Cyclic nucleotide-gated channel alpha 3 explained

Cyclic nucleotide-gated cation channel alpha-3 is a protein that in humans is encoded by the CNGA3 gene.^{[1] [2] [3] [4]}

Function

This gene encodes a member of the cyclic nucleotide-gated cation channel protein family, which is required for normal vision and olfactory signal transduction. CNGA3 is expressed in cone photoreceptors and is necessary for color vision.^[5] Missense mutations in this gene are associated with rod monochromacy and segregate in an autosomal recessive pattern. Two alternatively-spliced transcripts encoding different isoforms have been described.^[4]

Clinical relevance

Variants in this gene have been shown to cause achromatopsia^[6] and colour blindness.

See also

• Cyclic nucleotide-gated ion channel

Further reading

• Arbour NC, Zlotogora J, Knowlton RG, Merin S, Rosenmann A, Kanis AB, Rokhlina T, Stone EM, Sheffield VC . 6 . Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling . Human Molecular Genetics . 6 . 5 . 689–94 . May 1997 . 9158143 . 10.1093/hmg/6.5.689 . free .
• Kohl S, Marx T, Giddings I, Jägle H, Jacobson SG, Apfelstedt-Sylla E, Zrenner E, Sharpe LT, Wissinger B . 6 . Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel . Nature Genetics . 19 . 3 . 257–9 . July 1998 . 9662398 . 10.1038/935 . 12040233 .
• Wissinger B, Jägle H, Kohl S, Broghammer M, Baumann B, Hanna DB, Hedels C, Apfelstedt-Sylla E, Randazzo G, Jacobson SG, Zrenner E, Sharpe LT . 6 . Human rod monochromacy: linkage analysis and mapping of a cone photoreceptor expressed candidate gene on chromosome 2q11 . Genomics . 51 . 3 . 325–31 . August 1998 . 9721202 . 10.1006/geno.1998.5390 . free .
• Sundin OH, Yang JM, Li Y, Zhu D, Hurd JN, Mitchell TN, Silva ED, Maumenee IH . 6 . Genetic basis of total colourblindness among the Pingelapese islanders . Nature Genetics . 25 . 3 . 289–93 . July 2000 . 10888875 . 10.1038/77162 . 22948732 .
• 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 . 6 . CNGA3 mutations in hereditary cone photoreceptor disorders . American Journal of Human Genetics . 69 . 4 . 722–37 . October 2001 . 11536077 . 1226059 . 10.1086/323613 .
• Zhong H, Molday LL, Molday RS, Yau KW . The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry . Nature . 420 . 6912 . 193–8 . November 2002 . 12432397 . 2877395 . 10.1038/nature01201 . 2002Natur.420..193Z .
• Johnson S, Michaelides M, Aligianis IA, Ainsworth JR, Mollon JD, Maher ER, Moore AT, Hunt DM . 6 . Achromatopsia caused by novel mutations in both CNGA3 and CNGB3 . Journal of Medical Genetics . 41 . 2 . 20e–20 . February 2004 . 14757870 . 1735666 . 10.1136/jmg.2003.011437 .
• Faillace MP, Bernabeu RO, Korenbrot JI . Cellular processing of cone photoreceptor cyclic GMP-gated ion channels: a role for the S4 structural motif . The Journal of Biological Chemistry . 279 . 21 . 22643–53 . May 2004 . 15024024 . 10.1074/jbc.M400035200 . free .
• Peng C, Rich ED, Varnum MD . Subunit configuration of heteromeric cone cyclic nucleotide-gated channels . Neuron . 42 . 3 . 401–10 . May 2004 . 15134637 . 10.1016/S0896-6273(04)00225-9 . 16989789 . free .
• Nishiguchi KM, Sandberg MA, Gorji N, Berson EL, Dryja TP . Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases . Human Mutation . 25 . 3 . 248–58 . March 2005 . 15712225 . 10.1002/humu.20142 . 10889075 . free .
• Liu C, Varnum MD . Functional consequences of progressive cone dystrophy-associated mutations in the human cone photoreceptor cyclic nucleotide-gated channel CNGA3 subunit . American Journal of Physiology. Cell Physiology . 289 . 1 . C187-98 . July 2005 . 15743887 . 10.1152/ajpcell.00490.2004 .
• Varsányi B, Wissinger B, Kohl S, Koeppen K, Farkas A . Clinical and genetic features of Hungarian achromatopsia patients . Molecular Vision . 11 . 996–1001 . November 2005 . 16319819 .
• Goto-Omoto S, Hayashi T, Gekka T, Kubo A, Takeuchi T, Kitahara K . Compound heterozygous CNGA3 mutations (R436W, L633P) in a Japanese patient with congenital achromatopsia . Visual Neuroscience . 23 . 3–4 . 395–402 . 2006 . 16961972 . 10.1017/S095252380623308X . 22582346 .

External links

• GeneReviews/NIH/NCBI/UW entry on Achromatopsia
• OMIM entries on Achromatopsia

Notes and References

1. Distler M, Biel M, Flockerzi V, Hofmann F . Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells . Neuropharmacology . 33 . 11 . 1275–82 . November 1994 . 7532814 . 10.1016/0028-3908(94)90027-2 . 35784152 .
2. Wissinger B, Müller F, Weyand I, Schuffenhauer S, Thanos S, Kaupp UB, Zrenner E . Cloning, chromosomal localization and functional expression of the gene encoding the alpha-subunit of the cGMP-gated channel in human cone photoreceptors . The European Journal of Neuroscience . 9 . 12 . 2512–21 . December 1997 . 9517456 . 10.1111/j.1460-9568.1997.tb01680.x . 2839367 .
3. Hofmann F, Biel M, Kaupp UB . International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels . Pharmacological Reviews . 57 . 4 . 455–62 . December 2005 . 16382102 . 10.1124/pr.57.4.8 . 45853869 .
4. Web site: Entrez Gene: CNGA3 cyclic nucleotide gated channel alpha 3.
5. Kohl S, Marx T, Giddings I, Jägle H, Jacobson SG, Apfelstedt-Sylla E, Zrenner E, Sharpe LT, Wissinger B . 6 . Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel . Nature Genetics . 19 . 3 . 257–9 . July 1998 . 9662398 . 10.1038/935 . 12040233 .
6. Lam K, Guo H, Wilson GA, Kohl S, Wong F . Identification of variants in CNGA3 as cause for achromatopsia by exome sequencing of a single patient . Archives of Ophthalmology . 129 . 9 . 1212–7 . September 2011 . 21911670 . 10.1001/archophthalmol.2011.254 . 36011909 .