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CNGA3

Family: Cyclic nucleotide-regulated channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Activators
Tissue Distribution
Physiological Functions
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
General Comments
References
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 24-25
Mouse 6 1 631 1 B Cnga3 cyclic nucleotide gated channel alpha 3 5
Rat 6 1 611 9q21 Cnga3 cyclic nucleotide gated channel alpha 3 13
Previous and Unofficial Names
CNG3
CCNC1
CNGα2
CNCG3
ACHM2
CCNCa
cyclic nucleotide gated channel alpha 3
Database Links
Ensembl ENSG00000144191 (Hs), ENSMUSG00000026114 (Mm), ENSRNOG00000017582 (Rn)
Entrez Gene 1261 (Hs), 12790 (Mm), 85257 (Rn)
GeneCards CNGA3 (Hs)
GenitoUrinary Development Molecular Anatomy Project Cnga3 (Mm)
HomoloGene 994 (Hs)
Human Protein Reference Database 02504 (Hs)
InterPro Q16281 (Hs), Q9JJZ8 (Mm)
KEGG Gene hsa:1261 (Hs), mmu:12790 (Mm), rno:85257 (Rn)
OMIM 600053 (Hs)
Orphanet Gene ORPHA120671 (Hs)
PharmGKB Gene PA26660 (Hs)
PhosphoSitePlus Q16281 (Hs), Q9JJZ8 (Mm)
Protein Ontology (PRO) PRO:000000696 (Hs)
RefSeq Nucleotide NM_001298 (Hs), NM_009918 (Mm), NM_053495 (Rn)
RefSeq Protein NP_001073347 (Hs), NP_034048 (Mm), NP_445947 (Rn)
TreeFam ENSG00000144191 (Hs), ENSMUSG00000026114 (Mm), ENSRNOG00000017582 (Rn)
UniGene Hs. 234785 (Hs)
UniProt Q16281 (Hs), Q9JJZ8 (Mm)
Wikipedia CNGA3
Cyclic nucleotide-regulated channels
Search for 3D structures on the PDB
Search by keyword: Cyclic nucleotide-regulated channels CNGA3 Search by accession number: Q9JJZ8, Q16281
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Not determined
Ion Selectivity and Conductance
Species:  None
Rank order:  Ca2+ > Rb+ = Na+ = K+ > Li+ > Cs+ [28.0 - 41.0 pS]
References:  1,10,17,21,25
Activators (Human)
cGMP (EC50 ~ 30 μM) >> cAMP
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
cGMP Rn 5.48 – 5.54 (median: 5.51) pKd - -80.0 – 80.0 10
cGMP Hs 4.73 – 5.6 (median: 4.8) pKd - -60.0 – 80.0 16,24-25
cAMP Rn 3.6 pKd - -80.0 10
cAMP Hs 2.88 pKd - -60.0 – 80.0 16,25
View species-specific activator tables
Tissue Distribution
Retina.
Species:  Human
Technique:  Northern Blot
References:  24
Cone photoreceptors.
Species:  Human
Technique:  Immunohistochemistry
References:  24
Cone photoreceptors.
Species:  Mouse
Technique:  Immunohistochemistry
References:  1,5
Cone photoreceptors, subset of olfactory sensory neurons, taste buds.
Species:  Rat
Technique:  Immunohistochemistry
References:  11-12
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:  9,24
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

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:  Incomplete achromatopsia
References: 
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human T369S 20,23
Missense Human T224R 20,23
Disease:  Achromatopsia 2; ACHM2
OMIM:  216900
Orphanet:  49382
References: 
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human I312 23
Frameshift Human I482 6,14,23
Frameshift Human V451 6,14,23
Frameshift Human G49 6,14,23
Missense Human L633P 4,6,9,14-15,23
Missense Human E593K 4,6,9,14-15,23
Missense Human E590K 4,6,9,14-15,23
Missense Human Y573C 4,6,9,14-15,23
Missense Human R569H 4,6,9,14-15,23
Missense Human T565N 4,6,9,14-15,23
Missense Human R563H 4,6,9,14-15,23
Missense Human G557R 4,6,9,14-15,23
Missense Human G548R 4,6,9,14-15,23
Missense Human F547L 4,6,9,14-15,23
Missense Human V529M 4,6,9,14-15,23
Missense Human G524D 4,6,9,14-15,23
Missense Human I522T 4,6,9,14-15,23
Missense Human G516E 4,6,9,14-15,23
Missense Human G513E 4,6,9,14-15,23
Missense Human C510S 4,6,9,14-15,23
Missense Human D485V 4,6,9,14-15,23
Missense Human N471S 4,6,9,14-15,23
Missense Human R436W 4,6,9,14-15,23
Missense Human R427C 4,6,9,14-15,23
Missense Human R410W 4,6,9,14-15,23
Missense Human M406T 4,6,9,14-15,23
Missense Human S401P 4,6,9,14-15,23
Missense Human F380S 4,6,9,14-15,23
Missense Human P372S 4,6,9,14-15,23
Missense Human S341P 4,6,9,14-15,23
Missense Human T291R 4,6,9,14-15,23
Missense Human R283W 4,6,9,14-15,23
Missense Human R283Q 4,6,9,14-15,23
Missense Human R277H 4,6,9,14-15,23
Missense Human R277C 4,6,9,14-15,23
Missense Human G267D 4,6,9,14-15,23
Missense Human Y263D 4,6,9,14-15,23
Missense Human D260N 4,6,9,14-15,23
Missense Human F249S 4,6,9,14-15,23
Missense Human R223W 4,6,9,14-15,23
Missense Human E194K 4,6,9,14-15,23
Missense Human C191Y 4,6,9,14-15,23
Missense Human N186F 4,6,9,14-15,23
Missense Human N182C 4,6,9,14-15,23
Missense Human Y181C 4,6,9,14-15,23
Missense Human P163L 4,6,9,14-15,23
Missense Human D162V 4,6,9,14-15,23
Truncation Human Q655X 6,14,23
Truncation Human Q537X 6,14,23
Truncation Human W440X 6,14,23
Truncation Human E344X 6,14,23
Truncation Human W316X 6,14,23
Truncation Human R221X 6,14,23
Truncation Human Q196X 6,14,23
Truncation Human R23X 6,14,23
General Comments
CNGA3 is also expressed in bovine sperm [2,7,21-22]. The physiological relevance in this cell type is unclear. Mice lacking the CNGA3 subunit show normal fertility [1].

REFERENCES

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1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

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

8. 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]

9. 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]

10. 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]

11. 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]

12. 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. Neuroreport, 10 (4): 743-6. [PMID:10208541]

13. 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]

14. 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]

15. Patel, KA; Bartoli, KM; Fandino, RA; Ngatchou, AN; Woch, G; Carey, J; Tanaka, JC. (2005) Transmembrane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of function and impaired cellular trafficking of the cone CNG channel. Invest. Ophthalmol. Vis. Sci., 46 (7): 2282-90. [PMID:15980212]

16. 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]

17. 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]

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

19. 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]

20. Tränkner, D; Jägle, H; Kohl, S; Apfelstedt-Sylla, E; Sharpe, LT; Kaupp, UB; Zrenner, E; Seifert, R; Wissinger, B. (2004) Molecular basis of an inherited form of incomplete achromatopsia. J. Neurosci., 24 (1): 138-47. [PMID:14715947]

21. 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. Nature, 368 (6474): 859-63. [PMID:7512693]

22. 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]

23. 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]

24. 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]

25. 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:

Martin Biel, Franz Hofmann, U. Benjamin Kaupp.
Cyclic nucleotide-regulated channels: CNGA3. Last modified on 08/03/2013. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=396.


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