Retinitis pigmentosa 50

Summary

Retinitis pigmentosa 50 (MONDO:0013175) is a disease caused by BEST1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: BEST1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 50
Mondo ID	MONDO:0013175
MeSH	C567712
OMIM	613194
DOID	DOID:0110396
UMLS	C2750789
MedGen	442563
GARD	0015629
Is cancer (heuristic)	no

Also known as: BEST1 retinitis pigmentosa · retinitis pigmentosa 50 · retinitis pigmentosa caused by mutation in BEST1 · retinitis pigmentosa type 50 · retinitis pigmentosa-50 · RP50

Data availability: 26 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 › retinitis pigmentosa › retinitis pigmentosa 50

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 26, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 56, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 4, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 39, retinitis pigmentosa 43, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 62, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

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

26 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
143127	NM_004183.4(BEST1):c.763C>T (p.Arg255Trp)	BEST1	Pathogenic	criteria provided, multiple submitters, no conflicts
2039113	NM_004183.4(BEST1):c.508C>T (p.Gln170Ter)	BEST1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2738	NM_004183.4(BEST1):c.140G>A (p.Arg47His)	BEST1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2741	NM_004183.4(BEST1):c.598C>T (p.Arg200Ter)	BEST1	Pathogenic	criteria provided, multiple submitters, no conflicts
2747	NM_004183.4(BEST1):c.614T>C (p.Ile205Thr)	BEST1	Pathogenic	criteria provided, single submitter
2749	NM_004183.4(BEST1):c.680A>G (p.Tyr227Cys)	BEST1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
632163	NM_004183.4(BEST1):c.1415del (p.Leu472fs)	BEST1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99695	NM_004183.4(BEST1):c.240C>A (p.Phe80Leu)	BEST1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99725	NM_004183.4(BEST1):c.584C>T (p.Ala195Val)	BEST1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99726	NM_004183.4(BEST1):c.602T>C (p.Ile201Thr)	BEST1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99735	NM_004183.4(BEST1):c.652C>T (p.Arg218Cys)	BEST1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382257	NM_004183.4(BEST1):c.488T>G (p.Met163Arg)	BEST1	Likely pathogenic	criteria provided, single submitter
1487156	NM_004183.4(BEST1):c.56G>A (p.Arg19His)	BEST1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2748	NM_004183.4(BEST1):c.682G>A (p.Asp228Asn)	BEST1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2750	NM_004183.4(BEST1):c.418C>G (p.Leu140Val)	BEST1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1018244	NM_004183.4(BEST1):c.1532A>G (p.Lys511Arg)	BEST1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1441709	NM_004183.4(BEST1):c.861G>C (p.Trp287Cys)	BEST1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2137112	NM_004183.4(BEST1):c.362G>C (p.Gly121Ala)	BEST1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1181045	NM_004183.4(BEST1):c.867+327T>G	BEST1	Benign	criteria provided, multiple submitters, no conflicts
1192353	NM_004183.4(BEST1):c.868-99G>T	BEST1	Benign	criteria provided, multiple submitters, no conflicts
1192494	NM_004183.4(BEST1):c.636+44C>T	BEST1	Benign	criteria provided, multiple submitters, no conflicts
166752	NM_004183.4(BEST1):c.618G>A (p.Leu206=)	BEST1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
193666	NM_004183.4(BEST1):c.1410G>A (p.Thr470=)	BEST1	Benign	criteria provided, multiple submitters, no conflicts
99678	NM_004183.4(BEST1):c.109T>C (p.Leu37=)	BEST1	Benign	criteria provided, multiple submitters, no conflicts
99693	NM_004183.4(BEST1):c.219C>A (p.Ile73=)	BEST1	Benign	criteria provided, multiple submitters, no conflicts
99727	NM_004183.4(BEST1):c.619C>A (p.Leu207Ile)	BEST1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 22 · Orphanet: 7 · 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
BEST1	Definitive	Autosomal recessive	retinitis pigmentosa	22

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BEST1	Orphanet:1243	Best vitelliform macular dystrophy
BEST1	Orphanet:139455	Autosomal recessive bestrophinopathy
BEST1	Orphanet:263347	MRCS syndrome
BEST1	Orphanet:3086	Autosomal dominant vitreoretinochoroidopathy
BEST1	Orphanet:35612	Nanophthalmos
BEST1	Orphanet:791	Retinitis pigmentosa
BEST1	Orphanet:99000	Adult-onset foveomacular vitelliform 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
BEST1	HGNC:12703	ENSG00000167995	O76090	Bestrophin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BEST1	Bestrophin-1	Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+).

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)
BEST1	Other/Unknown	no		Bestrophin, Bestrophin-like

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
inferior olivary complex	1
lateral globus pallidus	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BEST1	209	ubiquitous	marker	pigmented layer of retina, lateral globus pallidus, inferior olivary complex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BEST1	959

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BEST1	O76090	19

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
Stimuli-sensing channels	1	135.9×	0.016	BEST1
Ion channel transport	1	96.0×	0.016	BEST1
Transport of small molecules	1	25.1×	0.040	BEST1

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
gamma-aminobutyric acid secretion, neurotransmission	1	8426.0×	0.001	BEST1
transepithelial chloride transport	1	1872.4×	0.002	BEST1
glutamate secretion	1	1685.2×	0.002	BEST1
regulation of calcium ion transport	1	802.5×	0.003	BEST1
protein complex oligomerization	1	674.1×	0.003	BEST1
detection of light stimulus involved in visual perception	1	648.1×	0.003	BEST1
chloride transport	1	455.5×	0.003	BEST1
regulation of synaptic plasticity	1	259.3×	0.005	BEST1
chloride transmembrane transport	1	237.3×	0.005	BEST1
monoatomic ion transmembrane transport	1	208.1×	0.005	BEST1
visual perception	1	79.5×	0.013	BEST1

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
BEST1	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	BEST1

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)
BEST1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.