CNGB1

Summary

CNGB1 (cyclic nucleotide gated channel subunit beta 1, HGNC:2151) is a protein-coding gene on chromosome 16q21, encoding Cyclic nucleotide-gated channel beta-1 (Q14028). Pore-forming subunit of the rod cyclic nucleotide-gated channel.

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.

Source: NCBI Gene 1258 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CNGB1-related retinopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 1,512 total — 81 pathogenic, 85 likely-pathogenic
• Phenotypes (HPO): 34
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001297

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2151
Approved symbol	CNGB1
Name	cyclic nucleotide gated channel subunit beta 1
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	RCNC2, RCNCb, GARP, GAR1, CNGB1B, RP45
Ensembl gene	ENSG00000070729
Ensembl biotype	protein_coding
OMIM	600724
Entrez	1258

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 retained_intron

ENST00000251102, ENST00000311183, ENST00000562761, ENST00000564448, ENST00000564450, ENST00000564654, ENST00000565942, ENST00000567568, ENST00000569643

RefSeq mRNA: 3 — MANE Select: NM_001297 NM_001135639, NM_001286130, NM_001297

CCDS: CCDS42169, CCDS45495, CCDS67042

Canonical transcript exons

ENST00000251102 — 33 exons

Exon	Start	End
ENSE00000565195	57917268	57917476
ENSE00000685926	57923273	57923380
ENSE00000686041	57919099	57919254
ENSE00000686328	57897796	57897914
ENSE00000852995	57920387	57920544
ENSE00000853007	57897397	57897543
ENSE00000853008	57887855	57888074
ENSE00000921074	57964130	57964202
ENSE00000921075	57962974	57963064
ENSE00000921076	57962842	57962872
ENSE00000921077	57962565	57962610
ENSE00000921078	57960840	57960915
ENSE00000921080	57959888	57960065
ENSE00000921081	57958410	57958485
ENSE00000921082	57957341	57957377
ENSE00000921083	57950381	57950540
ENSE00000921084	57916129	57916179
ENSE00000921085	57915249	57915335
ENSE00000921086	57912930	57912994
ENSE00000921087	57911753	57911875
ENSE00001046828	57931716	57931878
ENSE00001046832	57960482	57960530
ENSE00001046842	57949353	57949439
ENSE00001813342	57882340	57884457
ENSE00003485395	57901528	57901625
ENSE00003565438	57904734	57904875
ENSE00003582211	57964487	57964544
ENSE00003611798	57940234	57940321
ENSE00003631882	57903822	57903981
ENSE00003669963	57939430	57939592
ENSE00003678075	57901352	57901435
ENSE00003691880	57967128	57967294
ENSE00003893989	57971060	57971128

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 85.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1189 / max 384.7511, expressed in 103 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157590	0.4160	9
157591	0.3234	9
157588	0.1759	59
157587	0.0562	27
157589	0.0525	28
157584	0.0206	6
157583	0.0155	4
157585	0.0142	4
157586	0.0141	5
157580	0.0079	3

Top tissues by expression

259 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	85.81	silver quality
cervix squamous epithelium	UBERON:0006922	82.78	gold quality
olfactory bulb	UBERON:0002264	79.98	gold quality
type B pancreatic cell	CL:0000169	79.10	gold quality
gingival epithelium	UBERON:0001949	79.09	gold quality
choroid plexus epithelium	UBERON:0003911	78.76	silver quality
Brodmann (1909) area 10	UBERON:0013541	78.68	gold quality
male germ cell	CL:0000015	78.62	silver quality
endometrium epithelium	UBERON:0004811	78.47	gold quality
sperm	CL:0000019	78.40	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	77.93	gold quality
superficial temporal artery	UBERON:0001614	77.85	gold quality
squamous epithelium	UBERON:0006914	77.65	gold quality
tongue squamous epithelium	UBERON:0006919	77.63	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.66	gold quality
endothelial cell	CL:0000115	75.58	gold quality
gluteal muscle	UBERON:0002000	75.47	silver quality
triceps brachii	UBERON:0001509	75.33	gold quality
tendon of biceps brachii	UBERON:0008188	75.04	gold quality
cerebellar vermis	UBERON:0004720	75.01	gold quality
esophagus squamous epithelium	UBERON:0006920	75.01	gold quality
vastus lateralis	UBERON:0001379	74.50	gold quality
pancreatic ductal cell	CL:0002079	74.34	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.32	gold quality
epithelium of esophagus	UBERON:0001976	74.21	gold quality
quadriceps femoris	UBERON:0001377	73.73	gold quality
frontal pole	UBERON:0002795	73.46	gold quality
paraflocculus	UBERON:0005351	73.30	gold quality
parotid gland	UBERON:0001831	73.19	gold quality
retina	UBERON:0000966	73.10	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	2360.02
E-GEOD-137537	yes	2256.43
E-MTAB-11121	yes	767.18
E-GEOD-98556	yes	635.39
E-HCAD-30	no	62.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PARP1

miRNA regulators (miRDB)

60 targeting CNGB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-2116-5P	99.32	69.34	1273

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 15)

• we report targeting of cyclic nucleotide-gated channel(CNG) to rod outer segment required interaction with ankyrin-G; ankyrin-G localized to rod outer segments, coimmunoprecipitated with CNG channel & bound to C-terminal domain of channel beta1 subunit (PMID:19299621)
• When expressed in a heterologous expression system the corresponding mutant full-length CNGB1a subunit was more susceptible to proteosomal degradation compared to the wild-type counterpart (PMID:20126465)
• Deletion of the cyclic nucleotide gated channel CNGB1 alters response waveform but leaves light adaptation intact in a transgenic model. (PMID:21123569)
• The p.Arg86Gln mutation actually appears to be a polymorphism common in ethnic West Africans and not associated with RP. This change may provide a useful marker for West African ancestry. (PMID:23201897)
• Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3+Helios+ Tregs have more suppressive characteristics, compared with FoxP3+Helios- Tregs. (PMID:26343373)
• GARP2 expression in cones can be detrimental to cones. RDS/GARP interactions remain under investigation but are critical for both OS structure and function. (PMID:26720471)
• Here, we present the first case of RP45 caused by an unequivocal homozygous nonsense variant of CNGB1 identified by run of homozygosity (ROH) analysis. (PMID:26901671)
• Patients and animal models of CNGbeta1-deficient retinitis pigmentosa support gene augmentation approach. (PMID:29202463)
• Mutations in CNGB1 may cause an autosomal recessive retinitis pigmentosa-olfactory dysfunction syndrome characterized by a slow progression of retinal degeneration and variable anosmia or hyposmia. (PMID:29800053)
• The c.385delC (p.(L129WfsTer148)) mutation in the CNGB1 gene screened by exome sequencing is probably responsible for the retinitis pigmentosa phenotype in this family. (PMID:30451805)
• Variable expressivity in patients with autosomal recessive retinitis pigmentosa associated with the gene CNGB1. (PMID:33465333)
• CNGB1-related rod-cone dystrophy: A mutation review and update. (PMID:33847019)
• Functional Evaluation of Splicing for Variants of Uncertain Significance in Patients with Inherited Retinal Diseases. (PMID:34209753)
• Structural basis of the partially open central gate in the human CNGA1/CNGB1 channel explained by additional density for calmodulin in cryo-EM map. (PMID:34971760)
• Development of a translatable gene augmentation therapy for CNGB1-retinitis pigmentosa. (PMID:37056049)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cngb1	ENSMUSG00000031789
rattus_norvegicus	Cngb1	ENSRNOG00000031773
drosophila_melanogaster	sei	FBGN0003353
drosophila_melanogaster	Elk	FBGN0011589
drosophila_melanogaster	CG6026	FBGN0038676
drosophila_melanogaster	CngA	FBGN0261612
drosophila_melanogaster	Cngl	FBGN0263257
drosophila_melanogaster	CngB	FBGN0266346
caenorhabditis_elegans		WBGENE00000487
caenorhabditis_elegans	tax-2	WBGENE00006525
caenorhabditis_elegans		WBGENE00006526
caenorhabditis_elegans		WBGENE00006830
caenorhabditis_elegans		WBGENE00022295

Paralogs (17): KCNH2 (ENSG00000055118), KCNH4 (ENSG00000089558), HCN2 (ENSG00000099822), CNGA4 (ENSG00000132259), KCNH3 (ENSG00000135519), HCN4 (ENSG00000138622), KCNH5 (ENSG00000140015), KCNH1 (ENSG00000143473), HCN3 (ENSG00000143630), CNGA3 (ENSG00000144191), HCN1 (ENSG00000164588), CNGB3 (ENSG00000170289), KCNH6 (ENSG00000173826), CNGA2 (ENSG00000183862), KCNH8 (ENSG00000183960), KCNH7 (ENSG00000184611), CNGA1 (ENSG00000198515)

Protein

Protein identifiers

Cyclic nucleotide-gated channel beta-1 — Q14028 (reviewed: Q14028)

Alternative names: Cyclic nucleotide-gated cation channel 4, Cyclic nucleotide-gated cation channel gamma, Cyclic nucleotide-gated cation channel modulatory subunit, Glutamic acid-rich protein

All UniProt accessions (4): Q14028, A0A2R8Y6Y0, H3BQC3, H3BQW3

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming subunit of the rod cyclic nucleotide-gated channel. Mediates rod photoresponses at dim light converting transient changes in intracellular cGMP levels into electrical signals. In the dark, cGMP levels are high and keep the channel open enabling a steady inward current carried by Na(+) and Ca(2+) ions that leads to membrane depolarization and neurotransmitter release from synaptic terminals. Upon photon absorption cGMP levels decline leading to channel closure and membrane hyperpolarization that ultimately slows neurotransmitter release and signals the presence of light, the end point of the phototransduction cascade. Pore-forming subunit of the olfactory cyclic nucleotide-gated channel. Operates in the cilia of olfactory sensory neurons where chemical stimulation of the odorant is converted to an electrical signal. Mediates odorant-induced cAMP-dependent Ca(2+) influx triggering neuron depolarization. The rise of intracellular Ca(2+) levels potentiates the olfactory response by activating Ca(2+)-dependent Cl(-) channels, but it also serves as a negative feedback signal to desensitize the channel for rapid adaptation to odorants. Conducts cGMP- and cAMP-gated ion currents, with permeability for monovalent and divalent cations. The selectivity for Ca(2+) over Na(+) increases with cGMP concentrations, whereas the selectivity among monovalent ions is independent of the cGMP levels. High affinity rod photoreceptor phosphodiesterase (PDE6)-binding protein that modulates its catalytic properties: it is a regulator of spontaneous activation of rod PDE6, thereby serving to lower rod photoreceptor ‘dark noise’ and allowing these sensory cells to operate at the single photon detection limit.

Subunit / interactions. The rod cyclic nucleotide-gated channel is a heterotetramer composed of CNGA1 and CNGB1 subunits with 3:1 stoichiometry. CNGA1:CNGB1 channel binds Ca(2+)-bound CALM1 via CaM1 and CaM2 regions of the CNGB1 subunit; this interaction modulates the affinity of the channel for cNMPs in response to intracellular Ca(2+) levels. The olfactory cyclic nucleotide-gated channel is a heterotetramer composed of CNGA2, CNGA4 and CNGB1 subunits with 2:1:1 stoichiometry.

Subcellular location. Cell membrane. Cell projection. Cilium membrane.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The cyclic nucleotide-binding domain (CNBD) comprises three helices and a beta-roll of eight beta-strands from CNGA1 and CNGB1 subunits. Upon cNMP binding transmits the conformational changes to the C-linker domain of the S6 helix to open the ion conduction pathway. The ion conduction pathway consists of S5, S6 and pore helices from CNGA1 and CNGB1 subunits. It contains a central hydrophobic gate that opens upon cNMP binding. CNGB1 displays an additional charged arginine gate below the central gate to regulate ion permeation.

Miscellaneous. In the rod cells, the CNGB1 locus encodes the cyclic nucleotide-gated cation channel beta-1 subunit and several glutamic-acid-rich proteins (GARPs).

Similarity. Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGB1 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q14028-1	RCNC2B	yes
Q14028-2	RCNC2A
Q14028-3	GARP2, GARP
Q14028-4	4

RefSeq proteins (3): NP_001129111, NP_001273059, NP_001288* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000595	cNMP-bd_dom	Domain
IPR005821	Ion_trans_dom	Domain
IPR014710	RmlC-like_jellyroll	Homologous_superfamily
IPR018488	cNMP-bd_CS	Conserved_site
IPR018490	cNMP-bd_dom_sf	Homologous_superfamily
IPR050866	CNG_cation_channel	Family

Pfam: PF00027, PF00520

Catalyzed reactions (Rhea), 7 shown:

• NH4(+)(in) = NH4(+)(out) (RHEA:28747)
• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• Rb(+)(in) = Rb(+)(out) (RHEA:78547)
• Li(+)(in) = Li(+)(out) (RHEA:78551)
• Cs(+)(in) = Cs(+)(out) (RHEA:78555)

UniProt features (110 total): helix 21, sequence variant 17, strand 16, region of interest 11, compositionally biased region 9, topological domain 7, transmembrane region 7, binding site 6, splice variant 4, site 3, mutagenesis site 3, sequence conflict 3, chain 1, short sequence motif 1, turn 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
7RH9	ELECTRON MICROSCOPY	2.61
9UPG	ELECTRON MICROSCOPY	2.87
7RHG	ELECTRON MICROSCOPY	2.88
7RHJ	ELECTRON MICROSCOPY	2.88
7RHL	ELECTRON MICROSCOPY	3.03
7RHK	ELECTRON MICROSCOPY	3.27
7RHH	ELECTRON MICROSCOPY	3.31
7RHI	ELECTRON MICROSCOPY	3.31
9UPF	ELECTRON MICROSCOPY	3.59
8DGH	SOLUTION NMR
8DGK	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14028-F1	58.89	0.19

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 872 (central gate); 876 (central gate); 880 (occludes the pore below the central gate)

Ligand- & substrate-binding residues (6): 1029; 1030; 1032; 1042; 1042; 1043

Mutagenesis-validated functional residues (3):

Position	Phenotype
568	loss of calcium/calmodulin modulation.
848	increases the affinity to ca(2+) ions. does not affect heterotetrameric channel assembly.
880	increases channel conductance.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2485179	Activation of the phototransduction cascade
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-5620916	VxPx cargo-targeting to cilium
R-HSA-381753	Olfactory Signaling Pathway

MSigDB gene sets: 419 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, chr4q25, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_PHOTOTRANSDUCTION, GOBP_TELOMERE_ORGANIZATION

GO Biological Process (23): retina homeostasis (GO:0001895), monoatomic cation transport (GO:0006812), potassium ion transport (GO:0006813), sodium ion transport (GO:0006814), calcium ion transport (GO:0006816), G protein-coupled receptor signaling pathway (GO:0007186), visual perception (GO:0007601), phototransduction (GO:0007602), sensory perception of smell (GO:0007608), positive regulation of gene expression (GO:0010628), olfactory nerve maturation (GO:0021630), photoreceptor cell outer segment organization (GO:0035845), photoreceptor cell maintenance (GO:0045494), detection of light stimulus involved in visual perception (GO:0050908), detection of chemical stimulus involved in sensory perception of smell (GO:0050911), regulation of cytosolic calcium ion concentration (GO:0051480), membrane depolarization (GO:0051899), monoatomic cation transmembrane transport (GO:0098655), response to odorant (GO:1990834), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), sodium ion transmembrane transport (GO:0035725), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (12): intracellularly cAMP-activated cation channel activity (GO:0005222), intracellularly cGMP-activated cation channel activity (GO:0005223), calcium channel activity (GO:0005262), sodium channel activity (GO:0005272), ligand-gated monoatomic ion channel activity (GO:0015276), cAMP binding (GO:0030552), cGMP binding (GO:0030553), protein-containing complex binding (GO:0044877), nucleotide binding (GO:0000166), intracellularly cyclic nucleotide-activated monoatomic cation channel activity (GO:0005221), protein binding (GO:0005515), cyclic nucleotide-activated monoatomic ion channel activity (GO:0043855)

GO Cellular Component (11): photoreceptor outer segment (GO:0001750), plasma membrane (GO:0005886), intracellular cyclic nucleotide activated cation channel complex (GO:0017071), Golgi-associated vesicle membrane (GO:0030660), terminal bouton (GO:0043195), ciliary membrane (GO:0060170), non-motile cilium membrane (GO:0098804), rod photoreceptor outer segment (GO:0120200), transmembrane transporter complex (GO:1902495), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
The phototransduction cascade	2
Cargo trafficking to the periciliary membrane	1
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion transport	3
cellular anatomical structure	3
signal transduction	2
intracellularly cyclic nucleotide-activated monoatomic cation channel activity	2
monoatomic cation channel activity	2
cyclic nucleotide binding	2
anion binding	2
binding	2
bounding membrane of organelle	2
tissue homeostasis	1
monoatomic ion transport	1
G protein-coupled receptor activity	1
sensory perception of light stimulus	1
detection of light stimulus	1
sensory perception of chemical stimulus	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
olfactory nerve development	1
cranial nerve maturation	1
cellular component organization	1
photoreceptor cell development	1
retina homeostasis	1
multicellular organismal process	1
visual perception	1
detection of light stimulus involved in sensory perception	1
sensory perception of smell	1
detection of chemical stimulus involved in sensory perception	1
intracellular calcium ion homeostasis	1
regulation of membrane potential	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
response to chemical	1
transport	1
calcium ion transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
monoatomic ion channel activity	1
ligand-gated channel activity	1
adenyl ribonucleotide binding	1
guanyl ribonucleotide binding	1

Protein interactions and networks

STRING

1120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNGB1	CNGA2	Q16280	987
CNGB1	CNGA4	Q8IV77	987
CNGB1	CNGA1	P29973	986
CNGB1	PDE6A	P16499	851
CNGB1	ROM1	Q03395	851
CNGB1	SH3BGRL	O75368	834
CNGB1	PRPH2	P23942	832
CNGB1	CERKL	Q49MI3	823
CNGB1	RHO	P08100	815
CNGB1	PRCD	Q00LT1	811
CNGB1	PDE6B	P35913	808
CNGB1	EYS	Q5T1H1	806
CNGB1	TULP1	O00294	800
CNGB1	ABCA4	P78363	795
CNGB1	RPE65	Q16518	787

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CNGB1	GRB14	psi-mi:“MI:0915”(physical association)	0.510
GRB14	CNGB1	psi-mi:“MI:0915”(physical association)	0.510
CNGB1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
CSNK2B	TUBAL3	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): CNGB1 (Synthetic Lethality), CNGB1 (Affinity Capture-Western), CNGB1 (Affinity Capture-MS), CNGB1 (Affinity Capture-MS), GOLGA4 (Cross-Linking-MS (XL-MS)), CNGB1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZN27, A6X8Z5, E1AZ71, F1N8V3, O35668, O54963, O70318, P20689, P48165, P51954, P54256, P54257, P55917, P62025, P70278, Q01538, Q13029, Q13127, Q14028, Q16799, Q28139, Q28181, Q2M1Z3, Q3SYS4, Q3UH66, Q4KMM3, Q4V8B0, Q5DW34, Q5IS59, Q5TCY1, Q62100, Q63HN8, Q640N3, Q64548, Q6IR42, Q6PCN3, Q7Z6I6, Q811Q2, Q8BYM7, Q8C5W0

Diamond homologs: A0A8I5ZN27, A5K0N4, E1AZ71, P29973, P29974, P36600, P55934, Q00194, Q00195, Q03041, Q03611, Q14028, Q16280, Q16281, Q24278, Q28181, Q28279, Q28718, Q29441, Q2K5E1, Q3UW12, Q62398, Q62927, Q64359, Q8I719, Q8IV77, Q8MJD7, Q8TF77, Q90805, Q90980, Q9ER33, Q9JJZ8, Q9JJZ9, Q9NQW8, W7JX98, Q6BZG7, P49605, Q9LD40, Q03042, A0A509AKL0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1512 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	81
Likely pathogenic	85
Uncertain significance	655
Likely benign	472
Benign	45

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070100	NM_001297.5(CNGB1):c.1402C>T (p.Gln468Ter)	Pathogenic
1070225	NM_001297.5(CNGB1):c.112G>T (p.Glu38Ter)	Pathogenic
1070341	NM_001297.5(CNGB1):c.483G>A (p.Trp161Ter)	Pathogenic
1071667	NM_001297.5(CNGB1):c.339del (p.Ile114fs)	Pathogenic
1071898	NM_001297.5(CNGB1):c.2805del (p.Glu935fs)	Pathogenic
1072870	NM_001297.5(CNGB1):c.2492+1G>A	Pathogenic
1073917	NM_001297.5(CNGB1):c.2651_2658del (p.Gly884fs)	Pathogenic
1074505	NM_001297.5(CNGB1):c.346C>T (p.Gln116Ter)	Pathogenic
1075276	NM_001297.5(CNGB1):c.1333del (p.Glu445fs)	Pathogenic
1177437	NM_001297.5(CNGB1):c.1492del (p.Ser498fs)	Pathogenic
1322098	NM_001297.5(CNGB1):c.2775G>A (p.Trp925Ter)	Pathogenic
1371743	NM_001297.5(CNGB1):c.499G>T (p.Glu167Ter)	Pathogenic
1379068	NM_001297.5(CNGB1):c.1951dup (p.Leu651fs)	Pathogenic
1381625	NM_001297.5(CNGB1):c.2000G>A (p.Trp667Ter)	Pathogenic
1410292	NC_000016.9:g.(?57951152)(57951400_?)del	Pathogenic
1416106	NM_001297.5(CNGB1):c.2910del (p.Met970fs)	Pathogenic
1421601	NM_001297.5(CNGB1):c.2492+2T>G	Pathogenic
1431682	NM_001297.5(CNGB1):c.2086dup (p.Tyr696fs)	Pathogenic
1452158	NM_001297.5(CNGB1):c.2205_2206del (p.Arg736fs)	Pathogenic
1456620	NM_001297.5(CNGB1):c.118del (p.Glu40fs)	Pathogenic
1457340	NM_001297.5(CNGB1):c.1747A>T (p.Lys583Ter)	Pathogenic
1458949	NM_001297.5(CNGB1):c.169G>T (p.Glu57Ter)	Pathogenic
1507633	NM_001297.5(CNGB1):c.382-3C>G	Pathogenic
1906481	NM_001297.5(CNGB1):c.165dup (p.Glu56fs)	Pathogenic
1909667	NM_001297.5(CNGB1):c.2528dup (p.Ile844fs)	Pathogenic
195947	NM_001297.5(CNGB1):c.2556dup (p.Lys853fs)	Pathogenic
1998682	NM_001297.5(CNGB1):c.938G>A (p.Trp313Ter)	Pathogenic
2022426	NM_001297.5(CNGB1):c.1705C>T (p.Gln569Ter)	Pathogenic
2023004	NM_001297.5(CNGB1):c.1276del (p.Glu426fs)	Pathogenic
2023552	NM_001297.5(CNGB1):c.499del (p.Glu167fs)	Pathogenic

SpliceAI

5733 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57887849:CATTA:C	donor_loss	1.0000
16:57887850:ATTAC:A	donor_loss	1.0000
16:57887851:TTAC:T	donor_loss	1.0000
16:57887852:TAC:T	donor_loss	1.0000
16:57887853:A:C	donor_loss	1.0000
16:57887854:C:CA	donor_loss	1.0000
16:57897394:TAC:T	donor_loss	1.0000
16:57897395:A:AC	donor_gain	1.0000
16:57897395:AC:A	donor_gain	1.0000
16:57897395:ACCTG:A	donor_loss	1.0000
16:57897396:C:A	donor_loss	1.0000
16:57897396:C:CA	donor_gain	1.0000
16:57897396:CC:C	donor_gain	1.0000
16:57897396:CCT:C	donor_gain	1.0000
16:57897396:CCTG:C	donor_gain	1.0000
16:57897396:CCTGG:C	donor_gain	1.0000
16:57897539:GCAAG:G	acceptor_gain	1.0000
16:57897540:CAAG:C	acceptor_gain	1.0000
16:57897540:CAAGC:C	acceptor_gain	1.0000
16:57897543:GC:G	acceptor_loss	1.0000
16:57897544:C:CC	acceptor_gain	1.0000
16:57897550:C:CT	acceptor_gain	1.0000
16:57897551:A:T	acceptor_gain	1.0000
16:57901346:GCTCA:G	donor_loss	1.0000
16:57901347:CTCA:C	donor_loss	1.0000
16:57901348:TCA:T	donor_loss	1.0000
16:57901349:CA:C	donor_loss	1.0000
16:57901350:A:AG	donor_loss	1.0000
16:57901351:CCTT:C	donor_gain	1.0000
16:57901431:CAGCC:C	acceptor_gain	1.0000

AlphaMissense

8203 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57897478:A:G	L1054P	1.000
16:57897486:A:C	F1051L	1.000
16:57897486:A:T	F1051L	1.000
16:57897488:A:G	F1051L	1.000
16:57897805:C:T	G1029E	1.000
16:57897807:A:C	F1028L	1.000
16:57897807:A:T	F1028L	1.000
16:57897809:A:G	F1028L	1.000
16:57897889:A:T	I1001N	1.000
16:57903856:C:A	W920C	1.000
16:57903856:C:G	W920C	1.000
16:57903858:A:G	W920R	1.000
16:57903858:A:T	W920R	1.000
16:57903866:A:T	V917D	1.000
16:57904752:G:C	F872L	1.000
16:57904752:G:T	F872L	1.000
16:57904754:A:G	F872L	1.000
16:57904766:C:G	G868R	1.000
16:57897412:A:G	L1076P	0.999
16:57897454:A:G	L1062P	0.999
16:57897469:A:G	L1057P	0.999
16:57897469:A:T	L1057Q	0.999
16:57897478:A:T	L1054H	0.999
16:57897508:G:T	A1044D	0.999
16:57897515:G:T	R1042S	0.999
16:57897541:A:G	L1033S	0.999
16:57897543:G:C	S1032R	0.999
16:57897543:G:T	S1032R	0.999
16:57897797:T:G	S1032R	0.999
16:57897805:C:A	G1029V	0.999

dbSNP variants (sampled 300 via entrez): RS1000006018 (16:57901826 T>C,G), RS1000121813 (16:57902196 G>A,C,T), RS1000133431 (16:57938023 G>T), RS1000203638 (16:57949587 C>T), RS1000263538 (16:57943754 C>T), RS1000282275 (16:57906127 A>G), RS1000295701 (16:57938216 C>A,G), RS1000340221 (16:57955150 T>C), RS1000399206 (16:57910854 C>T), RS1000483299 (16:57971175 A>G), RS1000540448 (16:57922288 C>G,T), RS1000613511 (16:57885978 G>A), RS1000651889 (16:57891676 C>A,G,T), RS1000656405 (16:57922524 G>A), RS1000731059 (16:57973072 A>G)

Disease associations

OMIM: gene MIM:600724 | disease phenotypes: MIM:613767, MIM:268000, MIM:613756

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 45	Definitive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
CNGB1-related retinopathy	Definitive	AR

Mondo (7): retinitis pigmentosa 45 (MONDO:0013413), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200), CNGB1-related retinopathy (MONDO:0800403), retinal disorder (MONDO:0005283), optic atrophy (MONDO:0003608), retinitis pigmentosa 49 (MONDO:0013405)

Orphanet (2): Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000608	Macular degeneration
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels
HP:0007994	Peripheral visual field loss
HP:0008046	Abnormal retinal vascular morphology
HP:0011505	Cystoid macular edema
HP:0012426	Optic disc drusen

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004639_3	Prudent dietary pattern	1.000000e-06
GCST006633_32	Initial alcohol sensitivity	3.000000e-06
GCST010173_48	Triglyceride levels	5.000000e-37
GCST010204_13	Low density lipoprotein cholesterol levels	8.000000e-59
GCST010732_18	Sensory peripheral neuropathy in microtubule targeting agent-treated breast cancer	9.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0005260	response to antimicrotubule agent

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Cyclic nucleotide-regulated channels (CNG)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Benzo(a)pyrene	affects methylation	2
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
sulforaphane	decreases expression	1
tetrabromobisphenol A	decreases expression	1
aflatoxin B2	increases methylation	1
seocalcitol	increases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Zoledronic Acid	increases expression	1
Calcitriol	increases expression	1
Copper	affects cotreatment, decreases expression	1
Bucladesine	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Formaldehyde	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	decreases expression	1
Zinc	increases expression	1
Aflatoxin B1	increases methylation	1
Medroxyprogesterone Acetate	affects cotreatment, increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1084	BFTC-909	Cancer cell line	Male
CVCL_YB38	BFTC-909 pBabeAR1	Cancer cell line	Male
CVCL_YB39	BFTC-909 pBabeAR2	Cancer cell line	Male

Clinical trials (associated diseases)

259 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa