Reis-Bucklers corneal dystrophy

Summary

Reis-Bucklers corneal dystrophy (MONDO:0012043) is a disease caused by TGFBI (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TGFBI (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		81	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Reis-Bucklers corneal dystrophy
Mondo ID	MONDO:0012043
MeSH	C535476
OMIM	608470
Orphanet	98961
DOID	DOID:0060453
SNOMED CT	231930000
UMLS	C0339278
MedGen	83284
GARD	0009276
Is cancer (heuristic)	no

Also known as: anterior limiting membrane dystrophy type 1 · anterior limiting membrane dystrophy type I · atypical granular corneal dystrophy · CDB1 · CDRB · corneal dystrophy geographic · corneal dystrophy of Bowman layer type 1 · corneal dystrophy of Bowman layer type I · corneal dystrophy Reis Bucklers type · corneal dystrophy, REIS-Bucklers type · geographic corneal dystrophy · granular corneal dystrophy type 3 · granular corneal dystrophy type III · RBCD · Reis Bucklers corneal dystrophy · Reis Bucklers dystrophy · Reis-Bucklers corneal dystrophy · superficial granular corneal dystrophy

Data availability: 10 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › epithelial-stromal TGFBI dystrophy › Reis-Bucklers corneal dystrophy

Related subtypes (7): corneal granular dystrophy, epithelial basement membrane dystrophy, granular corneal dystrophy type I, lattice corneal dystrophy type I, Thiel-Behnke corneal dystrophy, granular corneal dystrophy type II, corneal dystrophy, lattice type 3A

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
7866	NM_000358.3(TGFBI):c.1663C>T (p.Arg555Trp)	TGFBI	Pathogenic	criteria provided, multiple submitters, no conflicts
7870	NM_000358.3(TGFBI):c.1618_1620del (p.Phe540del)	TGFBI	Pathogenic	no assertion criteria provided
7871	NM_000358.3(TGFBI):c.1501C>A (p.Pro501Thr)	TGFBI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7872	NM_000358.3(TGFBI):c.371G>T (p.Arg124Leu)	TGFBI	Pathogenic	criteria provided, multiple submitters, no conflicts
7876	NM_000358.3(TGFBI):c.1868G>A (p.Gly623Asp)	TGFBI	Pathogenic	no assertion criteria provided
2572628	NM_000358.3(TGFBI):c.1517_1518insCAAGGG (p.Met506delinsIleLysGly)	TGFBI	Likely pathogenic	criteria provided, single submitter
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: 0.