Sorsby fundus dystrophy
diseaseOn this page
Also known as SFDSorsby's pseudoinflammatory macular dystrophy
Summary
Sorsby fundus dystrophy (MONDO:0007640) is a disease caused by TIMP3 (GenCC Definitive), with 2 cohort genes.
At a glance
- Prevalence: Unknown (Worldwide)
- Causal gene: TIMP3 (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 113
- Phenotypes (HPO): 17
Clinical features
Signs & symptoms
Clinical features (HPO)
17 HPO clinical features (Orphanet curated; top 17 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000572 | Visual loss | Very frequent (80-99%) |
| HP:0007754 | Macular dystrophy | Very frequent (80-99%) |
| HP:0030500 | Yellow/white lesions of the macula | Very frequent (80-99%) |
| HP:0031528 | Subretinal deposits | Very frequent (80-99%) |
| HP:0000610 | Abnormal choroid morphology | Frequent (30-79%) |
| HP:0000662 | Nyctalopia | Frequent (30-79%) |
| HP:0001129 | Large central visual field defect | Frequent (30-79%) |
| HP:0011506 | Choroidal neovascularization | Frequent (30-79%) |
| HP:0030491 | Choriocapillaris atrophy | Frequent (30-79%) |
| HP:0030602 | Abnormal fundus autofluorescence imaging | Frequent (30-79%) |
| HP:0030625 | Hyporeflective spaces on macular OCT | Frequent (30-79%) |
| HP:0000533 | Chorioretinal atrophy | Occasional (5-29%) |
| HP:0000580 | Pigmentary retinopathy | Occasional (5-29%) |
| HP:0000618 | Blindness | Occasional (5-29%) |
| HP:0001105 | Retinal atrophy | Occasional (5-29%) |
| HP:0001141 | Severely reduced visual acuity | Occasional (5-29%) |
| HP:0007722 | Retinal pigment epithelial atrophy | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Sorsby fundus dystrophy |
| Mondo ID | MONDO:0007640 |
| MeSH | C564992 |
| OMIM | 136900 |
| Orphanet | 59181 |
| DOID | DOID:0090114 |
| ICD-11 | 796458172 |
| SNOMED CT | 193410003 |
| UMLS | C1850938 |
| MedGen | 338164 |
| GARD | 0016480 |
| Is cancer (heuristic) | no |
Also known as: SFD · Sorsby fundus dystrophy · Sorsby’s pseudoinflammatory macular dystrophy
Data availability: 113 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.
Disease family
An umbrella term covering 1 Mondo subtype.
Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › Sorsby fundus dystrophy
Related subtypes (104): retinal dystrophies primarily involving Bruch’s membrane, vitreoretinal dystrophy, dystrophies primarily involving the retinal pigment epithelium, retinal dystrophy in systemic or cerebroretinal lipidoses, age-related macular degeneration, helicoid peripapillary chorioretinal degeneration, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, pigmented paravenous retinochoroidal atrophy, retinoschisis, autosomal dominant, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, amaurosis-hypertrichosis syndrome, familial benign flecked retina, microcephaly and chorioretinopathy 1, ornithine aminotransferase deficiency, retinal degeneration-nanophthalmos-glaucoma syndrome, retinoschisis of fovea, Revesz syndrome, choroideremia, choroideremia-deafness-obesity syndrome, X-linked retinal dysplasia, X-linked retinoschisis, progressive bifocal chorioretinal atrophy, aceruloplasminemia, late-onset retinal degeneration, infantile cerebellar-retinal degeneration, progressive retinal dystrophy due to retinol transport defect, microcornea-myopic chorioretinal atrophy, retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies, macular degeneration, early-onset, cone-rod dystrophy, ectopia lentis-chorioretinal dystrophy-myopia syndrome, foveal hypoplasia-presenile cataract syndrome, MRCS syndrome, X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome, Leber congenital amaurosis, oligocone trichromacy, Oguchi disease, retinitis pigmentosa, hereditary macular dystrophy, RPE65-related recessive retinopathy, RPGR-related retinopathy, AIPL1-related retinopathy, RP2-related retinopathy, RDH5-related retinopathy, RLBP1-related retinopathy, LCA5-related retinopathy, ATF6-related retinopathy, RAB28-related retinopathy, FLVCR1-related retinopathy with or without ataxia, RPE65-related dominant retinopathy, GUCY2D retinopathy, PDE6A-related retinopathy, ELOVL4-related maculopathy, MAK-related retinopathy, KIZ-related retinopathy, TOPORS-related retinopathy, PRPF8-related retinopathy, RD3-related retinopathy, BEST1-related dominant retinopathy, BEST1-related recessive retinopathy, IMPG2-related recessive retinopathy, IMPG2-related dominant retinopathy, CACNA1F-related retinopathy, CACNA2D4-related retinopathy, CDHR1-related retinopathy, GUCA1A-related retinopathy, RHO-related retinopathy, SNRNP200-related dominant retinopathy, RDH12-related recessive retinopathy, RDH12-related dominant retinopathy, NMNAT1-related retinopathy, CNGA3-related retinopathy, EYS-related retinopathy, GNAT2-related retinopathy, IDH3B-related retinopathy, MERTK-related retinopathy, PRPF31-related retinopathy, GPR179-related retinopathy, GRM6-related retinopathy, ADAM9-related retinopathy, RP1-related recessive retinopathy, RP1-related dominant retinopathy, CERKL-related retinopathy, TRPM1-related retinopathy, CNGB1-related retinopathy, PCARE-related retinopathy, CNGA1-related retinopathy, ABCA4-related retinopathy, NYX-related retinopathy, retinal dystrophy, X-linked, Gardner-Hardcastle type, PDE6C-related retinopathy, PDE6G-related retinopathy, LRIT3-related retinopathy, IMPG1-related dominant retinopathy, IMPG1-related recessive retinopathy, TTLL5-related retinopathy, HGSNAT-related retinopathy, IMPDH1-related retinopathy, PRPH2-related retinopathy, PROM1-related retinopathy, KCNV2-related retinopathy, CRX-related retinopathy, REEP6-related retinopathy, SPATA7-related retinopathy
Subtypes (1): fundus dystrophy, pseudoinflammatory, recessive form
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
113 retrieved; paginated sample, class counts are floors:
66 uncertain significance, 35 benign, 4 conflicting classifications of pathogenicity, 3 pathogenic, 3 likely benign, 1 likely pathogenic, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 12677 | NM_000362.5(TIMP3):c.572A>G (p.Tyr191Cys) | SYN3 | Pathogenic | criteria provided, single submitter |
| 12676 | NM_000362.5(TIMP3):c.610A>T (p.Ser204Cys) | TIMP3 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 12678 | NM_000362.5(TIMP3):c.536C>G (p.Ser179Cys) | TIMP3 | Pathogenic | criteria provided, single submitter |
| 12679 | NM_000362.5(TIMP3):c.565G>T (p.Gly189Cys) | SYN3 | Likely pathogenic | criteria provided, single submitter |
| 1933247 | NM_000362.5(TIMP3):c.602dup (p.Asp202fs) | SYN3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 341348 | NM_000362.5(TIMP3):c.587G>A (p.Arg196Gln) | SYN3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 289421 | NM_000362.5(TIMP3):c.321C>T (p.Arg107=) | TIMP3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 341347 | NM_000362.5(TIMP3):c.516C>T (p.Phe172=) | TIMP3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 12680 | NM_000362.5(TIMP3):c.484G>T (p.Glu162Ter) | SYN3 | Uncertain significance | criteria provided, single submitter |
| 1687491 | NM_000362.5(TIMP3):c.454_455insGTA (p.Tyr152delinsCysAsn) | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341326 | NM_000362.4(TIMP3):c.-1136G>C | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341327 | NM_000362.4(TIMP3):c.-1082C>G | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341331 | NM_000362.4(TIMP3):c.-684T>C | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341334 | NM_000362.4(TIMP3):c.-433C>T | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341335 | NM_000362.4(TIMP3):c.-407G>A | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341336 | NM_000362.4(TIMP3):c.-390C>A | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341337 | NM_000362.4(TIMP3):c.-330C>T | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341339 | NM_000362.5(TIMP3):c.-270G>T | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341341 | NM_000362.5(TIMP3):c.-105G>C | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341342 | NM_000362.5(TIMP3):c.121+4A>G | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341346 | NM_000362.5(TIMP3):c.439-12A>T | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341349 | NM_000362.5(TIMP3):c.*87T>C | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341350 | NM_000362.5(TIMP3):c.*105C>A | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341352 | NM_000362.5(TIMP3):c.*506G>A | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341353 | NM_000362.5(TIMP3):c.*529G>A | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341355 | NM_000362.5(TIMP3):c.*541T>A | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341357 | NM_000362.5(TIMP3):c.*795A>G | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341359 | NM_000362.5(TIMP3):c.*990G>A | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341360 | NM_000362.5(TIMP3):c.*1179T>C | SYN3 | Uncertain significance | criteria provided, single submitter |
| 341362 | NM_000362.5(TIMP3):c.*1297T>C | SYN3 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · Orphanet: 1 · 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 |
|---|---|---|---|---|
| TIMP3 | Definitive | Autosomal dominant | Sorsby fundus dystrophy | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TIMP3 | Orphanet:59181 | Sorsby fundus dystrophy |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TIMP3 | HGNC:11822 | ENSG00000100234 | P35625 | Metalloproteinase inhibitor 3 | gencc,clinvar |
| SYN3 | HGNC:11496 | ENSG00000185666 | O14994 | Synapsin-3 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TIMP3 | Metalloproteinase inhibitor 3 | Mediates a variety of processes including matrix regulation and turnover, inflammation, and angiogenesis, through reversible inhibition of zinc protease superfamily enzymes, primarily matrix metalloproteinases (MMPs). |
| SYN3 | Synapsin-3 | May be involved in the regulation of neurotransmitter release and synaptogenesis. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0
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 |
|---|---|---|---|
| Other/Unknown | 2 | 1.8× | 0.312 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TIMP3 | Other/Unknown | no | Netrin_domain, TIMP, TIMP-like_OB-fold | |
| SYN3 | Other/Unknown | no | Synapsin, ATP_grasp_subdomain_1, PreATP-grasp_dom_sf |
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 |
|---|---|
| decidua | 1 |
| pigmented layer of retina | 1 |
| synovial joint | 1 |
| cortical plate | 1 |
| primary visual cortex | 1 |
| primordial germ cell in gonad | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TIMP3 | 299 | ubiquitous | marker | synovial joint, decidua, pigmented layer of retina |
| SYN3 | 176 | broad | marker | primordial germ cell in gonad, cortical plate, primary visual cortex |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TIMP3 | 2,921 |
| SYN3 | 1,601 |
Structural data
PDB: 2 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| TIMP3 | P35625 | 1 |
| SYN3 | O14994 | 1 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 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 |
|---|---|---|---|---|
| Serotonin Neurotransmitter Release Cycle | 1 | 317.2× | 0.009 | SYN3 |
| Dopamine Neurotransmitter Release Cycle | 1 | 248.3× | 0.009 | SYN3 |
| Neurotransmitter release cycle | 1 | 219.6× | 0.009 | SYN3 |
| Platelet degranulation | 1 | 43.9× | 0.031 | TIMP3 |
| Transmission across Chemical Synapses | 1 | 38.1× | 0.031 | SYN3 |
| Neuronal System | 1 | 22.1× | 0.045 | SYN3 |
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 |
|---|---|---|---|---|
| negative regulation of extracellular matrix disassembly | 1 | 1404.3× | 0.004 | TIMP3 |
| negative regulation of membrane protein ectodomain proteolysis | 1 | 936.2× | 0.004 | TIMP3 |
| synaptic vesicle clustering | 1 | 702.2× | 0.004 | SYN3 |
| regulation of synaptic transmission, GABAergic | 1 | 526.6× | 0.004 | SYN3 |
| neurotransmitter secretion | 1 | 351.1× | 0.005 | SYN3 |
| response to hormone | 1 | 216.1× | 0.007 | TIMP3 |
| response to cytokine | 1 | 187.2× | 0.007 | TIMP3 |
| synapse organization | 1 | 140.4× | 0.008 | SYN3 |
| visual perception | 1 | 39.8× | 0.025 | TIMP3 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1
Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TIMP3 | 1 | 3 |
| SYN3 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| SURAMIN | 3 | TIMP3 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| TIMP3 | 1 | Binding:1 |
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) |
|---|---|---|
| SURAMIN | 3 | TIMP3 |
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 | 1 | TIMP3 |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | SYN3 |
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) |
|---|---|---|
| SYN3 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.