Retinitis punctata albescens

Summary

Retinitis punctata albescens (MONDO:0018877) is a disease with 5 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 10
• Phenotypes (HPO): 19
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.125	Worldwide	Validated
Point prevalence	1-9 / 1 000 000	0.175	Europe	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0000529	Progressive visual loss	Very frequent (80-99%)
HP:0000662	Nyctalopia	Very frequent (80-99%)
HP:0008323	Abnormal light- and dark-adapted electroretinogram	Very frequent (80-99%)
HP:0030506	Yellow/white lesions of the retina	Very frequent (80-99%)
HP:0030825	Absent foveal reflex	Very frequent (80-99%)
HP:0000603	Central scotoma	Frequent (30-79%)
HP:0000613	Photophobia	Frequent (30-79%)
HP:0007675	Progressive night blindness	Frequent (30-79%)
HP:0007814	Retinal pigment epithelial mottling	Frequent (30-79%)
HP:0007843	Attenuation of retinal blood vessels	Frequent (30-79%)
HP:0007987	Progressive visual field defects	Frequent (30-79%)
HP:0007994	Peripheral visual field loss	Frequent (30-79%)
HP:0001105	Retinal atrophy	Occasional (5-29%)
HP:0001142	Lenticonus	Occasional (5-29%)
HP:0007401	Macular atrophy	Occasional (5-29%)
HP:0008527	Congenital sensorineural hearing impairment	Occasional (5-29%)
HP:0011505	Cystoid macular edema	Occasional (5-29%)
HP:0031605	Abnormality of fundus pigmentation	Occasional (5-29%)
HP:0000580	Pigmentary retinopathy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis punctata albescens
Mondo ID	MONDO:0018877
Orphanet	52427
ICD-11	567796529
SNOMED CT	715562001
UMLS	C1405854
MedGen	278050
GARD	0016655
Is cancer (heuristic)	no

Data availability: 10 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › hereditary macular dystrophy › familial flecked retinopathy › fundus albipunctatus › retinitis punctata albescens

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

10 retrieved; paginated sample, class counts are floors:

6 pathogenic, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
8003	NM_002905.5(RDH5):c.712G>T (p.Gly238Trp)	BLOC1S1-RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812394	NM_002905.5(RDH5):c.718dup (p.Ala240fs)	CD63	Pathogenic	criteria provided, single submitter
812316	NM_001142800.2(EYS):c.4361_4362delinsAG (p.Ser1454Ter)	EYS	Pathogenic	criteria provided, multiple submitters, no conflicts
13028	NM_000539.3(RHO):c.403C>T (p.Arg135Trp)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13097	NM_000326.5(RLBP1):c.452G>A (p.Arg151Gln)	RLBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
13099	NM_000326.5(RLBP1):c.141G>A (p.Lys47=)	RLBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
13100	NM_000326.5(RLBP1):c.700C>T (p.Arg234Trp)	RLBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13101	NM_000326.5(RLBP1):c.677T>A (p.Met226Lys)	RLBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191289	NM_000326.5(RLBP1):c.286_297del (p.Phe96_Phe99del)	RLBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
635160	NM_000326.5(RLBP1):c.79del (p.Thr27fs)	RLBP1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 31 · Orphanet: 17 · 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
PRPH2	Definitive	Semidominant	retinitis pigmentosa 7	21
RLBP1	Supportive	Autosomal dominant	retinitis punctata albescens	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RLBP1	Orphanet:227796	Fundus albipunctatus
RLBP1	Orphanet:52427	Retinitis punctata albescens
RLBP1	Orphanet:791	Retinitis pigmentosa
RLBP1	Orphanet:85128	Bothnia retinal dystrophy
PRPH2	Orphanet:1872	Cone rod dystrophy
PRPH2	Orphanet:227796	Fundus albipunctatus
PRPH2	Orphanet:52427	Retinitis punctata albescens
PRPH2	Orphanet:75377	Central areolar choroidal dystrophy
PRPH2	Orphanet:791	Retinitis pigmentosa
PRPH2	Orphanet:827	Stargardt disease
PRPH2	Orphanet:99000	Adult-onset foveomacular vitelliform dystrophy
PRPH2	Orphanet:99001	Butterfly-shaped pigment dystrophy
PRPH2	Orphanet:99003	Multifocal pattern dystrophy simulating fundus flavimaculatus
RHO	Orphanet:215	Congenital stationary night blindness
RHO	Orphanet:52427	Retinitis punctata albescens
RHO	Orphanet:791	Retinitis pigmentosa
EYS	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RLBP1	HGNC:10024	ENSG00000140522	P12271	Retinaldehyde-binding protein 1	gencc,clinvar
PRPH2	HGNC:9942	ENSG00000112619	P23942	Peripherin-2	gencc
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	clinvar
CD63	HGNC:1692	ENSG00000135404	P08962	CD63 antigen	clinvar
EYS	HGNC:21555	ENSG00000188107	Q5T1H1	Protein eyes shut homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RLBP1	Retinaldehyde-binding protein 1	Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors.
PRPH2	Peripherin-2	Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure.
RHO	Rhodopsin	Photoreceptor required for image-forming vision at low light intensity.
CD63	CD63 antigen	Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades.
EYS	Protein eyes shut homolog	Required to maintain the integrity of photoreceptor cells.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.2

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
GPCR	1	4.8×	0.269
Other/Unknown	4	1.4×	0.269

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RLBP1	Other/Unknown	no		CRAL-TRIO_dom, CRAL/TRIO_N_dom, CRAL/TRIO_N_dom_sf
PRPH2	Other/Unknown	no		Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
CD63	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
EYS	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G

Expression context

Cohort genes with no expression data: 0.

5 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
optic choroid	2
pigmented layer of retina	1
retina	1
hindlimb stylopod muscle	1
quadriceps femoris	1
vastus lateralis	1
diaphragm	1
neuron projection bundle connecting eye with brain	1
adult organism	1
stromal cell of endometrium	1
tendon of biceps brachii	1
islet of Langerhans	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RLBP1	126	tissue_specific	marker	pigmented layer of retina, retina, optic choroid
PRPH2	176	tissue_specific	marker	quadriceps femoris, vastus lateralis, hindlimb stylopod muscle
RHO	38	tissue_specific	marker	optic choroid, neuron projection bundle connecting eye with brain, diaphragm
CD63	305	ubiquitous	marker	stromal cell of endometrium, tendon of biceps brachii, adult organism
EYS	153	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RHO	3,578
CD63	3,521
EYS	1,877
PRPH2	1,234
RLBP1	1,078

Intra-cohort edges

A	B	Sources
EYS	PRPH2	string_interaction
PRPH2	RHO	string_interaction
PRPH2	RLBP1	string_interaction
RHO	RLBP1	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RLBP1	P12271	4
RHO	P08100	4
CD63	P08962	2
PRPH2	P23942	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EYS	Q5T1H1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 5 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
The canonical retinoid cycle in rods (twilight vision)	2	346.1×	2e-04	RLBP1, RHO
Defective visual phototransduction due to RDH5 loss of function	1	1903.3×	0.004	RLBP1
The retinoid cycle in cones (daylight vision)	1	543.8×	0.009	RLBP1
Opsins	1	423.0×	0.009	RHO
Activation of the phototransduction cascade	1	317.2×	0.009	RHO
VxPx cargo-targeting to cilium	1	173.0×	0.014	RHO
Inactivation, recovery and regulation of the phototransduction cascade	1	105.7×	0.020	RHO
Response to elevated platelet cytosolic Ca2+	1	54.4×	0.034	CD63
Platelet activation, signaling and aggregation	1	35.2×	0.047	CD63
Platelet degranulation	1	29.3×	0.051	CD63
G alpha (i) signalling events	1	13.0×	0.101	RHO
Hemostasis	1	12.0×	0.101	CD63
Innate Immune System	1	8.5×	0.131	CD63
Neutrophil degranulation	1	7.7×	0.133	CD63
Immune System	1	4.3×	0.214	CD63

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
detection of light stimulus involved in visual perception	2	259.3×	4e-04	EYS, PRPH2
visual perception	3	47.7×	4e-04	RLBP1, RHO, PRPH2
response to low light intensity stimulus	1	3370.4×	0.003	PRPH2
pigment granule maturation	1	3370.4×	0.003	CD63
thermotaxis	1	1685.2×	0.004	RHO
rod bipolar cell differentiation	1	1685.2×	0.004	RHO
detection of temperature stimulus involved in thermoception	1	1123.5×	0.005	RHO
regulation of vascular endothelial growth factor signaling pathway	1	842.6×	0.006	CD63
G protein-coupled opsin signaling pathway	1	674.1×	0.006	RHO
absorption of visible light	1	561.7×	0.007	RHO
vitamin A metabolic process	1	481.5×	0.007	RLBP1
response to light intensity	1	421.3×	0.007	RHO
podosome assembly	1	421.3×	0.007	RHO
endosome to melanosome transport	1	337.0×	0.008	CD63
phototransduction, visible light	1	259.3×	0.009	RHO
positive regulation of integrin-mediated signaling pathway	1	259.3×	0.009	CD63
negative regulation of epithelial cell migration	1	210.7×	0.009	CD63
photoreceptor cell outer segment organization	1	210.7×	0.009	PRPH2
protein heterooligomerization	1	210.7×	0.009	PRPH2
cellular response to light stimulus	1	210.7×	0.009	RHO
skeletal muscle tissue regeneration	1	177.4×	0.010	EYS
positive regulation of receptor internalization	1	140.4×	0.012	CD63
regulation of potassium ion transmembrane transport	1	124.8×	0.013	CD63
phototransduction	1	99.1×	0.016	RHO
photoreceptor cell maintenance	1	71.7×	0.021	RHO
positive regulation of cell adhesion	1	54.4×	0.027	CD63
retina development in camera-type eye	1	51.1×	0.027	PRPH2
epithelial cell differentiation	1	35.1×	0.038	CD63
cell-matrix adhesion	1	32.7×	0.038	CD63
protein maturation	1	32.7×	0.038	PRPH2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 5 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CD63	2	2
RLBP1	0	0
PRPH2	0	0
RHO	0	0
EYS	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LANRAPLENIB	2	CD63
BIIB-091	2	CD63

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CD63	3	Binding:3
RHO	1	Binding:1

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
LANRAPLENIB	2	CD63
BIIB-091	2	CD63

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	1	CD63
C	Druggable family + PDB, no drug	1	RHO
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	RLBP1, PRPH2, EYS

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)
RLBP1	0	—
PRPH2	0	—
RHO	1	—
EYS	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
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry