Nomenclature: CNGA3

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 1 676 2q11.2 CNGA3 cyclic nucleotide gated channel alpha 3 26,28
Mouse 6 1 631 1 B Cnga3 cyclic nucleotide gated channel alpha 3 7
Rat 6 1 611 9q21 Cnga3 cyclic nucleotide gated channel alpha 3 16
Previous and Unofficial Names
CNG3
CCNC1
CNGα2
CNCG3
ACHM2
CCNCa
cyclic nucleotide gated channel alpha 3
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
CNGB3 5,13
EMILIN1 21
CDH23 22
MyosinVIIa 22
Functional Characteristics
γ = 40 pS
PCa/PNa = 10.9
Ion Selectivity and Conductance
Species:  None
Rank order:  Ca2+ > Rb+ = Na+ = K+ > Li+ > Cs+ [28.0 - 41.0 pS]
References:  3,12,19,23,28
Activators (Human)
cGMP (EC50 ~ 30 μM) >> cAMP
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
cGMP Rn Agonist 5.48 – 5.54 (median: 5.51) pKd - -80.0 – 80.0 12
pKd 5.48 – 5.54 (median: 5.51) [12]
Holding voltage: -80.0 – 80.0 mV
cGMP Hs Agonist 4.73 – 5.6 (median: 4.8) pKd - -60.0 – 80.0 18,26,28
pKd 4.73 – 5.6 (median: 4.8) [18,26,28]
Holding voltage: -60.0 – 80.0 mV
cAMP Rn Agonist 3.6 pKd - -80.0 12
pKd 3.6 [12]
Holding voltage: -80.0 mV
cAMP Hs Agonist 2.88 pKd - -60.0 – 80.0 18,28
pKd 2.88 [18,28]
Holding voltage: -60.0 – 80.0 mV
View species-specific activator tables
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
L-(cis)-diltiazem Hs - - - - -
Tissue Distribution
Retina.
Species:  Human
Technique:  Northern Blot
References:  26
Cone photoreceptors.
Species:  Human
Technique:  Immunohistochemistry
References:  26
Cone photoreceptors.
Species:  Mouse
Technique:  Immunohistochemistry
References:  3,7
Cone photoreceptors, subset of olfactory sensory neurons, taste buds.
Species:  Rat
Technique:  Immunohistochemistry
References:  14-15
Cochlea
Species:  Rat
Technique:  Immunohistochemistry
References:  21
Physiological Functions
This subunit assembles with CNGB3 to form the native cone CNG channel. This channel mediates the Na+/Ca2+ influx that depolarises cone photoreceptors in the dark ("dark current").
Species:  Human
Tissue:  Retina.
References:  11,26
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cnga3tm1Biel|Gnat1tm1Clma|Opn4tm1Yau Cnga3tm1Biel/Cnga3tm1Biel,Gnat1tm1Clma/Gnat1tm1Clma,Opn4tm1Yau/Opn4tm1Yau
involves: 129 * C57BL/6
MGI:1341818  MGI:1353425  MGI:95778  MP:0001502 abnormal circadian rhythm PMID: 12808468 
Cnga3tm1Biel Cnga3tm1Biel/Cnga3tm1Biel
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341818  MP:0005551 abnormal eye electrophysiology PMID: 10377453 
Cnga3tm1Biel|Rpe65tm1Tmr Cnga3tm1Biel/Cnga3tm1Biel,Rpe65tm1Tmr/Rpe65tm1Tmr
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341818  MGI:98001  MP:0005551 abnormal eye electrophysiology PMID: 11528395 
Cnga3tm1Biel|Rhotm1Phm Cnga3tm1Biel/Cnga3tm1Biel,Rhotm1Phm/Rhotm1Phm
involves: C57BL/6
MGI:1341818  MGI:97914  MP:0005551 abnormal eye electrophysiology PMID: 15161873 
Cnga3tm1Biel Cnga3tm1Biel/Cnga3tm1Biel
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341818  MP:0005253 abnormal eye physiology PMID: 10377453 
Cnga3tm1Biel|Rhotm1Phm Cnga3tm1Biel/Cnga3tm1Biel,Rhotm1Phm/Rhotm1Phm
involves: C57BL/6
MGI:1341818  MGI:97914  MP:0006068 abnormal horizontal cell morphology PMID: 15161873 
Cnga3tm1Biel Cnga3tm1Biel/Cnga3tm1Biel
involves: 129S1/Sv * 129X1/SvJ
MGI:1341818  MP:0009943 abnormal olfactory bulb periglomerular cell morphology PMID: 17724338 
Cnga3tm1Biel Cnga3tm1Biel/Cnga3tm1Biel
involves: 129S1/Sv * 129X1/SvJ
MGI:1341818  MP:0001983 abnormal olfactory system physiology PMID: 17724338 
Cnga3tm1Biel|Gnat1tm1Clma|Opn4tm1Yau Cnga3tm1Biel/Cnga3tm1Biel,Gnat1tm1Clma/Gnat1tm1Clma,Opn4tm1Yau/Opn4tm1Yau
involves: 129 * C57BL/6
MGI:1341818  MGI:1353425  MGI:95778  MP:0002638 abnormal pupillary reflex PMID: 12808468 
Cnga3tm1Biel Cnga3tm1Biel/Cnga3tm1Biel
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341818  MP:0008449 abnormal retinal cone cell outer segment morphology PMID: 10377453 
Cnga3tm1Biel|Rhotm1Phm Cnga3tm1Biel/Cnga3tm1Biel,Rhotm1Phm/Rhotm1Phm
involves: C57BL/6
MGI:1341818  MGI:97914  MP:0006069 abnormal retinal neuronal layer morphology PMID: 15161873 
Cnga3tm1Biel|Rhotm1Phm Cnga3tm1Biel/Cnga3tm1Biel,Rhotm1Phm/Rhotm1Phm
involves: C57BL/6
MGI:1341818  MGI:97914  MP:0006074 abnormal retinal rod bipolar cell morphology PMID: 15161873 
Cnga3tm1Biel|Rhotm1Phm Cnga3tm1Biel/Cnga3tm1Biel,Rhotm1Phm/Rhotm1Phm
involves: C57BL/6
MGI:1341818  MGI:97914  MP:0001005 abnormal retinal rod cell morphology PMID: 15161873 
Cnga3tm1Biel Cnga3tm1Biel/Cnga3tm1Biel
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1341818  MP:0001327 decreased retinal photoreceptor cell number PMID: 10377453 
Cnga3tm1Biel|Rhotm1Phm Cnga3tm1Biel/Cnga3tm1Biel,Rhotm1Phm/Rhotm1Phm
involves: C57BL/6
MGI:1341818  MGI:97914  MP:0001327 decreased retinal photoreceptor cell number PMID: 15161873 
Cnga3tm1Biel|Gnat1tm1Clma|Opn4tm1Yau Cnga3tm1Biel/Cnga3tm1Biel,Gnat1tm1Clma/Gnat1tm1Clma,Opn4tm1Yau/Opn4tm1Yau
involves: 129 * C57BL/6
MGI:1341818  MGI:1353425  MGI:95778  MP:0002003 miotic pupils PMID: 12808468 
Cnga3tm1Biel|Rhotm1Phm Cnga3tm1Biel/Cnga3tm1Biel,Rhotm1Phm/Rhotm1Phm
involves: C57BL/6
MGI:1341818  MGI:97914  MP:0008450 retinal photoreceptor degeneration PMID: 15161873 
Cnga3tm1Biel|Gnat1tm1Clma|Opn4tm1Yau Cnga3tm1Biel/Cnga3tm1Biel,Gnat1tm1Clma/Gnat1tm1Clma,Opn4tm1Yau/Opn4tm1Yau
involves: 129 * C57BL/6
MGI:1341818  MGI:1353425  MGI:95778  MP:0002563 shortened circadian period PMID: 12808468 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Achromatopsia 2; ACHM2
OMIM:  216900
Orphanet:  49382
References: 
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human I312del 25
Frameshift Human G49fs 25
Frameshift Human I482 25
Frameshift Human V451fs 25
Missense Human Y573C 25
Missense Human R563H 25
Missense Human G525D 25
Missense Human I522T 25
Missense Human G516E 25
Missense Human G513E 25
Missense Human C510S 25
Missense Human D485V 25
Missense Human N471S 25
Missense Human M406T 25
Missense Human F380S 25
Missense Human R277H 25
Missense Human G267D 25
Missense Human D260N 25
Missense Human E194K 25
Missense Human C191Y 25
Missense Human N182y 25
Missense Human Y181C 25
Missense Human D162V 25
Missense Human S401P 17
Missense Human L633P 6
Missense Human R569H 8,25
Missense Human E593K 25
Missense Human E228K 20
Missense Human T224R 27
Missense Human T224R 25
Missense Human P372S 25
Missense Human L186F 25
Missense Human F249S 17
Missense Human G557R 11,25
Missense Human F547L 8,11,25
Missense Human V529M 11,17,25
Missense Human E590K 17
Missense Human T565M 17,25
Missense Human T291R 11,25
Missense Human R436W 6,8,17,25
Missense Human R427C 17,25
Missense Human R410W 17,25
Missense Human S341P 17,25
Missense Human R283Q 11,25
Missense Human G548R 8
Missense Human R283W 1,11,25
Missense Human P163L 11,25
Missense Human R277C 17,25
Missense Human Y263D 17
Missense Human R223W 8,17,25,27
Missense Human A621E 27
Missense Human R563C 10
Missense None A469T 20
Missense Human R439W 20
Missense Human L433W 10
Missense Human G397V 1
Missense Human T369S 25
Missense Human R274S 2
Missense Human D252N 10
Truncation Human W440X 25
Truncation Human W316X 25
Truncation Human R23X 8
Truncation Human Q537X 25
Truncation Human Q655X 25
Truncation Human E344X 17
Truncation Human R221X 8
Truncation Human Q196X 8
General Comments
CNGA3 is also expressed in bovine sperm [4,9,23-24]. The physiological relevance in this cell type is unclear. Mice lacking the CNGA3 subunit show normal fertility [3].

REFERENCES

1. Ahuja Y, Kohl S, Traboulsi EI. (2008) CNGA3 mutations in two United Arab Emirates families with achromatopsia. Mol. Vis.14: 1293-7. [PMID:18636117]

2. 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]

3. Biel M, Seeliger M, Pfeifer A, Kohler K, Gerstner A, Ludwig A, Jaissle G, Fauser S, Zrenner E, Hofmann F. (1999) Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3. Proc. Natl. Acad. Sci. U.S.A.96 (13): 7553-7. [PMID:10377453]

4. Biel M, Zong X, Distler M, Bosse E, Klugbauer N, Murakami M, Flockerzi V, Hofmann F. (1994) Another member of the cyclic nucleotide-gated channel family, expressed in testis, kidney, and heart. Proc. Natl. Acad. Sci. U.S.A.91 (9): 3505-9. [PMID:8170936]

5. 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]

6. Goto-Omoto S, Hayashi T, Gekka T, Kubo A, Takeuchi T, Kitahara K. (2006) Compound heterozygous CNGA3 mutations (R436W, L633P) in a Japanese patient with congenital achromatopsia. Vis. Neurosci.23 (3-4): 395-402. [PMID:16961972]

7. Hirano AA, Hack I, Wässle H, Duvoisin RM. (2000) Cloning and immunocytochemical localization of a cyclic nucleotide-gated channel alpha-subunit to all cone photoreceptors in the mouse retina. J. Comp. Neurol.421 (1): 80-94. [PMID:10813773]

8. 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]

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

10. Koeppen K, Reuter P, Kohl S, Baumann B, Ladewig T, Wissinger B. (2008) Functional analysis of human CNGA3 mutations associated with colour blindness suggests impaired surface expression of channel mutants A3(R427C) and A3(R563C). Eur. J. Neurosci.27 (9): 2391-401. [PMID:18445228]

11. Kohl S, Marx T, Giddings I, Jägle H, Jacobson SG, Apfelstedt-Sylla E, Zrenner E, Sharpe LT, Wissinger B. (1998) Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. Nat. Genet.19 (3): 257-9. [PMID:9662398]

12. Lee HM, Park YS, Kim W, Park CS. (2001) Electrophysiological characteristics of rat gustatory cyclic nucleotide--gated channel expressed in Xenopus oocytes. J. Neurophysiol.85 (6): 2335-49. [PMID:11387380]

13. 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]

14. Meyer MR, Angele A, Kremmer E, Kaupp UB, Muller F. (2000) A cGMP-signaling pathway in a subset of olfactory sensory neurons. Proc. Natl. Acad. Sci. U.S.A.97 (19): 10595-600. [PMID:10984544]

15. Misaka T, Ishimaru Y, Iwabuchi K, Kusakabe Y, Arai S, Emori Y, Abe K. (1999) A gustatory cyclic nucleotide-gated channels CNGgust, is expressed in the retina. Neuroreport10 (4): 743-6. [PMID:10208541]

16. Misaka T, Kusakabe Y, Emori Y, Gonoi T, Arai S, Abe K. (1997) Taste buds have a cyclic nucleotide-activated channel, CNGgust. J. Biol. Chem.272 (36): 22623-9. [PMID:9278419]

17. 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]

18. 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]

19. 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]

20. Reuter P, Koeppen K, Ladewig T, Kohl S, Baumann B, Wissinger B, Achromatopsia Clinical Study Group. (2008) Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia. Hum. Mutat.29 (10): 1228-36. [PMID:18521937]

21. Selvakumar D, Drescher MJ, Dowdall JR, Khan KM, Hatfield JS, Ramakrishnan NA, Drescher DG. (2012) CNGA3 is expressed in inner ear hair cells and binds to an intracellular C-terminus domain of EMILIN1. Biochem. J.443 (2): 463-76. [PMID:22248097]

22. Selvakumar D, Drescher MJ, Drescher DG. (2013) Cyclic nucleotide-gated channel α-3 (CNGA3) interacts with stereocilia tip-link cadherin 23 + exon 68 or alternatively with myosin VIIa, two proteins required for hair cell mechanotransduction. J. Biol. Chem.288 (10): 7215-29. [PMID:23329832]

23. Weyand I, Godde M, Frings S, Weiner J, Müller F, Altenhofen W, Hatt H, Kaupp UB. (1994) Cloning and functional expression of a cyclic-nucleotide-gated channel from mammalian sperm. Nature368 (6474): 859-63. [PMID:7512693]

24. Wiesner B, Weiner J, Middendorff R, Hagen V, Kaupp UB, Weyand I. (1998) Cyclic nucleotide-gated channels on the flagellum control Ca2+ entry into sperm. J. Cell Biol.142 (2): 473-84. [PMID:9679145]

25. Wissinger B, Gamer D, Jägle H, Giorda R, Marx T, Mayer S, Tippmann S, Broghammer M, Jurklies B, Rosenberg T, Jacobson SG, Sener EC, Tatlipinar S, Hoyng CB, Castellan C, Bitoun P, Andreasson S, Rudolph G, Kellner U, Lorenz B, Wolff G, Verellen-Dumoulin C, Schwartz M, Cremers FP, Apfelstedt-Sylla E, Zrenner E, Salati R, Sharpe LT, Kohl S. (2001) CNGA3 mutations in hereditary cone photoreceptor disorders. Am. J. Hum. Genet.69 (4): 722-37. [PMID:11536077]

26. Wissinger B, Müller F, Weyand I, Schuffenhauer S, Thanos S, Kaupp UB, Zrenner E. (1997) Cloning, chromosomal localization and functional expression of the gene encoding the alpha-subunit of the cGMP-gated channel in human cone photoreceptors. Eur. J. Neurosci.9 (12): 2512-21. [PMID:9517456]

27. 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]

28. Yu WP, Grunwald ME, Yau KW. (1996) Molecular cloning, functional expression and chromosomal localization of a human homolog of the cyclic nucleotide-gated ion channel of retinal cone photoreceptors. FEBS Lett.393 (2-3): 211-5. [PMID:8814292]

To cite this database page, please use the following:

Elvir Becirovic, Martin Biel.
Cyclic nucleotide-regulated channels: CNGA3. Last modified on 17/03/2014. Accessed on 30/08/2014. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=396.

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