CNGB3-related retinopathy

Summary

CNGB3-related retinopathy (MONDO:0100446) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	CNGB3-related retinopathy
Mondo ID	MONDO:0100446
GARD	0026221
Is cancer (heuristic)	no

Also known as: ACHM1 · ACHM1 (formerly) · ACHM1, formerly · ACHM3 · achromatopsia 3 · achromatopsia caused by mutation in CNGB3 · achromatopsia type 3 · achromatopsia with myopia · CNGB3 achromatopsia · CNGB3 retinopathy · RMCH1 · RMCH1 (formerly) · rod monochromacy 1 · Rod monochromacy 1 (formerly) · rod monochromacy 1, formerly · rod monochromatism 1 · Rod monochromatism 1 (formerly) · rod monochromatism 1, formerly · total colorblindness with myopia

Data availability: 7 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 › neuromuscular disease › muscular channelopathy › CNGB3-related retinopathy

Related subtypes (11): Andersen-Tawil syndrome, Morvan syndrome, Thomsen and Becker disease, malignant hyperthermia of anesthesia, Isaac syndrome, RYR1-related myopathy, SCN4A-related channelopathy, neurological muscular channelopathy due to a genetic sodium channel defect, neurological muscular channelopathy due to a genetic chloride channel defect, neurological muscular channelopathy due to a genetic calcium channel defect, neurological muscular channelopathy due to a genetic potassium channel defect

Subtypes (1): achromatopsia 3

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

7 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
188968	NM_019098.5(CNGB3):c.1006G>T (p.Glu336Ter)	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
592343	NM_019098.5(CNGB3):c.1898A>G (p.Asp633Gly)	CNGB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
768249	NM_019098.5(CNGB3):c.1732A>T (p.Thr578Ser)	CNGB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779102	NM_019098.5(CNGB3):c.1411A>G (p.Ile471Val)	CNGB3	Uncertain significance	criteria provided, single submitter
3779103	NM_019098.5(CNGB3):c.2368C>T (p.Pro790Ser)	CNGB3	Uncertain significance	criteria provided, single submitter
854439	NM_019098.5(CNGB3):c.2235G>C (p.Glu745Asp)	CNGB3	Uncertain significance	criteria provided, multiple submitters, no conflicts
864589	NM_019098.5(CNGB3):c.503C>T (p.Thr168Met)	CNGB3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNGB3	Orphanet:1871	Progressive cone dystrophy
CNGB3	Orphanet:49382	Achromatopsia
CNGB3	Orphanet:827	Stargardt disease

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
CNGB3	HGNC:2153	ENSG00000170289	Q9NQW8	Cyclic nucleotide-gated channel beta-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNGB3	Cyclic nucleotide-gated channel beta-3	Pore-forming subunit of the cone 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)
CNGB3	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
diaphragm	1
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNGB3	161	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, diaphragm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNGB3	919

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNGB3	Q9NQW8	9

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
monoatomic cation transport	1	766.0×	0.003	CNGB3
monoatomic cation transmembrane transport	1	624.1×	0.003	CNGB3
visual perception	1	79.5×	0.017	CNGB3
signal transduction	1	16.1×	0.062	CNGB3

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
CNGB3	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	CNGB3
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)
CNGB3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.