Usher syndrome type 1D

Summary

Usher syndrome type 1D (MONDO:0010984) is a disease caused by CDH23 (GenCC Definitive), with 4 cohort genes and 1 clinical trial.

At a glance

• Causal gene: CDH23 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 886
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Usher syndrome type 1D
Mondo ID	MONDO:0010984
OMIM	601067
DOID	DOID:0110831
UMLS	C1832845
MedGen	322051
GARD	0005438
Is cancer (heuristic)	no

Also known as: USH1D · Usher syndrome, type 1D · Usher syndrome, type 1D/F digenic · USHER syndrome, type ID

Data availability: 886 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Usher syndrome › Usher syndrome type 1 › Usher syndrome type 1D

Related subtypes (8): Usher syndrome type 1C, Usher syndrome type 1F, Usher syndrome type 1E, Usher syndrome type 1G, Usher syndrome type 1H, Usher syndrome type 1K, Usher syndrome, type 1D/F, Usher syndrome type 1B

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

600 retrieved; paginated sample, class counts are floors:

172 uncertain significance, 166 conflicting classifications of pathogenicity, 95 likely pathogenic, 49 pathogenic/likely pathogenic, 47 benign/likely benign, 41 benign, 28 pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1185587	NM_022124.6(CDH23):c.3353del (p.Gly1118fs)	C10orf105	Pathogenic	criteria provided, single submitter
1687244	NM_022124.6(CDH23):c.3431-1G>A	C10orf105	Pathogenic	criteria provided, single submitter
1027560	NM_022124.6(CDH23):c.271C>T (p.Gln91Ter)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
1064608	NM_022124.6(CDH23):c.1291-1G>A	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
1068921	NM_022124.6(CDH23):c.8383C>T (p.Arg2795Ter)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069075	NM_022124.6(CDH23):c.9254del (p.Leu3085fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070502	NM_022124.6(CDH23):c.5300_5303dup (p.His1769fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071895	NM_022124.6(CDH23):c.8432G>A (p.Trp2811Ter)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
1180612	NM_022124.6(CDH23):c.4562A>G (p.Asn1521Ser)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1185586	NM_022124.5(CDH23):c.337del	CDH23	Pathogenic	criteria provided, single submitter
1357019	NM_022124.6(CDH23):c.1143_1176del	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1371175	NM_022124.6(CDH23):c.8433G>A (p.Trp2811Ter)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
1393120	NM_022124.6(CDH23):c.9280_9286del	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1406663	NM_022124.6(CDH23):c.7274_7275del (p.Thr2425fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1710061	NM_022124.6(CDH23):c.8208_8209del (p.Val2737fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
178309	NM_022124.6(CDH23):c.6050-15G>A	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805315	NM_022124.6(CDH23):c.9246_9247del (p.Phe3083fs)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
2014525	NM_022124.6(CDH23):c.2476del (p.Leu826fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228328	NC_000010.11:g.71682535dup	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236429	NM_022124.6(CDH23):c.2398-1G>T	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236430	NM_022124.6(CDH23):c.7908C>G (p.Tyr2636Ter)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
2501245	NM_022124.6(CDH23):c.1152C>A (p.Ser384Arg)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2632950	NM_022124.6(CDH23):c.9381-2A>G	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2851982	NM_022124.6(CDH23):c.7557T>G (p.Tyr2519Ter)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3377178	NM_022124.6(CDH23):c.5256dup (p.Glu1753Ter)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3596931	NM_022124.6(CDH23):c.5985C>A (p.Tyr1995Ter)	CDH23	Pathogenic	criteria provided, single submitter
3597057	NM_022124.6(CDH23):c.7730_7734del (p.Phe2577fs)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
3601195	NM_022124.6(CDH23):c.2516_2517dup (p.Leu840fs)	CDH23	Pathogenic	criteria provided, single submitter
3601754	NM_022124.6(CDH23):c.9278_9278+3del	CDH23	Pathogenic	criteria provided, single submitter
397608	NM_022124.6(CDH23):c.1987-1G>A	CDH23	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 8 · 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
CDH23	Definitive	Unknown	Usher syndrome type 1	8

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
PCDH15	Orphanet:231169	Usher syndrome type 1
PCDH15	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDH23	HGNC:13733	ENSG00000107736	Q9H251	Cadherin-23	gencc,clinvar
PCDH15	HGNC:14674	ENSG00000150275	Q96QU1	Protocadherin-15	clinvar
C10orf105	HGNC:20304	ENSG00000214688	Q8TEF2	Uncharacterized protein C10orf105	clinvar
CDH23-AS1	HGNC:31433	ENSG00000223817		CDH23 antisense RNA 1	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.
PCDH15	Protocadherin-15	Calcium-dependent cell-adhesion protein.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · 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	4	1.8×	0.097

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDH23	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
PCDH15	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
C10orf105	Other/Unknown	no		DUF5527
CDH23-AS1	Other/Unknown	no

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	2
left ovary	1
right ovary	1
ventricular zone	1
adrenal tissue	1
left adrenal gland cortex	1
male germ line stem cell (sensu Vertebrata) in testis	1
cerebellar vermis	1
quadriceps femoris	1
monocyte	1
thoracic mammary gland	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
PCDH15	130	tissue_specific	marker	left adrenal gland cortex, male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue
C10orf105	107	tissue_specific	yes	quadriceps femoris, blood, cerebellar vermis
CDH23-AS1	51		yes	blood, monocyte, thoracic mammary gland

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PCDH15	1,732
CDH23	1,575
C10orf105	53
CDH23-AS1	0

Intra-cohort edges

A	B	Sources
C10orf105	CDH23	string_interaction
CDH23	PCDH15	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PCDH15	Q96QU1	8
CDH23	Q9H251	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C10orf105	Q8TEF2	63.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 4 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
Sensory processing of sound by outer hair cells of the cochlea	2	203.9×	7e-05	CDH23, PCDH15
Sensory processing of sound by inner hair cells of the cochlea	2	163.1×	7e-05	CDH23, PCDH15
Sensory processing of sound	1	154.3×	0.009	CDH23
Sensory Perception	1	47.6×	0.021	CDH23

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
equilibrioception	2	2407.4×	2e-06	CDH23, PCDH15
sensory perception of light stimulus	2	1872.4×	2e-06	CDH23, PCDH15
photoreceptor cell maintenance	2	358.6×	4e-05	CDH23, PCDH15
homophilic cell-cell adhesion	2	140.4×	2e-04	CDH23, PCDH15
sensory perception of sound	2	100.9×	3e-04	CDH23, PCDH15
obsolete cell-cell adhesion via plasma-membrane adhesion molecules	1	561.7×	0.005	CDH23
auditory receptor cell stereocilium organization	1	421.3×	0.006	CDH23
calcium-dependent cell-cell adhesion	1	240.7×	0.008	CDH23
cochlea development	1	234.1×	0.008	CDH23
regulation of cytosolic calcium ion concentration	1	191.5×	0.008	CDH23
inner ear development	1	187.2×	0.008	PCDH15
calcium ion transport	1	90.6×	0.015	CDH23
locomotory behavior	1	89.6×	0.015	CDH23
neuron projection development	1	61.1×	0.020	CDH23
visual perception	1	39.8×	0.028	CDH23
cell migration	1	30.8×	0.034	CDH23
cell adhesion	1	18.7×	0.053	PCDH15

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) 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
PCDH15	0	0
C10orf105	0	0
CDH23-AS1	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
PCDH15	9	Binding:9

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	CDH23, PCDH15, C10orf105, CDH23-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDH23	0	—
PCDH15	9	—
C10orf105	0	—
CDH23-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns