CNGA1

cyclic nucleotide gated channel subunit alpha 1, the group of Cyclic nucleotide gated channels

Basic information

Region (hg38): 4:47935977-48016681

Previous symbols: [ "CNCG1", "CNCG" ]

Links

ENSG00000198515 ∙ NCBI:1259 ∙ OMIM:123825 ∙ HGNC:2148 ∙ Uniprot:P29973 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 49 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 49 (Definitive), mode of inheritance: AR
• CNGA1-related retinopathy (Definitive), mode of inheritance: AR
• retinitis pigmentosa 49 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 49	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	7479749

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNGA1 gene.

• not_provided (381 variants)
• Inborn_genetic_diseases (69 variants)
• Retinitis_pigmentosa (61 variants)
• Retinitis_pigmentosa_49 (52 variants)
• Retinal_dystrophy (45 variants)
• CNGA1-related_disorder (13 variants)
• not_specified (6 variants)
• See_cases (2 variants)
• CNGA1-related_retinopathy (2 variants)
• Macular_dystrophy (1 variants)
• Cone-rod_dystrophy (1 variants)
• Optic_atrophy (1 variants)
• Retinitis_Pigmentosa,_Recessive (1 variants)
• Prostate_cancer (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNGA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001379270.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	95	1	99
missense	3	14	223	10	2	252
nonsense	14	9				23
start loss						0
frameshift	27	14	1			42
splice donor/acceptor (+/-2bp)		6	2			8
Total	44	43	229	105	3

Highest pathogenic variant AF is 0.0029052973

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNGA1	protein_coding	protein_coding	ENST00000402813	9	80696

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.76e-11	0.888	124720	0	152	124872	0.000609

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.441	358	382	0.936	0.0000196	5026
Missense in Polyphen		160	166.34	0.9619		2206
Synonymous	-0.0217	142	142	1.00	0.00000774	1387
Loss of Function	1.89	22	33.9	0.650	0.00000204	426

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00192	0.00192
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00178	0.00178
Finnish	0.00	0.00
European (Non-Finnish)	0.000540	0.000538
Middle Eastern	0.00178	0.00178
South Asian	0.000230	0.000229
Other	0.000994	0.000989

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 rod photoreceptors.
• Disease: DISEASE: Retinitis pigmentosa 49 (RP49) [MIM:613756]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:15570217, ECO:0000269|PubMed:7479749}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: cAMP signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Phototransduction - Homo sapiens (human);NO-cGMP-PKG mediated Neuroprotection;Signaling by GPCR;Signal Transduction;Visual signal transduction: Rods;G alpha (i) signalling events;Activation of the phototransduction cascade;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.340
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.34

Haploinsufficiency Scores

• pHI: 0.682
• hipred: N
• hipred_score: 0.251
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.927

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cnga1

Gene ontology

• Biological process: visual perception;rhodopsin mediated signaling pathway;regulation of rhodopsin mediated signaling pathway;cation transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;photoreceptor outer segment membrane
• Molecular function: intracellular cAMP-activated cation channel activity;intracellular cGMP-activated cation channel activity;protein binding;cGMP binding