CNGB1

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

Basic information

Region (hg38): 16:57882340-57971128

Previous symbols: [ "CNCG2", "CNCG3L" ]

Links

ENSG00000070729 ∙ NCBI:1258 ∙ OMIM:600724 ∙ HGNC:2151 ∙ Uniprot:Q14028 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 45 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 45 (Definitive), mode of inheritance: AR
• CNGB1-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 45	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	11379879; 15557452; 20126465

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNGB1 gene.

• not_provided (1088 variants)
• Inborn_genetic_diseases (186 variants)
• Retinitis_pigmentosa (163 variants)
• Retinal_dystrophy (145 variants)
• Retinitis_pigmentosa_45 (120 variants)
• not_specified (37 variants)
• CNGB1-related_disorder (35 variants)
• CNGB1-related_retinopathy (12 variants)
• Retinitis_Pigmentosa,_Recessive (5 variants)
• Autosomal_recessive_retinitis_pigmentosa (3 variants)
• Optic_atrophy (2 variants)
• Retinitis_pigmentosa_49 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNGB1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001297.5. 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	14	248	4	269
missense	7	18	513	64	3	605
nonsense	30	16	1			47
start loss			2			2
frameshift	29	35	2			66
splice donor/acceptor (+/-2bp)	7	42	2			51
Total	73	114	534	312	7

Highest pathogenic variant AF is 0.0011783175

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNGB1	protein_coding	protein_coding	ENST00000251102	32	87518

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.84e-37	0.0000281	124619	0	224	124843	0.000898

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.828	779	717	1.09	0.0000455	8109
Missense in Polyphen		199	181.43	1.0968		2004
Synonymous	0.286	292	298	0.979	0.0000209	2409
Loss of Function	0.529	59	63.6	0.928	0.00000289	787

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00371	0.00370
Ashkenazi Jewish	0.00	0.00
East Asian	0.000723	0.000723
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000823	0.000821
Middle Eastern	0.000723	0.000723
South Asian	0.00101	0.000850
Other	0.00148	0.00148

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Subunit of cyclic nucleotide-gated (CNG) channels, nonselective cation channels, which play important roles in both visual and olfactory signal transduction. When associated with CNGA1, it is involved in the regulation of ion flow into the rod photoreceptor outer segment (ROS), in response to light-induced alteration of the levels of intracellular cGMP.
• Disease: DISEASE: Retinitis pigmentosa 45 (RP45) [MIM:613767]: 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:11379879}. 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);Olfactory transduction - 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;VxPx cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.158
• rvis_EVS: 1.33
• rvis_percentile_EVS: 94.14

Haploinsufficiency Scores

• pHI: 0.731
• hipred: N
• hipred_score: 0.207
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.550

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cngb1
• 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); vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: retina homeostasis;cation transport;visual perception;sensory perception of smell;rhodopsin mediated signaling pathway;regulation of rhodopsin mediated signaling pathway;protein localization to organelle;photoreceptor cell outer segment organization;photoreceptor cell maintenance;detection of light stimulus involved in visual perception;protein heterotetramerization;regulation of cytosolic calcium ion concentration;cation transmembrane transport
• Cellular component: Golgi membrane;photoreceptor outer segment;plasma membrane;intracellular cyclic nucleotide activated cation channel complex;Golgi-associated vesicle membrane;terminal bouton;ciliary membrane;transmembrane transporter complex
• Molecular function: intracellular cAMP-activated cation channel activity;intracellular cGMP-activated cation channel activity;protein binding;ligand-gated ion channel activity;cAMP binding;cGMP binding