Macular degeneration, early-onset
diseaseOn this page
Also known as EOMD
Summary
Macular degeneration, early-onset (MONDO:0014501) is a disease with 1 cohort gene.
At a glance
- Cohort genes: 1
- ClinVar variants: 90
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | macular degeneration, early-onset |
| Mondo ID | MONDO:0014501 |
| OMIM | 616118 |
| UMLS | C4015286 |
| MedGen | 863723 |
| GARD | 0024995 |
| Is cancer (heuristic) | no |
Also known as: EOMD · macular degeneration, early-onset
Data availability: 90 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › macular degeneration, early-onset
Related subtypes (8): vitelliform macular dystrophy, degeneration of macula and posterior pole, macular retinal edema, autosomal recessive bestrophinopathy, occult macular dystrophy, Stargardt disease, patterned macular dystrophy, isolated macular 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
90 retrieved; paginated sample, class counts are floors:
38 conflicting classifications of pathogenicity, 32 uncertain significance, 6 benign, 6 benign/likely benign, 4 likely benign, 3 likely pathogenic, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1675083 | NM_001999.4(FBN2):c.3424T>G (p.Cys1142Gly) | FBN2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4531300 | NM_001999.4(FBN2):c.3724+3A>C | FBN2 | Likely pathogenic | criteria provided, single submitter |
| 930425 | NM_001999.4(FBN2):c.4055G>C (p.Cys1352Ser) | FBN2 | Likely pathogenic | criteria provided, single submitter |
| 930869 | NM_001999.4(FBN2):c.3592T>C (p.Cys1198Arg) | FBN2 | Likely pathogenic | criteria provided, single submitter |
| 1042687 | NM_001999.4(FBN2):c.704C>T (p.Thr235Met) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1302265 | NM_001999.4(FBN2):c.5983G>A (p.Gly1995Ser) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 137344 | NM_001999.4(FBN2):c.6511+5G>A | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 155797 | NM_001999.4(FBN2):c.7808T>C (p.Phe2603Ser) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 161445 | NM_001999.4(FBN2):c.3430G>A (p.Glu1144Lys) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1646797 | NM_001999.4(FBN2):c.7385A>G (p.Asn2462Ser) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 213228 | NM_001999.4(FBN2):c.3394G>A (p.Val1132Ile) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 213255 | NM_001999.4(FBN2):c.8239C>G (p.Leu2747Val) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 213318 | NM_001999.4(FBN2):c.3709C>T (p.Arg1237Cys) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 213364 | NM_001999.4(FBN2):c.7690C>G (p.Gln2564Glu) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 213366 | NM_001999.4(FBN2):c.7942C>A (p.Gln2648Lys) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 213377 | NM_001999.4(FBN2):c.8674G>T (p.Asp2892Tyr) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 213392 | NM_001999.4(FBN2):c.2536G>A (p.Glu846Lys) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 213404 | NM_001999.4(FBN2):c.5800+5G>A | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 234773 | NM_001999.4(FBN2):c.3304A>G (p.Ser1102Gly) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 234845 | NM_001999.4(FBN2):c.8058C>A (p.Phe2686Leu) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 263401 | NM_001999.4(FBN2):c.6077C>T (p.Ser2026Phe) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 263857 | NM_001999.4(FBN2):c.1720A>G (p.Ile574Val) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 263894 | NM_001999.4(FBN2):c.7418G>A (p.Arg2473Gln) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 264426 | NM_001999.4(FBN2):c.2557A>C (p.Ile853Leu) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 264520 | NM_001999.4(FBN2):c.1423G>A (p.Gly475Ser) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 289728 | NM_001999.4(FBN2):c.6982G>T (p.Ala2328Ser) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2903097 | NM_001999.4(FBN2):c.3725-3C>T | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 350759 | NM_001999.4(FBN2):c.8376C>G (p.Ile2792Met) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3591682 | NM_001999.4(FBN2):c.1232-17A>G | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 380412 | NM_001999.4(FBN2):c.2252A>C (p.Glu751Ala) | FBN2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 10 · 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 |
|---|---|---|---|---|
| FBN2 | Limited | Autosomal dominant | macular degeneration, early-onset | 10 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| FBN2 | Orphanet:115 | Congenital contractural arachnodactyly |
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 |
|---|---|---|---|---|---|
| FBN2 | HGNC:3604 | ENSG00000138829 | P35556 | Fibrillin-2 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| FBN2 | Fibrillin-2 | Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles. |
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) |
|---|---|---|---|---|
| FBN2 | Other/Unknown | no | EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_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 |
|---|---|
| adrenal tissue | 1 |
| cartilage tissue | 1 |
| placenta | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| FBN2 | 194 | ubiquitous | marker | cartilage tissue, placenta, adrenal tissue |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| FBN2 | 2,570 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| FBN2 | P35556 |
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 |
|---|---|---|---|---|
| Elastic fibre formation | 1 | 335.9× | 0.005 | FBN2 |
| Molecules associated with elastic fibres | 1 | 308.6× | 0.005 | FBN2 |
| Degradation of the extracellular matrix | 1 | 117.7× | 0.008 | FBN2 |
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 |
|---|---|---|---|---|
| obsolete sequestering of TGFbeta in extracellular matrix | 1 | 4213.0× | 0.002 | FBN2 |
| bone trabecula formation | 1 | 2106.5× | 0.002 | FBN2 |
| embryonic eye morphogenesis | 1 | 1532.0× | 0.002 | FBN2 |
| embryonic limb morphogenesis | 1 | 401.2× | 0.004 | FBN2 |
| positive regulation of bone mineralization | 1 | 391.9× | 0.004 | FBN2 |
| camera-type eye development | 1 | 358.6× | 0.004 | FBN2 |
| glucose metabolic process | 1 | 255.3× | 0.005 | FBN2 |
| positive regulation of osteoblast differentiation | 1 | 224.7× | 0.005 | FBN2 |
| glucose homeostasis | 1 | 130.6× | 0.008 | FBN2 |
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 |
|---|---|---|
| FBN2 | 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 | FBN2 |
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) |
|---|---|---|
| FBN2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: FBN2