CNGB1-related retinopathy

Summary

CNGB1-related retinopathy (MONDO:0800403) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	CNGB1-related retinopathy
Mondo ID	MONDO:0800403
GARD	0026553
Is cancer (heuristic)	no

Data availability: 12 ClinVar variants.

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 › CNGB1-related retinopathy

Related subtypes (104): retinal dystrophies primarily involving Bruch’s membrane, vitreoretinal dystrophy, dystrophies primarily involving the retinal pigment epithelium, retinal dystrophy in systemic or cerebroretinal lipidoses, age-related macular degeneration, helicoid peripapillary chorioretinal degeneration, Sorsby fundus dystrophy, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, pigmented paravenous retinochoroidal atrophy, retinoschisis, autosomal dominant, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, amaurosis-hypertrichosis syndrome, familial benign flecked retina, microcephaly and chorioretinopathy 1, ornithine aminotransferase deficiency, retinal degeneration-nanophthalmos-glaucoma syndrome, retinoschisis of fovea, Revesz syndrome, choroideremia, choroideremia-deafness-obesity syndrome, X-linked retinal dysplasia, X-linked retinoschisis, progressive bifocal chorioretinal atrophy, aceruloplasminemia, late-onset retinal degeneration, infantile cerebellar-retinal degeneration, progressive retinal dystrophy due to retinol transport defect, microcornea-myopic chorioretinal atrophy, retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies, macular degeneration, early-onset, cone-rod dystrophy, ectopia lentis-chorioretinal dystrophy-myopia syndrome, foveal hypoplasia-presenile cataract syndrome, MRCS syndrome, X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome, Leber congenital amaurosis, oligocone trichromacy, Oguchi disease, retinitis pigmentosa, hereditary macular dystrophy, RPE65-related recessive retinopathy, RPGR-related retinopathy, AIPL1-related retinopathy, RP2-related retinopathy, RDH5-related retinopathy, RLBP1-related retinopathy, LCA5-related retinopathy, ATF6-related retinopathy, RAB28-related retinopathy, FLVCR1-related retinopathy with or without ataxia, RPE65-related dominant retinopathy, GUCY2D retinopathy, PDE6A-related retinopathy, ELOVL4-related maculopathy, MAK-related retinopathy, KIZ-related retinopathy, TOPORS-related retinopathy, PRPF8-related retinopathy, RD3-related retinopathy, BEST1-related dominant retinopathy, BEST1-related recessive retinopathy, IMPG2-related recessive retinopathy, IMPG2-related dominant retinopathy, CACNA1F-related retinopathy, CACNA2D4-related retinopathy, CDHR1-related retinopathy, GUCA1A-related retinopathy, RHO-related retinopathy, SNRNP200-related dominant retinopathy, RDH12-related recessive retinopathy, RDH12-related dominant retinopathy, NMNAT1-related retinopathy, CNGA3-related retinopathy, EYS-related retinopathy, GNAT2-related retinopathy, IDH3B-related retinopathy, MERTK-related retinopathy, PRPF31-related retinopathy, GPR179-related retinopathy, GRM6-related retinopathy, ADAM9-related retinopathy, RP1-related recessive retinopathy, RP1-related dominant retinopathy, CERKL-related retinopathy, TRPM1-related retinopathy, PCARE-related retinopathy, CNGA1-related retinopathy, ABCA4-related retinopathy, NYX-related retinopathy, retinal dystrophy, X-linked, Gardner-Hardcastle type, PDE6C-related retinopathy, PDE6G-related retinopathy, LRIT3-related retinopathy, IMPG1-related dominant retinopathy, IMPG1-related recessive retinopathy, TTLL5-related retinopathy, HGSNAT-related retinopathy, IMPDH1-related retinopathy, PRPH2-related retinopathy, PROM1-related retinopathy, KCNV2-related retinopathy, CRX-related retinopathy, REEP6-related retinopathy, SPATA7-related retinopathy

Subtypes (1): retinitis pigmentosa 45

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

12 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
420197	NM_001297.5(CNGB1):c.2762_2765del (p.Tyr921fs)	CNGB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
166891	NM_001297.5(CNGB1):c.2957A>T (p.Asn986Ile)	CNGB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195667	NM_001297.5(CNGB1):c.2209C>T (p.Arg737Cys)	CNGB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196674	NM_001297.5(CNGB1):c.3115G>A (p.Gly1039Arg)	CNGB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
320060	NM_001297.5(CNGB1):c.3421G>A (p.Ala1141Thr)	CNGB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
856760	NM_001297.5(CNGB1):c.568G>A (p.Ala190Thr)	CNGB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
100568	NM_001297.5(CNGB1):c.2747G>A (p.Arg916His)	CNGB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1010175	NM_001297.5(CNGB1):c.2539G>A (p.Gly847Arg)	CNGB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3028371	NM_001297.5(CNGB1):c.3710T>C (p.Ile1237Thr)	CNGB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779099	NM_001297.5(CNGB1):c.1159G>A (p.Val387Met)	CNGB1	Uncertain significance	criteria provided, single submitter
3779100	NM_001297.5(CNGB1):c.2310G>A (p.Met770Ile)	CNGB1	Uncertain significance	criteria provided, single submitter
3779101	NM_001297.5(CNGB1):c.3345G>A (p.Met1115Ile)	CNGB1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNGB1	Orphanet:791	Retinitis pigmentosa

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
CNGB1	HGNC:2151	ENSG00000070729	Q14028	Cyclic nucleotide-gated channel beta-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNGB1	Cyclic nucleotide-gated channel beta-1	Pore-forming subunit of the rod cyclic nucleotide-gated channel.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CNGB1	Ion channel	yes		cNMP-bd_dom, Ion_trans_dom, RmlC-like_jellyroll

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
buccal mucosa cell	1
cervix squamous epithelium	1
olfactory bulb	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNGB1	152	tissue_specific	marker	buccal mucosa cell, cervix squamous epithelium, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNGB1	1,133

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNGB1	Q14028	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Activation of the phototransduction cascade	1	951.7×	0.004	CNGB1
VxPx cargo-targeting to cilium	1	519.1×	0.004	CNGB1
Inactivation, recovery and regulation of the phototransduction cascade	1	317.2×	0.004	CNGB1
Olfactory Signaling Pathway	1	144.6×	0.007	CNGB1

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
olfactory nerve maturation	1	5617.3×	0.003	CNGB1
response to odorant	1	2808.7×	0.003	CNGB1
retina homeostasis	1	1123.5×	0.004	CNGB1
photoreceptor cell outer segment organization	1	1053.2×	0.004	CNGB1
monoatomic cation transport	1	766.0×	0.004	CNGB1
detection of light stimulus involved in visual perception	1	648.1×	0.004	CNGB1
monoatomic cation transmembrane transport	1	624.1×	0.004	CNGB1
membrane depolarization	1	510.7×	0.004	CNGB1
phototransduction	1	495.6×	0.004	CNGB1
regulation of cytosolic calcium ion concentration	1	383.0×	0.005	CNGB1
photoreceptor cell maintenance	1	358.6×	0.005	CNGB1
sodium ion transport	1	271.8×	0.006	CNGB1
potassium ion transport	1	191.5×	0.007	CNGB1
calcium ion transport	1	181.2×	0.007	CNGB1
sensory perception of smell	1	156.0×	0.008	CNGB1
detection of chemical stimulus involved in sensory perception of smell	1	123.9×	0.010	CNGB1
visual perception	1	79.5×	0.014	CNGB1
positive regulation of gene expression	1	38.7×	0.027	CNGB1
G protein-coupled receptor signaling pathway	1	36.2×	0.028	CNGB1

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
CNGB1	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	1	CNGB1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
CNGB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.