Nomenclature: CNGB3

Family: Cyclic nucleotide-regulated channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 809 8q21-q22 CNGB3 cyclic nucleotide gated channel 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 beta 3
Previous and Unofficial Names
CNG6
CNGβ2
CCNC2
ACHM3
achromatopsia (rod monochromacy) 3
LOC500418
RGD1565364
RGD1565364_predicted
cyclic nucleotide gated channel beta 3
cyclic nucleotide-gated cation channel beta-3
similar to cyclic nucleotide-gated channel subunit CNG6
similar to cyclic nucleotide-gated channel subunit CNG6 (predicted)
Cngbeta2
Database Links
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
CNGA3 2,8
CNG-modulin 16
Calmodulin 13
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 Blocker Comments
L-cis-diltiazem binds to this subunit and inhibits the current flowing through the CNGA3/CNGB/3 channel [2,13].
Tissue Distribution
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
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 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
Disease:  Achromatopsia
OMIM:  262300
Orphanet:  49382
References: 
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human Q720-K726 7
Frameshift Human V433fs 7
Frameshift Human R296fs 7,18-19
Frameshift Human P273fs 5-7,11,17
Frameshift Human I236fs 7
Frameshift Human A228 7
Frameshift Human K10fs 7
Frameshift Human G548fs 19
Frameshift Human R274fs 18-19
Frameshift Human V609fs 1
Frameshift Human E199fs 3
Frameshift Human T383fs 3,5-7,9,11,17-21
Missense Human P309L 7
Missense Human S156F 7,17
Missense Human D633G 12
Missense Human S435R 21
Missense Human S435F 11
Missense Human F525N 3
Missense Human L595F 11
Missense Human G558C 11
Missense Human Y469D 11
Missense Human R403Q 5,9,11,18,21
Splice defect Human 1663-5T>G 20
Splice defect Human 1578+1G>A 6-7
Splice defect Human 991-3T>G 7,18-19
Splice defect Human 1781+1G>C 7
Splice defect Human 1781+1G>A 7
Splice defect Human 644-1G>C 7
Truncation Human E336X 6-7
Truncation Human R355X 7
Truncation Human E419X 7
Truncation Human R478X 7
Truncation Human W487X 7
Truncation Human W373X 7
Truncation Human Y545X 7,11
Truncation Human Q131X 7,11
Truncation Human Q38X 7,20
Truncation Human R203X 6-7
Truncation Human R216X 7
Truncation Human W234X 7
Disease:  Progressive cone dystrophy
Orphanet:  1871
References:  9
Mutations not determined
Disease:  Stargardt disease 1
OMIM:  248200
Orphanet:  827
References: 
Mutations not determined

REFERENCES

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, Wissinger B. (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, Jurklies B, Farkas A, Andreasson S, Weleber RG, Jacobson SG, Rudolph G, Castellan C, Dollfus H, Legius E, Anastasi M, Bitoun P, Lev D, Sieving PA, Munier FL, Zrenner E, Sharpe LT, Cremers FP, Wissinger B. (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. Neuron42 (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. Ophthalmology117 (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. Ophthalmology116 (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]

To cite this database page, please use the following:

Elvir Becirovic, Martin Biel.
Cyclic nucleotide-regulated channels: CNGB3. Last modified on 21/03/2014. Accessed on 24/09/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=399.

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