Disease relevance of CNGB1

• Impaired channel targeting and retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGB1 [1].
• OBJECTIVE: To evaluate whether familial aggregation of osteoarthritis differs by joint site in a sibling pair study (GARP) of patients with osteoarthritis at multiple sites [2].
• It will also lay the ground for the characterization of an amplicon surrounding GARP in breast cancer and for the search of disease genes within this region [3].
• Evidence for familial aggregation of hand, hip, and spine but not knee osteoarthritis in siblings with multiple joint involvement: the GARP study [2].

Psychiatry related information on CNGB1

• Here, we have analyzed the functional relevance of CNGB1 for olfaction by gene targeting in mice [4].

High impact information on CNGB1

• GARPs exist as two soluble forms, GARP1 and GARP2, and as a large cytoplasmic domain (GARP' part) of the beta-subunit of the cyclic GMP-gated channel [5].
• The canine homolog of the cyclic nucleotide-gated channel beta-subunit gene (CNGB3), responsible for the human ACHM3 disease phenotype, was mapped within the zero-recombination interval for the cd locus [6].
• Second, together with the CNGA4 subunit, CNGB1 is needed for ciliary targeting of the olfactory CNG channel [4].
• Electro-olfactogram responses of CNGB1-deficient (CNGB1(-/-)) mice displayed a reduced maximal amplitude and decelerated onset and recovery kinetics compared with wild-type mice [4].
• Domains within the GARP subunit Vps54 confer separate functions in complex assembly and early endosome recognition [7].

Biological context of CNGB1

• The CNGB1 locus consists of 33 exons, which span approximately 100kb of genomic DNA on chromosome 16 [8].
• We have defined the splice acceptor site for the 4.3 GARP gene by sequencing and by 5' RT-PCR and demonstrated microheterogeneity in GARP polyadenylation by 3' RT-PCR [9].
• In Saccharomyces cerevisiae, GARP is the main effector of the small GTPase Ypt6p and interacts with the SNARE Tlg1p to facilitate membrane fusion [10].
• METHODS: Polymorphisms were examined in two distinct cohorts of subjects: a population based sample from the Rotterdam study (n = 809), and affected siblings from the genetics, osteoarthrosis and progression (GARP) study (n = 382) [11].
• Unexpectedly, 14 days post-infection, procyclic forms frequently are negative for both PRS and GARP, suggesting that they might be expressing another stage-specific surface antigen at this point in the life cycle [12].

Anatomical context of CNGB1

• In the absence of CNGB1, only trace amounts of the CNGA1 subunit were found on the rod outer segment [1].
• At the age of approximately 1 year, CNGB1-/- animals were devoid of both rods and cones [1].
• CNG4 transcripts are present in retina, testis, kidney, heart, and brain [13].
• The core region of CNG4 is homologous to the second subunit of the human rod photoreceptor channel (hRCNC2b), suggesting that both proteins are alternatively spliced products of the bovine and human homologue of the same gene [13].
• This complex and soluble GARP proteins also interact with peripherin-2 oligomers in the rim region of outer segment disc membranes [14].

Associations of CNGB1 with chemical compounds

• In addition, the beta-subunit has a large glutamic acid- and proline-rich region called GARP that is also expressed as two soluble protein variants [14].
• The N-terminal part contains the human homolog of the bovine glutamic acid-rich protein called GARP [15].
• After initial assessment of GAR (GAR1), GAR was determined during doubled (GAR2) or quadrupled (GAR4) galactose infusion [16].
• A promoter test plasmid was constructed utilising the luciferase coding region flanked by the intergenic regions of a T. congolense gene encoding GARP, the glutamic acid and alanine rich protein on the surface of procyclic organisms [17].

Other interactions of CNGB1

• Two candidate genes KIFC3 and CNGB1 mapping to this critical interval have been screened for mutations [18].
• Segregation of a mutation in CNGB1 encoding the beta-subunit of the rod cGMP-gated channel in a family with autosomal recessive retinitis pigmentosa [18].
• Two of them were novel mutations in the genes TULP1 (c.1145T-->C, F382S) and CNGB1 (c.3444 + 1G-->A) [19].
• The results suggest that CNG4 forms functional heterooligomeric channels with CNG3 in vitro and probably also in intact tissues [13].
• These results suggest that channel/peripherin protein interactions mediated by the GARP part of the channel beta-subunit play a role in connecting the rim region of discs to the plasma membrane and in anchoring the channel.exchanger complex in the rod outer segment plasma membrane [14].

Analytical, diagnostic and therapeutic context of CNGB1

• In situ hybridization with sections of rat brain revealed the co-expression of CNG1, CNG4 and GARP in pinealocytes [20].
• In the GARP study, carriers of the A allele of SNP6 had an odds ratio of 2.0 (95% CI, 1.3 to 3.1, p = 0.004) for osteoarthritis of the first carpometacarpal joint (CMC1) as compared with the Rotterdam sample as a control group [11].

References