Late-onset retinal degeneration

disease
On this page

Also known as autosomal dominant late-onset retinal degenerationLORDpigmentary retinopathy

Summary

Late-onset retinal degeneration (MONDO:0011579) is a disease caused by C1QTNF5 (GenCC Definitive), with 3 cohort genes and 5 clinical trials.

At a glance

  • Prevalence: Unknown (Worldwide)
  • Causal gene: C1QTNF5 (GenCC Definitive)
  • Cohort genes: 3
  • ClinVar variants: 95
  • Phenotypes (HPO): 22
  • Clinical trials: 5

Clinical features

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO IDTermFrequency
HP:0030534Abnormal best corrected visual acuity testVery frequent (80-99%)
HP:0000533Chorioretinal atrophyFrequent (30-79%)
HP:0000572Visual lossFrequent (30-79%)
HP:0000608Macular degenerationFrequent (30-79%)
HP:0000662NyctalopiaFrequent (30-79%)
HP:0001141Severely reduced visual acuityFrequent (30-79%)
HP:0007791Patchy atrophy of the retinal pigment epitheliumFrequent (30-79%)
HP:0011506Choroidal neovascularizationFrequent (30-79%)
HP:0011510DrusenFrequent (30-79%)
HP:0031530Multifocal subretinal depositsFrequent (30-79%)
HP:0000552TritanomalyOccasional (5-29%)
HP:0000613PhotophobiaOccasional (5-29%)
HP:0000642Red-green dyschromatopsiaOccasional (5-29%)
HP:0001089Iris atrophyOccasional (5-29%)
HP:0001099Fundus atrophyOccasional (5-29%)
HP:0004328Abnormal anterior eye segment morphologyOccasional (5-29%)
HP:0007401Macular atrophyOccasional (5-29%)
HP:0012628Abnormal suspensory ligament of lens morphologyOccasional (5-29%)
HP:0012805Iris transillumination defectOccasional (5-29%)
HP:0500087Peripapillary atrophyOccasional (5-29%)
HP:0007906Ocular hypertensionVery rare (<1-4%)
HP:0100014Epiretinal membraneVery rare (<1-4%)

Identifiers

Disease identifiers

FieldValue
Canonical namelate-onset retinal degeneration
Mondo IDMONDO:0011579
MeSHC565309
OMIM605670
Orphanet67042
DOIDDOID:0060869
SNOMED CT719431007
UMLSC1854065
MedGen344198
GARD0004357
Is cancer (heuristic)no

Also known as: autosomal dominant late-onset retinal degeneration · late-onset retinal degeneration · LORD · pigmentary retinopathy

Data availability: 95 ClinVar variants · 3 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorderretinal disorderretinal degenerationinherited retinal dystrophylate-onset retinal degeneration

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, Sorsby fundus dystrophy, 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, 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

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

95 retrieved; paginated sample, class counts are floors:

59 uncertain significance, 25 conflicting classifications of pathogenicity, 5 benign/likely benign, 2 pathogenic/likely pathogenic, 2 likely benign, 1 pathogenic, 1 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
1687105NM_001278431.2(C1QTNF5):c.562C>A (p.Pro188Thr)C1QTNF5Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
2126NM_001278431.2(C1QTNF5):c.489C>G (p.Ser163Arg)MFRPPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
812376NM_000929.3(PLA2G5):c.280dup (p.Val94fs)PLA2G5Pathogenicno assertion criteria provided
813996NM_001278431.2(C1QTNF5):c.562C>G (p.Pro188Ala)MFRPLikely pathogeniccriteria provided, single submitter
167294NM_031433.4(MFRP):c.1014C>A (p.Ser338Arg)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
194544NM_001278431.2(C1QTNF5):c.294C>T (p.Cys98=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
196562NM_031433.4(MFRP):c.160C>G (p.Arg54Gly)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302925NM_001278431.2(C1QTNF5):c.567C>T (p.Ala189=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302941NM_031433.4(MFRP):c.*483T>CC1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302950NM_031433.4(MFRP):c.1516-4G>AC1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302951NM_031433.4(MFRP):c.1506C>T (p.Ser502=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302953NM_031433.4(MFRP):c.1461C>A (p.Ile487=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302956NM_031433.4(MFRP):c.976-14A>CC1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302961NM_031433.4(MFRP):c.909G>C (p.Gly303=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302962NM_031433.4(MFRP):c.897G>A (p.Ser299=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302963NM_031433.4(MFRP):c.861C>T (p.Asp287=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302964NM_031433.4(MFRP):c.807G>A (p.Gln269=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302966NM_031433.4(MFRP):c.773-8A>CC1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302967NM_031433.4(MFRP):c.705C>T (p.Phe235=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302974NM_031433.4(MFRP):c.303C>T (p.Ser101=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302975NM_031433.4(MFRP):c.271+10C>TC1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302977NM_031433.4(MFRP):c.192C>G (p.Arg64=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302984NM_031433.4(MFRP):c.-49G>AC1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
852164NM_001278431.2(C1QTNF5):c.393C>A (p.Asn131Lys)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
877118NM_031433.4(MFRP):c.321C>T (p.Ala107=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
877887NM_031433.4(MFRP):c.898+5G>AC1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
878728NM_001278431.2(C1QTNF5):c.354G>A (p.Pro118=)C1QTNF5Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
302928NM_001278431.2(C1QTNF5):c.341G>A (p.Arg114Gln)MFRPConflicting classifications of pathogenicitycriteria provided, conflicting classifications
302930NM_001278431.2(C1QTNF5):c.214+9G>AMFRPConflicting classifications of pathogenicitycriteria provided, conflicting classifications
288043NM_031433.4(MFRP):c.796C>T (p.Arg266Cys)C1QTNF5Uncertain significancecriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 4 · 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.

GeneClassificationInheritanceDiseaseRecords
C1QTNF5DefinitiveAutosomal dominantlate-onset retinal degeneration3

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
C1QTNF5Orphanet:67042Late-onset retinal degeneration
MFRPOrphanet:251279Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome
MFRPOrphanet:35612Nanophthalmos
PLA2G5Orphanet:363989Familial benign flecked retina

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence3

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
C1QTNF5HGNC:14344ENSG00000223953Q9BXJ0Complement C1q tumor necrosis factor-related protein 5gencc,clinvar
MFRPHGNC:18121ENSG00000235718Q9BY79Membrane frizzled-related proteinclinvar
PLA2G5HGNC:9038ENSG00000127472P39877Phospholipase A2 group Vclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
MFRPMembrane frizzled-related proteinMay play a role in eye development.
PLA2G5Phospholipase A2 group VSecretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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.

FamilyGenesFoldFDR
Other/Unknown31.8×0.174

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
C1QTNF5Other/UnknownnoC1q_dom, Collagen, Tumour_necrosis_fac-like_dom
MFRPOther/UnknownnoCUB_dom, LDrepeatLR_classA_rpt, Frizzled_dom
PLA2G5Other/UnknownnoPLA2, PLA2-like_dom, PLA2_Asp_AS

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)3
unknown0

Top tissues across cohort

TissueCohort genes
apex of heart2
ascending aorta1
gall bladder1
primordial germ cell in gonad1
stromal cell of endometrium1
sural nerve1
cardiac atrium1
right atrium auricular region1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
C1QTNF5128ubiquitousyesapex of heart, gall bladder, ascending aorta
MFRP29tissue_specificmarkerprimordial germ cell in gonad, stromal cell of endometrium, sural nerve
PLA2G5188broadmarkerright atrium auricular region, apex of heart, cardiac atrium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
MFRP858
PLA2G5522
C1QTNF5369

Intra-cohort edges

ABSources
C1QTNF5MFRPintact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
C1QTNF5Q9BXJ02
PLA2G5P398771

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
MFRPQ9BY7973.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 3 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.

PathwayCohort genesFoldFDRSample cohort genes
Acyl chain remodelling of PI1671.8×0.003PLA2G5
Acyl chain remodelling of PG1634.4×0.003PLA2G5
Acyl chain remodelling of PS1519.1×0.003PLA2G5
Acyl chain remodelling of PC1423.0×0.003PLA2G5
Acyl chain remodelling of PE1393.8×0.003PLA2G5
Synthesis of PA1292.8×0.003PLA2G5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
positive regulation of phagosome maturation15617.3×0.004PLA2G5
positive regulation of immune complex clearance by monocytes and macrophages12808.7×0.004PLA2G5
positive regulation of antifungal innate immune response11872.4×0.004PLA2G5
positive regulation of phospholipase activity11123.5×0.005PLA2G5
positive regulation of opsonization1561.7×0.006PLA2G5
phosphatidylglycerol metabolic process1468.1×0.006PLA2G5
leukotriene biosynthetic process1432.1×0.006PLA2G5
phosphatidylcholine catabolic process1432.1×0.006PLA2G5
phagosome-lysosome fusion1432.1×0.006PLA2G5
low-density lipoprotein particle remodeling1351.1×0.007PLA2G5
positive regulation of macrophage derived foam cell differentiation1280.9×0.007PLA2G5
eye photoreceptor cell development1280.9×0.007MFRP
phosphatidylcholine metabolic process1267.5×0.007PLA2G5
embryo development ending in birth or egg hatching1244.2×0.007MFRP
arachidonate secretion1234.1×0.007PLA2G5
inner ear development1124.8×0.012C1QTNF5
phospholipid metabolic process1114.6×0.012PLA2G5
negative regulation of T cell proliferation1110.1×0.012PLA2G5
positive regulation of phagocytosis1106.0×0.012PLA2G5
protein secretion187.8×0.013C1QTNF5
retina development in camera-type eye185.1×0.013MFRP
fatty acid metabolic process164.6×0.017PLA2G5
positive regulation of ERK1 and ERK2 cascade128.4×0.036PLA2G5
visual perception126.5×0.037MFRP

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
PLA2G512
C1QTNF500
MFRP00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
VARESPLADIB2PLA2G5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
PLA2G543Binding:41, Functional:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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.

CompoundMax phaseCohort target (bioactivity)
VARESPLADIB2PLA2G5

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved1PLA2G5
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug2C1QTNF5, MFRP

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
C1QTNF50
MFRP0

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified5

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05355415Not specifiedRECRUITINGAdaptive Optics Imaging of Outer Retinal Diseases
NCT03510234Not specifiedUNKNOWNSelf-confidence Study in Patients With Argus II Artificial Retina
NCT04360291Not specifiedUNKNOWNImpact of Visual Field Restriction on Visual Exploration
NCT04419285Not specifiedUNKNOWNMobility Protocol Adapted for Advanced Visually Impaired Subjects
NCT05179460Not specifiedCOMPLETEDA Study of Pentosan Polysulfate Sodium and the Development of Pigmentary Maculopathy and Pigmentary Retinopathy