	TGFBI	Uncertain significance	criteria provided, single submitter
906736	NM_000358.3(TGFBI):c.387G>C (p.Arg129Ser)	TGFBI	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 6 · 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
TGFBI	Definitive	Autosomal dominant	epithelial-stromal TGFBI dystrophy	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TGFBI	Orphanet:98956	Epithelial basement membrane dystrophy
TGFBI	Orphanet:98960	Thiel-Behnke corneal dystrophy
TGFBI	Orphanet:98961	Reis-Bücklers corneal dystrophy
TGFBI	Orphanet:98962	Granular corneal dystrophy type I
TGFBI	Orphanet:98963	Granular corneal dystrophy type II
TGFBI	Orphanet:98964	Lattice corneal dystrophy type I

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
TGFBI	HGNC:11771	ENSG00000120708	Q15582	Transforming growth factor-beta-induced protein ig-h3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TGFBI	Transforming growth factor-beta-induced protein ig-h3	Plays a role in cell adhesion.

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)
TGFBI	Other/Unknown	no		FAS1_domain, EMI_domain, TGFBI/POSTN

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
amniotic fluid	1
pericardium	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TGFBI	278	ubiquitous	marker	amniotic fluid, synovial joint, pericardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TGFBI	2,988

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TGFBI	Q15582	10

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
Amyloid fiber formation	1	102.9×	0.019	TGFBI
Metabolism of proteins	1	12.4×	0.081	TGFBI

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
negative regulation of cell adhesion	1	383.0×	0.012	TGFBI
chondrocyte differentiation	1	300.9×	0.012	TGFBI
extracellular matrix organization	1	122.1×	0.017	TGFBI
cell population proliferation	1	102.8×	0.017	TGFBI
visual perception	1	79.5×	0.018	TGFBI
angiogenesis	1	62.4×	0.019	TGFBI
cell adhesion	1	37.5×	0.027	TGFBI

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TGFBI	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TGFBI	1	Binding:1

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	TGFBI

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)
TGFBI	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06618508	Not specified	NOT_YET_RECRUITING	Manual Debridement vs Phototherapeutic Keratectomy in the Treatment of Corneal Basement Membrane Dystrophy
NCT06914817	Not specified	NOT_YET_RECRUITING	Brillouin Microscopy Used to Evaluate Corneal Mechanical Properties
NCT02373397	Not specified	TERMINATED	Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy
NCT02766907	Not specified	COMPLETED	Optimizing the Ocular Surface Prior to Cataract Surgery
NCT05770492	Not specified	UNKNOWN	Deep Learning Assisted Epithelial Basement Membrane Dystrophy Detection