Vitreoretinal degeneration
diseaseOn this page
Also known as degenerative vitreoretinopathy
Summary
Vitreoretinal degeneration (MONDO:0020248) is a disease (an umbrella term covering 9 Mondo subtypes) with 9 cohort genes.
At a glance
- Umbrella term: 9 Mondo subtypes
- Cohort genes: 9
- ClinVar variants: 226
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | vitreoretinal degeneration |
| Mondo ID | MONDO:0020248 |
| Orphanet | 98670 |
| SNOMED CT | 247182006 |
| UMLS | C0344290 |
| MedGen | 87480 |
| GARD | 0005506 |
| Is cancer (heuristic) | no |
Also known as: degenerative vitreoretinopathy
Data availability: 226 ClinVar variants · 1 HPO phenotype.
Disease family
An umbrella term covering 9 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › vitreous body disorder › vitreous disorder › vitreous syneresis › vitreoretinal degeneration
Subtypes (9): Wagner disease, snowflake vitreoretinal degeneration, X-linked retinoschisis, Stickler syndrome, exudative vitreoretinopathy, enhanced S-cone syndrome, CAPN5-related vitreoretinopathy, BEST1-related vitreoretinochoroidopathy, Knobloch syndrome
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
226 retrieved; paginated sample, class counts are floors:
70 benign, 61 uncertain significance, 49 conflicting classifications of pathogenicity, 34 benign/likely benign, 8 likely benign, 2 pathogenic, 1 pathogenic/likely pathogenic, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 99428 | NM_000350.3(ABCA4):c.6089G>A (p.Arg2030Gln) | ABCA4 | Pathogenic | reviewed by expert panel |
| 545640 | NM_001128922.2(LRRC32):c.1630C>T (p.Arg544Ter) | LRRC32 | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 523501 | NM_012338.4(TSPAN12):c.100del (p.Trp34fs) | TSPAN12 | Pathogenic | criteria provided, single submitter |
| 560373 | NM_002335.4(LRP5):c.2090A>G (p.Lys697Arg) | LRP5 | Likely pathogenic | no assertion criteria provided |
| 7892 | NM_000350.3(ABCA4):c.5908C>T (p.Leu1970Phe) | ABCA4 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 167819 | NM_004385.5(VCAN):c.927T>C (p.Thr309=) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 167825 | NM_004385.5(VCAN):c.5859G>T (p.Thr1953=) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 198510 | NM_004385.5(VCAN):c.3713G>C (p.Arg1238Thr) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 198796 | NM_004385.5(VCAN):c.6767T>C (p.Leu2256Pro) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 198801 | NM_004385.5(VCAN):c.6902T>G (p.Phe2301Cys) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 259362 | NM_004385.5(VCAN):c.2234A>C (p.Lys745Thr) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354388 | NM_004385.5(VCAN):c.109T>G (p.Ser37Ala) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354393 | NM_004385.5(VCAN):c.854C>T (p.Ala285Val) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354401 | NM_004385.5(VCAN):c.1931C>T (p.Pro644Leu) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354405 | NM_004385.5(VCAN):c.2315C>G (p.Ala772Gly) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354407 | NM_004385.5(VCAN):c.2542G>A (p.Glu848Lys) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354412 | NM_004385.5(VCAN):c.3094C>G (p.Gln1032Glu) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354419 | NM_004385.5(VCAN):c.3683C>T (p.Ala1228Val) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354432 | NM_004385.5(VCAN):c.6127G>A (p.Glu2043Lys) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354441 | NM_004385.5(VCAN):c.7480G>C (p.Glu2494Gln) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354443 | NM_004385.5(VCAN):c.7493G>T (p.Ser2498Ile) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354449 | NM_004385.5(VCAN):c.7884C>A (p.Asn2628Lys) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354450 | NM_004385.5(VCAN):c.7895C>T (p.Thr2632Ile) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354451 | NM_004385.5(VCAN):c.7966A>G (p.Thr2656Ala) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354453 | NM_004385.5(VCAN):c.8063C>T (p.Pro2688Leu) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354458 | NM_004385.5(VCAN):c.8362A>G (p.Met2788Val) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354460 | NM_004385.5(VCAN):c.8683G>C (p.Asp2895His) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354461 | NM_004385.5(VCAN):c.9025G>A (p.Glu3009Lys) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354466 | NM_004385.5(VCAN):c.9481C>G (p.Leu3161Val) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 843872 | NM_004385.5(VCAN):c.157C>T (p.Pro53Ser) | VCAN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 22 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CDH23 | Orphanet:231169 | Usher syndrome type 1 |
| CDH23 | Orphanet:2965 | Prolactinoma |
| CDH23 | Orphanet:314777 | Familial isolated pituitary adenoma |
| CDH23 | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| CDH23 | Orphanet:91347 | TSH-secreting pituitary adenoma |
| CDH23 | Orphanet:96253 | Cushing disease |
| TSPAN12 | Orphanet:891 | Familial exudative vitreoretinopathy |
| COL9A3 | Orphanet:166002 | Multiple epiphyseal dysplasia due to collagen 9 anomaly |
| COL9A3 | Orphanet:250984 | Autosomal recessive Stickler syndrome |
| VCAN | Orphanet:898 | Wagner disease |
| ABCA4 | Orphanet:1872 | Cone rod dystrophy |
| ABCA4 | Orphanet:791 | Retinitis pigmentosa |
| ABCA4 | Orphanet:827 | Stargardt disease |
| LRP5 | Orphanet:178377 | Osteosclerosis-developmental delay-craniosynostosis syndrome |
| LRP5 | Orphanet:2783 | Autosomal dominant osteopetrosis type 1 |
| LRP5 | Orphanet:2788 | Osteoporosis-pseudoglioma syndrome |
| LRP5 | Orphanet:2790 | Endosteal hyperostosis, Worth type |
| LRP5 | Orphanet:2924 | Isolated polycystic liver disease |
| LRP5 | Orphanet:3416 | Hyperostosis corticalis generalisata |
| LRP5 | Orphanet:498481 | LRP5-related primary osteoporosis |
| LRP5 | Orphanet:891 | Familial exudative vitreoretinopathy |
| LRP5 | Orphanet:90050 | Retinopathy of prematurity |
Cohort genes → proteins
9 cohort genes, 8 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 9 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| CDH23 | HGNC:13733 | ENSG00000107736 | Q9H251 | Cadherin-23 | clinvar |
| C10orf105 | HGNC:20304 | ENSG00000214688 | Q8TEF2 | Uncharacterized protein C10orf105 | clinvar |
| TSPAN12 | HGNC:21641 | ENSG00000106025 | O95859 | Tetraspanin-12 | clinvar |
| COL9A3 | HGNC:2219 | ENSG00000092758 | Q14050 | Collagen alpha-3(IX) chain | clinvar |
| VCAN | HGNC:2464 | ENSG00000038427 | P13611 | Versican core protein | clinvar |
| ABCA4 | HGNC:34 | ENSG00000198691 | P78363 | Retinal-specific phospholipid-transporting ATPase ABCA4 | clinvar |
| VCAN-AS1 | HGNC:40163 | ENSG00000249835 | VCAN antisense RNA 1 | clinvar | |
| LRRC32 | HGNC:4161 | ENSG00000137507 | Q14392 | Transforming growth factor beta activator LRRC32 | clinvar |
| LRP5 | HGNC:6697 | ENSG00000162337 | O75197 | Low-density lipoprotein receptor-related protein 5 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CDH23 | Cadherin-23 | Cadherins are calcium-dependent cell adhesion proteins. |
| TSPAN12 | Tetraspanin-12 | Regulator of cell surface receptor signal transduction. |
| COL9A3 | Collagen alpha-3(IX) chain | Structural component of hyaline cartilage and vitreous of the eye. |
| VCAN | Versican core protein | May play a role in intercellular signaling and in connecting cells with the extracellular matrix. |
| 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… |
| LRRC32 | Transforming growth factor beta activator LRRC32 | Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. |
| LRP5 | Low-density lipoprotein receptor-related protein 5 | Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins. |
Protein-family classification
Druggable: 2 · Difficult: 0 · Unknown: 7 · Druggable fraction: 0.22
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 | 29.8× | 0.099 |
| Transporter | 1 | 8.6× | 0.161 |
| Other/Unknown | 7 | 1.4× | 0.161 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| CDH23 | Other/Unknown | no | Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS | |
| C10orf105 | Other/Unknown | no | DUF5527 | |
| TSPAN12 | Other/Unknown | no | Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin | |
| COL9A3 | Other/Unknown | no | Collagen, Collagen_superfamily | |
| VCAN | Complement | yes | EGF-type_Asp/Asn_hydroxyl_site, Sushi_SCR_CCP_dom, Link_dom | |
| ABCA4 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABCA4/ABCR | |
| VCAN-AS1 | Other/Unknown | no | ||
| LRRC32 | Other/Unknown | no | LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp | |
| LRP5 | Other/Unknown | no | LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt |
Expression context
Cohort genes with no expression data: 0.
7 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) | 9 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| ventricular zone | 2 |
| left ovary | 1 |
| right ovary | 1 |
| blood | 1 |
| cerebellar vermis | 1 |
| quadriceps femoris | 1 |
| nephron tubule | 1 |
| oocyte | 1 |
| secondary oocyte | 1 |
| cartilage tissue | 1 |
| inferior vagus X ganglion | 1 |
| tibia | 1 |
| leukocyte | 1 |
| monocyte | 1 |
| mononuclear cell | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| pigmented layer of retina | 1 |
| primordial germ cell in gonad | 1 |
| calcaneal tendon | 1 |
| granulocyte | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CDH23 | 161 | broad | marker | ventricular zone, left ovary, right ovary |
| C10orf105 | 107 | tissue_specific | yes | quadriceps femoris, blood, cerebellar vermis |
| TSPAN12 | 267 | ubiquitous | marker | oocyte, nephron tubule, secondary oocyte |
| COL9A3 | 218 | broad | marker | tibia, cartilage tissue, inferior vagus X ganglion |
| VCAN | 293 | ubiquitous | marker | monocyte, mononuclear cell, leukocyte |
| ABCA4 | 164 | tissue_specific | marker | pigmented layer of retina, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis |
| VCAN-AS1 | 126 | yes | ventricular zone, granulocyte, calcaneal tendon | |
| LRRC32 | 220 | ubiquitous | marker | right coronary artery, left coronary artery, right lung |
| LRP5 | 224 | ubiquitous | marker | right lobe of liver, mucosa of transverse colon, ascending aorta |
Protein interactions among cohort
Intra-cohort edges: 2.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| VCAN | 2,806 |
| LRP5 | 2,619 |
| CDH23 | 1,575 |
| ABCA4 | 1,532 |
| COL9A3 | 1,482 |
| LRRC32 | 1,441 |
| TSPAN12 | 686 |
| C10orf105 | 53 |
| VCAN-AS1 | 0 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| C10orf105 | CDH23 | string_interaction |
| LRP5 | TSPAN12 | string_interaction |
Structural data
PDB: 5 · AlphaFold-only: 3 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| ABCA4 | P78363 | 8 |
| CDH23 | Q9H251 | 6 |
| LRRC32 | Q14392 | 6 |
| COL9A3 | Q14050 | 4 |
| TSPAN12 | O95859 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| LRP5 | O75197 | 78.65 |
| C10orf105 | Q8TEF2 | 63.46 |
| VCAN | P13611 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 43. Enrichment computed across 9 evidence-associated genes (5 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 5 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 | 2284.0× | 0.009 | ABCA4 |
| ECM proteoglycans | 2 | 60.1× | 0.009 | COL9A3, VCAN |
| Retinoid cycle disease events | 1 | 571.0× | 0.013 | ABCA4 |
| Diseases associated with visual transduction | 1 | 571.0× | 0.013 | ABCA4 |
| Diseases of the neuronal system | 1 | 571.0× | 0.013 | ABCA4 |
| Sensory Perception | 2 | 38.1× | 0.013 | CDH23, ABCA4 |
| Signaling by LRP5 mutants | 1 | 326.3× | 0.015 | LRP5 |
| Defective CHST3 causes SEDCJD | 1 | 285.5× | 0.015 | VCAN |
| Defective CHST14 causes EDS, musculocontractural type | 1 | 285.5× | 0.015 | VCAN |
| Defective CHSY1 causes TPBS | 1 | 285.5× | 0.015 | VCAN |
| Signaling by RNF43 mutants | 1 | 253.8× | 0.015 | LRP5 |
| DS-GAG biosynthesis | 1 | 190.3× | 0.019 | VCAN |
| Negative regulation of TCF-dependent signaling by WNT ligand antagonists | 1 | 142.8× | 0.020 | LRP5 |
| Signaling by WNT in cancer | 1 | 120.2× | 0.020 | LRP5 |
| Defective B4GALT7 causes EDS, progeroid type | 1 | 114.2× | 0.020 | VCAN |
| Defective B3GAT3 causes JDSSDHD | 1 | 114.2× | 0.020 | VCAN |
| Defective B3GALT6 causes EDSP2 and SEMDJL1 | 1 | 114.2× | 0.020 | VCAN |
| CS-GAG biosynthesis | 1 | 108.8× | 0.020 | VCAN |
| CS/DS degradation | 1 | 108.8× | 0.020 | VCAN |
| The canonical retinoid cycle in rods (twilight vision) | 1 | 103.8× | 0.020 | ABCA4 |
| Regulation of FZD by ubiquitination | 1 | 103.8× | 0.020 | LRP5 |
| Glycosaminoglycan-protein linkage region biosynthesis | 1 | 78.8× | 0.025 | VCAN |
| Disassembly of the destruction complex and recruitment of AXIN to the membrane | 1 | 71.4× | 0.026 | LRP5 |
| Sensory processing of sound | 1 | 61.7× | 0.029 | CDH23 |
| Visual phototransduction | 1 | 51.9× | 0.031 | ABCA4 |
| Collagen chain trimerization | 1 | 51.9× | 0.031 | COL9A3 |
| Signaling by PDGF | 1 | 50.8× | 0.031 | COL9A3 |
| NCAM1 interactions | 1 | 49.6× | 0.031 | COL9A3 |
| Sensory processing of sound by outer hair cells of the cochlea | 1 | 40.8× | 0.035 | CDH23 |
| Assembly of collagen fibrils and other multimeric structures | 1 | 40.1× | 0.035 | COL9A3 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Norrin signaling pathway | 2 | 1123.5× | 9e-05 | TSPAN12, LRP5 |
| photoreceptor cell maintenance | 2 | 119.5× | 0.005 | CDH23, ABCA4 |
| establishment of protein localization to extracellular region | 1 | 1404.3× | 0.015 | LRRC32 |
| phospholipid transfer to membrane | 1 | 936.2× | 0.015 | ABCA4 |
| cell-cell signaling involved in mammary gland development | 1 | 936.2× | 0.015 | LRP5 |
| mesodermal cell migration | 1 | 561.7× | 0.015 | LRP5 |
| extracellular matrix-cell signaling | 1 | 561.7× | 0.015 | LRP5 |
| anatomical structure regression | 1 | 561.7× | 0.015 | LRP5 |
| apoptotic process involved in blood vessel morphogenesis | 1 | 468.1× | 0.015 | LRP5 |
| establishment of blood-retinal barrier | 1 | 468.1× | 0.015 | LRP5 |
| glucose catabolic process | 1 | 401.2× | 0.015 | LRP5 |
| equilibrioception | 1 | 401.2× | 0.015 | CDH23 |
| retinal blood vessel morphogenesis | 1 | 401.2× | 0.015 | LRP5 |
| visual perception | 2 | 26.5× | 0.015 | CDH23, ABCA4 |
| cell recognition | 1 | 312.1× | 0.016 | VCAN |
| sensory perception of light stimulus | 1 | 312.1× | 0.016 | CDH23 |
| retina morphogenesis in camera-type eye | 1 | 312.1× | 0.016 | LRP5 |
| cell migration involved in gastrulation | 1 | 255.3× | 0.016 | LRP5 |
| bone marrow development | 1 | 255.3× | 0.016 | LRP5 |
| glial cell migration | 1 | 234.1× | 0.016 | VCAN |
| osteoblast proliferation | 1 | 234.1× | 0.016 | LRP5 |
| branching involved in mammary gland duct morphogenesis | 1 | 234.1× | 0.016 | LRP5 |
| establishment of blood-brain barrier | 1 | 234.1× | 0.016 | LRP5 |
| phototransduction, visible light | 1 | 216.1× | 0.016 | ABCA4 |
| positive regulation of osteoblast proliferation | 1 | 200.6× | 0.016 | LRP5 |
| secondary palate development | 1 | 200.6× | 0.016 | LRRC32 |
| obsolete cell-cell adhesion via plasma-membrane adhesion molecules | 1 | 187.2× | 0.016 | CDH23 |
| negative regulation of activated T cell proliferation | 1 | 175.5× | 0.016 | LRRC32 |
| osteoblast development | 1 | 165.2× | 0.016 | LRP5 |
| gastrulation with mouth forming second | 1 | 156.0× | 0.016 | LRP5 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 9
Druggability breadth: 1 of 9 evidence-associated genes (11%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| CDH23 | 0 | 0 |
| C10orf105 | 0 | 0 |
| TSPAN12 | 0 | 0 |
| COL9A3 | 0 | 0 |
| VCAN | 0 | 0 |
| ABCA4 | 0 | 0 |
| VCAN-AS1 | 0 | 0 |
| LRRC32 | 0 | 0 |
| LRP5 | 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 |
|---|---|---|
| LRP5 | 1 | Binding:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 8; 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 | 1 | VCAN |
| E | Difficult family or no structure, no drug | 7 | CDH23, C10orf105, TSPAN12, COL9A3, VCAN-AS1, LRRC32, LRP5 |
Undrugged target profiles
9 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| CDH23 | 0 | — |
| C10orf105 | 0 | — |
| TSPAN12 | 0 | — |
| COL9A3 | 0 | — |
| VCAN | 0 | — |
| ABCA4 | 0 | — |
| VCAN-AS1 | 0 | — |
| LRRC32 | 0 | — |
| LRP5 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.