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CNGB3

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Target id: 399

Nomenclature: CNGB3

Family: Cyclic nucleotide-regulated channels (CNG)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 809 8q21.3 CNGB3 cyclic nucleotide gated channel subunit beta 3 6,17
Mouse 6 1 694 4 A3 Cngb3 cyclic nucleotide gated channel beta 3 2
Rat - 0 690 5q13 Cngb3 cyclic nucleotide gated channel subunit beta 3
Previous and Unofficial Names Click here for help
CCNC2 | CNGβ2 | CNG6 | ACHM3 | achromatopsia (rod monochromacy) 3
Database Links Click here for help
Alphafold Q9NQW8 (Hs), Q9JJZ9 (Mm)
CATH/Gene3D 2.60.120.10
Ensembl Gene ENSG00000170289 (Hs), ENSMUSG00000056494 (Mm), ENSRNOG00000006084 (Rn)
Entrez Gene 54714 (Hs), 30952 (Mm), 500418 (Rn)
Human Protein Atlas ENSG00000170289 (Hs)
KEGG Gene hsa:54714 (Hs), mmu:30952 (Mm), rno:500418 (Rn)
OMIM 605080 (Hs)
Orphanet ORPHA120678 (Hs)
Pharos Q9NQW8 (Hs)
RefSeq Nucleotide NM_019098 (Hs), NM_013927 (Mm)
RefSeq Protein NP_061971 (Hs), NP_038955 (Mm)
UniProtKB Q9NQW8 (Hs), Q9JJZ9 (Mm)
Wikipedia CNGB3 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
CNG-modulin 16
CNGA3 2,8
Calmodulin 13

Download all structure-activity data for this target as a CSV file go icon to follow link

Activator Comments
When co-expressed with CNGA3 this subunit slightly increases cAMP sensitivity and decreases cGMP sensitivity [2,14].
Gating Inhibitor Comments
In CNGA3/CNGB3 channels, CNBG3 confers sensitivity to inhibition by Ca2+-calmodulin [13].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
L-(cis)-diltiazem Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Antagonist 5.5 pIC50 - 0.0 2
⤷ pIC50 5.5 Channel blocker when CNGB3 coexpressed with CNGA3 [2]
Holding voltage: 0.0 mV
Channel Blocker Comments
L-cis-diltiazem binds to this subunit and inhibits the current flowing through the CNGA3/CNGB/3 channel [2,13].
Tissue Distribution Click here for help
Retina.
Species:  Human
Technique:  Northern Blot
References:  6
Cone photoreceptors.
Species:  Mouse
Technique:  Immunohistochemistry
References:  10
Retina, testis.
Species:  Mouse
Technique:  Northern Blot, in situ hybridisation.
References:  2
Physiological Functions Click here for help
This subunit assembles with CNGA3 to form the native cone CNG channel. This channel mediates the Na+/Ca2+ influx that depolarises cone photoreceptors in the dark.
Species:  None
Tissue:  Retina.
References:  4,6,15,17
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cngb3tm1Dgen Cngb3tm1Dgen/Cngb3tm1Dgen
involves: C57BL/6		 MGI:1353562  MP:0004022 abnormal cone electrophysiology PMID: 19767295 
Cngb3tm1Dgen Cngb3tm1Dgen/Cngb3tm1Dgen
involves: C57BL/6		 MGI:1353562  MP:0005253 abnormal eye physiology PMID: 19767295 
Cngb3tm1Dgen Cngb3tm1Dgen/Cngb3tm1Dgen
involves: C57BL/6		 MGI:1353562  MP:0006072 abnormal retinal apoptosis PMID: 19767295 
Cngb3tm1Dgen Cngb3tm1Dgen/Cngb3tm1Dgen
involves: C57BL/6		 MGI:1353562  MP:0008449 abnormal retinal cone cell outer segment morphology PMID: 19767295 
Cngb3tm1Dgen Cngb3tm1Dgen/Cngb3tm1Dgen
involves: C57BL/6		 MGI:1353562  MP:0008446 decreased retinal cone cell number PMID: 19767295 
Cngb3tm1Dgen Cngb3tm1Dgen/Cngb3tm1Dgen
involves: C57BL/6		 MGI:1353562  MP:0008586 disorganized photoreceptor outer segment PMID: 19767295 
Cngb3tm1Dgen Cngb3tm1Dgen/Cngb3tm1Dgen
involves: C57BL/6		 MGI:1353562  MP:0008444 retinal cone cell degeneration PMID: 19767295 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Achromatopsia 3; ACHM3
Synonyms: Achromatopsia [Orphanet: ORPHA49382] [Disease Ontology: DOID:13911]
Disease Ontology: DOID:13911
OMIM: 262300
Orphanet: ORPHA49382
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human Q720_K726del c.2160-2180del21 Exon 18 7
Frameshift: Deletion Human E199fs 595delG 3
Frameshift: Deletion Human P273fsX c.819–826del8 Exon 6 5-7,11,17
Frameshift: Deletion Human T383fsX c.1148delC Exon 10 3,5-7,9,11,17-21
Frameshift: Deletion Human V433fsX c.1298_1299delTG Exon 11 7
Frameshift: Deletion Human V609WfsX9 c.1825delG 1
Frameshift: Deletion Human R274VfsX12 c.819_826del8 Exon 6 18-19
Frameshift: Deletion Human G548VfsX35 c.1642delG Exon 14 19
Frameshift: Insertion Human K10fsX c.29_30insA Exon 1 7
Frameshift: Insertion Human A228fsX c.682_683insG Exon 6 7
Frameshift: Insertion Human I236fsX c.706delAinsTT Exon 6 7
Frameshift: Insertion Human R296fsX c.886–896del11insT Exon 7 7,18-19
Missense Human S156F 7,17
Missense Human P309L 7
Missense Human R403Q 5,9,11,18,21
Missense Human S435R 21
Missense Human S435F 11
Missense Human Y469D 11
Missense Human F525N 3
Missense Human G558C 11
Missense Human L595F 11
Missense Human D633G 12
Nonsense Human Q38X c.112C>T Exon 1 7,20
Nonsense Human Q131X c.391C>T Exon 4 7,11
Nonsense Human R203X c.607C>T Exon 5 6-7
Nonsense Human R216X c.646C>T Exon 6 7
Nonsense Human W234X c.702G>A Exon 6 7
Nonsense Human E336X c.1006G>T Exon 9 6-7
Nonsense Human R355X c.1063C>T Exon 10 7
Nonsense Human W373X c.1119G>A Exon 10 7
Nonsense Human E419X c.1255G>T Exon 11 7
Nonsense Human R478X c.1432C>T Exon 12 7
Nonsense Human W487X c.1460G>A Exon 12 7
Nonsense Human Y545X c.1635A>T Exon 14 7,11
Splice defect Human c.991-3T>G Intron 8 7,18-19
Splice defect Human c.1578+1G>A Intron 13 6-7
Splice defect Human 1663-5T>G Intron 14 20
Splice defect Human c.1781+1G>C Intron 15 7
Splice defect Human c.1781+1G>A Intron 15 7
Splice site Human c.644-1G>C Intron 5 7
Disease:  Progressive cone dystrophy
Orphanet: ORPHA1871
References:  9
Disease:  Stargardt disease 1
OMIM: 248200
Orphanet: ORPHA827

References

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1. Azam M, Collin RW, Shah ST, Shah AA, Khan MI, Hussain A, Sadeque A, Strom TM, Thiadens AA, Roosing S et al.. (2010) Novel CNGA3 and CNGB3 mutations in two Pakistani families with achromatopsia. Mol Vis, 16: 774-81. [PMID:20454696]

2. Gerstner A, Zong X, Hofmann F, Biel M. (2000) Molecular cloning and functional characterization of a new modulatory cyclic nucleotide-gated channel subunit from mouse retina. J Neurosci, 20 (4): 1324-32. [PMID:10662822]

3. Johnson S, Michaelides M, Aligianis IA, Ainsworth JR, Mollon JD, Maher ER, Moore AT, Hunt DM. (2004) Achromatopsia caused by novel mutations in both CNGA3 and CNGB3. J Med Genet, 41 (2): e20. [PMID:14757870]

4. Kaupp UB, Seifert R. (2002) Cyclic nucleotide-gated ion channels. Physiol Rev, 82 (3): 769-824. [PMID:12087135]

5. Khan NW, Wissinger B, Kohl S, Sieving PA. (2007) CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function. Invest Ophthalmol Vis Sci, 48 (8): 3864-71. [PMID:17652762]

6. Kohl S, Baumann B, Broghammer M, Jägle H, Sieving P, Kellner U, Spegal R, Anastasi M, Zrenner E, Sharpe LT et al.. (2000) Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum Mol Genet, 9 (14): 2107-16. [PMID:10958649]

7. Kohl S, Varsanyi B, Antunes GA, Baumann B, Hoyng CB, Jägle H, Rosenberg T, Kellner U, Lorenz B, Salati R et al.. (2005) CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur J Hum Genet, 13 (3): 302-8. [PMID:15657609]

8. Matveev AV, Quiambao AB, Browning Fitzgerald J, Ding XQ. (2008) Native cone photoreceptor cyclic nucleotide-gated channel is a heterotetrameric complex comprising both CNGA3 and CNGB3: a study using the cone-dominant retina of Nrl-/- mice. J Neurochem, 106 (5): 2042-55. [PMID:18665891]

9. Michaelides M, Aligianis IA, Ainsworth JR, Good P, Mollon JD, Maher ER, Moore AT, Hunt DM. (2004) Progressive cone dystrophy associated with mutation in CNGB3. Invest Ophthalmol Vis Sci, 45 (6): 1975-82. [PMID:15161866]

10. Michalakis S, Geiger H, Haverkamp S, Hofmann F, Gerstner A, Biel M. (2005) Impaired opsin targeting and cone photoreceptor migration in the retina of mice lacking the cyclic nucleotide-gated channel CNGA3. Invest Ophthalmol Vis Sci, 46 (4): 1516-24. [PMID:15790924]

11. Nishiguchi KM, Sandberg MA, Gorji N, Berson EL, Dryja TP. (2005) Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. Hum Mutat, 25 (3): 248-58. [PMID:15712225]

12. Okada A, Ueyama H, Toyoda F, Oda S, Ding WG, Tanabe S, Yamade S, Matsuura H, Ohkubo I, Kani K. (2004) Functional role of hCngb3 in regulation of human cone cng channel: effect of rod monochromacy-associated mutations in hCNGB3 on channel function. Invest Ophthalmol Vis Sci, 45 (7): 2324-32. [PMID:15223812]

13. Peng C, Rich ED, Thor CA, Varnum MD. (2003) Functionally important calmodulin-binding sites in both NH2- and COOH-terminal regions of the cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit. J Biol Chem, 278 (27): 24617-23. [PMID:12730238]

14. Peng C, Rich ED, Varnum MD. (2003) Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels. J Biol Chem, 278 (36): 34533-40. [PMID:12815043]

15. Peng C, Rich ED, Varnum MD. (2004) Subunit configuration of heteromeric cone cyclic nucleotide-gated channels. Neuron, 42 (3): 401-10. [PMID:15134637]

16. Rebrik TI, Botchkina I, Arshavsky VY, Craft CM, Korenbrot JI. (2012) CNG-modulin: a novel Ca-dependent modulator of ligand sensitivity in cone photoreceptor cGMP-gated ion channels. J Neurosci, 32 (9): 3142-53. [PMID:22378887]

17. Sundin OH, Yang JM, Li Y, Zhu D, Hurd JN, Mitchell TN, Silva ED, Maumenee IH. (2000) Genetic basis of total colourblindness among the Pingelapese islanders. Nat Genet, 25 (3): 289-93. [PMID:10888875]

18. Thiadens AA, Roosing S, Collin RW, van Moll-Ramirez N, van Lith-Verhoeven JJ, van Schooneveld MJ, den Hollander AI, van den Born LI, Hoyng CB, Cremers FP et al.. (2010) Comprehensive analysis of the achromatopsia genes CNGA3 and CNGB3 in progressive cone dystrophy. Ophthalmology, 117 (4): 825-30.e1. [PMID:20079539]

19. Thiadens AA, Slingerland NW, Roosing S, van Schooneveld MJ, van Lith-Verhoeven JJ, van Moll-Ramirez N, van den Born LI, Hoyng CB, Cremers FP, Klaver CC. (2009) Genetic etiology and clinical consequences of complete and incomplete achromatopsia. Ophthalmology, 116 (10): 1984-9.e1. [PMID:19592100]

20. Varsányi B, Wissinger B, Kohl S, Koeppen K, Farkas A. (2005) Clinical and genetic features of Hungarian achromatopsia patients. Mol Vis, 11: 996-1001. [PMID:16319819]

21. Wiszniewski W, Lewis RA, Lupski JR. (2007) Achromatopsia: the CNGB3 p.T383fsX mutation results from a founder effect and is responsible for the visual phenotype in the original report of uniparental disomy 14. Hum Genet, 121 (3-4): 433-9. [PMID:17265047]

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