Macular degeneration, age-related, 3
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Also known as age-related macular degeneration caused by mutation in FBLN5ARMD3FBLN5 age-related macular degenerationHNARMDmacular Degeneration, age-related, type 3
Summary
Macular degeneration, age-related, 3 (MONDO:0012145) is a disease with 1 cohort gene.
At a glance
- Cohort genes: 1
- ClinVar variants: 67
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | macular degeneration, age-related, 3 |
| Mondo ID | MONDO:0012145 |
| MeSH | C563838 |
| OMIM | 608895 |
| UMLS | C1837187 |
| MedGen | 373276 |
| GARD | 0024848 |
| Is cancer (heuristic) | no |
Also known as: age-related macular degeneration caused by mutation in FBLN5 · ARMD3 · FBLN5 age-related macular degeneration · HNARMD · macular degeneration, age-related, 3 · macular Degeneration, age-related, type 3
Data availability: 67 ClinVar variants · 1 GenCC gene-disease record.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › macular degeneration › degeneration of macula and posterior pole › age-related macular degeneration › macular degeneration, age-related, 3
Related subtypes (14): wet macular degeneration, age related macular degeneration 2, age related macular degeneration 1, age related macular degeneration 7, age related macular degeneration 4, age related macular degeneration 9, age related macular degeneration 10, age related macular degeneration 11, age related macular degeneration 6, age related macular degeneration 8, age related macular degeneration 12, age related macular degeneration 14, macular dystrophy with central cone involvement, dry age related macular degeneration
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
67 retrieved; paginated sample, class counts are floors:
32 uncertain significance, 15 conflicting classifications of pathogenicity, 11 benign, 8 benign/likely benign, 1 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 689758 | NM_006329.4(FBLN5):c.1201_1202del (p.Ser401fs) | FBLN5 | Pathogenic | criteria provided, single submitter |
| 21453 | NM_006329.4(FBLN5):c.604G>A (p.Gly202Arg) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 218359 | NM_006329.4(FBLN5):c.268G>A (p.Gly90Ser) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 218360 | NM_006329.4(FBLN5):c.376G>A (p.Val126Met) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 287193 | NM_006329.4(FBLN5):c.621T>C (p.Asp207=) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 314861 | NM_006329.4(FBLN5):c.*648G>A | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 314871 | NM_006329.4(FBLN5):c.1191G>A (p.Thr397=) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 314874 | NM_006329.4(FBLN5):c.989+9C>T | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 314875 | NM_006329.4(FBLN5):c.862+12C>T | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 314877 | NM_006329.4(FBLN5):c.676G>A (p.Gly226Ser) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 5479 | NM_006329.4(FBLN5):c.259C>T (p.Pro87Ser) | FBLN5 | Conflicting classifications of pathogenicity | no assertion criteria provided |
| 5480 | NM_006329.4(FBLN5):c.506T>C (p.Ile169Thr) | FBLN5 | Conflicting classifications of pathogenicity | no assertion criteria provided |
| 5482 | NM_006329.4(FBLN5):c.1087G>A (p.Ala363Thr) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 885290 | NM_006329.4(FBLN5):c.1241G>A (p.Arg414Gln) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 886256 | NM_006329.4(FBLN5):c.573A>G (p.Thr191=) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 887258 | NM_006329.4(FBLN5):c.273G>A (p.Pro91=) | FBLN5 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1172837 | NM_006329.4(FBLN5):c.245A>C (p.Asn82Thr) | FBLN5 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1342917 | NM_006329.4(FBLN5):c.992G>A (p.Arg331His) | FBLN5 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1463161 | NM_006329.4(FBLN5):c.1076G>A (p.Arg359His) | FBLN5 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1519738 | NM_006329.4(FBLN5):c.834C>G (p.Ile278Met) | FBLN5 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 314859 | NM_006329.4(FBLN5):c.*775A>C | FBLN5 | Uncertain significance | criteria provided, single submitter |
| 314860 | NM_006329.4(FBLN5):c.*653G>A | FBLN5 | Uncertain significance | criteria provided, single submitter |
| 314865 | NM_006329.4(FBLN5):c.*458T>C | FBLN5 | Uncertain significance | criteria provided, single submitter |
| 314867 | NM_006329.4(FBLN5):c.*363C>T | FBLN5 | Uncertain significance | criteria provided, single submitter |
| 314870 | NM_006329.4(FBLN5):c.*98G>A | FBLN5 | Uncertain significance | criteria provided, single submitter |
| 314879 | NM_006329.4(FBLN5):c.388G>A (p.Glu130Lys) | FBLN5 | Uncertain significance | criteria provided, single submitter |
| 314880 | NM_006329.4(FBLN5):c.251A>G (p.Tyr84Cys) | FBLN5 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 314884 | NM_006329.4(FBLN5):c.-139C>T | FBLN5 | Uncertain significance | criteria provided, single submitter |
| 314886 | NM_006329.4(FBLN5):c.-382C>G | FBLN5 | Uncertain significance | criteria provided, single submitter |
| 314887 | NM_006329.4(FBLN5):c.-389C>A | FBLN5 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 14 · Orphanet: 3 · 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 |
|---|---|---|---|---|
| FBLN5 | Moderate | Autosomal dominant | macular degeneration, age-related, 3 | 14 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| FBLN5 | Orphanet:280598 | Hereditary sensorimotor neuropathy with hyperelastic skin |
| FBLN5 | Orphanet:90348 | Autosomal dominant cutis laxa |
| FBLN5 | Orphanet:90349 | Autosomal recessive cutis laxa type 1 |
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 |
|---|---|---|---|---|---|
| FBLN5 | HGNC:3602 | ENSG00000140092 | Q9UBX5 | Fibulin-5 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| FBLN5 | Fibulin-5 | Essential for elastic fiber formation, is involved in the assembly of continuous elastin (ELN) polymer and promotes the interaction of microfibrils and ELN. |
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) |
|---|---|---|---|---|
| FBLN5 | 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 |
|---|---|
| ascending aorta | 1 |
| descending thoracic aorta | 1 |
| thoracic aorta | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| FBLN5 | 261 | ubiquitous | marker | thoracic aorta, ascending aorta, descending thoracic aorta |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| FBLN5 | 2,301 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| FBLN5 | Q9UBX5 | 83.69 |
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 |
|---|---|---|---|---|
| Elastic fibre formation | 1 | 335.9× | 0.003 | FBLN5 |
| Molecules associated with elastic fibres | 1 | 308.6× | 0.003 | FBLN5 |
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 |
|---|---|---|---|---|
| intramembranous bone growth | 1 | 16852.0× | 6e-04 | FBLN5 |
| regulation of removal of superoxide radicals | 1 | 2808.7× | 0.002 | FBLN5 |
| secretion | 1 | 2106.5× | 0.002 | FBLN5 |
| elastic fiber assembly | 1 | 1532.0× | 0.002 | FBLN5 |
| positive regulation of osteoblast proliferation | 1 | 1203.7× | 0.002 | FBLN5 |
| protein localization to cell surface | 1 | 495.6× | 0.003 | FBLN5 |
| negative regulation of angiogenesis | 1 | 168.5× | 0.008 | FBLN5 |
| cell-matrix adhesion | 1 | 163.6× | 0.008 | FBLN5 |
| negative regulation of transcription by RNA polymerase II | 1 | 17.7× | 0.063 | FBLN5 |
| positive regulation of transcription by RNA polymerase II | 1 | 14.9× | 0.067 | FBLN5 |
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 |
|---|---|---|
| FBLN5 | 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 | FBLN5 |
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) |
|---|---|---|
| FBLN5 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: FBLN5