Age related macular degeneration 4
diseaseOn this page
Also known as age related macular degeneration type 4age-related macular degeneration caused by mutation in CFHARMD4CFH age-related macular degenerationmacular degeneration, age-related, 4macular Degeneration, age-related, type 4
Summary
Age related macular degeneration 4 (MONDO:0012540) is a disease with 1 cohort gene.
At a glance
- Cohort genes: 1
- ClinVar variants: 558
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | age related macular degeneration 4 |
| Mondo ID | MONDO:0012540 |
| MeSH | C565196 |
| OMIM | 610698 |
| DOID | DOID:0110017 |
| UMLS | C1853147 |
| MedGen | 339914 |
| GARD | 0024872 |
| Is cancer (heuristic) | no |
Also known as: age related macular degeneration type 4 · age-related macular degeneration caused by mutation in CFH · ARMD4 · CFH age-related macular degeneration · macular degeneration, age-related, 4 · macular Degeneration, age-related, type 4
Data availability: 558 ClinVar variants · 17 cell lines.
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 4
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 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
558 retrieved; paginated sample, class counts are floors:
345 uncertain significance, 55 conflicting classifications of pathogenicity, 36 benign/likely benign, 33 benign, 26 likely benign, 23 likely pathogenic, low penetrance, 12 pathogenic, 11 likely pathogenic, 6 pathogenic, low penetrance, 5 pathogenic/likely pathogenic, 2 risk factor, 1 likely pathogenic/likely pathogenic, low penetrance, 1 pathogenic/likely pathogenic/pathogenic, low penetrance, 1 pathogenic; risk factor, 1 pathogenic/likely pathogenic, low penetrance
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1068249 | NM_000186.4(CFH):c.157C>T (p.Arg53Cys) | CFH | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1343348 | NM_000186.4(CFH):c.740del (p.Gly247fs) | CFH | Likely pathogenic/Likely pathogenic, low penetrance | criteria provided, multiple submitters, no conflicts |
| 1417726 | NM_000186.4(CFH):c.213G>A (p.Trp71Ter) | CFH | Pathogenic/Likely pathogenic/Pathogenic, low penetrance | criteria provided, multiple submitters, no conflicts |
| 1450348 | NM_000186.4(CFH):c.1873G>T (p.Glu625Ter) | CFH | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1454075 | NM_000186.4(CFH):c.2602dup (p.Ile868fs) | CFH | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 16545 | NM_000186.4(CFH):c.3572C>T (p.Ser1191Leu) | CFH | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 16549 | NM_000186.4(CFH):c.1204= (p.His402=) | CFH | Pathogenic; risk factor | no assertion criteria provided |
| 16560 | NM_000186.4(CFH):c.1222C>T (p.Gln408Ter) | CFH | Pathogenic | criteria provided, single submitter |
| 2025535 | NM_000186.4(CFH):c.2575C>T (p.Gln859Ter) | CFH | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 294526 | NM_000186.4(CFH):c.3643C>T (p.Arg1215Ter) | CFH | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4291289 | NM_000186.4(CFH):c.504C>A (p.Tyr168Ter) | CFH | Pathogenic, low penetrance | criteria provided, single submitter |
| 4291295 | NM_000186.4(CFH):c.550del (p.Ile184fs) | CFH | Pathogenic | criteria provided, single submitter |
| 4291305 | NM_000186.4(CFH):c.593G>A (p.Trp198Ter) | CFH | Pathogenic | criteria provided, single submitter |
| 4291308 | NM_000186.4(CFH):c.607_610dup (p.Lys204fs) | CFH | Pathogenic | criteria provided, single submitter |
| 4291316 | NM_000186.4(CFH):c.652G>T (p.Gly218Ter) | CFH | Pathogenic | criteria provided, single submitter |
| 4291329 | NM_000186.4(CFH):c.790+1G>A | CFH | Pathogenic | criteria provided, single submitter |
| 4291358 | NM_000186.4(CFH):c.1075G>T (p.Glu359Ter) | CFH | Pathogenic, low penetrance | criteria provided, single submitter |
| 4291421 | NM_000186.4(CFH):c.1778T>A (p.Leu593Ter) | CFH | Pathogenic | criteria provided, single submitter |
| 4291426 | NM_000186.4(CFH):c.1833C>A (p.Cys611Ter) | CFH | Pathogenic/Likely pathogenic, low penetrance | criteria provided, multiple submitters, no conflicts |
| 4291450 | NM_000186.4(CFH):c.2141C>G (p.Ser714Ter) | CFH | Pathogenic | criteria provided, single submitter |
| 4291505 | NM_000186.4(CFH):c.2748C>G (p.Tyr916Ter) | CFH | Pathogenic | criteria provided, single submitter |
| 4291525 | NM_000186.4(CFH):c.244+2T>C | CFH | Pathogenic, low penetrance | criteria provided, single submitter |
| 4291547 | NM_000186.4(CFH):c.3226C>T (p.Gln1076Ter) | CFH | Pathogenic, low penetrance | criteria provided, single submitter |
| 4291652 | NM_000186.4(CFH):c.901del (p.Ala301fs) | CFH | Pathogenic | criteria provided, single submitter |
| 4291678 | NM_000186.4(CFH):c.351-2A>G | CFH | Pathogenic | criteria provided, single submitter |
| 4291697 | NM_000186.4(CFH):c.428-2A>G | CFH | Pathogenic, low penetrance | criteria provided, single submitter |
| 635491 | NM_000186.4(CFH):c.1126C>T (p.Gln376Ter) | CFH | Pathogenic, low penetrance | criteria provided, single submitter |
| 16551 | NM_000186.4(CFH):c.1291T>A (p.Cys431Ser) | CFH | Likely pathogenic, low penetrance | criteria provided, single submitter |
| 1936765 | NM_000186.4(CFH):c.2236+1G>C | CFH | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3381091 | NM_000186.4(CFH):c.1673G>A (p.Trp558Ter) | CFH | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CFH | Orphanet:200421 | Immunodeficiency with factor H anomaly |
| CFH | Orphanet:244242 | HELLP syndrome |
| CFH | Orphanet:244275 | De novo thrombotic microangiopathy after kidney transplantation |
| CFH | Orphanet:329903 | Immunoglobulin-mediated membranoproliferative glomerulonephritis |
| CFH | Orphanet:544472 | Atypical hemolytic uremic syndrome with complement gene abnormality |
| CFH | Orphanet:75376 | Familial drusen |
| CFH | Orphanet:93571 | Dense deposit disease |
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 |
|---|---|---|---|---|---|
| CFH | HGNC:4883 | ENSG00000000971 | P08603 | Complement factor H | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CFH | Complement factor H | Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. |
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) |
|---|---|---|---|---|
| CFH | Complement | yes | Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med |
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 |
|---|---|
| calcaneal tendon | 1 |
| right coronary artery | 1 |
| urethra | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CFH | 267 | ubiquitous | marker | urethra, calcaneal tendon, right coronary artery |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| CFH | 1,844 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| CFH | P08603 | 51 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. 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 |
|---|---|---|---|---|
| Regulation of Complement cascade | 1 | 233.1× | 0.004 | CFH |
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 complement activation, alternative pathway | 1 | 8426.0× | 9e-04 | CFH |
| regulation of complement-dependent cytotoxicity | 1 | 3370.4× | 0.001 | CFH |
| regulation of complement activation | 1 | 2106.5× | 0.001 | CFH |
| complement activation, alternative pathway | 1 | 991.3× | 0.002 | CFH |
| central nervous system myelination | 1 | 991.3× | 0.002 | CFH |
| complement activation | 1 | 624.1× | 0.002 | CFH |
| inflammatory response | 1 | 37.7× | 0.029 | CFH |
| proteolysis | 1 | 34.2× | 0.029 | CFH |
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 |
|---|---|---|
| CFH | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| CFH | 1 | Binding:1 |
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 | CFH |
| 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) |
|---|---|---|
| CFH | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: CFH