Achromatopsia 3

Summary

Achromatopsia 3 (MONDO:0009875) is a disease caused by CNGB3 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CNGB3 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 301

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	achromatopsia 3
Mondo ID	MONDO:0009875
OMIM	262300
DOID	DOID:0110008
UMLS	C1849792
MedGen	340413
GARD	0009650
Is cancer (heuristic)	no

Also known as: ACHM1 (formerly) · ACHM3 · achromatopsia 3 · achromatopsia caused by mutation in CNGB3 · achromatopsia type 3 · CNGB3 achromatopsia · RMCH1 (formerly) · Rod monochromacy 1 (formerly) · Rod monochromatism 1 (formerly)

Data availability: 301 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › perceptual disorders › vision disorder › color vision disorder › achromatopsia › achromatopsia 3

Related subtypes (5): achromatopsia 2, blue cone monochromacy, achromatopsia 6, achromatopsia 4, achromatopsia 7

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

301 retrieved; paginated sample, class counts are floors:

90 pathogenic, 63 uncertain significance, 55 likely pathogenic, 36 conflicting classifications of pathogenicity, 27 pathogenic/likely pathogenic, 21 benign, 8 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
5224	NM_019098.5(CNGB3):c.[442A>G;446_447insT]		Pathogenic	no assertion criteria provided
860883	NM_001298.3(CNGA3):c.1315C>T (p.Arg439Trp)	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9480	NM_001298.3(CNGA3):c.1585G>A (p.Val529Met)	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048157	NM_019098.5(CNGB3):c.1167_1168insC (p.Glu390fs)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066851	NM_019098.5(CNGB3):c.2181_2184del (p.Glu729fs)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070133	NM_019098.5(CNGB3):c.2179_2182del (p.Gln727fs)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071430	NM_019098.5(CNGB3):c.886_890del (p.Thr296fs)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322099	NM_019098.5(CNGB3):c.442_446delinsGAAAAT (p.Lys148fs)	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
1354843	NM_019098.5(CNGB3):c.2105del (p.Lys702fs)	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
1408511	NM_019098.5(CNGB3):c.839dup (p.Gly281fs)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1514783	NM_019098.5(CNGB3):c.990+1G>T	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188780	NM_019098.5(CNGB3):c.644-1G>C	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
188822	NM_019098.5(CNGB3):c.391C>T (p.Gln131Ter)	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
188827	NM_019098.5(CNGB3):c.991-3T>G	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
188828	NM_019098.5(CNGB3):c.112C>T (p.Gln38Ter)	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
188844	NM_019098.5(CNGB3):c.646C>T (p.Arg216Ter)	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
188968	NM_019098.5(CNGB3):c.1006G>T (p.Glu336Ter)	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
189031	NM_019098.5(CNGB3):c.1578+1G>A	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189190	NM_019098.5(CNGB3):c.1119G>A (p.Trp373Ter)	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
2691557	NM_019098.5(CNGB3):c.1155G>A (p.Trp385Ter)	CNGB3	Pathogenic	criteria provided, single submitter
3366382	NC_000008.10:g.(87656102_87656849)_(87660116_87666239)del	CNGB3	Pathogenic	criteria provided, single submitter
3366414	NC_000008.10:g.(87656915_87660028)_(87666291_87679152)del	CNGB3	Pathogenic	criteria provided, single submitter
3384125	NM_019098.5(CNGB3):c.1318C>T (p.Gln440Ter)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
363876	NM_019098.5(CNGB3):c.886_896delinsT (p.Thr296fs)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370089	NM_019098.5(CNGB3):c.1937del (p.Leu645_Leu646insTer)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370100	NM_019098.5(CNGB3):c.446_447insT (p.Lys149fs)	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
370177	NM_019098.5(CNGB3):c.11C>A (p.Ser4Ter)	CNGB3	Pathogenic	criteria provided, single submitter
370459	NM_019098.5(CNGB3):c.1579-1G>A	CNGB3	Pathogenic	criteria provided, multiple submitters, no conflicts
370539	NM_019098.5(CNGB3):c.1908del (p.Ile637fs)	CNGB3	Pathogenic	criteria provided, single submitter
370817	NM_019098.5(CNGB3):c.412del (p.Arg138fs)	CNGB3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 5 · 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
CNGB3	Definitive	Autosomal recessive	achromatopsia 3	5

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
CNGA3	Orphanet:1872	Cone rod dystrophy
CNGA3	Orphanet:49382	Achromatopsia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CNGB3	HGNC:2153	ENSG00000170289	Q9NQW8	Cyclic nucleotide-gated channel beta-3	gencc,clinvar
CNGA3	HGNC:2150	ENSG00000144191	Q16281	Cyclic nucleotide-gated channel alpha-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.
CNGA3	Cyclic nucleotide-gated channel alpha-3	Pore-forming subunit of the cone cyclic nucleotide-gated channel.

Protein-family classification

Druggable: 2 · 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	2	111.5×	8e-05

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CNGB3	Ion channel	yes		cNMP-bd_dom, Ion_trans_dom, RmlC-like_jellyroll
CNGA3	Ion channel	yes		cNMP-bd_dom, Ion_trans_dom, RmlC-like_jellyroll

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
diaphragm	1
pigmented layer of retina	1
ganglionic eminence	1
ventricular zone	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
CNGA3	110	tissue_specific	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNGA3	1,166
CNGB3	919

Intra-cohort edges

A	B	Sources
CNGA3	CNGB3	biogrid_interaction, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNGA3	Q16281	10
CNGB3	Q9NQW8	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 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	2	766.0×	1e-05	CNGB3, CNGA3
monoatomic cation transmembrane transport	2	624.1×	1e-05	CNGB3, CNGA3
visual perception	2	79.5×	4e-04	CNGB3, CNGA3
inorganic cation import across plasma membrane	1	4213.0×	5e-04	CNGA3
response to magnesium ion	1	702.2×	0.002	CNGA3
response to cAMP	1	255.3×	0.004	CNGA3
signal transduction	2	16.1×	0.004	CNGB3, CNGA3
retina development in camera-type eye	1	127.7×	0.008	CNGA3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
CNGA3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	CNGB3, CNGA3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CNGB3	0	—
CNGA3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.