Age related macular degeneration 9: genes and variants
Age related macular degeneration 9 is linked to 7 analyzed proteins (ABCA4, CFH, APOE, C3, CETP, FBN2 and LIPC). 44 DNA variants are known to cause it; 173 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Age related macular degeneration 1; age related macular degeneration 2; age related macular degeneration 4; age-related macular degeneration
Genes linked to Age related macular degeneration 9
ABCA4: Retinal-specific phospholipid-transporting ATPase ABCA4
It flips retinal-derived lipid adducts across photoreceptor disc membranes so they can be cleared during the visual cycle. Biallelic loss-of-function variants cause Stargardt disease and can also produce cone-rod dystrophy or retinitis pigmentosa.
41 disease-causing and 21 uncertain variants in ABCA4 are linked to Age related macular degeneration 9.
CFH: Complement factor H
It restrains the alternative complement pathway on host surfaces and in plasma, protecting tissues from uncontrolled complement amplification. Pathogenic variants or risk alleles are associated with atypical hemolytic uremic syndrome, C3 glomerulopathy, and age-related macular degeneration.
2 disease-causing and 10 uncertain variants in CFH are linked to Age related macular degeneration 9.
APOE: Apolipoprotein E
It redistributes cholesterol and other lipids between tissues by directing remnant lipoproteins to LDL-receptor-family members. The common epsilon4 isoform strongly increases late-onset Alzheimer disease risk and also influences plasma lipids and cardiovascular risk.
1 disease-causing and 0 uncertain variants in APOE are linked to Age related macular degeneration 9.
C3: Complement C3
It is cleaved during complement activation to generate C3a and C3b, which amplify inflammation, opsonize targets, and drive formation of downstream complement complexes. Deficiency causes severe susceptibility to bacterial infection, while dysregulated activation contributes to complement-mediated kidney and inflammatory diseases.
0 disease-causing and 142 uncertain variants in C3 are linked to Age related macular degeneration 9.
CETP: Cholesteryl ester transfer protein
It transfers cholesteryl esters and triglycerides between HDL and apoB-containing lipoproteins, strongly influencing circulating lipoprotein composition. Loss-of-function variants can raise HDL cholesterol, while pharmacologic CETP inhibition has been developed to lower atherosclerotic cardiovascular risk.
0 disease-causing and 0 uncertain variants in CETP are linked to Age related macular degeneration 9.
FBN2: Fibrillin-2
It contributes to extracellular microfibrils that guide elastic-fiber formation and tissue organization during development. Heterozygous pathogenic variants cause congenital contractural arachnodactyly, characterized by long limbs and fingers, contractures, and characteristic ear abnormalities.
0 disease-causing and 0 uncertain variants in FBN2 are linked to Age related macular degeneration 9.
LIPC: Hepatic triacylglycerol lipase
It hydrolyzes triglycerides and phospholipids in HDL and remnant particles at the liver surface, helping remodel circulating lipoproteins. Loss-of-function variants can raise HDL cholesterol and alter remnant metabolism, with variable effects on atherosclerotic risk.
0 disease-causing and 0 uncertain variants in LIPC are linked to Age related macular degeneration 9.
Where Age related macular degeneration 9 variants cluster
- ABCA4 ABC transporter 1 (positions 929–1160): 10 of 41 disease-causing changes, 2.4× more than its size predicts.
Known disease-causing variants in Age related macular degeneration 9
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ABCA4 C1488F | 1488 | Extracellular | Disease-causing (★★) |
| ABCA4 G65E | 65 | Extracellular | Disease-causing (★★) |
| ABCA4 D576H | 576 | Extracellular | Disease-causing (★★) |
| ABCA4 T971N | 971 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 T1019A | 1019 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 G1091E | 1091 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 C1488R | 1488 | Extracellular | Disease-causing (★★) |
| ABCA4 K1978E | 1978 | ABC transporter 2 | Disease-causing (★★) |
| ABCA4 L2060R | 2060 | ABC transporter 2 | Disease-causing (★★) |
| ABCA4 T972N | 972 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 S1071L | 1071 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 D1102Y | 1102 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 R1129H | 1129 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 R1640W | 1640 | Extracellular | Disease-causing (★★) |
| ABCA4 I1846T | 1846 | Transmembrane | Disease-causing (★★) |
| ABCA4 E2131K | 2131 | ABC transporter 2 | Disease-causing (★★) |
| ABCA4 P143L | 143 | Extracellular | Disease-causing (★★) |
| ABCA4 E328V | 328 | Extracellular | Disease-causing (★★) |
| ABCA4 R1640Q | 1640 | Extracellular | Disease-causing (★★) |
| ABCA4 L1784P | 1784 | Extracellular | Disease-causing (★★) |
| ABCA4 F2188S | 2188 | Cytoplasmic | Disease-causing (★★) |
| ABCA4 R24C | 24 | Transmembrane | Disease-causing (★★) |
| ABCA4 C230S | 230 | Extracellular | Disease-causing (★★) |
| ABCA4 D645N | 645 | Extracellular | Disease-causing (★★) |
| ABCA4 W821R | 821 | Extracellular | Disease-causing (★★) |
| ABCA4 R1443C | 1443 | Extracellular | Disease-causing (★★) |
| ABCA4 L1729P | 1729 | Transmembrane | Disease-causing (★★) |
| ABCA4 Y1858N | 1858 | Extracellular | Disease-causing (★★) |
| ABCA4 T2240A | 2240 | Cytoplasmic | Disease-causing (★★) |
| ABCA4 N96D | 96 | Extracellular | Disease-causing (★★) |
| ABCA4 E1036K | 1036 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 G1050D | 1050 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 D1532N | 1532 | Extracellular | Disease-causing (★★) |
| ABCA4 A1598D | 1598 | Extracellular | Disease-causing (★★) |
| ABCA4 A1881V | 1881 | Transmembrane | Disease-causing (★★) |
| ABCA4 T1981R | 1981 | ABC transporter 2 | Disease-causing (★★) |
| ABCA4 R220C | 220 | Extracellular | Disease-causing (★★) |
| ABCA4 P309R | 309 | Extracellular | Disease-causing (★★) |
| ABCA4 M448V | 448 | Extracellular | Disease-causing (★★) |
| ABCA4 G991V | 991 | ABC transporter 1 | Disease-causing (★★) |
| ABCA4 R1860W | 1860 | Extracellular | Disease-causing (★★) |
| APOE R43C | 43 | Disease-causing (★★) | |
| CFH C431S | 431 | Sushi 7 | Disease-causing (★) |
| CFH C325Y | 325 | Sushi 6 | Disease-causing (★) |
Which prediction tools work for Age related macular degeneration 9
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- REVEL: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 93 out of 100
- MetaLR: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 90 out of 100
- phyloP: 89 out of 100
- PolyPhen-2: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 79 out of 100
Same protein, different disease
- Severe early-childhood-onset retinal dystrophy is also caused by ABCA4 variants; they fall mostly in different places as the Age related macular degeneration 9 variants (148 disease-causing).
- ABCA4-related retinopathy is also caused by ABCA4 variants; they fall mostly in different places as the Age related macular degeneration 9 variants (60 disease-causing).
- Retinitis pigmentosa is also caused by ABCA4 variants; they fall mostly in different places as the Age related macular degeneration 9 variants (58 disease-causing).
- Stargardt disease is also caused by ABCA4 variants; they fall mostly in different places as the Age related macular degeneration 9 variants (41 disease-causing).
- Cone-rod dystrophy is also caused by ABCA4 variants; they fall mostly in different places as the Age related macular degeneration 9 variants (29 disease-causing).
- Atypical hemolytic-uremic syndrome is also caused by CFH variants; they fall mostly in different places as the Age related macular degeneration 9 variants (12 disease-causing).
- Factor H deficiency is also caused by CFH variants; they fall mostly in different places as the Age related macular degeneration 9 variants (4 disease-causing).
- Familial type 3 hyperlipoproteinemia is also caused by APOE variants; they fall mostly in different places as the Age related macular degeneration 9 variants (10 disease-causing).
- Familial hypercholesterolemia is also caused by APOE variants; they fall mostly in different places as the Age related macular degeneration 9 variants (3 disease-causing).
Diseases related to Age related macular degeneration 9
- Retinal disorder, also linked to ABCA4, C3, CETP and CFH
- Type 2 diabetes mellitus, also linked to APOE and LIPC
- Atypical hemolytic-uremic syndrome, also linked to C3 and CFH
- Familial thoracic aortic aneurysm and aortic dissection, also linked to FBN2
- Retinitis pigmentosa, also linked to ABCA4
- Familial hypercholesterolemia, also linked to APOE
- Leber congenital amaurosis, also linked to ABCA4
- Severe early-childhood-onset retinal dystrophy, also linked to ABCA4
- Alzheimer disease, also linked to APOE
- ABCA4-related retinopathy, also linked to ABCA4
- Stargardt disease, also linked to ABCA4
- Cone-rod dystrophy, also linked to ABCA4
Frequently asked questions
Which genes are linked to Age related macular degeneration 9?
In CATVariant, Age related macular degeneration 9 is linked to 7 analyzed proteins: ABCA4 (Retinal-specific phospholipid-transporting ATPase ABCA4), CFH (Complement factor H), APOE (Apolipoprotein E), C3 (Complement C3), CETP (Cholesteryl ester transfer protein), FBN2 (Fibrillin-2) and 1 more.
How many genetic variants are linked to Age related macular degeneration 9?
234 variants: 44 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 173 are of uncertain significance or have conflicting reports.
Which uncertain variants in Age related macular degeneration 9 look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Age related macular degeneration 9?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.93, based on 40 disease-causing and 78 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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