Achromatopsia 2

Summary

Achromatopsia 2 (MONDO:0009003) is a disease caused by CNGA3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CNGA3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 228

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	achromatopsia 2
Mondo ID	MONDO:0009003
MeSH	C536128
OMIM	216900
DOID	DOID:0110007
NCIT	C168757
UMLS	C1857618
MedGen	387867
GARD	0009649
Is cancer (heuristic)	no

Also known as: ACHM2 · achromatopsia 2 · achromatopsia caused by mutation in CNGA3 · achromatopsia type 2 · CNGA3 achromatopsia · RMCH2 · rod monochromacy 2 · rod monochromatism 2

Data availability: 228 ClinVar variants · 3 GenCC gene-disease records · 1 cell line.

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 2

Related subtypes (5): achromatopsia 3, 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

228 retrieved; paginated sample, class counts are floors:

52 uncertain significance, 45 pathogenic, 45 likely pathogenic, 45 conflicting classifications of pathogenicity, 25 pathogenic/likely pathogenic, 7 benign, 7 benign/likely benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1034766	NM_001298.3(CNGA3):c.1775C>T (p.Pro592Leu)	CNGA3	Pathogenic	criteria provided, single submitter
1056891	NM_001298.3(CNGA3):c.1537G>A (p.Gly513Arg)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1064462	NM_001298.3(CNGA3):c.1063A>G (p.Ser355Gly)	CNGA3	Pathogenic	criteria provided, single submitter
1064464	NM_001298.3(CNGA3):c.1115C>T (p.Pro372Leu)	CNGA3	Pathogenic	criteria provided, single submitter
1064470	NM_001298.3(CNGA3):c.1519del (p.Asp507fs)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1064474	NM_001298.3(CNGA3):c.1708A>G (p.Ser570Gly)	CNGA3	Pathogenic	criteria provided, single submitter
1064475	NM_001298.3(CNGA3):c.1717T>C (p.Tyr573His)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1064483	NM_001298.3(CNGA3):c.464del (p.Lys155fs)	CNGA3	Pathogenic	no assertion criteria provided
1064498	NM_001298.3(CNGA3):c.992G>A (p.Gly331Glu)	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065327	NC_000002.12:g.98393909_98399093del	CNGA3	Pathogenic	no assertion criteria provided
1071996	NM_001298.3(CNGA3):c.542A>G (p.Tyr181Cys)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1075088	NM_001298.3(CNGA3):c.1495C>T (p.Arg499Ter)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1299243	NM_001298.3(CNGA3):c.77del (p.Asn26fs)	CNGA3	Pathogenic	criteria provided, single submitter
1432595	NM_001298.3(CNGA3):c.1565T>C (p.Ile522Thr)	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1444606	NM_001298.3(CNGA3):c.1074G>A (p.Trp358Ter)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1444626	NM_001298.3(CNGA3):c.1201T>C (p.Ser401Pro)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1453949	NM_001298.3(CNGA3):c.450-1G>A	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1458185	NM_001298.3(CNGA3):c.485A>T (p.Asp162Val)	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686891	NM_001298.3(CNGA3):c.1235_1236del (p.Glu412fs)	CNGA3	Pathogenic	no assertion criteria provided
1687513	NM_001298.3(CNGA3):c.62C>G (p.Ser21Ter)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
191120	NM_001298.3(CNGA3):c.955T>C (p.Cys319Arg)	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191122	NM_001298.3(CNGA3):c.1573G>A (p.Gly525Ser)	CNGA3	Pathogenic	criteria provided, single submitter
1929274	NM_001298.3(CNGA3):c.271C>T (p.Gln91Ter)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
2203121	NM_001298.3(CNGA3):c.1443dup (p.Ile482fs)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
236461	NM_001298.3(CNGA3):c.248G>A (p.Trp83Ter)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
265467	NM_001298.3(CNGA3):c.1688G>A (p.Arg563His)	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734247	NM_001298.3(CNGA3):c.396-11C>G	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3258069	NM_001298.3(CNGA3):c.1231del (p.Ala411fs)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
337652	NM_001298.3(CNGA3):c.67C>T (p.Arg23Ter)	CNGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3773704	NM_001298.3(CNGA3):c.1088T>C (p.Leu363Pro)	CNGA3	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
CNGA3	Definitive	Autosomal recessive	achromatopsia 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNGA3	Orphanet:1872	Cone rod dystrophy
CNGA3	Orphanet:49382	Achromatopsia

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
CNGA3	HGNC:2150	ENSG00000144191	Q16281	Cyclic nucleotide-gated channel alpha-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNGA3	Cyclic nucleotide-gated channel alpha-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)
CNGA3	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
ganglionic eminence	1
male germ line stem cell (sensu Vertebrata) in testis	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNGA3	1,166

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNGA3	Q16281	10

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
inorganic cation import across plasma membrane	1	8426.0×	9e-04	CNGA3
response to magnesium ion	1	1404.3×	0.003	CNGA3
monoatomic cation transport	1	766.0×	0.003	CNGA3
monoatomic cation transmembrane transport	1	624.1×	0.003	CNGA3
response to cAMP	1	510.7×	0.003	CNGA3
retina development in camera-type eye	1	255.3×	0.005	CNGA3
visual perception	1	79.5×	0.014	CNGA3
signal transduction	1	16.1×	0.062	CNGA3

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
CNGA3	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	CNGA3
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)
CNGA3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.