Age related macular degeneration 14

Summary

Age related macular degeneration 14 (MONDO:0014207) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 70

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	age related macular degeneration 14
Mondo ID	MONDO:0014207
OMIM	615489
DOID	DOID:0110026
UMLS	C3809653
MedGen	815983
GARD	0024978
Is cancer (heuristic)	no

Also known as: age related macular degeneration type 14 · ARMD14 · macular degeneration, age-related, 14 · macular degeneration, age-related, 14, reduced risk of, digenic dominant · macular Degeneration, age-related, type 14

Data availability: 70 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 14

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 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, 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

70 retrieved; paginated sample, class counts are floors:

31 uncertain significance, 20 conflicting classifications of pathogenicity, 11 benign/likely benign, 5 likely benign, 1 protective, 1 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
50634	NM_000063.6(C2):c.841_849+19del	C2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1032161	NM_000063.6(C2):c.2171C>T (p.Pro724Leu)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356243	NM_000063.6(C2):c.218C>T (p.Pro73Leu)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356247	NM_000063.6(C2):c.1130-11C>T	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356250	NM_000063.6(C2):c.1450A>G (p.Ile484Val)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356259	NM_000063.6(C2):c.2080-8T>C	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356261	NM_000063.6(C2):c.2253C>T (p.Pro751=)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
369520	NM_000063.6(C2):c.1778G>A (p.Arg593Gln)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904584	NM_000063.6(C2):c.73C>T (p.Pro25Ser)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904652	NM_000063.6(C2):c.980A>G (p.Asn327Ser)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904727	NM_000063.6(C2):c.1613C>T (p.Ala538Val)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
905372	NM_000063.6(C2):c.245C>T (p.Ala82Val)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
905442	NM_000063.6(C2):c.1109C>T (p.Ala370Val)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
905958	NM_000063.6(C2):c.1413C>T (p.Asn471=)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
906027	NM_000063.6(C2):c.2200C>T (p.Arg734Cys)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
906980	NM_000063.6(C2):c.442+15T>G	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
906981	NM_000063.6(C2):c.443-4G>A	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908037	NM_000063.6(C2):c.1577A>G (p.Lys526Arg)	C2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
907959	NM_000063.6(C2):c.936C>G (p.Asn312Lys)	C2-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1575611	NM_001710.6(CFB):c.1778+8C>T	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
992561	NM_001710.6(CFB):c.658+7T>C	CFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12131	NM_000063.6(C2):c.1360+62G>T	C2	protective	no assertion criteria provided
356241	NM_000063.4(C2):c.-37C>A	C2	Uncertain significance	criteria provided, single submitter
356244	NM_000063.6(C2):c.313G>A (p.Gly105Arg)	C2	Uncertain significance	criteria provided, single submitter
356246	NM_000063.6(C2):c.1066C>T (p.Leu356Phe)	C2	Uncertain significance	criteria provided, single submitter
356248	NM_000063.6(C2):c.1239G>C (p.Val413=)	C2	Uncertain significance	criteria provided, single submitter
356252	NM_000063.6(C2):c.1602T>C (p.Leu534=)	C2	Uncertain significance	criteria provided, single submitter
356253	NM_000063.6(C2):c.1716G>C (p.Lys572Asn)	C2	Uncertain significance	criteria provided, multiple submitters, no conflicts
356255	NM_000063.6(C2):c.1902+5G>A	C2	Uncertain significance	criteria provided, multiple submitters, no conflicts
356260	NM_000063.6(C2):c.2201G>T (p.Arg734Leu)	C2	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
CFB	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
C2	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFB	HGNC:1037	ENSG00000243649	P00751	Complement factor B	clinvar
C2	HGNC:1248	ENSG00000166278	P06681	Complement C2	clinvar
C2-AS1	HGNC:49464	ENSG00000281756		C2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFB	Complement factor B	Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the…
C2	Complement C2	Precursor of the catalytic component of the C3 and C5 convertase complexes, which are part of the complement pathway, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive i…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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	2	24.4×	0.004
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFB	Protease	yes	3.4.21.47	Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
C2	Protease	yes		Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
C2-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lobe of liver	3
liver	2
gall bladder	1
placenta	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFB	134	broad	marker	right lobe of liver, liver, gall bladder
C2	138	ubiquitous	marker	liver, right lobe of liver, placenta
C2-AS1	120		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFB	1,997
C2	937
C2-AS1	0

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFB	P00751	26
C2	P06681	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of C3 and C5	2	1268.9×	2e-06	CFB, C2
Regulation of Complement cascade	2	233.1×	4e-05	CFB, C2
Alternative complement activation	1	1142.0×	0.001	CFB
Initial triggering of complement	1	300.5×	0.003	C2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
complement activation	2	624.1×	2e-05	CFB, C2
response to bacterium	2	193.7×	1e-04	CFB, C2
positive regulation of apoptotic cell clearance	1	1203.7×	0.002	C2
response to thyroid hormone	1	1053.2×	0.002	C2
proteolysis	2	34.2×	0.002	CFB, C2
complement activation, GZMK pathway	1	648.1×	0.003	C2
complement activation, alternative pathway	1	495.6×	0.003	CFB
complement activation, classical pathway	1	271.8×	0.005	C2
response to nutrient	1	147.8×	0.008	C2
response to lipopolysaccharide	1	62.4×	0.016	C2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CFB	IPTACOPAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CFB	1	4
C2	0	0
C2-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IPTACOPAN	4	CFB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CFB	33	Binding:33
C2	4	Binding:4

Cohort enzymes (BRENDA EC)

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
IPTACOPAN	4	CFB

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CFB
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	C2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	C2-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
C2	4	—
C2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.