GNB3

G protein subunit beta 3, the group of WD repeat domain containing|G protein subunits beta

Basic information

Region (hg38): 12:6839954-6847393

Links

ENSG00000111664 ∙ NCBI:2784 ∙ OMIM:139130 ∙ HGNC:4400 ∙ Uniprot:P16520 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital stationary night blindness (Supportive), mode of inheritance: AD
• congenital stationary night blindness 1H (Limited), mode of inheritance: AR
• congenital stationary night blindness 1H (Strong), mode of inheritance: AR
• congenital stationary night blindness 1H (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Night blindness, congenital stationary, type 1H	AR	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	Ophthalmologic	27063057

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNB3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNB3 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			2	52	8	62
missense			132	1	2	135
nonsense			6			6
start loss			1			1
frameshift			7			7
inframe indel			3			3
splice donor/acceptor (+/-2bp)			4			4
splice region			4	9		13
non coding				67	20	87
Total	0	0	155	120	30

Variants in GNB3

This is a list of pathogenic ClinVar variants found in the GNB3 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-6841239-G-A			Benign (May 12, 2021)
12-6841289-T-C			Uncertain significance (Dec 02, 2022)
12-6841291-G-A			Uncertain significance (Apr 10, 2023)
12-6841292-G-A			Uncertain significance (May 24, 2023)
12-6841295-A-G			Uncertain significance (May 06, 2021)
12-6841298-T-C			Uncertain significance (Dec 18, 2023)
12-6841309-C-T			Uncertain significance (Nov 20, 2023)
12-6841310-G-A			Uncertain significance (Jan 06, 2024)
12-6841315-G-A			Uncertain significance (Mar 17, 2020)
12-6841319-C-T		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
12-6841320-G-A			Likely benign (Aug 02, 2021)
12-6841320-G-T			Likely benign (Nov 24, 2022)
12-6841323-G-C			Uncertain significance (Jun 13, 2022)
12-6841326-G-A			Likely benign (Jul 17, 2023)
12-6841328-T-G			Uncertain significance (Jul 30, 2022)
12-6841332-G-A			Likely benign (Oct 03, 2023)
12-6841343-C-T			Uncertain significance (Aug 15, 2022)
12-6841350-T-C			Uncertain significance (Aug 22, 2022)
12-6841358-C-T			Likely benign (Mar 08, 2023)
12-6841363-C-T			Likely benign (May 25, 2022)
12-6841559-CTCCCCTGATGTCTGCTTTCCCTGCAGGA-C			Uncertain significance (Sep 07, 2022)
12-6841567-A-G			Likely benign (Nov 13, 2023)
12-6841577-T-C			Likely benign (Jan 08, 2024)
12-6841601-T-C			Uncertain significance (Jun 05, 2023)
12-6841608-A-G			Uncertain significance (Aug 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNB3	protein_coding	protein_coding	ENST00000229264	9	7440

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.33e-11	0.0882	125692	0	56	125748	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	175	219	0.801	0.0000137	2230
Missense in Polyphen		56	75.972	0.73711		773
Synonymous	-0.0823	88	87.0	1.01	0.00000602	664
Loss of Function	0.322	17	18.5	0.919	9.72e-7	191

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000724	0.000721
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000111	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000170	0.000167
Middle Eastern	0.000111	0.000109
South Asian	0.000438	0.000425
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: Night blindness, congenital stationary, 1H (CSNB1H) [MIM:617024]: A form of congenital stationary night blindness, a non-progressive retinal disorder characterized by impaired night vision or in dim light, with good vision only on bright days. CSNB1H patients present with childhood-onset night blindness and middle age-onset photophobia, but have near-normal vision and do not exhibit nystagmus or high myopia. CSNB1H inheritance is autosomal recessive. {ECO:0000269|PubMed:27063057}. 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);Taste transduction - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Alcoholism - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;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;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signaling by GPCR;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;Signaling by WNT;Signal Transduction;Glucagon signaling in metabolic regulation;GPCR Dopamine D1like receptor;GPCR Adenosine A2A receptor;Thromboxane signalling through TP receptor;GPCR GroupI metabotropic glutamate receptor;Metabolism of proteins;GPCR signaling-G alpha q;ADP signalling through P2Y purinoceptor 12;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Chaperonin-mediated protein folding;Metabolism;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;CRH;Thrombin signalling through proteinase activated receptors (PARs);Glucagon-type ligand receptors;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits;Activation of GABAB receptors;Ca2+ pathway;Beta-catenin independent WNT signaling;ADP signalling through P2Y purinoceptor 1;Hemostasis;Protein folding;G-protein activation;GABA B receptor activation;GABA receptor activation;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Opioid Signalling;G alpha (i) signalling events;G alpha (12/13) signalling events;G alpha (z) signalling events;GPCR signaling-G alpha i;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;Visual signal transduction: Cones (Consensus)

Recessive Scores

• pRec: 0.281

Intolerance Scores

• loftool: 0.710
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.151
• hipred: N
• hipred_score: 0.412
• ghis: 0.552

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.517

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gnb3
• Phenotype: vision/eye phenotype; 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)

Gene ontology

• Biological process: protein folding;cell volume homeostasis;G protein-coupled receptor signaling pathway;regulation of blood pressure;regulation of gene expression;regulation of glucose metabolic process;regulation of hormone metabolic process;regulation of fat cell differentiation;regulation of feeding behavior;regulation of cholesterol metabolic process;regulation of triglyceride metabolic process;regulation of locomotion involved in locomotory behavior;regulation of phospholipid metabolic process
• Cellular component: cytosol;plasma membrane;dendrite;cell body;extracellular exosome
• Molecular function: GTPase activity;protein binding;spectrin binding;GTPase binding