Usher syndrome type 2D
diseaseOn this page
Also known as USH2DUsher syndrome caused by mutation in WHRNUSHER syndrome, type IIDWHRN Usher syndrome
Summary
Usher syndrome type 2D (MONDO:0012662) is a disease caused by WHRN (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: WHRN (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 154
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Usher syndrome type 2D |
| Mondo ID | MONDO:0012662 |
| OMIM | 611383 |
| DOID | DOID:0110840 |
| UMLS | C1568249 |
| MedGen | 292821 |
| GARD | 0015514 |
| Is cancer (heuristic) | no |
Also known as: USH2D · Usher syndrome caused by mutation in WHRN · Usher syndrome type 2D · USHER syndrome, type IID · WHRN Usher syndrome
Data availability: 154 ClinVar variants · 5 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › Usher syndrome › Usher syndrome type 2 › Usher syndrome type 2D
Related subtypes (2): Usher syndrome type 2A, Usher syndrome type 2C
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
154 retrieved; paginated sample, class counts are floors:
77 uncertain significance, 42 conflicting classifications of pathogenicity, 13 benign, 7 benign/likely benign, 7 likely pathogenic, 6 pathogenic, 2 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 198565 | NM_015404.4(WHRN):c.1417-1G>A | WHRN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2500690 | NM_015404.4(WHRN):c.35C>A (p.Ser12Ter) | WHRN | Pathogenic | criteria provided, single submitter |
| 2689 | NM_015404.4(WHRN):c.2332C>T (p.Arg778Ter) | WHRN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2690 | NM_015404.4(WHRN):c.307C>T (p.Gln103Ter) | WHRN | Pathogenic | no assertion criteria provided |
| 2691 | NM_015404.4(WHRN):c.837+1G>A | WHRN | Pathogenic | no assertion criteria provided |
| 31704 | NM_015404.4(WHRN):c.737del (p.Pro246fs) | WHRN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 31705 | NM_015404.4(WHRN):c.680dup (p.Tyr228fs) | WHRN | Pathogenic | criteria provided, single submitter |
| 420550 | NM_015404.4(WHRN):c.856dup (p.Asp286fs) | WHRN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3061951 | NM_015404.4(WHRN):c.2140C>T (p.Gln714Ter) | WHRN | Likely pathogenic | criteria provided, single submitter |
| 3596344 | NM_015404.4(WHRN):c.2418+1G>A | WHRN | Likely pathogenic | criteria provided, single submitter |
| 3596345 | NM_015404.4(WHRN):c.2238del (p.Ala747fs) | WHRN | Likely pathogenic | criteria provided, single submitter |
| 3596346 | NM_015404.4(WHRN):c.2236+2T>G | WHRN | Likely pathogenic | criteria provided, single submitter |
| 3596348 | NM_015404.4(WHRN):c.816_817delinsTT (p.Gln273Ter) | WHRN | Likely pathogenic | criteria provided, single submitter |
| 3596349 | NM_015404.4(WHRN):c.618+2del | WHRN | Likely pathogenic | criteria provided, single submitter |
| 632034 | NM_015404.4(WHRN):c.2345C>A (p.Ser782Ter) | WHRN | Likely pathogenic | criteria provided, single submitter |
| 163048 | NM_015404.4(WHRN):c.1627-5T>A | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 178336 | NM_015404.4(WHRN):c.1992G>A (p.Pro664=) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 179353 | NM_015404.4(WHRN):c.19G>C (p.Gly7Arg) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 193718 | NM_015404.4(WHRN):c.2237-10C>G | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 194094 | NM_015404.4(WHRN):c.2644C>A (p.Arg882Ser) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 227287 | NM_015404.4(WHRN):c.1716C>T (p.Thr572=) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 227290 | NM_015404.4(WHRN):c.1887G>A (p.Pro629=) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 227292 | NM_015404.4(WHRN):c.2322C>T (p.Ser774=) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 287879 | NM_015404.4(WHRN):c.1455G>A (p.Pro485=) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 288922 | NM_015404.4(WHRN):c.1075G>A (p.Val359Ile) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 289015 | NM_015404.4(WHRN):c.933A>C (p.Pro311=) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 364678 | NM_015404.4(WHRN):c.*37C>G | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 364684 | NM_015404.4(WHRN):c.2130C>A (p.Gly710=) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 364687 | NM_015404.4(WHRN):c.1626+8T>G | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 364691 | NM_015404.4(WHRN):c.1305C>T (p.Asn435=) | WHRN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 11 · Orphanet: 2 · 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 |
|---|---|---|---|---|
| WHRN | Definitive | Unknown | Usher syndrome type 2D | 11 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| WHRN | Orphanet:231178 | Usher syndrome type 2 |
| WHRN | Orphanet:90636 | Rare autosomal recessive non-syndromic sensorineural deafness type DFNB |
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 |
|---|---|---|---|---|---|
| WHRN | HGNC:16361 | ENSG00000095397 | Q9P202 | Whirlin | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| WHRN | Whirlin | Involved in hearing and vision as member of the USH2 complex. |
Protein-family classification
Druggable: 0 · Difficult: 1 · Unknown: 0 · 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 |
|---|---|---|---|
| Scaffold/PPI | 1 | 17.3× | 0.058 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| WHRN | Scaffold/PPI | no | PDZ, Whirlin_HN-like_dom2, PDZ_sf |
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 |
|---|---|
| left adrenal gland | 1 |
| right adrenal gland | 1 |
| right adrenal gland cortex | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| WHRN | 226 | ubiquitous | marker | right adrenal gland cortex, left adrenal gland, right adrenal gland |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| WHRN | 2,499 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| WHRN | Q9P202 | 5 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 2. 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 |
|---|---|---|---|---|
| Sensory processing of sound by outer hair cells of the cochlea | 1 | 203.9× | 0.006 | WHRN |
| Sensory processing of sound by inner hair cells of the cochlea | 1 | 163.1× | 0.006 | WHRN |
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 |
|---|---|---|---|---|
| cerebellar Purkinje cell layer formation | 1 | 8426.0× | 7e-04 | WHRN |
| paranodal junction maintenance | 1 | 8426.0× | 7e-04 | WHRN |
| inner ear receptor cell differentiation | 1 | 3370.4× | 0.001 | WHRN |
| sensory perception of light stimulus | 1 | 1872.4× | 0.002 | WHRN |
| retina homeostasis | 1 | 1123.5× | 0.002 | WHRN |
| detection of mechanical stimulus involved in sensory perception of sound | 1 | 936.2× | 0.002 | WHRN |
| auditory receptor cell stereocilium organization | 1 | 842.6× | 0.002 | WHRN |
| inner ear receptor cell stereocilium organization | 1 | 842.6× | 0.002 | WHRN |
| establishment of protein localization | 1 | 432.1× | 0.003 | WHRN |
| establishment of localization in cell | 1 | 160.5× | 0.007 | WHRN |
| sensory perception of sound | 1 | 100.9× | 0.011 | WHRN |
| positive regulation of gene expression | 1 | 38.7× | 0.026 | WHRN |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 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 |
|---|---|---|
| WHRN | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
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 | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | WHRN |
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) |
|---|---|---|
| WHRN | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: WHRN