RCBTB1-related retinopathy

Summary

RCBTB1-related retinopathy (MONDO:0014955) is a disease caused by RCBTB1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RCBTB1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	RCBTB1-related retinopathy
Mondo ID	MONDO:0014955
OMIM	617175
UMLS	C4310680
MedGen	934647
GARD	0018241
Is cancer (heuristic)	no

Also known as: RCBTB1-related retinopathy · RDEOA · retinal dystrophy with or without extraocular anomalies

Data availability: 13 ClinVar variants · 5 GenCC gene-disease records · 3 cell lines.

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 › patterned dystrophy of the retinal pigment epithelium › reticular dystrophy of the retinal pigment epithelium › RCBTB1-related retinopathy

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

13 retrieved; paginated sample, class counts are floors:

5 benign, 4 pathogenic/likely pathogenic, 2 uncertain significance, 1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
224622	NM_018191.4(RCBTB1):c.707del (p.Asn236fs)	RCBTB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253016	NM_018191.4(RCBTB1):c.919G>A (p.Val307Met)	RCBTB1	Pathogenic/Likely pathogenic	no assertion criteria provided
253020	NM_018191.4(RCBTB1):c.1164G>T (p.Leu388Phe)	RCBTB1	Pathogenic/Likely pathogenic	no assertion criteria provided
2834248	NM_018191.4(RCBTB1):c.1262_1263del (p.Tyr421fs)	RCBTB1	Pathogenic	criteria provided, multiple submitters, no conflicts
840798	NM_018191.4(RCBTB1):c.170del (p.Gly57fs)	RCBTB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253018	NM_018191.4(RCBTB1):c.973C>T (p.His325Tyr)	RCBTB1	Likely pathogenic	criteria provided, single submitter
3780937	NM_018191.4(RCBTB1):c.444+741G>C	RCBTB1	Uncertain significance	criteria provided, single submitter
962426	NM_018191.4(RCBTB1):c.1543C>G (p.Leu515Val)	RCBTB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1166149	NM_018191.4(RCBTB1):c.1017C>G (p.Pro339=)	RCBTB1	Benign	criteria provided, multiple submitters, no conflicts
1170496	NM_018191.4(RCBTB1):c.643C>T (p.Leu215=)	RCBTB1	Benign	criteria provided, multiple submitters, no conflicts
1170499	NM_018191.4(RCBTB1):c.71C>T (p.Ala24Val)	RCBTB1	Benign	criteria provided, multiple submitters, no conflicts
1265543	NM_018191.4(RCBTB1):c.*6A>G	RCBTB1	Benign	criteria provided, multiple submitters, no conflicts
1277037	NM_018191.4(RCBTB1):c.603+36T>C	RCBTB1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 1 · 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
RCBTB1	Strong	Autosomal recessive	RCBTB1-related retinopathy	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RCBTB1	Orphanet:99002	Reticular dystrophy of the retinal pigment epithelium

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
RCBTB1	HGNC:18243	ENSG00000136144	Q8NDN9	RCC1 and BTB domain-containing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RCBTB1	RCC1 and BTB domain-containing protein 1	May be involved in cell cycle regulation by chromatin remodeling.

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)
RCBTB1	Other/Unknown	no		BTB/POZ_dom, Reg_chr_condens, RCC1/BLIP-II

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
decidua	1
mucosa of paranasal sinus	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RCBTB1	280	ubiquitous	marker	mucosa of paranasal sinus, pigmented layer of retina, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RCBTB1	1,081

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RCBTB1	Q8NDN9	92.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
chromatin organization	1	99.1×	0.010	RCBTB1

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
RCBTB1	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	RCBTB1

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)
RCBTB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.