CNGB3

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

Basic information

Region (hg38): 8:86553977-86743675

Previous symbols: [ "ACHM3", "ACHM1", "RMCH" ]

Links

ENSG00000170289 ∙ NCBI:54714 ∙ OMIM:605080 ∙ HGNC:2153 ∙ Uniprot:Q9NQW8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• achromatopsia 3 (Strong), mode of inheritance: AR
• cone dystrophy (Supportive), mode of inheritance: AD
• achromatopsia (Supportive), mode of inheritance: AR
• achromatopsia 3 (Definitive), mode of inheritance: AR
• severe early-childhood-onset retinal dystrophy (Limited), mode of inheritance: AR
• achromatopsia 3 (Strong), mode of inheritance: AR
• severe early-childhood-onset retinal dystrophy (Limited), mode of inheritance: Unknown
• CNGB3-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Achromatopsia 3; Macular degeneration, juvenile	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	4192495; 1347967; 10888875; 15712225; 17265047; 17652762; 19767295; 20454696; 23362848

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNGB3 gene.

• not provided (91 variants)
• Achromatopsia 3 (29 variants)
• Achromatopsia (9 variants)
• Retinal dystrophy (4 variants)
• Abnormality of the eye (2 variants)
• Abnormal electroretinogram;Nystagmus (1 variants)
• Leber congenital amaurosis (1 variants)
• Inborn genetic diseases (1 variants)
• Achromatopsia 3;Severe early-childhood-onset retinal dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNGB3 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	284	4	289
missense	2	3	267	14	7	293
nonsense	31	16	1	3		51
start loss		3				3
frameshift	51	28	4	2		85
inframe indel	1		5	4		10
splice donor/acceptor (+/-2bp)	11	44	1			56
splice region		3	17	55	2	77
non coding	1	1	35	172	32	241
Total	97	95	314	479	43

Highest pathogenic variant AF is 0.0000657

Variants in CNGB3

This is a list of pathogenic ClinVar variants found in the CNGB3 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-86554925-C-G		not specified	Uncertain significance (Mar 29, 2024)
8-86554947-G-A		not specified	Uncertain significance (Dec 16, 2023)
8-86554952-G-A		not specified	Uncertain significance (Jan 05, 2022)
8-86573923-A-G		Achromatopsia • Stargardt Disease, Recessive	Benign (Jun 14, 2016)
8-86574071-A-G		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 13, 2018)
8-86574099-T-G		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 13, 2018)
8-86574103-G-A		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 13, 2018)
8-86574150-G-A		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 12, 2018)
8-86574165-G-T		Severe early-childhood-onset retinal dystrophy • Achromatopsia 3	Benign (Jan 13, 2018)
8-86574166-C-T		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Benign (Jan 12, 2018)
8-86574328-A-T		Severe early-childhood-onset retinal dystrophy • Achromatopsia 3	Uncertain significance (Jan 13, 2018)
8-86574334-C-G		Severe early-childhood-onset retinal dystrophy • Achromatopsia 3	Uncertain significance (Jan 12, 2018)
8-86574345-G-A		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 13, 2018)
8-86574373-C-T		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 13, 2018)
8-86574433-C-A		Severe early-childhood-onset retinal dystrophy • Achromatopsia 3	Uncertain significance (Jan 13, 2018)
8-86574436-A-G		Severe early-childhood-onset retinal dystrophy • Achromatopsia 3	Uncertain significance (Jan 13, 2018)
8-86574501-C-T		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Benign (Jan 12, 2018)
8-86574586-G-A		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 13, 2018)
8-86574621-A-G		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 12, 2018)
8-86574661-A-G		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 13, 2018)
8-86574711-G-A		Severe early-childhood-onset retinal dystrophy • Achromatopsia 3	Uncertain significance (Jan 13, 2018)
8-86574807-T-C		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Benign/Likely benign (Apr 27, 2017)
8-86574889-C-G		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Benign (Apr 27, 2017)
8-86574893-CAT-C		Stargardt Disease, Recessive • Achromatopsia	Likely benign (Jun 14, 2016)
8-86575004-G-C		Achromatopsia 3 • Severe early-childhood-onset retinal dystrophy	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNGB3	protein_coding	protein_coding	ENST00000320005	18	189699

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.77e-19	0.186	125081	2	665	125748	0.00266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.18	485	417	1.16	0.0000221	5289
Missense in Polyphen		107	99.568	1.0746		1321
Synonymous	-0.619	160	150	1.06	0.00000846	1527
Loss of Function	1.46	34	44.5	0.765	0.00000246	555

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00516	0.00515
Ashkenazi Jewish	0.00140	0.00139
East Asian	0.000707	0.000707
Finnish	0.00282	0.00282
European (Non-Finnish)	0.00330	0.00328
Middle Eastern	0.000707	0.000707
South Asian	0.000922	0.000915
Other	0.00294	0.00294

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 cGMP which leads to an opening of the cation channel and thereby causing a depolarization of rod 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 efficiency of the channel when coexpressed with CNGA3 (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 3 (ACHM3) [MIM:262300]: 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. Achromatopsia type 3 patients manifest severe myopia. {ECO:0000269|PubMed:10888875, ECO:0000269|PubMed:10958649, ECO:0000269|PubMed:12357335, ECO:0000269|PubMed:14757870, ECO:0000269|PubMed:15657609, ECO:0000269|PubMed:15712225}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: cAMP signaling pathway - Homo sapiens (human);NO-cGMP-PKG mediated Neuroprotection;Visual signal transduction: Cones (Consensus)

Intolerance Scores

• loftool: 0.221
• rvis_EVS: 1.67
• rvis_percentile_EVS: 96.33

Haploinsufficiency Scores

• pHI: 0.0889
• hipred: N
• hipred_score: 0.234
• ghis: 0.423

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.256

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cngb3
• Phenotype: cellular 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)

Gene ontology

• Biological process: cation transport;signal transduction;visual perception;cation transmembrane transport
• Cellular component: photoreceptor outer segment;transmembrane transporter complex
• Molecular function: intracellular cAMP-activated cation channel activity;intracellular cGMP-activated cation channel activity;cGMP binding