CNGA3

cyclic nucleotide gated channel subunit alpha 3, the group of Cyclic nucleotide gated channels

Basic information

Region (hg38): 2:98346188-98398601

Previous symbols: [ "CNCG3", "ACHM2" ]

Links

ENSG00000144191 ∙ NCBI:1261 ∙ OMIM:600053 ∙ HGNC:2150 ∙ Uniprot:Q16281 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• achromatopsia 2 (Strong), mode of inheritance: AR
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• achromatopsia (Supportive), mode of inheritance: AR
• achromatopsia 2 (Strong), mode of inheritance: AR
• achromatopsia 2 (Definitive), mode of inheritance: AR
• achromatopsia 2 (Definitive), mode of inheritance: AR
• Leber congenital amaurosis 9 (Limited), mode of inheritance: AR
• CNGA3-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Achromatopsia 2; Leber congenital amaurosis	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	9662398; 11536077; 15059731; 15980212; 16961972; 18636117; 20454696; 21901789; 21911670; 21912902; 23362848; 25616768

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNGA3 gene.

• not provided (88 variants)
• Achromatopsia 2 (32 variants)
• Achromatopsia (16 variants)
• Retinal dystrophy (14 variants)
• Cone dystrophy (2 variants)
• Abnormality of the eye (2 variants)
• Macular dystrophy (1 variants)
• Galactosylceramide beta-galactosidase deficiency (1 variants)
• CNGA3-related disorder (1 variants)
• Fabry disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNGA3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	2	120	5	128
missense	44	46	205	13	1	309
nonsense	24	6				30
start loss						0
frameshift	24	4	1			29
inframe indel	2		4			6
splice donor/acceptor (+/-2bp)	2	3	1			6
splice region			11	9		20
non coding	1		27	28	9	65
Total	97	60	240	161	15

Highest pathogenic variant AF is 0.000394

Variants in CNGA3

This is a list of pathogenic ClinVar variants found in the CNGA3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-98346189-A-G		Achromatopsia 2	Conflicting classifications of pathogenicity (Nov 01, 2022)
2-98346191-A-G		Achromatopsia 2	Uncertain significance (Jan 13, 2018)
2-98346246-G-A		Achromatopsia 2	Uncertain significance (Jan 12, 2018)
2-98346285-C-T		Achromatopsia	Uncertain significance (Jun 14, 2016)
2-98346286-C-T		Achromatopsia 2	Benign (Jan 13, 2018)
2-98346301-G-A		Achromatopsia 2	Uncertain significance (Jan 13, 2018)
2-98346507-G-C		Achromatopsia 2	Uncertain significance (Jan 13, 2018)
2-98346529-G-A		Achromatopsia 2	Uncertain significance (Jan 13, 2018)
2-98369938-G-C		Achromatopsia	Conflicting classifications of pathogenicity (Oct 12, 2021)
2-98369976-A-T		Achromatopsia 2	Uncertain significance (Apr 15, 2021)
2-98369979-G-C			Uncertain significance (Jul 12, 2022)
2-98369983-AG-A			Pathogenic (Apr 08, 2022)
2-98369999-C-G			Pathogenic (Jan 12, 2022)
2-98370002-C-A			Likely benign (Sep 01, 2022)
2-98370023-C-G			Likely benign (Jul 06, 2022)
2-98370025-A-G			Uncertain significance (Apr 04, 2022)
2-98370032-G-T			Uncertain significance (Aug 05, 2021)
2-98370034-C-T		Achromatopsia 2 • CNGA3-related disorder	Benign/Likely benign (Jan 22, 2024)
2-98370037-C-G		Achromatopsia 2	Pathogenic (Jul 03, 2023)
2-98370041-C-T		Achromatopsia 2	Uncertain significance (Apr 15, 2021)
2-98370042-C-T		Achromatopsia 2 • Achromatopsia	Pathogenic (Nov 16, 2023)
2-98370043-G-A		Achromatopsia 2	Uncertain significance (Nov 27, 2023)
2-98370047-T-C		not specified • Achromatopsia 2	Benign (Jan 31, 2024)
2-98370049-T-C			Uncertain significance (Oct 01, 2022)
2-98370050-CA-C		Achromatopsia 2	Pathogenic (Oct 04, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNGA3	protein_coding	protein_coding	ENST00000393504	7	52447

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.03e-20	0.00104	125612	0	136	125748	0.000541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0368	404	402	1.01	0.0000257	4535
Missense in Polyphen		119	124.98	0.95217		1443
Synonymous	-0.405	183	176	1.04	0.0000117	1392
Loss of Function	-0.397	28	25.8	1.08	0.00000139	301

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000428	0.000423
Ashkenazi Jewish	0.00580	0.00577
East Asian	0.000652	0.000653
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000326	0.000325
Middle Eastern	0.000652	0.000653
South Asian	0.000360	0.000359
Other	0.000981	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Visual signal transduction is mediated by a G-protein coupled cascade using cGMP as second messenger. This protein can be activated by cyclic GMP which leads to an opening of the cation channel and thereby causing a depolarization of cone photoreceptors. Induced a flickering channel gating, weakened the outward rectification in the presence of extracellular calcium, increased sensitivity for L-cis diltiazem and enhanced the cAMP efficacy of the channel when coexpressed with CNGB3 (By similarity). Essential for the generation of light-evoked electrical responses in the red-, green- and blue sensitive cones. {ECO:0000250, ECO:0000269|PubMed:10888875}.
• Disease: DISEASE: Achromatopsia 2 (ACHM2) [MIM:216900]: An autosomal recessive, ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus. {ECO:0000269|PubMed:11536077, ECO:0000269|PubMed:14757870, ECO:0000269|PubMed:15712225, ECO:0000269|PubMed:15743887, ECO:0000269|PubMed:18521937, ECO:0000269|PubMed:24903488, ECO:0000269|PubMed:26493561, ECO:0000269|PubMed:9662398}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: cAMP signaling pathway - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);NO-cGMP-PKG mediated Neuroprotection;Visual signal transduction: Cones (Consensus)

Recessive Scores

• pRec: 0.183

Intolerance Scores

• loftool: 0.0506
• rvis_EVS: -0.66
• rvis_percentile_EVS: 16.12

Haploinsufficiency Scores

• pHI: 0.298
• hipred: N
• hipred_score: 0.342
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.296

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cnga3
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); taste/olfaction phenotype

Gene ontology

• Biological process: cation transport;signal transduction;visual perception;response to corticosteroid;response to magnesium ion;response to cAMP;inorganic cation import across plasma membrane
• Cellular component: cytoplasm;plasma membrane;dendrite;axon initial segment;perikaryon;glial cell projection;transmembrane transporter complex
• Molecular function: intracellular cAMP-activated cation channel activity;intracellular cGMP-activated cation channel activity;protein C-terminus binding;ligand-gated ion channel activity;cGMP binding