Fundus albipunctatus

Summary

Fundus albipunctatus (MONDO:0007639) is a disease caused by variants in RDH5, PRPH2, and RLBP1, with 5 cohort genes and 1 clinical trial. The dominant Reactome pathway is The canonical retinoid cycle in rods (twilight vision) (3 cohort genes).

At a glance

• Prevalence: Unknown (Europe)
• Causal genes: RDH5 (GenCC Definitive), PRPH2 (GenCC Strong), RLBP1 (GenCC Strong)
• Cohort genes: 5
• ClinVar variants: 244
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fundus albipunctatus
Mondo ID	MONDO:0007639
MeSH	C562733
OMIM	136880
Orphanet	227796
DOID	DOID:11105
ICD-11	1981512475
SNOMED CT	68222009
UMLS	C0311338
MedGen	86317
GARD	0013809
Is cancer (heuristic)	no

Also known as: fundus albipunctatus · pigmentary retinal dystrophy · retinitis punctata albescens

Data availability: 244 ClinVar variants · 10 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

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

Related subtypes (4): Doyne honeycomb retinal dystrophy, Bietti crystalline corneoretinal dystrophy, Kandori fleck retina, Stargardt disease

Subtypes (1): 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

244 retrieved; paginated sample, class counts are floors:

81 uncertain significance, 57 conflicting classifications of pathogenicity, 28 benign, 22 pathogenic, 19 pathogenic/likely pathogenic, 18 benign/likely benign, 17 likely pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1458210	NM_002905.5(RDH5):c.95del (p.Phe32fs)	BLOC1S1-RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279881	NM_002905.5(RDH5):c.160C>T (p.Arg54Ter)	BLOC1S1-RDH5	Pathogenic	criteria provided, multiple submitters, no conflicts
309814	NM_002905.5(RDH5):c.500G>A (p.Arg167His)	BLOC1S1-RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3385045	NM_002905.5(RDH5):c.758T>G (p.Met253Arg)	BLOC1S1-RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775434	NM_002905.5(RDH5):c.832C>T (p.Arg278Ter)	BLOC1S1-RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8003	NM_002905.5(RDH5):c.712G>T (p.Gly238Trp)	BLOC1S1-RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8009	NM_002905.5(RDH5):c.928delinsGAAG (p.Leu310delinsGluVal)	BLOC1S1-RDH5	Pathogenic	criteria provided, multiple submitters, no conflicts
8010	NM_002905.5(RDH5):c.469C>T (p.Arg157Trp)	BLOC1S1-RDH5	Pathogenic	criteria provided, multiple submitters, no conflicts
812392	NM_002905.5(RDH5):c.412del (p.Met138fs)	BLOC1S1-RDH5	Pathogenic	no assertion criteria provided
942928	NM_002905.5(RDH5):c.103G>A (p.Gly35Ser)	BLOC1S1-RDH5	Pathogenic	criteria provided, multiple submitters, no conflicts
8006	NM_002905.5(RDH5):c.880G>C (p.Ala294Pro)	CD63	Pathogenic	criteria provided, single submitter
866580	NM_002905.5(RDH5):c.625C>T (p.Arg209Ter)	CD63	Pathogenic	criteria provided, multiple submitters, no conflicts
1076073	NM_000322.5(PRPH2):c.692C>G (p.Ser231Ter)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1175277	NM_000322.5(PRPH2):c.914del (p.Gly305fs)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
1686100	NM_000322.5(PRPH2):c.2T>G (p.Met1Arg)	PRPH2	Pathogenic	criteria provided, single submitter
931938	NM_000322.5(PRPH2):c.498C>A (p.Cys166Ter)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
98666	NM_000322.5(PRPH2):c.422A>G (p.Tyr141Cys)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98671	NM_000322.5(PRPH2):c.469G>A (p.Asp157Asn)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98683	NM_000322.5(PRPH2):c.609_625del (p.Tyr204fs)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
1323522	NM_002905.5(RDH5):c.625del (p.Arg209fs)	RDH5	Pathogenic	criteria provided, single submitter
208608	NM_002905.5(RDH5):c.285G>A (p.Trp95Ter)	RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236445	NM_002905.5(RDH5):c.536A>G (p.Lys179Arg)	RDH5	Pathogenic	criteria provided, multiple submitters, no conflicts
635161	NM_002905.5(RDH5):c.382G>A (p.Asp128Asn)	RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8005	NM_002905.5(RDH5):c.839G>A (p.Arg280His)	RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812391	NM_002905.5(RDH5):c.71_74del (p.Leu24fs)	RDH5	Pathogenic	criteria provided, multiple submitters, no conflicts
812393	NM_002905.5(RDH5):c.547G>T (p.Glu183Ter)	RDH5	Pathogenic	no assertion criteria provided
963051	NM_002905.5(RDH5):c.388C>T (p.Gln130Ter)	RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13013	NM_000539.3(RHO):c.68C>A (p.Pro23His)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13021	NM_000539.3(RHO):c.266G>A (p.Gly89Asp)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
13045	NM_000539.3(RHO):c.269G>A (p.Gly90Asp)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 50 · 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
RDH5	Definitive	Semidominant	fundus albipunctatus	6
PRPH2	Strong	Autosomal dominant	fundus albipunctatus	21
RLBP1	Strong	Autosomal recessive	fundus albipunctatus	10
RHO	Limited	Unknown	fundus albipunctatus	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RHO	Orphanet:215	Congenital stationary night blindness
RHO	Orphanet:52427	Retinitis punctata albescens
RHO	Orphanet:791	Retinitis pigmentosa
RLBP1	Orphanet:227796	Fundus albipunctatus
RLBP1	Orphanet:52427	Retinitis punctata albescens
RLBP1	Orphanet:791	Retinitis pigmentosa
RLBP1	Orphanet:85128	Bothnia retinal dystrophy
RDH5	Orphanet:227796	Fundus albipunctatus
RDH5	Orphanet:52427	Retinitis punctata albescens
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

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
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	gencc,clinvar
RLBP1	HGNC:10024	ENSG00000140522	P12271	Retinaldehyde-binding protein 1	gencc,clinvar
RDH5	HGNC:9940	ENSG00000135437	Q92781	Retinol dehydrogenase 5	gencc,clinvar
PRPH2	HGNC:9942	ENSG00000112619	P23942	Peripherin-2	gencc,clinvar
CD63	HGNC:1692	ENSG00000135404	P08962	CD63 antigen	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RHO	Rhodopsin	Photoreceptor required for image-forming vision at low light intensity.
RLBP1	Retinaldehyde-binding protein 1	Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors.
RDH5	Retinol dehydrogenase 5	Catalyzes the oxidation of cis-isomers of retinol, including 11-cis-, 9-cis-, and 13-cis-retinol in an NAD-dependent manner.
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.
CD63	CD63 antigen	Functions as a cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.4

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×	0.530
Enzyme (other)	1	2.4×	0.530
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
RLBP1	Other/Unknown	no		CRAL-TRIO_dom, CRAL/TRIO_N_dom, CRAL/TRIO_N_dom_sf
RDH5	Enzyme (other)	yes	1.1.1.300	SDR_fam, NAD(P)-bd_dom_sf
PRPH2	Other/Unknown	no		Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS
CD63	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin

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
diaphragm	1
neuron projection bundle connecting eye with brain	1
pigmented layer of retina	1
retina	1
adipose tissue	1
right lobe of liver	1
subcutaneous adipose tissue	1
hindlimb stylopod muscle	1
quadriceps femoris	1
vastus lateralis	1
adult organism	1
stromal cell of endometrium	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RHO	38	tissue_specific	marker	optic choroid, neuron projection bundle connecting eye with brain, diaphragm
RLBP1	126	tissue_specific	marker	pigmented layer of retina, retina, optic choroid
RDH5	141	broad	marker	subcutaneous adipose tissue, right lobe of liver, adipose tissue
PRPH2	176	tissue_specific	marker	quadriceps femoris, vastus lateralis, hindlimb stylopod muscle
CD63	305	ubiquitous	marker	stromal cell of endometrium, tendon of biceps brachii, adult organism

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RHO	3,578
CD63	3,521
PRPH2	1,234
RLBP1	1,078
RDH5	907

Intra-cohort edges

A	B	Sources
PRPH2	RDH5	string_interaction
PRPH2	RHO	string_interaction
PRPH2	RLBP1	string_interaction
RDH5	RHO	string_interaction
RDH5	RLBP1	biogrid_interaction, 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
RHO	P08100	4
RLBP1	P12271	4
CD63	P08962	2
PRPH2	P23942	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RDH5	Q92781	96.02

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 5 evidence-associated genes (4 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 4 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)	3	389.3×	4e-07	RHO, RLBP1, RDH5
Defective visual phototransduction due to RDH5 loss of function	2	2855.0×	7e-07	RLBP1, RDH5
The retinoid cycle in cones (daylight vision)	1	407.9×	0.013	RLBP1
Opsins	1	317.2×	0.013	RHO
Activation of the phototransduction cascade	1	237.9×	0.013	RHO
VxPx cargo-targeting to cilium	1	129.8×	0.019	RHO
RA biosynthesis pathway	1	119.0×	0.019	RDH5
Inactivation, recovery and regulation of the phototransduction cascade	1	79.3×	0.025	RHO
Response to elevated platelet cytosolic Ca2+	1	40.8×	0.043	CD63
Platelet activation, signaling and aggregation	1	26.4×	0.060	CD63
Platelet degranulation	1	22.0×	0.065	CD63
G alpha (i) signalling events	1	9.7×	0.131	RHO
Hemostasis	1	9.0×	0.131	CD63
Innate Immune System	1	6.4×	0.169	CD63
Neutrophil degranulation	1	5.8×	0.173	CD63
Immune System	1	3.2×	0.275	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
visual perception	4	63.6×	5e-06	RHO, RLBP1, RDH5, PRPH2
response to low light intensity stimulus	1	3370.4×	0.004	PRPH2
pigment granule maturation	1	3370.4×	0.004	CD63
thermotaxis	1	1685.2×	0.005	RHO
rod bipolar cell differentiation	1	1685.2×	0.005	RHO
detection of temperature stimulus involved in thermoception	1	1123.5×	0.006	RHO
regulation of vascular endothelial growth factor signaling pathway	1	842.6×	0.007	CD63
G protein-coupled opsin signaling pathway	1	674.1×	0.007	RHO
absorption of visible light	1	561.7×	0.008	RHO
vitamin A metabolic process	1	481.5×	0.008	RLBP1
response to light intensity	1	421.3×	0.008	RHO
podosome assembly	1	421.3×	0.008	RHO
endosome to melanosome transport	1	337.0×	0.009	CD63
phototransduction, visible light	1	259.3×	0.010	RHO
positive regulation of integrin-mediated signaling pathway	1	259.3×	0.010	CD63
negative regulation of epithelial cell migration	1	210.7×	0.010	CD63
photoreceptor cell outer segment organization	1	210.7×	0.010	PRPH2
protein heterooligomerization	1	210.7×	0.010	PRPH2
cellular response to light stimulus	1	210.7×	0.010	RHO
positive regulation of receptor internalization	1	140.4×	0.014	CD63
detection of light stimulus involved in visual perception	1	129.6×	0.015	PRPH2
regulation of potassium ion transmembrane transport	1	124.8×	0.015	CD63
retinoid metabolic process	1	99.1×	0.016	RDH5
phototransduction	1	99.1×	0.016	RHO
retinol metabolic process	1	99.1×	0.016	RDH5
photoreceptor cell maintenance	1	71.7×	0.021	RHO
steroid metabolic process	1	67.4×	0.022	RDH5
positive regulation of cell adhesion	1	54.4×	0.026	CD63
retina development in camera-type eye	1	51.1×	0.027	PRPH2
epithelial cell differentiation	1	35.1×	0.038	CD63

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
RHO	0	0
RLBP1	0	0
RDH5	0	0
PRPH2	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): 1.

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

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

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RDH5	1.1.1.300, 1.1.1.315	NADP-retinol dehydrogenase, 11-cis-retinol dehydrogenase

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	1	RDH5
E	Difficult family or no structure, no drug	2	RLBP1, PRPH2

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)
RHO	1	—
RLBP1	0	—
RDH5	0	—
PRPH2	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