Age related macular degeneration 1

disease
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Also known as age related macular degeneration type 1ARMD1macular degeneration, age-relatedmacular degeneration, age-related, 1macular degeneration, age-related, reduced risk ofmacular Degeneration, age-related, type 1

Summary

Age related macular degeneration 1 (MONDO:0011285) is a disease with 5 cohort genes and 14 clinical trials. Top therapeutic interventions include faricimab, metformin, and pegcetacoplan.

At a glance

  • Cohort genes: 5
  • ClinVar variants: 498
  • Clinical trials: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameage related macular degeneration 1
Mondo IDMONDO:0011285
MeSHC566411
OMIM603075
DOIDDOID:0110014
UMLSC1864205
MedGen400475
GARD0024788
Is cancer (heuristic)no

Also known as: age related macular degeneration type 1 · ARMD1 · macular degeneration, age-related · macular degeneration, age-related, 1 · macular degeneration, age-related, reduced risk of · macular Degeneration, age-related, type 1

Data availability: 498 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorderretinal disorderretinal degenerationmacular degenerationdegeneration of macula and posterior poleage-related macular degenerationage related macular degeneration 1

Related subtypes (14): wet macular degeneration, age related macular degeneration 2, macular degeneration, age-related, 3, 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

498 retrieved; paginated sample, class counts are floors:

255 uncertain significance, 102 conflicting classifications of pathogenicity, 60 benign, 47 benign/likely benign, 32 likely benign, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
17880NM_000041.4(APOE):c.127C>T (p.Arg43Cys)APOEPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
217863NM_031935.3(HMCN1):c.4163del (p.Pro1388fs)HMCN1Pathogenicno assertion criteria provided
440842NM_000041.4(APOE):c.91G>A (p.Glu31Lys)APOEConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1678086NM_002113.3(CFHR1):c.19del (p.Ser6_Val7insTer)CFHR1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1979364NM_031935.3(HMCN1):c.11743G>A (p.Val3915Ile)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
2205NM_031935.3(HMCN1):c.16034A>G (p.Gln5345Arg)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294097NM_031935.3(HMCN1):c.602A>G (p.Asp201Gly)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294103NM_031935.3(HMCN1):c.959G>A (p.Arg320Gln)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294104NM_031935.3(HMCN1):c.1021+8T>CHMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294107NM_031935.3(HMCN1):c.1338G>A (p.Pro446=)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294114NM_031935.3(HMCN1):c.2098+12C>AHMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294116NM_031935.3(HMCN1):c.2119G>T (p.Val707Phe)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294122NM_031935.3(HMCN1):c.2385C>T (p.Phe795=)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294127NM_031935.3(HMCN1):c.3048+12A>GHMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294134NM_031935.3(HMCN1):c.3684C>T (p.Ile1228=)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294137NM_031935.3(HMCN1):c.3764C>T (p.Thr1255Met)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294139NM_031935.3(HMCN1):c.4029A>G (p.Glu1343=)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294150NM_031935.3(HMCN1):c.4499A>G (p.Asn1500Ser)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294157NM_031935.3(HMCN1):c.4910-14A>GHMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294158NM_031935.3(HMCN1):c.4920G>A (p.Met1640Ile)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294161NM_031935.3(HMCN1):c.5669T>C (p.Leu1890Ser)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294162NM_031935.3(HMCN1):c.5706C>T (p.Asn1902=)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294164NM_031935.3(HMCN1):c.5852-12T>GHMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294173NM_031935.3(HMCN1):c.6435G>A (p.Leu2145=)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294179NM_031935.3(HMCN1):c.7017A>G (p.Val2339=)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294189NM_031935.3(HMCN1):c.7589C>G (p.Ser2530Cys)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294196NM_031935.3(HMCN1):c.8241A>G (p.Ala2747=)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294198NM_031935.3(HMCN1):c.8485+14C>THMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294205NM_031935.3(HMCN1):c.9047-12A>GHMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
294206NM_031935.3(HMCN1):c.9057T>A (p.Thr3019=)HMCN1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 8 · 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.

GeneClassificationInheritanceDiseaseRecords
CFHR1LimitedUnknownage related macular degeneration 14
HMCN1LimitedAutosomal dominantage related macular degeneration 14

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CFHR1Orphanet:329931C3 glomerulonephritis
CFHR1Orphanet:93571Dense deposit disease
CFHR3Orphanet:329931C3 glomerulonephritis
FBLN5Orphanet:280598Hereditary sensorimotor neuropathy with hyperelastic skin
FBLN5Orphanet:90348Autosomal dominant cutis laxa
FBLN5Orphanet:90349Autosomal recessive cutis laxa type 1
APOEOrphanet:329481Lipoprotein glomerulopathy
APOEOrphanet:412Dysbetalipoproteinemia

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence5

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
HMCN1HGNC:19194ENSG00000143341Q96RW7Hemicentin-1gencc,clinvar
CFHR1HGNC:4888ENSG00000244414Q03591Complement factor H-related protein 1gencc,clinvar
CFHR3HGNC:16980ENSG00000116785Q02985Complement factor H-related protein 3clinvar
FBLN5HGNC:3602ENSG00000140092Q9UBX5Fibulin-5clinvar
APOEHGNC:613ENSG00000130203P02649Apolipoprotein Eclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
HMCN1Hemicentin-1Involved in transforming growth factor beta-mediated rearrangement of the podocyte cytoskeleton which includes reduction of F-actin fibers and broadening, flattening and elongation of podocytes.
CFHR1Complement factor H-related protein 1Involved in complement regulation.
CFHR3Complement factor H-related protein 3Might be involved in complement regulation.
FBLN5Fibulin-5Essential for elastic fiber formation, is involved in the assembly of continuous elastin (ELN) polymer and promotes the interaction of microfibrils and ELN.
APOEApolipoprotein EAPOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.6

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.

FamilyGenesFoldFDR
Complement2107.2×4e-04
Antibody/Immunoglobulin15.8×0.240
Other/Unknown20.7×0.877

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
HMCN1Antibody/ImmunoglobulinyesEGF-type_Asp/Asn_hydroxyl_site, EGF, TSP1_rpt
CFHR1ComplementyesSushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
CFHR3ComplementyesSushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
FBLN5Other/UnknownnoEGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
APOEOther/UnknownnoApoA_E, Apolipoprotein_A1/A4/E

Expression context

Cohort genes with no expression data: 0.

5 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)5
unknown0

Top tissues across cohort

TissueCohort genes
ascending aorta2
descending thoracic aorta2
thoracic aorta2
liver2
male germ line stem cell (sensu Vertebrata) in testis2
right lobe of liver2
left adrenal gland1
left adrenal gland cortex1
right adrenal gland cortex1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
HMCN1211ubiquitousmarkerdescending thoracic aorta, thoracic aorta, ascending aorta
CFHR1125markerright lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
CFHR3127tissue_specificmarkerright lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
FBLN5261ubiquitousmarkerthoracic aorta, ascending aorta, descending thoracic aorta
APOE267ubiquitousmarkerleft adrenal gland, left adrenal gland cortex, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

SymbolInteractor count
APOE6,793
FBLN52,301
HMCN11,369
CFHR1599
CFHR3373

Intra-cohort edges

ABSources
CFHR1HMCN1string_interaction
CFHR3HMCN1string_interaction

Structural data

PDB: 2 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
APOEP0264929
CFHR1Q035912

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
CFHR3Q0298591.93
FBLN5Q9UBX583.69
HMCN1Q96RW7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Regulation of Complement cascade2116.5×0.004CFHR1, CFHR3
Chylomicron clearance1571.0×0.026APOE
Chylomicron assembly1285.5×0.026APOE
Chylomicron remodeling1285.5×0.026APOE
HDL remodeling1285.5×0.026APOE
Plasma lipoprotein assembly1178.4×0.028APOE
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors1158.6×0.028APOE
Scavenging by Class A Receptors1150.3×0.028APOE
Binding and Uptake of Ligands by Scavenger Receptors1135.9×0.028APOE
Plasma lipoprotein remodeling1119.0×0.028APOE
Plasma lipoprotein clearance1119.0×0.028APOE
NR1H2 and NR1H3-mediated signaling198.5×0.028APOE
Metabolism of fat-soluble vitamins195.2×0.028APOE
Nuclear signaling by ERBB4186.5×0.028APOE
Elastic fibre formation184.0×0.028FBLN5
Molecules associated with elastic fibres177.2×0.028FBLN5
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux177.2×0.028APOE
Signaling by ERBB4168.0×0.030APOE
Visual phototransduction164.9×0.030APOE
Retinoid metabolism and transport162.1×0.030APOE
Plasma lipoprotein assembly, remodeling, and clearance157.1×0.031APOE
Metabolism of vitamins and cofactors129.1×0.057APOE
Amyloid fiber formation125.7×0.058APOE
Signaling by Nuclear Receptors125.5×0.058APOE
Post-translational protein phosphorylation125.0×0.058APOE
Sensory Perception123.8×0.059APOE
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)121.6×0.062APOE
Signaling by Receptor Tyrosine Kinases112.9×0.099APOE
Vesicle-mediated transport18.7×0.140APOE
Transport of small molecules16.3×0.185APOE

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
complement activation2249.7×0.003CFHR1, CFHR3
lipid transport involved in lipid storage13370.4×0.005APOE
maintenance of location in cell13370.4×0.005APOE
intermediate-density lipoprotein particle clearance13370.4×0.005APOE
intramembranous bone growth13370.4×0.005FBLN5
positive regulation of lipid transport across blood-brain barrier13370.4×0.005APOE
regulation of cellular response to very-low-density lipoprotein particle stimulus13370.4×0.005APOE
triglyceride-rich lipoprotein particle clearance11685.2×0.007APOE
regulation of amyloid-beta clearance11685.2×0.007APOE
regulation of amyloid fibril formation11685.2×0.007APOE
positive regulation of low-density lipoprotein particle receptor catabolic process11123.5×0.008APOE
negative regulation of triglyceride metabolic process1842.6×0.008APOE
positive regulation of phospholipid efflux1842.6×0.008APOE
regulation of behavioral fear response1842.6×0.008APOE
very-low-density lipoprotein particle clearance1674.1×0.008APOE
acylglycerol homeostasis1674.1×0.008APOE
cellular response to lipoprotein particle stimulus1674.1×0.008APOE
AMPA glutamate receptor clustering1674.1×0.008APOE
NMDA glutamate receptor clustering1674.1×0.008APOE
positive regulation of lipoprotein transport1674.1×0.008APOE
positive regulation of dendritic spine maintenance1674.1×0.008APOE
regulation of amyloid precursor protein catabolic process1674.1×0.008APOE
positive regulation of amyloid fibril formation1674.1×0.008APOE
chylomicron remnant clearance1561.7×0.008APOE
lipoprotein biosynthetic process1561.7×0.008APOE
regulation of removal of superoxide radicals1561.7×0.008FBLN5
high-density lipoprotein particle clearance1481.5×0.008APOE
lipoprotein catabolic process1481.5×0.008APOE
negative regulation of cholesterol biosynthetic process1481.5×0.008APOE
very-low-density lipoprotein particle remodeling1421.3×0.008APOE

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 0 of 5 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
HMCN100
CFHR100
CFHR300
FBLN500
APOE00

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1CFHR1
DDruggable family + AlphaFold only, no drug2HMCN1, CFHR3
EDifficult family or no structure, no drug2FBLN5, APOE

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
HMCN10
CFHR10
CFHR30
FBLN50
APOE0

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified8
PHASE25
PHASE41

Top trials by phase / activity

NCTPhaseStatusTitle
NCT07403825PHASE4RECRUITINGEfficacy of Faricimab in Patients With Subretinal Hyper-reflective Material
NCT06722157PHASE2ACTIVE_NOT_RECRUITINGA Study to Test Whether BI 771716 Helps People With an Advanced Form of Age-related Macular Degeneration (AMD) Called Geographic Atrophy
NCT02684578PHASE2COMPLETEDMetformin for the Minimization of Geographic Atrophy Progression in Patients With AMD
NCT03038880PHASE2COMPLETEDStudy to Evaluate Faricimab (RO6867461; RG7716) for Extended Durability in the Treatment of Neovascular Age Related Macular Degeneration
NCT03972709PHASE2TERMINATEDA Study Assessing the Safety, Tolerability, and Efficacy of Galegenimab (FHTR2163) in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD)
NCT04607148PHASE2TERMINATEDA Study Assessing the Long-Term Safety and Tolerability of Galegenimab (FHTR2163) in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration
NCT06582511Not specifiedACTIVE_NOT_RECRUITINGEvaluating Metabolic Changes Induced by PhotoBioModulation Through Spectrally Resolved Autofluorescence in Dry Age-Related Macular Degeneration Patients
NCT03418220Not specifiedCOMPLETEDComparison of Cytokine Profiles in Aqueous Humor of Patients With Age Related Macular Degeneration (AMD)
NCT03794752Not specifiedTERMINATEDVisual Enhancement Device in Low Vision Patients
NCT05593913Not specifiedCOMPLETEDClinical Evaluation of VeriSee AMD in Screening for Age-Related Macular Degeneration
NCT05677685Not specifiedCOMPLETEDVISUPRIME® Eye Drops
NCT05961332Not specifiedCOMPLETEDCOmparison of Clarus and Optos Ultrawide Field Imaging Systems for Geographic Atrophy
NCT05988827Not specifiedCOMPLETEDEffect of Minimizing Light Exposure Intensity on Macular Function After Cataract Surgery in Patients With Early or Intermediate AMD
NCT07255885Not specifiedCOMPLETEDCRYSTALSIGHT: ‘‘Cohort 1.5 Clinical Investigation Study With OCCUTRACK and Tan Tock Seng Eye Clinic to Further Develop Remote Monitoring of Maculopathy at Home Using Artificial Intelligence for Eye Tracking

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
FARICIMAB41
METFORMIN41
PEGCETACOPLAN41
GALEGENIMAB22