* 600724

CYCLIC NUCLEOTIDE-GATED CHANNEL, BETA-1; CNGB1


Alternative titles; symbols

CYCLIC NUCLEOTIDE-GATED CHANNEL, PHOTORECEPTOR, cGMP-GATED, 2; CNCG2
CYCLIC NUCLEOTIDE-GATED CHANNEL, PHOTORECEPTOR, cGMP-GATED, 3-LIKE; CNCG3L
GLUTAMIC ACID-RICH PROTEIN 1; GAR1; GARP
RETINAL ROD cGMP-GATED CHANNEL, BETA SUBUNIT
RETINAL ROD cGMP-GATED CHANNEL, GAMMA SUBUNIT


HGNC Approved Gene Symbol: CNGB1

Cytogenetic location: 16q21     Genomic coordinates (GRCh38): 16:57,882,340-57,971,128 (from NCBI)


Gene-Phenotype Relationships
Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
16q21 Retinitis pigmentosa 45 613767 AR 3

TEXT

Description

The CNGB1 and CNGA1 (123825) gene products form the heterotetrameric rod photoreceptor cyclic nucleotide-gated (CNG) channel, which conducts a cation current in response to changes in intracellular levels of cGMP and mediates the electrical response to light (summary by Kondo et al., 2004).


Cloning and Expression

The human and bovine rod photoreceptor cGMP-gated cation channel consists of 2 subunits: alpha (63 kD, CNGA1) and beta (240 kD). Ardell et al. (1996) provided evidence that the human GAR1 protein is encoded by the N-terminal region of the gene encoding the beta subunit of the cGMP-gated photoreceptor channel.

Sugimoto et al. (1991) identified a unique glutamic acid-rich protein in bovine rod photoreceptors. Chen et al. (1994) suggested that this protein is a third subunit (gamma) of the rod cGMP-gated cation channel. Ardell et al. (1995) characterized the CNCG3L gene (also referred to by them as GAR1) that encodes a human homolog of the bovine gamma subunit. Sequence analysis of cDNA clones encoding human CNCG3L revealed an open reading frame predicting a protein of 299 amino acids (approximately 32 kD), half the size of the bovine gamma subunit. Within the first 31 amino acids, they found 90% identity between the human and bovine sequences, and only 60% homology was found throughout the remainder of the protein sequence. As in bovine gamma, the predicted isoelectric point of the human protein is very acidic despite the absence of the bovine C-terminal glutamic acid-rich domain.

Ardell et al. (1996) presented the complete sequence of the human beta subunit and stated that the GAR1 gene previously reported by Ardell et al. (1995) encodes the beta subunit N-terminal region. Using PCR, RNA blot, and genomic DNA analysis, Ardell et al. (1996) provided evidence that the beta subunit is produced from a locus on chromosome 16 consisting of 2 nonoverlapping transcription units that is capable of generating independent transcripts corresponding to GAR1 and the C-terminal two-thirds of the beta subunit. They showed that the CNCG-beta subunit mRNA encodes the first 291 amino acids of human GAR1, 337 amino acids present only in the beta subunit, and the entire 623 amino acids predicted from the 2a cDNA sequence reported by Chen et al. (1993).


Gene Structure

Ardell et al. (1995) demonstrated that the protein coding region of the human CNGB1 gene consists of 12 exons spanning approximately 11 kb with sequence identical to that of the cDNA clones.


Mapping

Ardell et al. (1995) demonstrated localization of the CNCG3L gene to chromosome 16 by PCR of somatic cell hybrid DNA with primer pairs that amplified a portion of the gene. The location of the gene was further delimited by fluorescence in situ hybridization, which placed the gene at 16q13. Ardell et al. (1996) localized the CNCG2 gene to chromosome 16q13 by somatic hybrid cell DNA analysis.

Gross (2018) mapped the CNGB1 gene to chromosome 16q21 based on an alignment of the CNGB1 sequence (GenBank AF042498) with the genomic sequence (GRCh38).


Gene Function

Korschen et al. (1999) identified glutamic acid-rich proteins (GARPs) as multivalent proteins that interact with the key players of cGMP signaling, phosphodiesterase (see 602676) and guanylate cyclase (see 600179), and with the retina-specific ATP-binding cassette transporter (ABCR; 601691), through 4 short repetitive sequences. In electron micrographs, GARPs are restricted to the rim region and incisures of discs in close proximity to the guanylate cyclase and ABCR, whereas the phosphodiesterase is randomly distributed. GARP2 associates more strongly with light-activated than with inactive phosphodiesterase, and GARP2 potently inhibits phosphodiesterase activity. Korschen et al. (1999) concluded that the GARPs organize a dynamic protein complex near the disc rim that may control cGMP turnover and possibly other light-dependent processes.

Kizhatil et al. (2009) found that targeting of cyclic nucleotide-gated (CNG) channels to the rod outer segment required their interaction with ankyrin-G (600465). Ankyrin-G localized exclusively to rod outer segments, coimmunoprecipitated with the CNG channel, and bound to the C-terminal domain of the channel beta-1 subunit. Ankyrin-G depletion in neonatal mouse retinas markedly reduced CNG channel expression. Transgenic expression of CNG channel beta-subunit mutants in Xenopus rods showed that ankyrin-G binding was necessary and sufficient for targeting of the beta-1 subunit to outer segments. Thus, Kizhatil et al. (2009) concluded that ankyrin-G is required for transport of CNG channels to the plasma membrane of rod outer segments.


Biochemical Features

Zhong et al. (2002) reported the identification of a leucine zipper homology domain named CLZ (carboxy-terminal leucine zipper) that is present in the distal C terminus of CNG channel A subunits but is absent from B subunits and mediates an inter-subunit interaction. With crosslinking, nondenaturing gel electrophoresis, and analytical centrifugation, this CLZ domain was found to mediate a trimeric interaction. In addition, a mutant cone CNG channel A subunit with its CLZ domain replaced by a generic trimeric leucine zipper produced channels that behaved much like the wildtype, but less so if replaced by a dimeric or tetrameric leucine zipper. This A-subunit-only, trimeric interaction suggested that heteromeric CNG channels actually adopt a 3A:1B stoichiometry. Biochemical analysis of the purified bovine rod CNG channel confirmed this conclusion. Zhong et al. (2002) concluded that this revised stoichiometry provides a new foundation for understanding the structure and function of the CNG channel family.

In Xenopus oocytes, Trudeau and Zagotta (2002) showed that CNGA1-RP, a mutant form of the CNGA1 subunit which lacks the final 37 amino acids in the C-terminal region (123825.0004), formed normally-expressed functional homomeric channels similar to wildtype. In contrast, coexpression of CNGA1-RP and wildtype CNGB1 resulted in heteromeric channels that did not convey current and were not detectable at the membrane surface, despite the presence of these subunit proteins within the cell interior. Studies revealed a protein-protein interaction between the C-terminal region of CGNA1, which is deleted in CNGA1-RP, and an N-terminal region of CNGB1. In the absence of this interaction, an exposed short N-terminal region in CNGB1 prevented membrane expression of the heteromeric channel.

Zheng and Zagotta (2004) found that when cRNA for 3 rat olfactory CNG channel subunits, Cnga2 (300338), Cnga4 (609472), and Cngb1b, a splice variant of Cngb1, were coinjected into Xenopus oocytes, functional channels in the surface membrane contained a fixed ratio of Cnga2:Cnga4:Cngb1b of 2:1:1. When expressed individually with Cnga2, the Cnga4 and Cngb1b subunits were present as single copies, and when expressed alone, they did not self-assemble.


Molecular Genetics

Bareil et al. (2001) studied a consanguineous French family with autosomal recessive retinitis pigmentosa (RP45; 613767). Bareil et al. (2001) excluded linkage to known loci involved in RP and by homozygosity mapping localized the disease gene in this family to chromosome 16q13-q21. They noted 2 candidate genes, KIFC3 (604535) and CNGB1. Mutation analysis demonstrated that CNGB1 was mutated in this family.

In a 67-year-old Japanese man with RP, Kondo et al. (2004) identified homozygosity for a splice site mutation in the CNGB1 gene (600724.0002).

Fu et al. (2013) screened 31 unrelated Chinese families with autosomal recessive RP for mutations in 163 retinal disease genes and identified homozygosity for a missense mutation at a conserved residue in the CNGB1 gene (P530R; 600724.0003) that segregated with disease in 1 family.


ALLELIC VARIANTS ( 3 Selected Examples):

.0001 RETINITIS PIGMENTOSA 45

CNGB1, GLY993VAL
  
RCV000009448

In a consanguineous French family affected by autosomal recessive retinitis pigmentosa (RP45; 613767) Bareil et al. (2001) found that affected individuals were homozygous for a 2978G-T transversion in exon 30 of the CNGB1 gene, predicted to result in a gly993-to-val (G993V) amino acid change in the protein. This mutation was not found in normal samples or in other RP samples. Gly993 is a conserved residue; the missense G993V change was predicted to change the cyclic nucleotide-binding domain of the beta-subunit of the rod cGMP-gated channel.


.0002 RETINITIS PIGMENTOSA 45

CNGB1, IVS32DS, G-A, +1
  
RCV000009449

In a 67-year-old Japanese man who noticed night blindness at school age and who had received the diagnosis of retinitis pigmentosa (RP45; 613767) at the age of 30, Kondo et al. (2004) found a novel homozygous splice site mutation at the donor site of exon 32 of the CNGB1 gene (3444+1G-A) that resulted in frameshift and truncation of the last 28 amino acids.


.0003 RETINITIS PIGMENTOSA 45

CNGB1, PRO530ARG
  
RCV000191921...

In a Chinese patient with retinitis pigmentosa (RP45; 613767), Fu et al. (2013) identified homozygosity for a c.1589C-G transversion (c.1589C-G, NM_001297.4) in the CNGB1 gene, resulting in a pro530-to-arg (P530R) substitution at a conserved residue. The mutation segregated with disease in the family and was not found in the 1000 Genomes Project, dbSNP (build 135), or Exome Sequencing Project databases.


REFERENCES

  1. Ardell, M. D., Aragon, I., Oliveira, L., Porche, G. E., Burke, E., Pittler, S. J. The beta subunit of human rod photoreceptor cGMP-gated cation channel is generated from a complex transcription unit. FEBS Lett. 389: 213-218, 1996. [PubMed: 8766832, related citations] [Full Text]

  2. Ardell, M. D., Makhija, A. K., Oliveira, L., Miniou, P., Viegas-Pequignot, E., Pittler, S. J. cDNA, gene structure, and chromosomal localization of human GAR1 (CNCG3L), a homolog of the third subunit of bovine photoreceptor cGMP-gated channel. Genomics 28: 32-38, 1995. [PubMed: 7590744, related citations] [Full Text]

  3. Bareil, C., Hamel, C. P., Delague, V., Arnaud, B., Demaille, J., Claustres, M. Segregation of a mutation in CNGB1 encoding the beta-subunit of the rod cGMP-gated channel in a family with autosomal recessive retinitis pigmentosa. Hum. Genet. 108: 328-334, 2001. [PubMed: 11379879, related citations] [Full Text]

  4. Chen, T. Y., Peng, Y. W., Dhallan, R. S., Ahamed, B., Reed, R. R., Yau, K. W. A new subunit of the cyclic nucleotide-gated cation channel in retinal rods. Nature 362: 764-767, 1993. [PubMed: 7682292, related citations] [Full Text]

  5. Chen, T.-Y., Illing, M., Molday, L. L., Hsu, Y.-T., Yau, K.-W., Molday, R. S. Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation. Proc. Nat. Acad. Sci. 91: 11757-11761, 1994. [PubMed: 7526403, related citations] [Full Text]

  6. Fu, Q., Wang, F., Wang, H., Xu, F., Zaneveld, J. E., Ren, H., Keser, V., Lopez, I., Tuan, H.-F., Salvo, J. S., Wang, X., Zhao, L., Wang, K., Li, Y., Koenekoop, R. K., Chen, R., Sui, R. Next-generation sequencing-based molecular diagnosis of a Chinese cohort with autosomal recessive retinitis pigmentosa. Invest. Ophthal. Vis. Sci. 54: 4158-4166, 2013. [PubMed: 23661369, images, related citations] [Full Text]

  7. Gross, M. B. Personal Communication. Baltimore, Md. 12/3/2018.

  8. Kizhatil, K., Baker, S. A., Arshavsky, V. Y., Bennett, V. Ankyrin-G promotes cyclic nucleotide-gated channel transport to rod photoreceptor sensory cilia. Science 323: 1614-1617, 2009. [PubMed: 19299621, images, related citations] [Full Text]

  9. Kondo, H., Qin, M., Mizota, A., Kondo, M., Hayashi, H., Hayashi, K., Oshima, K., Tahira, T., Hayashi, K. A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. Invest. Ophthal. Vis. Sci. 45: 4433-4439, 2004. [PubMed: 15557452, related citations] [Full Text]

  10. Korschen, H. G., Beyermann, M., Muller, F., Heck, M., Vantler, M., Koch, K.-W., Kellner, R., Wolfrum, U., Bode, C., Hofmann, K. P., Kaupp, U. B. Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors. Nature 400: 761-766, 1999. [PubMed: 10466724, related citations] [Full Text]

  11. Sugimoto, Y., Yatsunami, K., Tsujimoto, M., Khorana, H. G., Ichikawa, A. The amino acid sequence of a glutamic acid-rich protein from bovine retina as deduced from the cDNA sequence. Proc. Nat. Acad. Sci. 88: 3116-3119, 1991. [PubMed: 2014230, related citations] [Full Text]

  12. Trudeau, M. C., Zagotta, W. N. An intersubunit interaction regulates trafficking of rod cyclic nucleotide-gated channels and is disrupted in an inherited form of blindness. Neuron 34: 197-207, 2002. Note: Erratum: Neuron 37: 181, 2003. [PubMed: 11970862, related citations] [Full Text]

  13. Zheng, J., Zagotta, W. N. Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels. Neuron 42: 411-421, 2004. [PubMed: 15134638, related citations] [Full Text]

  14. Zhong, H., Molday, L. L., Molday, R. S., Yau, K.-W. The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature 420: 193-198, 2002. [PubMed: 12432397, images, related citations] [Full Text]


Matthew B. Gross - updated : 12/03/2018
Marla J. F. O'Neill - updated : 9/25/2015
Ada Hamosh - updated : 6/18/2009
Patricia A. Hartz - updated : 4/19/2005
Anne M. Stumpf - updated : 1/11/2005
Cassandra L. Kniffin - updated : 2/19/2003
Ada Hamosh - updated : 11/13/2002
Victor A. McKusick - updated : 5/7/2001
Ada Hamosh - updated : 2/9/2000
Mark H. Paalman - updated : 5/30/1997
Creation Date:
Victor A. McKusick : 8/17/1995
mgross : 12/03/2018
carol : 09/25/2015
carol : 9/25/2015
alopez : 2/24/2011
alopez : 2/24/2011
joanna : 7/27/2010
alopez : 7/10/2009
alopez : 6/24/2009
terry : 6/18/2009
alopez : 2/18/2009
alopez : 2/10/2009
mgross : 7/12/2005
mgross : 4/19/2005
alopez : 1/11/2005
carol : 8/19/2004
ckniffin : 6/16/2003
cwells : 2/28/2003
ckniffin : 2/19/2003
alopez : 11/13/2002
terry : 11/12/2002
mcapotos : 5/18/2001
mcapotos : 5/11/2001
terry : 5/7/2001
alopez : 6/26/2000
alopez : 2/9/2000
alopez : 7/28/1998
mark : 6/2/1997
mark : 6/2/1997
alopez : 6/2/1997
mark : 5/30/1997
mark : 5/12/1997
mark : 8/17/1995

* 600724

CYCLIC NUCLEOTIDE-GATED CHANNEL, BETA-1; CNGB1


Alternative titles; symbols

CYCLIC NUCLEOTIDE-GATED CHANNEL, PHOTORECEPTOR, cGMP-GATED, 2; CNCG2
CYCLIC NUCLEOTIDE-GATED CHANNEL, PHOTORECEPTOR, cGMP-GATED, 3-LIKE; CNCG3L
GLUTAMIC ACID-RICH PROTEIN 1; GAR1; GARP
RETINAL ROD cGMP-GATED CHANNEL, BETA SUBUNIT
RETINAL ROD cGMP-GATED CHANNEL, GAMMA SUBUNIT


HGNC Approved Gene Symbol: CNGB1

Cytogenetic location: 16q21     Genomic coordinates (GRCh38): 16:57,882,340-57,971,128 (from NCBI)


Gene-Phenotype Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
16q21 Retinitis pigmentosa 45 613767 Autosomal recessive 3

TEXT

Description

The CNGB1 and CNGA1 (123825) gene products form the heterotetrameric rod photoreceptor cyclic nucleotide-gated (CNG) channel, which conducts a cation current in response to changes in intracellular levels of cGMP and mediates the electrical response to light (summary by Kondo et al., 2004).


Cloning and Expression

The human and bovine rod photoreceptor cGMP-gated cation channel consists of 2 subunits: alpha (63 kD, CNGA1) and beta (240 kD). Ardell et al. (1996) provided evidence that the human GAR1 protein is encoded by the N-terminal region of the gene encoding the beta subunit of the cGMP-gated photoreceptor channel.

Sugimoto et al. (1991) identified a unique glutamic acid-rich protein in bovine rod photoreceptors. Chen et al. (1994) suggested that this protein is a third subunit (gamma) of the rod cGMP-gated cation channel. Ardell et al. (1995) characterized the CNCG3L gene (also referred to by them as GAR1) that encodes a human homolog of the bovine gamma subunit. Sequence analysis of cDNA clones encoding human CNCG3L revealed an open reading frame predicting a protein of 299 amino acids (approximately 32 kD), half the size of the bovine gamma subunit. Within the first 31 amino acids, they found 90% identity between the human and bovine sequences, and only 60% homology was found throughout the remainder of the protein sequence. As in bovine gamma, the predicted isoelectric point of the human protein is very acidic despite the absence of the bovine C-terminal glutamic acid-rich domain.

Ardell et al. (1996) presented the complete sequence of the human beta subunit and stated that the GAR1 gene previously reported by Ardell et al. (1995) encodes the beta subunit N-terminal region. Using PCR, RNA blot, and genomic DNA analysis, Ardell et al. (1996) provided evidence that the beta subunit is produced from a locus on chromosome 16 consisting of 2 nonoverlapping transcription units that is capable of generating independent transcripts corresponding to GAR1 and the C-terminal two-thirds of the beta subunit. They showed that the CNCG-beta subunit mRNA encodes the first 291 amino acids of human GAR1, 337 amino acids present only in the beta subunit, and the entire 623 amino acids predicted from the 2a cDNA sequence reported by Chen et al. (1993).


Gene Structure

Ardell et al. (1995) demonstrated that the protein coding region of the human CNGB1 gene consists of 12 exons spanning approximately 11 kb with sequence identical to that of the cDNA clones.


Mapping

Ardell et al. (1995) demonstrated localization of the CNCG3L gene to chromosome 16 by PCR of somatic cell hybrid DNA with primer pairs that amplified a portion of the gene. The location of the gene was further delimited by fluorescence in situ hybridization, which placed the gene at 16q13. Ardell et al. (1996) localized the CNCG2 gene to chromosome 16q13 by somatic hybrid cell DNA analysis.

Gross (2018) mapped the CNGB1 gene to chromosome 16q21 based on an alignment of the CNGB1 sequence (GenBank AF042498) with the genomic sequence (GRCh38).


Gene Function

Korschen et al. (1999) identified glutamic acid-rich proteins (GARPs) as multivalent proteins that interact with the key players of cGMP signaling, phosphodiesterase (see 602676) and guanylate cyclase (see 600179), and with the retina-specific ATP-binding cassette transporter (ABCR; 601691), through 4 short repetitive sequences. In electron micrographs, GARPs are restricted to the rim region and incisures of discs in close proximity to the guanylate cyclase and ABCR, whereas the phosphodiesterase is randomly distributed. GARP2 associates more strongly with light-activated than with inactive phosphodiesterase, and GARP2 potently inhibits phosphodiesterase activity. Korschen et al. (1999) concluded that the GARPs organize a dynamic protein complex near the disc rim that may control cGMP turnover and possibly other light-dependent processes.

Kizhatil et al. (2009) found that targeting of cyclic nucleotide-gated (CNG) channels to the rod outer segment required their interaction with ankyrin-G (600465). Ankyrin-G localized exclusively to rod outer segments, coimmunoprecipitated with the CNG channel, and bound to the C-terminal domain of the channel beta-1 subunit. Ankyrin-G depletion in neonatal mouse retinas markedly reduced CNG channel expression. Transgenic expression of CNG channel beta-subunit mutants in Xenopus rods showed that ankyrin-G binding was necessary and sufficient for targeting of the beta-1 subunit to outer segments. Thus, Kizhatil et al. (2009) concluded that ankyrin-G is required for transport of CNG channels to the plasma membrane of rod outer segments.


Biochemical Features

Zhong et al. (2002) reported the identification of a leucine zipper homology domain named CLZ (carboxy-terminal leucine zipper) that is present in the distal C terminus of CNG channel A subunits but is absent from B subunits and mediates an inter-subunit interaction. With crosslinking, nondenaturing gel electrophoresis, and analytical centrifugation, this CLZ domain was found to mediate a trimeric interaction. In addition, a mutant cone CNG channel A subunit with its CLZ domain replaced by a generic trimeric leucine zipper produced channels that behaved much like the wildtype, but less so if replaced by a dimeric or tetrameric leucine zipper. This A-subunit-only, trimeric interaction suggested that heteromeric CNG channels actually adopt a 3A:1B stoichiometry. Biochemical analysis of the purified bovine rod CNG channel confirmed this conclusion. Zhong et al. (2002) concluded that this revised stoichiometry provides a new foundation for understanding the structure and function of the CNG channel family.

In Xenopus oocytes, Trudeau and Zagotta (2002) showed that CNGA1-RP, a mutant form of the CNGA1 subunit which lacks the final 37 amino acids in the C-terminal region (123825.0004), formed normally-expressed functional homomeric channels similar to wildtype. In contrast, coexpression of CNGA1-RP and wildtype CNGB1 resulted in heteromeric channels that did not convey current and were not detectable at the membrane surface, despite the presence of these subunit proteins within the cell interior. Studies revealed a protein-protein interaction between the C-terminal region of CGNA1, which is deleted in CNGA1-RP, and an N-terminal region of CNGB1. In the absence of this interaction, an exposed short N-terminal region in CNGB1 prevented membrane expression of the heteromeric channel.

Zheng and Zagotta (2004) found that when cRNA for 3 rat olfactory CNG channel subunits, Cnga2 (300338), Cnga4 (609472), and Cngb1b, a splice variant of Cngb1, were coinjected into Xenopus oocytes, functional channels in the surface membrane contained a fixed ratio of Cnga2:Cnga4:Cngb1b of 2:1:1. When expressed individually with Cnga2, the Cnga4 and Cngb1b subunits were present as single copies, and when expressed alone, they did not self-assemble.


Molecular Genetics

Bareil et al. (2001) studied a consanguineous French family with autosomal recessive retinitis pigmentosa (RP45; 613767). Bareil et al. (2001) excluded linkage to known loci involved in RP and by homozygosity mapping localized the disease gene in this family to chromosome 16q13-q21. They noted 2 candidate genes, KIFC3 (604535) and CNGB1. Mutation analysis demonstrated that CNGB1 was mutated in this family.

In a 67-year-old Japanese man with RP, Kondo et al. (2004) identified homozygosity for a splice site mutation in the CNGB1 gene (600724.0002).

Fu et al. (2013) screened 31 unrelated Chinese families with autosomal recessive RP for mutations in 163 retinal disease genes and identified homozygosity for a missense mutation at a conserved residue in the CNGB1 gene (P530R; 600724.0003) that segregated with disease in 1 family.


ALLELIC VARIANTS 3 Selected Examples):

.0001   RETINITIS PIGMENTOSA 45

CNGB1, GLY993VAL
SNP: rs121918532, gnomAD: rs121918532, ClinVar: RCV000009448

In a consanguineous French family affected by autosomal recessive retinitis pigmentosa (RP45; 613767) Bareil et al. (2001) found that affected individuals were homozygous for a 2978G-T transversion in exon 30 of the CNGB1 gene, predicted to result in a gly993-to-val (G993V) amino acid change in the protein. This mutation was not found in normal samples or in other RP samples. Gly993 is a conserved residue; the missense G993V change was predicted to change the cyclic nucleotide-binding domain of the beta-subunit of the rod cGMP-gated channel.


.0002   RETINITIS PIGMENTOSA 45

CNGB1, IVS32DS, G-A, +1
SNP: rs1567360969, ClinVar: RCV000009449

In a 67-year-old Japanese man who noticed night blindness at school age and who had received the diagnosis of retinitis pigmentosa (RP45; 613767) at the age of 30, Kondo et al. (2004) found a novel homozygous splice site mutation at the donor site of exon 32 of the CNGB1 gene (3444+1G-A) that resulted in frameshift and truncation of the last 28 amino acids.


.0003   RETINITIS PIGMENTOSA 45

CNGB1, PRO530ARG
SNP: rs201553871, gnomAD: rs201553871, ClinVar: RCV000191921, RCV000490531, RCV001119868, RCV001489289

In a Chinese patient with retinitis pigmentosa (RP45; 613767), Fu et al. (2013) identified homozygosity for a c.1589C-G transversion (c.1589C-G, NM_001297.4) in the CNGB1 gene, resulting in a pro530-to-arg (P530R) substitution at a conserved residue. The mutation segregated with disease in the family and was not found in the 1000 Genomes Project, dbSNP (build 135), or Exome Sequencing Project databases.


REFERENCES

  1. Ardell, M. D., Aragon, I., Oliveira, L., Porche, G. E., Burke, E., Pittler, S. J. The beta subunit of human rod photoreceptor cGMP-gated cation channel is generated from a complex transcription unit. FEBS Lett. 389: 213-218, 1996. [PubMed: 8766832] [Full Text: https://doi.org/10.1016/0014-5793(96)00588-1]

  2. Ardell, M. D., Makhija, A. K., Oliveira, L., Miniou, P., Viegas-Pequignot, E., Pittler, S. J. cDNA, gene structure, and chromosomal localization of human GAR1 (CNCG3L), a homolog of the third subunit of bovine photoreceptor cGMP-gated channel. Genomics 28: 32-38, 1995. [PubMed: 7590744] [Full Text: https://doi.org/10.1006/geno.1995.1102]

  3. Bareil, C., Hamel, C. P., Delague, V., Arnaud, B., Demaille, J., Claustres, M. Segregation of a mutation in CNGB1 encoding the beta-subunit of the rod cGMP-gated channel in a family with autosomal recessive retinitis pigmentosa. Hum. Genet. 108: 328-334, 2001. [PubMed: 11379879] [Full Text: https://doi.org/10.1007/s004390100496]

  4. Chen, T. Y., Peng, Y. W., Dhallan, R. S., Ahamed, B., Reed, R. R., Yau, K. W. A new subunit of the cyclic nucleotide-gated cation channel in retinal rods. Nature 362: 764-767, 1993. [PubMed: 7682292] [Full Text: https://doi.org/10.1038/362764a0]

  5. Chen, T.-Y., Illing, M., Molday, L. L., Hsu, Y.-T., Yau, K.-W., Molday, R. S. Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation. Proc. Nat. Acad. Sci. 91: 11757-11761, 1994. [PubMed: 7526403] [Full Text: https://doi.org/10.1073/pnas.91.24.11757]

  6. Fu, Q., Wang, F., Wang, H., Xu, F., Zaneveld, J. E., Ren, H., Keser, V., Lopez, I., Tuan, H.-F., Salvo, J. S., Wang, X., Zhao, L., Wang, K., Li, Y., Koenekoop, R. K., Chen, R., Sui, R. Next-generation sequencing-based molecular diagnosis of a Chinese cohort with autosomal recessive retinitis pigmentosa. Invest. Ophthal. Vis. Sci. 54: 4158-4166, 2013. [PubMed: 23661369] [Full Text: https://doi.org/10.1167/iovs.13-11672]

  7. Gross, M. B. Personal Communication. Baltimore, Md. 12/3/2018.

  8. Kizhatil, K., Baker, S. A., Arshavsky, V. Y., Bennett, V. Ankyrin-G promotes cyclic nucleotide-gated channel transport to rod photoreceptor sensory cilia. Science 323: 1614-1617, 2009. [PubMed: 19299621] [Full Text: https://doi.org/10.1126/science.1169789]

  9. Kondo, H., Qin, M., Mizota, A., Kondo, M., Hayashi, H., Hayashi, K., Oshima, K., Tahira, T., Hayashi, K. A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. Invest. Ophthal. Vis. Sci. 45: 4433-4439, 2004. [PubMed: 15557452] [Full Text: https://doi.org/10.1167/iovs.04-0544]

  10. Korschen, H. G., Beyermann, M., Muller, F., Heck, M., Vantler, M., Koch, K.-W., Kellner, R., Wolfrum, U., Bode, C., Hofmann, K. P., Kaupp, U. B. Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors. Nature 400: 761-766, 1999. [PubMed: 10466724] [Full Text: https://doi.org/10.1038/23468]

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Contributors:
Matthew B. Gross - updated : 12/03/2018
Marla J. F. O'Neill - updated : 9/25/2015
Ada Hamosh - updated : 6/18/2009
Patricia A. Hartz - updated : 4/19/2005
Anne M. Stumpf - updated : 1/11/2005
Cassandra L. Kniffin - updated : 2/19/2003
Ada Hamosh - updated : 11/13/2002
Victor A. McKusick - updated : 5/7/2001
Ada Hamosh - updated : 2/9/2000
Mark H. Paalman - updated : 5/30/1997

Creation Date:
Victor A. McKusick : 8/17/1995

Edit History:
mgross : 12/03/2018
carol : 09/25/2015
carol : 9/25/2015
alopez : 2/24/2011
alopez : 2/24/2011
joanna : 7/27/2010
alopez : 7/10/2009
alopez : 6/24/2009
terry : 6/18/2009
alopez : 2/18/2009
alopez : 2/10/2009
mgross : 7/12/2005
mgross : 4/19/2005
alopez : 1/11/2005
carol : 8/19/2004
ckniffin : 6/16/2003
cwells : 2/28/2003
ckniffin : 2/19/2003
alopez : 11/13/2002
terry : 11/12/2002
mcapotos : 5/18/2001
mcapotos : 5/11/2001
terry : 5/7/2001
alopez : 6/26/2000
alopez : 2/9/2000
alopez : 7/28/1998
mark : 6/2/1997
mark : 6/2/1997
alopez : 6/2/1997
mark : 5/30/1997
mark : 5/12/1997
mark : 8/17/1995