Usher syndrome type 2
diseaseOn this page
Also known as USH2
Summary
Usher syndrome type 2 (MONDO:0016484) is a disease caused by variants in ADGRV1 and USH2A, with 8 cohort genes and 6 clinical trials. The dominant Reactome pathway is Sensory processing of sound by outer hair cells of the cochlea (4 cohort genes). Top therapeutic interventions include ciliary neurotrophic factor and ultevursen.
At a glance
- Prevalence: 1-9 / 100 000 (Denmark) [Orphanet-validated]
- Causal genes: ADGRV1 (GenCC Definitive), USH2A (GenCC Definitive)
- Cohort genes: 8
- ClinVar variants: 112
- Phenotypes (HPO): 21
- Clinical trials: 6
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Point prevalence | 1-9 / 100 000 | 2.2 | Denmark | Validated |
| Point prevalence | 1-9 / 100 000 | Europe | Not yet validated |
Signs & symptoms
Clinical features (HPO)
21 HPO clinical features (Orphanet curated; top 21 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000359 | Abnormality of the inner ear | Very frequent (80-99%) |
| HP:0000407 | Sensorineural hearing impairment | Very frequent (80-99%) |
| HP:0000510 | Rod-cone dystrophy | Very frequent (80-99%) |
| HP:0000512 | Abnormal electroretinogram | Very frequent (80-99%) |
| HP:0000572 | Visual loss | Very frequent (80-99%) |
| HP:0000575 | Scotoma | Very frequent (80-99%) |
| HP:0007730 | Iris hypopigmentation | Very frequent (80-99%) |
| HP:0000518 | Cataract | Frequent (30-79%) |
| HP:0000545 | Myopia | Frequent (30-79%) |
| HP:0000662 | Nyctalopia | Frequent (30-79%) |
| HP:0001133 | Constriction of peripheral visual field | Frequent (30-79%) |
| HP:0002360 | Sleep abnormality | Frequent (30-79%) |
| HP:0007663 | Reduced visual acuity | Frequent (30-79%) |
| HP:0007994 | Peripheral visual field loss | Frequent (30-79%) |
| HP:0012378 | Fatigue | Frequent (30-79%) |
| HP:0000551 | Color vision defect | Occasional (5-29%) |
| HP:0000716 | Depression | Occasional (5-29%) |
| HP:0000739 | Anxiety | Occasional (5-29%) |
| HP:0002141 | Gait imbalance | Occasional (5-29%) |
| HP:0032036 | Reduced contrast sensitivity | Occasional (5-29%) |
| HP:0001751 | Abnormal vestibular function | Very rare (<1-4%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Usher syndrome type 2 |
| Mondo ID | MONDO:0016484 |
| Orphanet | 231178 |
| DOID | DOID:0110827 |
| ICD-11 | 33632175 |
| NCIT | C126328 |
| SNOMED CT | 232058008 |
| UMLS | C0339534 |
| MedGen | 83288 |
| GARD | 0005440 |
| Is cancer (heuristic) | no |
Also known as: USH2 · Usher syndrome type 2
Data availability: 112 ClinVar variants · 6 GenCC gene-disease records · 17 cell lines.
Disease family
An umbrella term covering 3 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › syndromic disease › Usher syndrome › Usher syndrome type 2
Related subtypes (4): Usher syndrome type 1, retinitis pigmentosa-deafness syndrome, Usher syndrome type 3, Usher syndrome, type 4
Subtypes (3): Usher syndrome type 2A, Usher syndrome type 2C, Usher syndrome type 2D
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
112 retrieved; paginated sample, class counts are floors:
47 pathogenic, 28 conflicting classifications of pathogenicity, 23 pathogenic/likely pathogenic, 10 uncertain significance, 4 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 46275 | NM_032119.4(ADGRV1):c.14973-2A>G | ADGRV1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 695021 | NM_032119.4(ADGRV1):c.10458G>A (p.Trp3486Ter) | ADGRV1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 695022 | NM_032119.4(ADGRV1):c.17974-1G>C | ADGRV1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 76051 | NM_032119.4(ADGRV1):c.9679C>T (p.Arg3227Ter) | ADGRV1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 812215 | NM_032119.4(ADGRV1):c.12125del (p.Met4042fs) | ADGRV1 | Pathogenic | no assertion criteria provided |
| 812216 | NM_032119.4(ADGRV1):c.15494del (p.Lys5165fs) | ADGRV1 | Pathogenic | no assertion criteria provided |
| 813149 | NM_032119.4(ADGRV1):c.3195dup (p.Gly1066fs) | ADGRV1 | Pathogenic | criteria provided, single submitter |
| 813150 | NM_032119.4(ADGRV1):c.2241-2A>G | ADGRV1 | Pathogenic | criteria provided, single submitter |
| 813030 | NM_022124.6(CDH23):c.9077+1G>A | CDH23 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1352951 | NM_206933.4(USH2A):c.2779C>T (p.Gln927Ter) | LOC122152296 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 143179 | NM_206933.4(USH2A):c.2802T>G (p.Cys934Trp) | LOC122152296 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 374742 | NM_000260.4(MYO7A):c.137_138dup (p.Trp47fs) | MYO7A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 813193 | NM_000260.4(MYO7A):c.1853T>G (p.Leu618Arg) | MYO7A | Pathogenic | criteria provided, single submitter |
| 813194 | NM_000260.4(MYO7A):c.1997G>C (p.Arg666Pro) | MYO7A | Pathogenic | criteria provided, single submitter |
| 424972 | NM_153676.4(USH1C):c.841_848del (p.Ser281fs) | USH1C | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 813102 | NM_153676.4(USH1C):c.263del (p.Val88fs) | USH1C | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 813103 | NM_153676.4(USH1C):c.580-2A>T | USH1C | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1069548 | NM_206933.4(USH2A):c.11235C>A (p.Tyr3745Ter) | USH2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1377611 | NM_206933.4(USH2A):c.11516del (p.Gln3839fs) | USH2A | Pathogenic | criteria provided, single submitter |
| 1415173 | NM_206933.4(USH2A):c.9602_9611del (p.Lys3201fs) | USH2A | Pathogenic | criteria provided, single submitter |
| 1453731 | NM_206933.4(USH2A):c.13000C>T (p.Gln4334Ter) | USH2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1455422 | NM_206933.4(USH2A):c.7168G>T (p.Gly2390Ter) | USH2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1723456 | NM_206933.4(USH2A):c.1850G>A (p.Cys617Tyr) | USH2A | Pathogenic | no assertion criteria provided |
| 1723459 | NM_206933.4(USH2A):c.6638_6641del (p.Lys2213fs) | USH2A | Pathogenic | no assertion criteria provided |
| 1723460 | NM_206933.4(USH2A):c.9187A>T (p.Lys3063Ter) | USH2A | Pathogenic | no assertion criteria provided |
| 1723461 | NM_206933.4(USH2A):c.7809C>A (p.Cys2603Ter) | USH2A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1723462 | NM_206933.4(USH2A):c.12313_12319del (p.Asp4105fs) | USH2A | Pathogenic | criteria provided, single submitter |
| 1727006 | NM_206933.4(USH2A):c.1645-2A>G | USH2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1727007 | NM_206933.4(USH2A):c.9914_9915del (p.Glu3305fs) | USH2A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1727205 | NM_206933.4(USH2A):c.1860C>A (p.Cys620Ter) | USH2A | Pathogenic | no assertion criteria provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 42 · Orphanet: 18 · 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 |
|---|---|---|---|---|
| ADGRV1 | Definitive | Autosomal recessive | Usher syndrome type 2 | 8 |
| MYO7A | Definitive | Autosomal recessive | Usher syndrome type 1 | 15 |
| USH2A | Definitive | Unknown | Usher syndrome type 2 | 8 |
| WHRN | Definitive | Unknown | Usher syndrome type 2D | 11 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| USH2A | Orphanet:231178 | Usher syndrome type 2 |
| USH2A | Orphanet:791 | Retinitis pigmentosa |
| ADGRV1 | Orphanet:231178 | Usher syndrome type 2 |
| ADGRV1 | Orphanet:36387 | Genetic epilepsy with febrile seizure plus |
| MYO7A | Orphanet:231169 | Usher syndrome type 1 |
| MYO7A | Orphanet:231178 | Usher syndrome type 2 |
| MYO7A | Orphanet:90635 | Rare autosomal dominant non-syndromic sensorineural deafness type DFNA |
| MYO7A | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| WHRN | Orphanet:231178 | Usher syndrome type 2 |
| WHRN | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| USH1C | Orphanet:231169 | Usher syndrome type 1 |
| USH1C | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
| 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 |
Cohort genes → proteins
8 cohort genes, 6 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 8 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| USH2A | HGNC:12601 | ENSG00000042781 | O75445 | Usherin | gencc,clinvar |
| ADGRV1 | HGNC:17416 | ENSG00000164199 | Q8WXG9 | Adhesion G-protein coupled receptor V1 | gencc,clinvar |
| MYO7A | HGNC:7606 | ENSG00000137474 | Q13402 | Unconventional myosin-VIIa | gencc,clinvar |
| WHRN | HGNC:16361 | ENSG00000095397 | Q9P202 | Whirlin | gencc |
| USH1C | HGNC:12597 | ENSG00000006611 | Q9Y6N9 | Harmonin | clinvar |
| CDH23 | HGNC:13733 | ENSG00000107736 | Q9H251 | Cadherin-23 | clinvar |
| USH2A-AS2 | HGNC:40605 | ENSG00000233620 | USH2A antisense RNA 2 | clinvar | |
| USH2A-AS1 | HGNC:40606 | ENSG00000236292 | USH2A antisense RNA 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| USH2A | Usherin | Involved in hearing and vision as member of the USH2 complex. |
| ADGRV1 | Adhesion G-protein coupled receptor V1 | G-protein coupled receptor which has an essential role in the development of hearing and vision. |
| MYO7A | Unconventional myosin-VIIa | Myosins are actin-based motor molecules with ATPase activity. |
| WHRN | Whirlin | Involved in hearing and vision as member of the USH2 complex. |
| USH1C | Harmonin | Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. |
| CDH23 | Cadherin-23 | Cadherins are calcium-dependent cell adhesion proteins. |
Protein-family classification
Druggable: 2 · Difficult: 3 · Unknown: 3 · Druggable fraction: 0.25
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 |
|---|---|---|---|
| Scaffold/PPI | 3 | 6.5× | 0.035 |
| Antibody/Immunoglobulin | 1 | 3.6× | 0.386 |
| GPCR | 1 | 3.0× | 0.386 |
| Other/Unknown | 3 | 0.7× | 0.919 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| USH2A | Antibody/Immunoglobulin | yes | Laminin_G, LE_dom, FN3_dom | |
| ADGRV1 | GPCR | yes | GPCR_2_secretin-like, Calx_beta, EPTP | |
| MYO7A | Scaffold/PPI | no | IQ_motif_EF-hand-BS, FERM_domain, MyTH4_dom | |
| WHRN | Scaffold/PPI | no | PDZ, Whirlin_HN-like_dom2, PDZ_sf | |
| USH1C | Scaffold/PPI | no | PDZ, Harmonin_N, PDZ_sf | |
| CDH23 | Other/Unknown | no | Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS | |
| USH2A-AS2 | Other/Unknown | no | ||
| USH2A-AS1 | Other/Unknown | no |
Expression context
Cohort genes with no expression data: 0.
6 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) | 8 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| left adrenal gland | 3 |
| right adrenal gland | 3 |
| right adrenal gland cortex | 3 |
| buccal mucosa cell | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| right lobe of liver | 1 |
| C1 segment of cervical spinal cord | 1 |
| mucosa of transverse colon | 1 |
| rectum | 1 |
| left ovary | 1 |
| right ovary | 1 |
| ventricular zone | 1 |
| anterior cingulate cortex | 1 |
| cerebellar vermis | 1 |
| quadriceps femoris | 1 |
| bone marrow | 1 |
| liver | 1 |
| spinal cord | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| USH2A | 30 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, buccal mucosa cell |
| ADGRV1 | 196 | broad | marker | right adrenal gland cortex, right adrenal gland, left adrenal gland |
| MYO7A | 186 | broad | marker | right adrenal gland cortex, right adrenal gland, left adrenal gland |
| WHRN | 226 | ubiquitous | marker | right adrenal gland cortex, left adrenal gland, right adrenal gland |
| USH1C | 203 | broad | marker | mucosa of transverse colon, C1 segment of cervical spinal cord, rectum |
| CDH23 | 161 | broad | marker | ventricular zone, left ovary, right ovary |
| USH2A-AS2 | 54 | yes | quadriceps femoris, anterior cingulate cortex, cerebellar vermis | |
| USH2A-AS1 | 21 | yes | liver, bone marrow, spinal cord |
Protein interactions among cohort
Intra-cohort edges: 8.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| WHRN | 2,499 |
| USH2A | 2,332 |
| ADGRV1 | 1,658 |
| CDH23 | 1,575 |
| USH1C | 291 |
| MYO7A | 43 |
| USH2A-AS2 | 0 |
| USH2A-AS1 | 0 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ADGRV1 | CDH23 | string_interaction |
| ADGRV1 | USH2A | string_interaction |
| ADGRV1 | WHRN | string_interaction |
| CDH23 | USH1C | biogrid_interaction, intact |
| CDH23 | USH2A | string_interaction |
| CDH23 | WHRN | string_interaction |
| MYO7A | USH1C | biogrid_interaction |
| USH2A | WHRN | string_interaction |
Structural data
PDB: 4 · AlphaFold-only: 2 · No structure: 2
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| USH1C | Q9Y6N9 | 11 |
| CDH23 | Q9H251 | 6 |
| WHRN | Q9P202 | 5 |
| MYO7A | Q13402 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| USH2A | O75445 | |
| ADGRV1 | Q8WXG9 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 8 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 |
|---|---|---|---|---|
| Sensory processing of sound by outer hair cells of the cochlea | 4 | 163.1× | 2e-08 | MYO7A, USH1C, CDH23, WHRN |
| Sensory processing of sound by inner hair cells of the cochlea | 4 | 130.5× | 3e-08 | MYO7A, USH1C, CDH23, WHRN |
| Sensory processing of sound | 2 | 123.5× | 3e-04 | MYO7A, CDH23 |
| Sensory Perception | 2 | 38.1× | 0.002 | MYO7A, CDH23 |
| The canonical retinoid cycle in rods (twilight vision) | 1 | 103.8× | 0.017 | MYO7A |
| EGR2 and SOX10-mediated initiation of Schwann cell myelination | 1 | 73.7× | 0.020 | ADGRV1 |
| Visual phototransduction | 1 | 51.9× | 0.025 | MYO7A |
| Nervous system development | 1 | 8.6× | 0.125 | ADGRV1 |
| Developmental Biology | 1 | 2.9× | 0.301 | ADGRV1 |
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 |
|---|---|---|---|---|
| sensory perception of light stimulus | 6 | 1872.4× | 2e-19 | USH2A, ADGRV1, MYO7A, USH1C, CDH23, WHRN |
| sensory perception of sound | 6 | 100.9× | 3e-11 | USH2A, ADGRV1, MYO7A, USH1C, CDH23, WHRN |
| inner ear receptor cell differentiation | 3 | 1685.2× | 5e-09 | USH2A, ADGRV1, WHRN |
| equilibrioception | 3 | 1203.7× | 1e-08 | MYO7A, USH1C, CDH23 |
| photoreceptor cell maintenance | 4 | 239.0× | 1e-08 | USH2A, ADGRV1, USH1C, CDH23 |
| auditory receptor cell stereocilium organization | 3 | 421.3× | 2e-07 | MYO7A, CDH23, WHRN |
| inner ear receptor cell stereocilium organization | 3 | 421.3× | 2e-07 | ADGRV1, USH1C, WHRN |
| establishment of protein localization | 3 | 216.1× | 2e-06 | USH2A, ADGRV1, WHRN |
| visual perception | 4 | 53.0× | 2e-06 | USH2A, ADGRV1, MYO7A, CDH23 |
| maintenance of animal organ identity | 2 | 1123.5× | 6e-06 | USH2A, ADGRV1 |
| inner ear auditory receptor cell differentiation | 2 | 401.2× | 5e-05 | USH2A, USH1C |
| detection of mechanical stimulus involved in sensory perception of sound | 2 | 312.1× | 8e-05 | ADGRV1, WHRN |
| cochlea development | 2 | 156.0× | 3e-04 | MYO7A, CDH23 |
| pigment granule transport | 1 | 2808.7× | 0.001 | MYO7A |
| establishment of localization in cell | 2 | 53.5× | 0.002 | USH2A, WHRN |
| cerebellar Purkinje cell layer formation | 1 | 1404.3× | 0.002 | WHRN |
| protein localization to microvillus | 1 | 1404.3× | 0.002 | USH1C |
| paranodal junction maintenance | 1 | 1404.3× | 0.002 | WHRN |
| parallel actin filament bundle assembly | 1 | 936.2× | 0.003 | USH1C |
| auditory receptor cell morphogenesis | 1 | 702.2× | 0.004 | USH1C |
| phagolysosome assembly | 1 | 561.7× | 0.005 | MYO7A |
| mechanoreceptor differentiation | 1 | 561.7× | 0.005 | MYO7A |
| regulation of microvillus length | 1 | 401.2× | 0.006 | USH1C |
| brush border assembly | 1 | 401.2× | 0.006 | USH1C |
| hair cell differentiation | 1 | 351.1× | 0.007 | USH2A |
| self proteolysis | 1 | 255.3× | 0.009 | ADGRV1 |
| retinal cone cell development | 1 | 234.1× | 0.009 | USH1C |
| nervous system process | 1 | 200.6× | 0.010 | ADGRV1 |
| retina homeostasis | 1 | 187.2× | 0.010 | WHRN |
| obsolete cell-cell adhesion via plasma-membrane adhesion molecules | 1 | 187.2× | 0.010 | CDH23 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 8
Druggability breadth: 0 of 8 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| USH2A | 0 | 0 |
| ADGRV1 | 0 | 0 |
| MYO7A | 0 | 0 |
| WHRN | 0 | 0 |
| USH1C | 0 | 0 |
| CDH23 | 0 | 0 |
| USH2A-AS2 | 0 | 0 |
| USH2A-AS1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 6; 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 | 0 | |
| D | Druggable family + AlphaFold only, no drug | 2 | USH2A, ADGRV1 |
| E | Difficult family or no structure, no drug | 6 | MYO7A, WHRN, USH1C, CDH23, USH2A-AS2, USH2A-AS1 |
Undrugged target profiles
8 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| USH2A | 0 | — |
| ADGRV1 | 0 | — |
| MYO7A | 0 | — |
| WHRN | 0 | — |
| USH1C | 0 | — |
| CDH23 | 0 | — |
| USH2A-AS2 | 0 | — |
| USH2A-AS1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 6.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| PHASE2 | 3 |
| PHASE2/PHASE3 | 2 |
| PHASE1/PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05158296 | PHASE2/PHASE3 | TERMINATED | Study to Evaluate the Efficacy Safety and Tolerability of Ultevursen in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene (Sirius) |
| NCT05176717 | PHASE2/PHASE3 | TERMINATED | Study to Evaluate the Efficacy Safety and Tolerability of QR-421a in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene With Early to Moderate Vision Loss (Celeste) |
| NCT06627179 | PHASE2 | RECRUITING | Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene |
| NCT01530659 | PHASE2 | COMPLETED | Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa |
| NCT03780257 | PHASE1/PHASE2 | COMPLETED | Study to Evaluate Safety and Tolerability of QR-421a in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene |
| NCT05085964 | PHASE2 | TERMINATED | An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| CILIARY NEUROTROPHIC FACTOR | 3 | 1 |
| ULTEVURSEN | 2 | 1 |