GNB1

G protein subunit beta 1, the group of G protein subunits beta|WD repeat domain containing

Basic information

Region (hg38): 1:1785284-1892292

Links

ENSG00000078369 ∙ NCBI:2782 ∙ OMIM:139380 ∙ HGNC:4396 ∙ Uniprot:P62873 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 42 (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 42 (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 42 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual development disorder, autosomal dominant 42	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Ophthalmologic	27108799

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNB1 gene.

• not provided (209 variants)
• Intellectual disability, autosomal dominant 42 (32 variants)
• Inborn genetic diseases (10 variants)
• Neurodevelopmental Disability;Hypotonia;Seizure (8 variants)
• Intellectual disability (4 variants)
• not specified (3 variants)
• Global developmental delay (2 variants)
• Acute lymphoid leukemia (2 variants)
• Neurodevelopmental delay (2 variants)
• See cases (2 variants)
• Myelodysplastic syndrome;Intellectual disability, autosomal dominant 42;Acute lymphoid leukemia (2 variants)
• Global developmental delay-neuro-ophthalmological abnormalities-seizures-intellectual disability syndrome (2 variants)
• Cerebral palsy (1 variants)
• 7 conditions (1 variants)
• Neurodevelopmental disorder (1 variants)
• Microcephaly (1 variants)
• Myelodysplastic syndrome (1 variants)
• Intellectual disability;Global developmental delay;Hypotonia;Infantile muscular hypotonia (1 variants)
• 14 conditions (1 variants)
• Global developmental delay;Hypotonia (1 variants)
• Hypotonia (1 variants)
• 8 conditions (1 variants)
• 11 conditions (1 variants)
• GNB1-Related Disorder (1 variants)
• Intellectual disability;Global developmental delay;Bilateral tonic-clonic seizure;Hypotonia;Seizure (1 variants)
• 13 conditions (1 variants)
• 10 conditions (1 variants)
• LEUKEMIA, CHRONIC LYMPHOCYTIC, SOMATIC (1 variants)
• Neurodevelopmental abnormality (1 variants)
• Autism spectrum disorder (1 variants)
• Atypical behavior;Dystonic disorder (1 variants)
• GNB1-related condition (1 variants)
• Autosomal dominant non-syndromic intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNB1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				70	3	73
missense	8	17	42	2	7	76
nonsense	1		2			3
start loss						0
frameshift	1	1	2			4
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)	2	3	1			6
splice region			4	12	3	19
non coding			4	20	9	33
Total	13	21	52	92	19

Highest pathogenic variant AF is 0.00000657

Variants in GNB1

This is a list of pathogenic ClinVar variants found in the GNB1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-1785747-C-G		Intellectual disability, autosomal dominant 42	Uncertain significance (Aug 06, 2021)
1-1787203-C-A			Benign (May 12, 2021)
1-1787332-T-C			Likely benign (Dec 27, 2023)
1-1787332-T-G			Uncertain significance (Nov 17, 2021)
1-1787340-GATC-G		Inborn genetic diseases	Pathogenic (Apr 25, 2016)
1-1787345-T-G			Uncertain significance (Dec 07, 2022)
1-1787347-A-T		Intellectual disability, autosomal dominant 42	Uncertain significance (May 22, 2022)
1-1787365-CCT-C			Uncertain significance (Mar 09, 2020)
1-1787370-C-T			Likely benign (Dec 20, 2023)
1-1787377-G-C			Uncertain significance (Mar 04, 2022)
1-1787377-G-T			Uncertain significance (Jul 19, 2022)
1-1787378-C-T		Intellectual disability;Global developmental delay;Bilateral tonic-clonic seizure;Hypotonia;Seizure • Neurodevelopmental Disability;Hypotonia;Seizure • Intellectual disability, autosomal dominant 42	Likely pathogenic (Feb 02, 2022)
1-1787383-C-T			Uncertain significance (Mar 14, 2023)
1-1787384-C-T			Uncertain significance (Dec 08, 2023)
1-1787388-G-A			Likely benign (Jul 09, 2023)
1-1787397-G-A			Likely benign (Dec 25, 2023)
1-1787399-C-G		Intellectual disability, autosomal dominant 42	Uncertain significance (Mar 13, 2020)
1-1787403-G-A			Likely benign (Oct 09, 2023)
1-1787411-C-T			Uncertain significance (Dec 06, 2022)
1-1787412-G-A			Likely benign (Dec 07, 2023)
1-1787418-G-A			Likely benign (Nov 08, 2022)
1-1787424-C-A			Likely benign (Jan 14, 2024)
1-1787429-C-A			Uncertain significance (Oct 28, 2023)
1-1787429-C-T			Uncertain significance (Feb 14, 2023)
1-1787433-G-A			Likely benign (Aug 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNB1	protein_coding	protein_coding	ENST00000378609	9	105767

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000801	125083	0	1	125084	0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.83	64	226	0.283	0.0000145	2239
Missense in Polyphen		11	77.385	0.14215		821
Synonymous	0.328	86	90.0	0.956	0.00000623	667
Loss of Function	4.21	0	20.6	0.00	0.00000122	190

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein- effector interaction.
• Disease: DISEASE: Mental retardation, autosomal dominant 42 (MRD42) [MIM:616973]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD42 patients manifest global developmental delay commonly accompanied by hypotonia, seizures of various types, ophthalmological manifestations, and poor growth. {ECO:0000269|PubMed:25485910, ECO:0000269|PubMed:27108799, ECO:0000269|PubMed:27668284, ECO:0000269|PubMed:28087732}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Phototransduction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Alcoholism - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Excitatory Neural Signalling Through 5-HTR 4 and Serotonin;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Intracellular Signalling Through Prostacyclin Receptor and Prostacyclin;Corticotropin Activation of Cortisol Production;Excitatory Neural Signalling Through 5-HTR 7 and Serotonin ;Excitatory Neural Signalling Through 5-HTR 6 and Serotonin ;Vasopressin Regulation of Water Homeostasis;Intracellular Signalling Through PGD2 receptor and Prostaglandin D2;Intracellular Signalling Through LHCGR Receptor and Luteinizing Hormone/Choriogonadotropin;Intracellular Signalling Through FSH Receptor and Follicle Stimulating Hormone;Intracellular Signalling Through Histamine H2 Receptor and Histamine;Dopamine Activation of Neurological Reward System;Nicotine Activity on Dopaminergic Neurons;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Corticotropin-releasing hormone signaling pathway;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;Chemokine signaling pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Ras Signaling;Calcium Regulation in the Cardiac Cell;Estrogen signaling pathway;Signaling by GPCR;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;Signaling by WNT;Signal Transduction;bioactive peptide induced signaling pathway;g-protein signaling through tubby proteins;visual signal transduction;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;aspirin blocks signaling pathway involved in platelet activation;regulation of ck1/cdk5 by type 1 glutamate receptors;cxcr4 signaling pathway;corticosteroids and cardioprotection;phospholipids as signalling intermediaries;cystic fibrosis transmembrane conductance regulator (cftr) and beta 2 adrenergic receptor (b2ar) pathway;ion channels and their functional role in vascular endothelium;ccr3 signaling in eosinophils;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;chrebp regulation by carbohydrates and camp;signaling pathway from g-protein families;thrombin signaling and protease-activated receptors;how progesterone initiates the oocyte maturation;attenuation of gpcr signaling;role of -arrestins in the activation and targeting of map kinases;activation of camp-dependent protein kinase pka;Glucagon signaling in metabolic regulation;Thromboxane signalling through TP receptor;Metabolism of proteins;ADP signalling through P2Y purinoceptor 12;Chaperonin-mediated protein folding;Metabolism;Olfactory Signaling Pathway;G alpha (s) signalling events;Presynaptic function of Kainate receptors;Activation of kainate receptors upon glutamate binding;Adrenaline,noradrenaline inhibits insulin secretion;Transport of small molecules;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Regulation of insulin secretion;Signal amplification;Neuronal System;roles of arrestin dependent recruitment of src kinases in gpcr signaling;CRH;Thrombin signalling through proteinase activated receptors (PARs);regulation of spermatogenesis by crem;actions of nitric oxide in the heart;Glucagon-type ligand receptors;Class B/2 (Secretin family receptors);GPCR ligand binding;Platelet activation, signaling and aggregation;Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits;Activation of GABAB receptors;Signaling events mediated by HDAC Class II;Ca2+ pathway;Beta-catenin independent WNT signaling;ADP signalling through P2Y purinoceptor 1;CXCR4-mediated signaling events;fmlp induced chemokine gene expression in hmc-1 cells;Hemostasis;-arrestins in gpcr desensitization;Visual signal transduction: Rods;Thromboxane A2 receptor signaling;Protein folding;G-protein activation;GABA B receptor activation;Rapid glucocorticoid signaling;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Opioid Signalling;G alpha (i) signalling events;Activation of the phototransduction cascade;G alpha (12/13) signalling events;G alpha (z) signalling events;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;Vasopressin regulates renal water homeostasis via Aquaporins;Aquaporin-mediated transport;Activation of G protein gated Potassium channels;G beta:gamma signalling through PLC beta;Prostacyclin signalling through prostacyclin receptor;Integration of energy metabolism;Platelet homeostasis;G alpha (q) signalling events;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;G protein gated Potassium channels;Inwardly rectifying K+ channels;Potassium Channels;PAR4-mediated thrombin signaling events;PAR1-mediated thrombin signaling events;LPA receptor mediated events;IL8- and CXCR1-mediated signaling events;CXCR3-mediated signaling events;Plasma membrane estrogen receptor signaling;Nongenotropic Androgen signaling;Hedgehog signaling events mediated by Gli proteins;IL8- and CXCR2-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.260

Intolerance Scores

• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.862
• hipred: Y
• hipred_score: 0.783
• ghis: 0.676

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.873

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Gnb1
• Phenotype: cellular phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype

Zebrafish Information Network

• Gene name: gnb1a
• Affected structure: neuromast
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein folding;signal transduction;G protein-coupled receptor signaling pathway;adenylate cyclase-activating dopamine receptor signaling pathway;phospholipase C-activating G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;G protein-coupled acetylcholine receptor signaling pathway;Wnt signaling pathway, calcium modulating pathway;Ras protein signal transduction;cell population proliferation;cardiac muscle cell apoptotic process;rhodopsin mediated signaling pathway;platelet activation;sensory perception of taste;retina development in camera-type eye;protein heterotrimerization;cellular response to prostaglandin E stimulus;cellular response to hypoxia;cellular response to catecholamine stimulus
• Cellular component: photoreceptor inner segment;lysosomal membrane;cytosol;heterotrimeric G-protein complex;plasma membrane;membrane;dendrite;photoreceptor outer segment membrane;myelin sheath;cell body;extracellular exosome;photoreceptor disc membrane;extracellular vesicle
• Molecular function: GTPase activity;protein binding;spectrin binding;protein-containing complex binding;alkylglycerophosphoethanolamine phosphodiesterase activity;GTPase binding