CNGB1

protein-coding

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

Gene summary

In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. Defects in this gene are a cause of cause of retinitis pigmentosa type 45. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

Previous symbols:

CNCG2
CNCG3L

MANE transcript

NM_001297.5

Inheritance

AR, AD

ClinVar variants

P:226U:615B:362

Top phenotype

Retinitis pigmentosa 45

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr16:57,882,340-57,971,128

External References & Databases

Ensembl (ENSG00000070729)

Transcript & Mutation Effects

hg38 • Region Span ~88.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

CNGB1-related retinopathyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0800403

Submitter: ClinGen

*CNGB1* was first reported in relation to autosomal recessive retinitis pigmentosa in 2001 (Bareil et al., PMID: 11379879). 8 publications were added with 5 included for evidence (PMIDs: 11379879, 15557452, 23661369, 28056120, and 23977260) in this curation. *CNGB1* variants within the channel‐encoding part of the sequence result in olfactory symptoms, in addition to phenotypes associated with retinitis pigmentosa. Because of the broad spectrum of potential phenotypes, these cases with causal variants in *CNGB1* have been curated under the inclusive disease name *CNGB1*-related retinopathy (MONDO:0800403). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is reported to be LOF. This gene-disease association is also supported by experimental evidence. In summary, *CNGB1* is definitively associated with *CNGB1*-related retinopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification has been approved by the ClinGen Retina GCEP on September 1st, 2022 (SOP Version 9).

retinitis pigmentosaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Orphanet

retinitis pigmentosa 45DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013413

Submitter: G2P

retinitis pigmentosa 45STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013413

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Retinitis pigmentosa 45AR

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 11379879; 15557452; 20126465

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CNGB1 variants in ClinVar

13 Conditions Cataloged

not providedTotal: 1248

CNGB1-related disorderTotal: 231

Inborn genetic diseasesTotal: 212

not specifiedTotal: 200

Retinitis pigmentosaTotal: 164

Retinitis pigmentosa 45Total: 128

Retinal dystrophyTotal: 128

CNGB1-related retinopathyTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001297.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	17 clinvar	286 clinvar	3 clinvar	307
missense	6 clinvar	21 clinvar	587 clinvar	70 clinvar	3 clinvar	687
nonsense	31 clinvar	27 clinvar	2 clinvar			60
start loss			2 clinvar			2
frameshift	24 clinvar	49 clinvar	4 clinvar			77
splice donor/acceptor (+/-2bp)	12 clinvar	55 clinvar	3 clinvar			70
Total	73	153	615	356	6	1203

Highest pathogenic variant AF is 0.0011783175

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001297.5	RefSeq	NP_001288.3	32	MANE Select
ENST00000251102.13	Ensembl	ENSP00000251102.8	32	MANE Select
NM_001135639.2	RefSeq	NP_001129111.1	12	Standard
NM_001286130.2	RefSeq	NP_001273059.1	32	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

retina homeostasis
cation transport
visual perception
sensory perception of smell
rhodopsin mediated signaling pathway

Molecular Function

intracellular cAMP-activated cation channel activity
intracellular cGMP-activated cation channel activity
protein binding
ligand-gated ion channel activity
cAMP binding

Cellular Component

Golgi membrane
photoreceptor outer segment
plasma membrane
intracellular cyclic nucleotide activated cation channel complex
Golgi-associated vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000251102
Coding exons: 32
Length: 87518
Individuals with no LoFs: 124619
Homozygous LoFs: 0
Heterozygous LoFs: 224
Defined: 124843
p: 0.000898

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.828	779	717	1.09	0.0000455	8109
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0025	0.0025	notable
Latino/Admixed American	0.0012	0.0012	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00072	0.00072	rare
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.00082	0.00082	rare
South Asian	0.0010	0.00085	notable
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.158
RVIS EVS: 1.33
RVIS percentile EVS: 94.14

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.550

Gene Damage Prediction

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