Retinitis pigmentosa-deafness syndrome

Summary

Retinitis pigmentosa-deafness syndrome (MONDO:0010775) is a disease with 5 cohort genes.

At a glance

• Cohort genes: 5
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa-deafness syndrome
Mondo ID	MONDO:0010775
OMIM	500004
DOID	DOID:0110829
SNOMED CT	57838006
UMLS	C5779620
MedGen	1830314
GARD	0004684
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 21 · retinitis pigmentosa 8 · retinitis pigmentosa-deafness syndrome · RP21, formerly · RP8, formerly

Data availability: 18 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Usher syndrome › retinitis pigmentosa-deafness syndrome

Related subtypes (4): Usher syndrome type 1, Usher syndrome type 2, Usher syndrome type 3, Usher syndrome, type 4

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

18 retrieved; paginated sample, class counts are floors:

9 benign, 5 benign/likely benign, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
5732	NM_201253.3(CRB1):c.2290C>T (p.Arg764Cys)	CRB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9560	NC_012920.1(MT-TS2):m.12258C>A	MT-TS2	Likely pathogenic	reviewed by expert panel
46040	NM_022124.6(CDH23):c.7823G>A (p.Arg2608His)	CDH23	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45677	NM_015404.4(WHRN):c.33C>G (p.Ser11Arg)	WHRN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
45913	NM_022124.6(CDH23):c.3293A>G (p.Asn1098Ser)	C10orf105	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
45937	NM_022124.6(CDH23):c.4051A>G (p.Asn1351Asp)	C10orf105	Benign	criteria provided, multiple submitters, no conflicts
45872	NM_022124.6(CDH23):c.1469G>C (p.Gly490Ala)	CDH23	Benign	criteria provided, multiple submitters, no conflicts
45891	NM_022124.6(CDH23):c.2263C>T (p.His755Tyr)	CDH23	Benign	reviewed by expert panel
45955	NM_022124.6(CDH23):c.4723G>A (p.Ala1575Thr)	CDH23	Benign	criteria provided, multiple submitters, no conflicts
45978	NM_022124.6(CDH23):c.5411G>A (p.Arg1804Gln)	CDH23	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
46002	NM_022124.6(CDH23):c.6130G>A (p.Glu2044Lys)	CDH23	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
46028	NM_022124.6(CDH23):c.7139C>T (p.Pro2380Leu)	CDH23	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
46072	NM_022124.6(CDH23):c.9373T>C (p.Phe3125Leu)	CDH23	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
802586	NM_022124.6(CDH23):c.4846-16805A>C	CDH23	Benign	criteria provided, multiple submitters, no conflicts
802587	NM_022124.6(CDH23):c.4846-4260A>G	CDH23	Benign	criteria provided, multiple submitters, no conflicts
45647	NM_015404.4(WHRN):c.1318G>A (p.Ala440Thr)	WHRN	Benign	criteria provided, multiple submitters, no conflicts
45661	NM_015404.4(WHRN):c.1684C>G (p.Pro562Ala)	WHRN	Benign	criteria provided, multiple submitters, no conflicts
45674	NM_015404.4(WHRN):c.2388C>A (p.Asn796Lys)	WHRN	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 15 · 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
WHRN	Orphanet:231178	Usher syndrome type 2
WHRN	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CRB1	Orphanet:251295	Pigmented paravenous retinochoroidal atrophy
CRB1	Orphanet:35612	Nanophthalmos
CRB1	Orphanet:65	Leber congenital amaurosis
CRB1	Orphanet:791	Retinitis pigmentosa
MT-TS2	Orphanet:231183	Usher syndrome type 3
MT-TS2	Orphanet:550	MELAS
MT-TS2	Orphanet:551	MERRF

Cohort genes → proteins

5 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDH23	HGNC:13733	ENSG00000107736	Q9H251	Cadherin-23	clinvar
WHRN	HGNC:16361	ENSG00000095397	Q9P202	Whirlin	clinvar
C10orf105	HGNC:20304	ENSG00000214688	Q8TEF2	Uncharacterized protein C10orf105	clinvar
CRB1	HGNC:2343	ENSG00000134376	P82279	Protein crumbs homolog 1	clinvar
MT-TS2	HGNC:7498	ENSG00000210184		mitochondrially encoded tRNA-Ser (AGU/C) 2	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.
WHRN	Whirlin	Involved in hearing and vision as member of the USH2 complex.
CRB1	Protein crumbs homolog 1	Plays a role in photoreceptor morphogenesis in the retina.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	3.5×	0.269
Other/Unknown	4	1.4×	0.269

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDH23	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
WHRN	Scaffold/PPI	no		PDZ, Whirlin_HN-like_dom2, PDZ_sf
C10orf105	Other/Unknown	no		DUF5527
CRB1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
MT-TS2	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

4 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
left ovary	1
right ovary	1
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1
blood	1
cerebellar vermis	1
quadriceps femoris	1
endothelial cell	1
ganglionic eminence	1
apex of heart	1
prefrontal cortex	1
sural nerve	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
WHRN	226	ubiquitous	marker	right adrenal gland cortex, left adrenal gland, right adrenal gland
C10orf105	107	tissue_specific	yes	quadriceps femoris, blood, cerebellar vermis
CRB1	163	broad	marker	ganglionic eminence, ventricular zone, endothelial cell
MT-TS2	116	ubiquitous	marker	sural nerve, apex of heart, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WHRN	2,499
CDH23	1,575
CRB1	1,075
C10orf105	53
MT-TS2	0

Intra-cohort edges

A	B	Sources
C10orf105	CDH23	string_interaction
CDH23	WHRN	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDH23	Q9H251	6
WHRN	Q9P202	5
CRB1	P82279	1

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 5 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, WHRN
Sensory processing of sound by inner hair cells of the cochlea	2	163.1×	7e-05	CDH23, WHRN
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 3 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	2	1248.3×	3e-05	CDH23, WHRN
auditory receptor cell stereocilium organization	2	561.7×	8e-05	CDH23, WHRN
photoreceptor cell maintenance	2	239.0×	3e-04	CDH23, CRB1
camera-type eye photoreceptor cell development	1	5617.3×	0.002	CRB1
cerebellar Purkinje cell layer formation	1	2808.7×	0.002	WHRN
post-embryonic retina morphogenesis in camera-type eye	1	2808.7×	0.002	CRB1
paranodal junction maintenance	1	2808.7×	0.002	WHRN
sensory perception of sound	2	67.3×	0.002	CDH23, WHRN
establishment of bipolar cell polarity involved in cell morphogenesis	1	1872.4×	0.002	CRB1
inner ear receptor cell differentiation	1	1123.5×	0.004	WHRN
equilibrioception	1	802.5×	0.005	CDH23
retina homeostasis	1	374.5×	0.007	WHRN
obsolete cell-cell adhesion via plasma-membrane adhesion molecules	1	374.5×	0.007	CDH23
photoreceptor cell outer segment organization	1	351.1×	0.007	CRB1
cellular response to light stimulus	1	351.1×	0.007	CRB1
detection of mechanical stimulus involved in sensory perception of sound	1	312.1×	0.007	WHRN
plasma membrane organization	1	295.6×	0.007	CRB1
glial cell differentiation	1	295.6×	0.007	CRB1
inner ear receptor cell stereocilium organization	1	280.9×	0.007	WHRN
retina layer formation	1	216.1×	0.009	CRB1
detection of light stimulus involved in visual perception	1	216.1×	0.009	CRB1
establishment or maintenance of epithelial cell apical/basal polarity	1	193.7×	0.009	CRB1
calcium-dependent cell-cell adhesion	1	160.5×	0.011	CDH23
cochlea development	1	156.0×	0.011	CDH23
establishment of protein localization	1	144.0×	0.011	WHRN
establishment or maintenance of cell polarity	1	133.8×	0.011	CRB1
blood vessel remodeling	1	127.7×	0.011	CRB1
regulation of cytosolic calcium ion concentration	1	127.7×	0.011	CDH23
heterophilic cell-cell adhesion	1	112.3×	0.012	CRB1
calcium ion transport	1	60.4×	0.021	CDH23

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 0 of 5 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
CDH23	0	0
WHRN	0	0
C10orf105	0	0
CRB1	0	0
MT-TS2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	5	CDH23, WHRN, C10orf105, CRB1, MT-TS2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDH23	0	—
WHRN	0	—
C10orf105	0	—
CRB1	0	—
MT-TS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.