corneal dystrophy, Fuchs endothelial, 8

Summary

corneal dystrophy, Fuchs endothelial, 8 (MONDO:0014228) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	corneal dystrophy, Fuchs endothelial, 8
Mondo ID	MONDO:0014228
OMIM	615523
UMLS	C3809798
MedGen	816128
GARD	0018223
Is cancer (heuristic)	no

Also known as: AGBL1 Fuchs’ endothelial dystrophy · corneal dystrophy, Fuchs endothelial, 8 · corneal dystrophy, Fuchs endothelial, type 8 · FECD8 · Fuchs’ endothelial dystrophy caused by mutation in AGBL1

Data availability: 9 ClinVar variants · 2 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 › Fuchs’ endothelial dystrophy › corneal dystrophy, Fuchs endothelial, 8

Related subtypes (7): corneal dystrophy, Fuchs endothelial, 1, corneal dystrophy, fuchs endothelial, 2, corneal dystrophy, Fuchs endothelial, 3, corneal dystrophy, Fuchs endothelial, 4, corneal dystrophy, fuchs endothelial, 5, corneal dystrophy, Fuchs endothelial, 6, corneal dystrophy, fuchs endothelial, 7

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

9 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 4 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
88758	NM_001386094.1(AGBL1):c.3044G>C (p.Cys1015Ser)	AGBL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1685507	NM_152336.4(AGBL1):c.3323+1G>A	AGBL1	Uncertain significance	criteria provided, single submitter
2671673	NM_001386094.1(AGBL1):c.785A>C (p.Gln262Pro)	AGBL1	Uncertain significance	criteria provided, single submitter
88757	NM_001386094.1(AGBL1):c.3157C>T (p.Arg1053Trp)	AGBL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
932010	NM_001386094.1(AGBL1):c.985A>T (p.Thr329Ser)	AGBL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3242368	NM_001386094.1(AGBL1):c.1641G>T (p.Met547Ile)	AGBL1	Benign	no assertion criteria provided
3338240	NM_001386094.1(AGBL1):c.861C>T (p.Pro287=)	AGBL1	Benign	criteria provided, single submitter
3338241	NM_001386094.1(AGBL1):c.2423G>C (p.Ser808Thr)	AGBL1	Benign	criteria provided, single submitter
3338242	NM_152336.4(AGBL1):c.3285A>C (p.Thr1095=)	AGBL1	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
AGBL1	Supportive	Autosomal dominant	Fuchs’ endothelial dystrophy	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AGBL1	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
AGBL1	HGNC:26504	ENSG00000273540	Q96MI9	Cytosolic carboxypeptidase 4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AGBL1	Cytosolic carboxypeptidase 4	Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AGBL1	Protease	yes		Peptidase_M14, ARM-like, ARM-type_fold

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
biceps brachii	1
deltoid	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AGBL1	82	broad	marker	biceps brachii, hindlimb stylopod muscle, deltoid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AGBL1	442

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AGBL1	Q96MI9	78.53

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
Carboxyterminal post-translational modifications of tubulin	1	237.9×	0.013	AGBL1
Post-translational protein modification	1	19.2×	0.078	AGBL1
Metabolism of proteins	1	12.4×	0.081	AGBL1

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
C-terminal protein deglutamylation	1	4213.0×	5e-04	AGBL1
protein side chain deglutamylation	1	2808.7×	5e-04	AGBL1
proteolysis	1	34.2×	0.029	AGBL1

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
AGBL1	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	1	AGBL1
E	Difficult family or no structure, no drug	0

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)
AGBL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.