Age related macular degeneration 2

Summary

Age related macular degeneration 2 (MONDO:0007932) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 236

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	age related macular degeneration 2
Mondo ID	MONDO:0007932
MeSH	C562479
OMIM	153800
DOID	DOID:0110015
UMLS	C3495438
MedGen	501183
GARD	0024587
Is cancer (heuristic)	no

Also known as: age related macular degeneration type 2 · ARMD2 · macular degeneration, age-related, 2 · macular Degeneration, age-related, type 2

Data availability: 236 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 › age related macular degeneration 2

Related subtypes (14): wet macular degeneration, 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, 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

236 retrieved; paginated sample, class counts are floors:

79 pathogenic/likely pathogenic, 60 pathogenic, 41 conflicting classifications of pathogenicity, 19 uncertain significance, 16 benign, 12 likely pathogenic, 6 benign/likely benign, 2 likely benign, 1 pathogenic/likely pathogenic; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
1001082	NM_000350.3(ABCA4):c.1019A>C (p.Tyr340Ser)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1062657	NM_000350.3(ABCA4):c.2294GTG[1] (p.Gly766del)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067357	NM_000350.3(ABCA4):c.3522+1G>A	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073468	NM_000350.3(ABCA4):c.1761-2A>G	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1275763	NM_000350.3(ABCA4):c.5578C>T (p.Arg1860Trp)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143076	NM_000350.3(ABCA4):c.6119G>A (p.Arg2040Gln)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452669	NM_000350.3(ABCA4):c.2972G>T (p.Gly991Val)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456034	NM_000350.3(ABCA4):c.3304G>T (p.Asp1102Tyr)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456725	NM_000350.3(ABCA4):c.5714+1G>A	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
1476832	NM_000350.3(ABCA4):c.4327C>T (p.Arg1443Cys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685486	NM_000350.3(ABCA4):c.4571del (p.Asp1524fs)	ABCA4	Pathogenic	criteria provided, single submitter
1685487	NM_000350.3(ABCA4):c.2919-2A>G	ABCA4	Pathogenic	criteria provided, single submitter
198720	NM_000350.3(ABCA4):c.880C>T (p.Gln294Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
212727	NM_000350.3(ABCA4):c.1964T>G (p.Phe655Cys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236078	NM_000350.3(ABCA4):c.1086T>A (p.Tyr362Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
236080	NM_000350.3(ABCA4):c.1293G>A (p.Trp431Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
236095	NM_000350.3(ABCA4):c.2875A>G (p.Thr959Ala)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236096	NM_000350.3(ABCA4):c.2894A>G (p.Asn965Ser)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
236100	NM_000350.3(ABCA4):c.3292C>T (p.Arg1098Cys)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236102	NM_000350.3(ABCA4):c.3482G>A (p.Arg1161His)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236106	NM_000350.3(ABCA4):c.3871C>T (p.Gln1291Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
236110	NM_000350.3(ABCA4):c.4253+5G>A	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236115	NM_000350.3(ABCA4):c.4519G>A (p.Gly1507Arg)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236122	NM_000350.3(ABCA4):c.4773+3A>G	ABCA4	Pathogenic	reviewed by expert panel
236127	NM_000350.3(ABCA4):c.5196+1056A>G	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236128	NM_000350.3(ABCA4):c.5312+1G>A	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
236129	NM_000350.3(ABCA4):c.5318C>T (p.Ala1773Val)	ABCA4	Pathogenic	reviewed by expert panel
236144	NM_000350.3(ABCA4):c.6077T>C (p.Leu2026Pro)	ABCA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236149	NM_000350.3(ABCA4):c.6647C>T (p.Ala2216Val)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts
265008	NM_000350.3(ABCA4):c.655A>T (p.Arg219Ter)	ABCA4	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 9 · 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
ABCA4	Strong	Autosomal recessive	ABCA4-related retinopathy	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCA4	Orphanet:1872	Cone rod dystrophy
ABCA4	Orphanet:791	Retinitis pigmentosa
ABCA4	Orphanet:827	Stargardt disease
MT-TL1	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-TL1	Orphanet:324525	Hypertrophic cardiomyopathy with kidney anomalies due to mitochondrial DNA mutation
MT-TL1	Orphanet:480	Kearns-Sayre syndrome
MT-TL1	Orphanet:550	MELAS
MT-TL1	Orphanet:551	MERRF
MT-TL1	Orphanet:663	Mitochondrial DNA-related progressive external ophthalmoplegia

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABCA4	HGNC:34	ENSG00000198691	P78363	Retinal-specific phospholipid-transporting ATPase ABCA4	gencc,clinvar
MT-TL1	HGNC:7490	ENSG00000209082		mitochondrially encoded tRNA-Leu (UUA/G) 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCA4	Retinal-specific phospholipid-transporting ATPase ABCA4	Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leafl…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCA4	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABCA4/ABCR
MT-TL1	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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1
primordial germ cell in gonad	1
caudate nucleus	1
frontal cortex	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCA4	164	tissue_specific	marker	pigmented layer of retina, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
MT-TL1	118	ubiquitous	marker	frontal cortex, right frontal lobe, caudate nucleus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCA4	1,532
MT-TL1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCA4	P78363	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 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
Defective visual phototransduction due to ABCA4 loss of function	1	11420.0×	9e-04	ABCA4
Retinoid cycle disease events	1	2855.0×	9e-04	ABCA4
Diseases associated with visual transduction	1	2855.0×	9e-04	ABCA4
Diseases of the neuronal system	1	2855.0×	9e-04	ABCA4
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.004	ABCA4
Visual phototransduction	1	259.6×	0.006	ABCA4
ABC-family protein mediated transport	1	121.5×	0.012	ABCA4
Sensory Perception	1	95.2×	0.013	ABCA4
Transport of small molecules	1	25.1×	0.044	ABCA4
Disease	1	13.1×	0.076	ABCA4

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
phospholipid transfer to membrane	1	5617.3×	0.002	ABCA4
phototransduction, visible light	1	1296.3×	0.003	ABCA4
retinal metabolic process	1	936.2×	0.003	ABCA4
phospholipid translocation	1	624.1×	0.004	ABCA4
retinoid metabolic process	1	495.6×	0.004	ABCA4
photoreceptor cell maintenance	1	358.6×	0.004	ABCA4
lipid transport	1	263.3×	0.005	ABCA4
transmembrane transport	1	168.5×	0.007	ABCA4
visual perception	1	79.5×	0.013	ABCA4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
ABCA4	0	0
MT-TL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	ABCA4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MT-TL1

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)
ABCA4	0	—
MT-TL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.