Age related macular degeneration 9

Summary

Age related macular degeneration 9 (MONDO:0012659) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 392

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	age related macular degeneration 9
Mondo ID	MONDO:0012659
MeSH	C566958
OMIM	611378
DOID	DOID:0110021
UMLS	C1969651
MedGen	370717
GARD	0024877
Is cancer (heuristic)	no

Also known as: age related macular degeneration type 9 · age-related macular degeneration caused by mutation in C3 · ARMD9 · C3 age-related macular degeneration · macular degeneration, age-related, 9 · macular Degeneration, age-related, type 9

Data availability: 392 ClinVar variants.

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 › age related macular degeneration 9

Related subtypes (14): wet macular degeneration, age related macular degeneration 2, age related macular degeneration 1, macular degeneration, age-related, 3, age related macular degeneration 7, age related macular degeneration 4, 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

392 retrieved; paginated sample, class counts are floors:

208 uncertain significance, 75 conflicting classifications of pathogenicity, 38 benign, 36 likely benign, 24 benign/likely benign, 7 likely pathogenic, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1455261	NM_000064.4(C3):c.373dup (p.Leu125fs)	C3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17060	NM_000064.4(C3):c.1775G>A (p.Arg592Gln)	C3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2972902	NM_000064.4(C3):c.2290C>T (p.Arg764Ter)	C3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3584123	NM_000064.4(C3):c.2825_2826del (p.Val942fs)	C3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3584072	NM_000064.4(C3):c.4918del (p.Glu1640fs)	C3	Likely pathogenic	criteria provided, single submitter
3584099	NM_000064.4(C3):c.3687del (p.Asn1229fs)	C3	Likely pathogenic	criteria provided, single submitter
3584120	NM_000064.4(C3):c.2863+1G>T	C3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3584127	NM_000064.4(C3):c.2615del (p.Phe872fs)	C3	Likely pathogenic	criteria provided, single submitter
3584178	NM_000064.4(C3):c.1003+1G>A	C3	Likely pathogenic	criteria provided, single submitter
3584182	NM_000064.4(C3):c.774-1G>T	C3	Likely pathogenic	criteria provided, single submitter
3584194	NM_000064.4(C3):c.276del (p.Asn93fs)	C3	Likely pathogenic	criteria provided, single submitter
1402622	NM_000064.4(C3):c.1887G>A (p.Pro629=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1408822	NM_000064.4(C3):c.1215C>T (p.Gly405=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1430457	NM_000064.4(C3):c.1686G>A (p.Ser562=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1606550	NM_000064.4(C3):c.2441-16G>T	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1627203	NM_000064.4(C3):c.1923C>T (p.Asp641=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1630092	NM_000064.4(C3):c.683-4C>G	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1674240	NM_000064.4(C3):c.987C>T (p.Thr329=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1678448	NM_000064.4(C3):c.3131G>A (p.Gly1044Glu)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2069494	NM_000064.4(C3):c.4947C>T (p.Leu1649=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3012516	NM_000064.4(C3):c.3155-17CT[3]	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330269	NM_000064.4(C3):c.4941G>A (p.Gln1647=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330271	NM_000064.4(C3):c.4855A>C (p.Ser1619Arg)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330272	NM_000064.4(C3):c.4850+12C>A	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330273	NM_000064.4(C3):c.4827C>T (p.Ser1609=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330274	NM_000064.4(C3):c.4803C>T (p.His1601=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330275	NM_000064.4(C3):c.4767G>A (p.Lys1589=)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330276	NM_000064.4(C3):c.4759C>T (p.Pro1587Ser)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330281	NM_000064.4(C3):c.4535G>A (p.Arg1512His)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
330284	NM_000064.4(C3):c.4319A>C (p.Asp1440Ala)	C3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
C3	Orphanet:280133	Complement component 3 deficiency
C3	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality

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
C3	HGNC:1318	ENSG00000125730	P01024	Complement C3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C3	Complement C3	Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adapt…

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
Complement	1	268.0×	0.004

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
C3	Complement	yes	3.4.21.47	Anaphylatoxin/fibulin, Netrin_domain, Macroglobln_a2

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
palpebral conjunctiva	1
parietal pleura	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C3	289	ubiquitous	marker	parietal pleura, right lobe of liver, palpebral conjunctiva

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C3	3,199

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C3	P01024	75

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Alternative complement activation	1	2284.0×	0.004	C3
Activation of C3 and C5	1	1268.9×	0.004	C3
Purinergic signaling in leishmaniasis infection	1	423.0×	0.008	C3
Regulation of Complement cascade	1	233.1×	0.011	C3
Post-translational protein phosphorylation	1	100.2×	0.017	C3
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.017	C3
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.017	C3
Peptide ligand-binding receptors	1	74.2×	0.017	C3
G alpha (i) signalling events	1	39.0×	0.029	C3
Neutrophil degranulation	1	23.1×	0.043	C3

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
regulation of triglyceride biosynthetic process	1	8426.0×	9e-04	C3
complement-dependent cytotoxicity	1	8426.0×	9e-04	C3
positive regulation of type IIa hypersensitivity	1	5617.3×	9e-04	C3
positive regulation of activation of membrane attack complex	1	5617.3×	9e-04	C3
oviduct epithelium development	1	5617.3×	9e-04	C3
vertebrate eye-specific patterning	1	5617.3×	9e-04	C3
complement-mediated synapse pruning	1	4213.0×	0.001	C3
positive regulation of apoptotic cell clearance	1	2407.4×	0.002	C3
positive regulation of D-glucose transmembrane transport	1	2106.5×	0.002	C3
positive regulation of lipid storage	1	1404.3×	0.002	C3
positive regulation of phagocytosis, engulfment	1	1296.3×	0.002	C3
complement activation, GZMK pathway	1	1296.3×	0.002	C3
neuron remodeling	1	1203.7×	0.002	C3
complement receptor mediated signaling pathway	1	1123.5×	0.002	C3
positive regulation of G protein-coupled receptor signaling pathway	1	1053.2×	0.002	C3
complement activation, alternative pathway	1	991.3×	0.002	C3
amyloid-beta clearance	1	936.2×	0.002	C3
positive regulation of receptor-mediated endocytosis	1	802.5×	0.002	C3
complement activation	1	624.1×	0.003	C3
complement activation, classical pathway	1	543.6×	0.003	C3
positive regulation of vascular endothelial growth factor production	1	495.6×	0.003	C3
B cell activation	1	455.5×	0.003	C3
positive regulation of protein phosphorylation	1	276.3×	0.005	C3
fatty acid metabolic process	1	193.7×	0.006	C3
response to bacterium	1	193.7×	0.006	C3
positive regulation of angiogenesis	1	115.4×	0.010	C3
immune response	1	47.1×	0.024	C3
inflammatory response	1	37.7×	0.028	C3
G protein-coupled receptor signaling pathway	1	36.2×	0.029	C3
signal transduction	1	16.1×	0.062	C3

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
C3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
C3	15	Binding:15

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
C3	3.4.21.47	alternative-complement-pathway C3/C5 convertase

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	1	C3
D	Druggable family + AlphaFold only, no drug	0
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)
C3	15	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.