Bothnia retinal dystrophy

Summary

Bothnia retinal dystrophy (MONDO:0011838) is a disease caused by RLBP1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: RLBP1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 21
• Phenotypes (HPO): 23

Clinical features

Signs & symptoms

Clinical features (HPO)

23 HPO clinical features (Orphanet curated; top 23 by frequency):

HPO ID	Term	Frequency
HP:0000529	Progressive visual loss	Very frequent (80-99%)
HP:0000551	Color vision defect	Very frequent (80-99%)
HP:0001123	Visual field defect	Very frequent (80-99%)
HP:0030469	Abnormal dark-adapted electroretinogram	Very frequent (80-99%)
HP:0030474	Undetectable dark-adapted electroretinogram	Very frequent (80-99%)
HP:0030618	Increased OCT-measured foveal thickness	Very frequent (80-99%)
HP:0000493	Abnormal foveal morphology	Frequent (30-79%)
HP:0000539	Abnormality of refraction	Frequent (30-79%)
HP:0000546	Retinal degeneration	Frequent (30-79%)
HP:0000580	Pigmentary retinopathy	Frequent (30-79%)
HP:0000608	Macular degeneration	Frequent (30-79%)
HP:0007814	Retinal pigment epithelial mottling	Frequent (30-79%)
HP:0032118	Retinitis	Frequent (30-79%)
HP:0000510	Rod-cone dystrophy	Occasional (5-29%)
HP:0000603	Central scotoma	Occasional (5-29%)
HP:0000610	Abnormal choroid morphology	Occasional (5-29%)
HP:0000662	Nyctalopia	Occasional (5-29%)
HP:0001129	Large central visual field defect	Occasional (5-29%)
HP:0007722	Retinal pigment epithelial atrophy	Occasional (5-29%)
HP:0007984	Electronegative electroretinogram	Occasional (5-29%)
HP:0030528	Paracentral scotoma	Occasional (5-29%)
HP:0030529	Ring scotoma	Occasional (5-29%)
HP:0007737	Bone spicule pigmentation of the retina	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Bothnia retinal dystrophy
Mondo ID	MONDO:0011838
MeSH	C564392
OMIM	607475
Orphanet	85128
DOID	DOID:0050683
ICD-11	2110390212
SNOMED CT	715647007
UMLS	C1843816
MedGen	334499
GARD	0016734
Is cancer (heuristic)	no

Also known as: Bothnia retinal dystrophy · Vasterbotten dystrophy · VC$sterbotten dystrophy · Västerbotten dystrophy

Data availability: 21 ClinVar variants · 3 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 › RLBP1-related retinopathy › Bothnia retinal dystrophy

Related subtypes (2): fundus albipunctatus, Newfoundland cone-rod dystrophy

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

21 retrieved; paginated sample, class counts are floors:

6 pathogenic/likely pathogenic, 5 likely pathogenic, 4 pathogenic, 3 uncertain significance, 2 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1074473	NM_000326.5(RLBP1):c.466C>T (p.Arg156Ter)	RLBP1	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
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
1400422	NM_000326.5(RLBP1):c.250del (p.Val84fs)	RLBP1	Pathogenic	criteria provided, single submitter
1482179	NM_000326.5(RLBP1):c.832del (p.Gln278fs)	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
4277810	NM_000326.5(RLBP1):c.12+1G>A	RLBP1	Pathogenic	criteria provided, single submitter
503712	NM_000326.5(RLBP1):c.141+2T>C	RLBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
844049	NM_000326.5(RLBP1):c.282del (p.Phe95fs)	RLBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066003	NM_000326.5(RLBP1):c.12+2del	RLBP1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3064481	NM_000326.5(RLBP1):c.341T>C (p.Leu114Pro)	RLBP1	Likely pathogenic	criteria provided, single submitter
3065593	NM_000326.5(RLBP1):c.203del (p.Glu68fs)	RLBP1	Likely pathogenic	criteria provided, single submitter
3775881	NM_000326.5(RLBP1):c.685-2A>G	RLBP1	Likely pathogenic	criteria provided, single submitter
3892291	NM_000326.5(RLBP1):c.256G>T (p.Glu86Ter)	RLBP1	Likely pathogenic	criteria provided, single submitter
498474	NM_000326.5(RLBP1):c.25C>T (p.Arg9Cys)	RLBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
812398	NM_000326.5(RLBP1):c.602T>C (p.Ile201Thr)	RLBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3064717	NM_000326.5(RLBP1):c.467G>A (p.Arg156Gln)	RLBP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
317237	NM_000326.5(RLBP1):c.647G>A (p.Arg216Gln)	RLBP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
860583	NM_000326.5(RLBP1):c.304G>A (p.Ala102Thr)	RLBP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
378479	NM_000326.5(RLBP1):c.684+20C>T	RLBP1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 4 · 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
RLBP1	Definitive	Autosomal recessive	Bothnia retinal dystrophy	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

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
RLBP1	HGNC:10024	ENSG00000140522	P12271	Retinaldehyde-binding protein 1	gencc,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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

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

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
optic choroid	1
pigmented layer of retina	1
retina	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RLBP1	1,078

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RLBP1	P12271	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Defective visual phototransduction due to RDH5 loss of function	1	5710.0×	5e-04	RLBP1
The retinoid cycle in cones (daylight vision)	1	1631.4×	9e-04	RLBP1
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.002	RLBP1

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
vitamin A metabolic process	1	2407.4×	8e-04	RLBP1
visual perception	1	79.5×	0.013	RLBP1

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
RLBP1	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	RLBP1

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)
RLBP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.