Alternative titles; symbols
HGNC Approved Gene Symbol: GNB5
SNOMEDCT: 1186711002;
Cytogenetic location: 15q21.2 Genomic coordinates (GRCh38): 15:52,115,100-52,191,392 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 15q21.2 | Lodder-Merla syndrome, type 1, with impaired intellectual development and cardiac arrhythmia | 617173 | Autosomal recessive | 3 |
| Lodder-Merla syndrome, type 2, with developmental delay and with or without cardiac arrhythmia | 617182 | Autosomal recessive | 3 |
The GNB5 gene encodes a beta subunit of heterotrimeric GTP-binding proteins (G proteins). GNB5 forms complexes with members of the R7 regulator family of RGS proteins (see, e.g., RGS7, 602517 and RGS9, 604067) as well as with R7-binding protein (RGS7BP; 610890), and is essential for the structural integrity and proteolytic stability of R7 RGS complexes, which serve as negative regulators of G protein-coupled receptor (GPCR) signaling. GNB5 is expressed in the brain and plays a role in neurotransmitter signaling, including via the dopamine D2 receptor (DRD2; 126450) (summary by Xie et al., 2012 and Shamseldin et al., 2016). GNB5 also interacts with G protein-coupled inward rectifier potassium channels (GIRK; see, e.g., GIRK2, 600877) involved in the hyperpolarization of cell membranes (summary by Lodder et al., 2016).
For structural information about G proteins, see 600874.
Using a degenerate PCR approach to screen a human brain cDNA library, Jones et al. (1998) cloned the beta-5 subunit, symbolized GNB5, of G protein. In contrast to beta subunits 1 through 4, which are at least 83% homologous, GNB5 is only 50% homologous to the other beta subunits. On the other hand, the predicted 353-amino acid protein sequence is 99.4% homologous to the mouse beta-5 protein, with only 2 conservative amino acid differences. Northern blot analysis revealed that mouse Gnb5 is expressed predominantly in brain (Watson et al., 1994), whereas human GNB5 is expressed at high levels not only in brain but also in pancreas, kidney, and heart (Jones et al., 1998), as a major 3.0- and minor 2.0- and 9.0-kb transcripts. Within the brain, Jones et al. (1998) detected highest expression in cerebellum, cerebral cortex, occipital pole, frontal lobe, temporal lobe, and caudate putamen, and lowest expression in corpus callosum and spinal cord.
Watson et al. (1996) reported the cloning of a retina-specific cDNA, termed G-beta-5L, in the mouse, which is identical to GNB5 except for an additional 126-bp 5-prime exon.
Rosskopf et al. (2003) determined that the GNB5 gene contains 12 exons. The first exon is noncoding and exons 2 and 3 contain alternate ATG translational start codons.
Gross (2018) mapped the GNB5 gene to chromosome 15q21.2 based on an alignment of the GNB5 sequence (GenBank BC013997) with the genomic sequence (GRCh38).
GNB5 interacts with regulator of G protein signaling (RGS) proteins containing the G protein gamma-like (GGL) domain: RGS6 (603894), RGS7 (602517), RGS9 (604067), and RGS11 (603895). Chen et al. (2003) presented data indicating that GNB5 and GGL domain-containing RGS proteins are obligate partners and supporting the notion that GNB5 functions as a component of the GTPase-accelerating protein (GAP) complex.
In mouse hippocampus and striatum, Xie et al. (2012) found expression of Gnb5 in pre- and postsynaptic regions and in dendritic shafts and spines of neurons. Localization was observed both at the plasma membrane and in intracellular regions, as well as at the active zone of the axonal terminals.
Lodder-Merla Syndrome Type 1 with Impaired Intellectual Development and Cardiac Arrhythmia
In 6 patients from 4 unrelated families with Lodder-Merla syndrome type 1 with impaired intellectual development and cardiac arrhythmia (LDMLS1; 617173), Lodder et al. (2016) identified homozygous or compound heterozygous truncating mutations in the GNB5 gene (604447.0001-604447.0005). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Functional studies of the variants were not performed; studies of patient cells, performed only in 1 family (family A) with compound heterozygous truncating variants, demonstrated that both alleles were subject to nonsense-mediated mRNA, resulting in a putative complete loss of function.
In a consanguineous Turkish family in which 5 sibs and their second cousin had LDMLS1, Turkdogan et al. (2017) identified homozygosity for a 1-bp deletion in the GNB5 gene (604447.0007) that segregated with disease in the family.
In a 2-year-old boy with severe developmental delay and bradycardia, Vernon et al. (2018) identified compound heterozygosity for a 5-bp deletion (604447.0008) and a missense mutation (R246Q; 604447.0009) in the GNB5 gene. The mutations segregated with disease in the family and were not found in the ExAC database.
In a 3-year-old girl of South Asian descent with global developmental delay, seizures, severe bradycardia, and retinopathy, Shao et al. (2020) identified homozygosity for a nonsense mutation in the GNB5 gene (Y344X; 604447.0010).
In 5 children from 4 families with LDMLS1, Poke et al. (2019) identified homozygosity for mutations in the GNB5 gene (see, e.g., 604447.0005, 604447.0010, and 604447.0011). The variants segregated with disease in all families and were either not found or were present at very low minor allele frequency in public variant databases.
In 2 Pakistani brothers, 18 and 22 years of age, with severe global cognitive and motor delay, nocturnal seizures, cortical visual impairment, and sick sinus syndrome, Yazdani et al. (2020) identified homozygosity for the previously reported Y344X mutation (604447.0005) in the GNB5 gene. Their mother was heterozygous for the mutation; DNA was unavailable from their father.
In a 6-month-old Han Chinese boy with LDMLS1, Tang et al. (2020) identified compound heterozygosity for a previously reported nonsense mutation (Y344X; 604447.0010) and a missense mutation (C153Y; 604447.0012). The missense substitution was inherited from his mother, whereas the nonsense mutation arose de novo; neither was found in public variant databases.
Lodder-Merla Syndrome Type 2 with Developmental Delay and with or without Cardiac Arrhythmia (LDMLS2)
In 3 patients from 2 unrelated families (family E of Moroccan ancestry and family F from Brazil) with Lodder-Merla syndrome type 2 with developmental delay and cardiac arrhythmia (LDMLS2; 617182), Lodder et al. (2016) identified a homozygous missense mutation in the GNB5 gene (S81L; 604447.0006). Functional studies of the variant were not performed. These patients were part of a cohort of 9 patients from 6 families who were found to have GNB5 mutations: those with truncating mutations had a more severe phenotype (LDMLS1) than those with the missense mutation, suggesting a genotype/phenotype correlation.
In 5 girls from a large consanguineous Saudi family with LDMLS2 without cardiac arrhythmia, Shamseldin et al. (2016) identified a homozygous S81L substitution in the GNB5 gene. The mutation, which was found by a combination of linkage analysis and exome sequencing, segregated with the disorder in the family. In vitro functional expression assays showed that the S81L mutation resulted in severe but incomplete loss of function, leading to weaker activity of RGS complexes and a decreased ability to deactivate DRD2-mediated signaling by dopamine. Shamseldin et al. (2016) noted that knockdown of the Gnb5 gene in C. elegans results in increased locomotor activity (Porter et al., 2010), and that knockdown of the mouse ortholog results in hyperactivity and abnormal motor coordination (Xie et al., 2012), making the gene a candidate for attention deficit-hyperactivity disorder (see ANIMAL MODEL).
In a 2.5-year-old girl with moderate psychomotor delay and sinus node dysfunction, Malerba et al. (2018) identified compound heterozygosity for 2 previously reported mutations in the GNB5 gene: an S81L substitution (604447.0006) and a 5-bp deletion (604447.0008). Her unaffected parents were heterozygous for the variants.
The 'flailer' (flr) mouse exhibits a phenotype consisting of frequent falling, convulsive limb movements (leg flailing), and ataxia persistent into adulthood. Jones et al. (2000) determined that the flailer mouse expresses a novel gene combining the promoter and first 2 exons of Gnb5 with the C-terminal exons of the closely linked myosin-5A (MyoVA) gene (Myo5a; 160777). Biochemical and genetic studies indicated that the flailer protein, which is expressed predominantly in brain, competes with wildtype MyoVA in vivo, preventing the localization of smooth endoplasmic reticulum vesicles in the dendritic spines of cerebellar Purkinje cells. The flailer protein thus has a dominant-negative mechanism of action with a recessive mode of inheritance due to the dependence of competitive binding on the ratio between mutant and wildtype proteins. The chromosomal arrangement of Myo5a upstream of Gnb5 is consistent with nonhomologous recombination as the mutational mechanism.
Zhang et al. (2011) found that homozygous Gnb5-knockout mice were runty at birth and exhibited persistent smaller body size compared with wildtype littermates. Knockout mice showed significantly delayed or absent surface righting reflex, and markedly abnormal placing responses, indicating impaired neurobehavioral development. Mice lacking Gnb5 also displayed abnormal gait, balance, gross motor coordination, and motor learning, as well as hyperactivity. Consistent with these findings, the authors confirmed defects in cerebellar and hippocampal development in Gnb5-knockout mice. Multiple genes were dysregulated in brains of knockout mice. Zhang et al. (2011) concluded that GNB5 regulates dendritic arborization and/or synapse formation during development, partly by regulating gene expression.
Xie et al. (2012) found that Gnb5-null mice had hyperactivity and motor learning deficits, as well as a paradoxical adaptation to a novel environment. Gnb5-null mouse brains had lower levels of extracellular dopamine as well as slowed dopamine release and reuptake compared to wildtype. There was also increased sensitivity to inhibitory pre- and postsynaptic G-protein coupled receptor signaling, consistent with the loss of the inhibitory effects of Gnb5/RGS on other receptor signaling pathways. Pharmacologic treatment with monoamine reuptake inhibitors were ineffective in reducing hyperactivity; however, NMDA receptor blockade completely reversed hyperactivity, suggesting that the mutant mice had changes in glutamatergic signaling. The findings indicated that Gnb5-RGS complexes serve as key modulators of signaling pathways that control neuronal excitability and motor activity.
Lodder et al. (2016) used CRISPR/Cas9 genome editing to generate complete loss of gnb5 function in zebrafish; mutant zebrafish had impaired swimming activity, remained small, and died 7 to 14 days post-fertilization, likely due to an inability to feed. Treatment of mutant larvae with carbachol, a parasympathomimetic compound that activates the GNB5/RGS/GIRK (G protein-coupled inward rectifier potassium) channel pathway, resulted in a strong decrease in heart rate compared to controls. Treatment with a sympathetic agonist resulted in an increased heart rate similar to controls. These findings indicated that loss of gnb5 caused a loss of negative regulation of the cardiac GIRK channel and parasympathetic control, without effects on sympathetic control. Mutant larvae were predominantly unresponsive to repeated tactile stimulation, apparently due to neurologic deficits, not muscle dysfunction, and showed impaired optokinetic responses, also with normal eye muscle function. The findings indicated that Gnb5 is important for neuronal signaling and autonomic function.
In 2 sisters of Italian descent (family A) with Lodder-Merla syndrome type 1 with impaired intellectual development and cardiac arrhythmia (LDMLS1; 617173), Lodder et al. (2016) identified compound heterozygous mutations in the GNB5 gene: a c.249G-A transition (c.249G-A, NM_006578.3) at the last nucleotide of exon 2, resulting in a splice site mutation, and a c.994C-T transition, resulting in an arg332-to-ter (R332X; 604447.0002) substitution. Analysis of patient cells showed that the c.249G-A variant caused aberrant splicing with the inclusion of intron 2, and was predicted to encode a truncated protein (Asp84Valfs52Ter). The transcripts of both alleles were demonstrated to result in nonsense-mediated mRNA decay, consistent with a complete loss of function. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither mutation was found in the found in the dbSNP (build 138) database; the c.249G-A mutation was not found in the ExAC database, whereas the R332X was found at a low frequency (8.24 x 10(-6)) in the ExAC database.
For discussion of the c.994C-T transition (c.994C-T, NM_006578.3) in the GNB5 gene, resulting in an arg332-to-ter (R332X) substitution that was found in compound heterozygous state in 2 sisters with Lodder-Merla syndrome type 1 with impaired intellectual development and cardiac arrhythmia (LDMLS1; 617173) by Lodder et al. (2016), see 604447.0001.
In a 6-year-old girl, born of consanguineous parents of Jordanian descent (family B), with Lodder-Merla syndrome type 1 with impaired intellectual development and cardiac arrhythmia (LDMLS1; 617173), Lodder et al. (2016) identified a homozygous G-to-T transversion in intron 2 of the GNB5 gene (c.249+1G-T, NM_006578.3), resulting in a splice site alteration and predicted to encode a truncated protein (Asp84Leufs31Ter). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and was not found in the dbSNP (build 138) or ExAC databases. The mutation was predicted to result in a loss of function, but functional studies of the variant and studies of patient cells were not performed.
In 2 sibs, born of consanguineous parents of Puerto Rican descent (family C), with Lodder-Merla syndrome type 1 with impaired intellectual development and cardiac arrhythmia (LDMLS1; 617173), Lodder et al. (2016) identified a homozygous A-to-G transition in intron 2 of the GNB5 gene (c.249+3A-G, NM_006578.3), resulting in a splice site alteration and predicted to encode a truncated protein (Asp84Valfs31Ter). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP (build 138) or ExAC databases. The mutation was predicted to result in a loss of function, but functional studies of the variant and studies of patient cells were not performed.
In a 12-year-old girl of Indian descent (family D) with Lodder-Merla syndrome type 1 with impaired intellectual development and cardiac arrhythmia (LDMLS1; 617173), Lodder et al. (2016) identified a homozygous c.906C-G transversion (c.906C-G, NM_006578.3) in the GNB5 gene, resulting in a tyr302-to-ter (Y302X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the dbSNP (build 138) database, but was found at a low frequency (8.26 x 10(-6)) in the ExAC database. The mutation was predicted to result in a loss of function, but functional studies of the variant and studies of patient cells were not performed.
In a 3-year-old Pakistani boy (patient 2) with infantile spasms and bradycardia with 6.9-second pauses, who was nonverbal and nonambulatory, Poke et al. (2019) identified homozygosity for the previously reported Y302X mutation in the GNB5 gene.
In 2 Pakistani brothers, 18 and 22 years of age, with severe global cognitive and motor delay, nocturnal seizures, cortical visual impairment, and sick sinus syndrome, Yazdani et al. (2020) identified homozygosity for a c.1032C-G transversion (c.1032C-G, NM_016194.3) in the GNB5 gene, resulting in a Y344X substitution in the GNB5 gene. Their mother was heterozygous for the mutation; DNA was unavailable from their father. Poke et al. (2019) noted that the base positions c.906C and c.1032C are equivalent in the transcripts NM_006578.3 and NM_016194.3, respectively.
In 3 patients from 2 unrelated families (family E of Moroccan ancestry and family F from Brazil) with Lodder-Merla syndrome type 2 with developmental delay and cardiac arrhythmia (LDMLS2; 617182) Lodder et al. (2016) identified a homozygous c.242C-T transition (c.242C-T, NM_006578.3) in exon 2 of the GNB5 gene, resulting in a ser81-to-leu (S81L) substitution at a highly conserved residue in the first WD40 domain in a beta-strand close to the central pore. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. The variant was not found in the dbSNP (build 138) database; it was present at a frequency of less than 5 x 10(-5) in the ExAC database (6 in 121,000), and 4.3 x 10(-4) in Latinos (5 in 11,574). Among individuals from Morocco, the prevalence of the variant was 1 in 1,260 (7.94 x 10(-4)). Molecular modeling suggested that the S81L substitution could induce localized structural changes that could impair both the central pore and the binding kinetics to regulator proteins, possibly leading to impaired function. Functional studies of the variant and studies of patient cells were not performed.
In 5 girls from a large consanguineous Saudi family with LDMLS2 without cardiac arrhythmia, Shamseldin et al. (2016) identified a homozygous S81L substitution in the GNB5 gene. The mutation, which was found by a combination of linkage analysis and exome sequencing, segregated with the disorder in the family and was not found in the 1000 Genomes Project database or in 2,379 Saudi exomes. Patient cells showed decreased levels of the mutant protein, suggesting instability, and transfection studies in HEK293 cells showed that the mutation also had a detrimental effect on the folding or stability of R7 RGS complexes. In vitro functional expression assays showed that the S81L mutation resulted in severe but incomplete loss of function, resulting in weaker activity of RGS complexes and a decreased ability to deactivate DRD2-mediated signaling by dopamine.
In a 2.5-year-old girl with moderate psychomotor delay and sinus node dysfunction, Malerba et al. (2018) identified compound heterozygosity for mutations in exon 2 of the GNB5 gene: the S81L substitution and a 5-bp deletion (604447.0008). Her unaffected parents were heterozygous for the variants.
In a 10-year-old girl and her 2-year-old affected second cousin from a consanguineous Turkish family with early infantile epileptic encephalopathy, severe neurologic developmental delay, nystagmus, retinal degeneration, cardiac conduction disorder, and premature sudden death (LDMLS1; 617173), Turkdogan et al. (2017) identified homozygosity for a 1-bp deletion (c.355delG) in the GNB5 gene, causing a frameshift predicted to result in a premature termination codon (Ala119ProfsTer16). Both sets of unaffected parents and 2 unaffected sisters of the proband were heterozygous for the deletion; DNA was unavailable from the proband's 4 affected sibs who had died.
LDMLS1
In a 2-year-old boy with severe developmental delay and bradycardia (LDMLS1; 617173), Vernon et al. (2018) identified compound heterozygosity for mutations in the GNB5 gene: a 5-bp deletion (c.222_226delTAAGA, NM_006578.3), causing a frameshift predicted to result in a premature termination codon (Asp74GlufsTer52), and a c.737G-A transition, resulting in an arg246-to-gln (R246W; 604447.0009) substitution at a conserved residue on the binding surface of the central pore. The authors noted that the c.737G-A variant, involving the last nucleotide of exon 7, might alternatively affect splicing. The proband's unaffected parents were each heterozygous for 1 of the variants, neither of which was found in the ExAC database. The proband was nonverbal, could not sit independently, and made minimal voluntary movements.
LDMLS2
In a 2.5-year-old girl with moderate psychomotor delay and sinus node dysfunction (LDMLS2; 617182) Malerba et al. (2018) identified compound heterozygosity for mutations in exon 2 of the GNB5 gene: a previously reported S81L substitution (604447.0006) and a 5-bp deletion (c.222_226delTAAGA). Her unaffected parents were heterozygous for the variants. The proband spoke 12 words and used sign language, and was ambulatory with a wide-based gait.
For discussion of the c.737G-A transition (c.737G-A, NM_006578.3) in the GNB5 gene, resulting in an arg246-to-gln (R246Q) substitution, that was found in compound heterozygous state in a 2-year-old boy with Lodder-Merla syndrome type 1 with impaired intellectual development and cardiac arrhythmia (LDMLS1; 617173) by Vernon et al. (2018), see 604447.0008.
In a 3-year-old girl of South Asian descent with global developmental delay, seizures, severe bradycardia, and retinopathy (LDMLS1; 617173), Shao et al. (2020) identified homozygosity for a c.906C-A transversion (c.906C-A, NM_006578.3) in the GNB5 gene, resulting in a tyr302-to-ter (Y302X) substitution in the short GNB5 transcript. The mutation was designated Y344X in the long transcript (c.1032C-A, NM_016194.3). The mutation status of her parents was not reported.
In a 3-year-old girl (patient 5) with profound intellectual disability who was nonverbal and nonambulatory, and had seizures, sinus bradycardia with 4.2-second pauses, nystagmus, and retinopathy, Poke et al. (2019) identified homozygosity for the Y302X (c.906C-A) substitution in the GNB5 gene. Her parents were heterozygous for the mutation, which was not found in the ExAC database, but was present in 1 allele in the gnomAD database (minor allele frequency, 0.000003982).
In a 6-month-old Han Chinese boy with LDMLS1, Tang et al. (2020) identified compound heterozygous mutation in the GNB gene: the previously reported Y344X (c.1032C-A, NM_016194) mutation and a c.458G-A transition, resulting in a cys153-to-tyr (C153Y; 604447.0012) substitution at a highly conserved residue within the first WD domain. The missense substitution was inherited from his mother, whereas the nonsense mutation arose de novo; neither was found in public variant databases.
In 2 Algerian sisters (patients 3 and 4) with profound intellectual disability and bradycardia, who were nonverbal and nonambulatory (LDMLS1; 617173), Poke et al. (2019) identified homozygosity for a c.242C-A transversion (c.242C-A, NM_006578.3) in the short transcript of the GNB5 gene, resulting in a ser81-to-ter (S81X) substitution. The mutation was designated c.368C-A/S123X in the long isoform (c.368C-A, NM_016194). Their first-cousin parents were heterozygous for the mutation, which was not found in the ExAC or gnomAD databases. The older sister (patient 3) died in her sleep at age 13 years.
For discussion of the c.458G-A transition (c.458G-A, NM_016194) in the GNB5 gene, resulting in a cys153-to-tyr (C153Y) substitution, that was found in compound heterozygous state in a 6-month-old Han Chinese boy with Lodder-Merla syndrome type 1 (LDMLS1; 617173) by Tang et al. (2020), see 604447.0010.
Chen, C.-K., Eversole-Cire, P., Zhang, H., Mancino, V., Chen, Y.-J., He, W., Wensel, T. G., Simon, M. I. Instability of GGL domain-containing RGS proteins in mice lacking the G protein beta-subunit G-beta-5. Proc. Nat. Acad. Sci. 100: 6604-6609, 2003. [PubMed: 12738888] [Full Text: https://doi.org/10.1073/pnas.0631825100]
Gross, M. B. Personal Communication. Baltimore, Md. 7/16/2018.
Jones, J. M., Huang, J.-D., Mermall, V., Hamilton, B. A., Mooseker, M. S., Escayg, A., Copeland, N. G., Jenkins, N. A., Meisler, M. H. The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a. Hum. Molec. Genet. 9: 821-828, 2000. [PubMed: 10749990] [Full Text: https://doi.org/10.1093/hmg/9.5.821]
Jones, P. G., Lombardi, S. J., Cockett, M. I. Cloning and tissue distribution of the human G protein beta-5 cDNA. Biochim. Biophys. Acta 1402: 288-291, 1998. [PubMed: 9606987] [Full Text: https://doi.org/10.1016/s0167-4889(98)00017-2]
Lodder, E. M., De Nittis, P., Koopman, C. D., Wiszniewski, W., Moura de Souza, C. F., Lahrouchi, N., Guex, N., Napolioni, V., Tessadori, F., Beekman, L., Nannenberg, E. A., Boualla, L., and 21 others. GNB5 mutations cause an autosomal-recessive multisystem syndrome with sinus bradycardia and cognitive disability. Am. J. Hum. Genet. 99: 704-710, 2016. Note: Erratum: Am. J. Hum. Genet. 99: 786 only, 2016. [PubMed: 27523599] [Full Text: https://doi.org/10.1016/j.ajhg.2016.06.025]
Malerba, N., Towner, S., Keating, K., Squeo, G. M., Wilson, W., Merla, G. A NGS-targeted autism/ID panel reveals compound heterozygous GNB5 variants in a novel patient. Front. Genet. 9: 626, 2018. [PubMed: 30631341] [Full Text: https://doi.org/10.3389/fgene.2018.00626]
Poke, G., King, C., Muir, A., de Valles-Ibanez, G., Germano, M., Moura de Souza, C. F., Fung, J., Chung, B., Fung, C. W., Mignot, C., Ilea, A., Keren, B., and 11 others. The epileptology of GNB5 encephalopathy. Epilepsia 60: e121-e127, 2019. [PubMed: 31631344] [Full Text: https://doi.org/10.1111/epi.16372]
Porter, M. Y., Xie, K., Pozharski, E., Koelle, M. R., Martemyanov, K. A. A conserved protein interaction interface on the type 5 G protein beta subunit controls proteolytic stability and activity of R7 family regulator of G protein signaling proteins. J. Biol. Chem. 285: 41100-41112, 2010. [PubMed: 20959458] [Full Text: https://doi.org/10.1074/jbc.M110.163600]
Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W. The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction. FEBS Lett. 544: 27-32, 2003. [PubMed: 12782285] [Full Text: https://doi.org/10.1016/s0014-5793(03)00441-1]
Shamseldin, H. E., Masuho, I., Alenizi, A., Alyamani, S., Patil, D. N., Ibrahim, N., Martemyanov, K. A., Alkuraya, F. S. GNB5 mutation causes a novel neuropsychiatric disorder featuring attention deficit hyperactivity disorder, severely impaired language development and normal cognition. Genome Biol. 17: 195, 2016. Note: Electronic Article. [PubMed: 27677260] [Full Text: https://doi.org/10.1186/s13059-016-1061-6]
Shao, Z., Tumber, A., Maynes, J., Tavares, E., Kannu, P., Heon, E., Vincent, A. Unique retinal signaling defect in GNB5-related disease. Docum. Ophthal. 140: 273-277, 2020. [PubMed: 31720979] [Full Text: https://doi.org/10.1007/s10633-019-09735-1]
Tang, M., Wang, Y., Xu, Y., Tong, W., Jin, D., Yang, X. A. IDDCA syndrome in a Chinese infant due to GNB5 biallelic mutations. J. Hum. Genet. 65: 627-631, 2020. [PubMed: 32203251] [Full Text: https://doi.org/10.1038/s10038-020-0742-x]
Turkdogan, D., Usluer, S., Akalin, F., Agyuz, U., Aslan, E. S. Familial early infantile epileptic encephalopathy and cardiac conduction disorder: A rare cause of SUDEP in infancy. Seizure 50: 171-172, 2017. [PubMed: 28697420] [Full Text: https://doi.org/10.1016/j.seizure.2017.06.019]
Vernon, H., Cohen, J., De Nittis, P., Fatemi, A., McClellan, R., Goldstein, A., Malerba, N., Guex, N., Reymond, A., Merla, G. Intellectual developmental disorder with cardiac arrhythmia syndrome in a child with compound heterozygous GNB5 variants. Clin. Genet. 93: 1254-1256, 2018. [PubMed: 29368331] [Full Text: https://doi.org/10.1111/cge.13194]
Watson, A. J., Aragay, A. M., Slepak, V. Z., Simon, M. I. A novel form of the G protein beta subunit G-beta-5 is specifically expressed in the vertebrate retina. J. Biol. Chem. 271: 28154-28160, 1996. [PubMed: 8910430] [Full Text: https://doi.org/10.1074/jbc.271.45.28154]
Watson, A. J., Katz, A., Simon, M. I. A fifth member of the mammalian G-protein beta subunit family: expression in brain and activation of the beta-2 isotype of phospholipase C. J. Biol. Chem. 269: 22150-22156, 1994. [PubMed: 8071339]
Xie, K., Ge, S., Collins, V. E., Haynes, C. L., Renner, K. J., Meisel, R. L., Lujan, R., Martemyanov, K. A. G-beta5-RGS complexes are gatekeepers of hyperactivity involved in control of multiple neurotransmitter systems. Psychopharmacology 219: 823-834, 2012. [PubMed: 21766168] [Full Text: https://doi.org/10.1007/s00213-011-2409-y]
Yazdani, S., Badjatiya, A., Dorrani, N., Lee, H., Grody, W. W., Nelson, S. F., Dipple, K. M. Genetic characterization and long-term management of severely affected siblings with intellectual developmental disorder with cardiac arrhythmia syndrome. Molec. Genet. Metab. Rep. 23: 100582, 2020. [PubMed: 32280589] [Full Text: https://doi.org/10.1016/j.ymgmr.2020.100582]
Zhang, J.-H., Pandey, M., Seigneur, E. M., Panicker, L. M., Koo, L., Schwartz, O. M., Chen, W., Chen, C.-K., Simonds, W. F. Knockout of G protein beta-5 impairs brain development and causes multiple neurologic abnormalities in mice. J. Neurochem. 119: 544-554, 2011. [PubMed: 21883221] [Full Text: https://doi.org/10.1111/j.1471-4159.2011.07457.x]