GNB2

G protein subunit beta 2, the group of WD repeat domain containing|G protein subunits beta

Basic information

Region (hg38): 7:100673567-100679174

Links

ENSG00000172354 ∙ NCBI:2783 ∙ OMIM:139390 ∙ HGNC:4398 ∙ Uniprot:P62879 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sick sinus syndrome 4 (Limited), mode of inheritance: Unknown
• neurodevelopmental disorder with hypotonia and dysmorphic facies (Strong), mode of inheritance: AD
• neurodevelopmental disorder with hypotonia and dysmorphic facies (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Sick sinus syndrome 4; Neurodevelopmental disorder with hypotonia and dysmorphic facies	AD	Cardiovascular; Renal	Individuals with Sick sinus syndrome have been described with arrhthymias, and awareness may allow prompt diagnosis and management (eg, pacemaker implantation has been described); Among other features, Neurodevelopmental disorder with hypotonia and dysmorphic facies can include congenital cardiovascular and renal anomalies, which may require medical and/or surgical interventions to help manage sequelae	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal	28219978; 31698099; 33971351; 34183358

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNB2 gene.

• Neurodevelopmental disorder with hypotonia and dysmorphic facies (2 variants)
• not provided (2 variants)
• GNB2-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNB2 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				1	1	2
missense	3	5	30	1		39
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				2		2
Total	3	5	31	4	1

Variants in GNB2

This is a list of pathogenic ClinVar variants found in the GNB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-100676163-CCTGCATCCCCCAGGCCTCGGGCCAGCGGCCAGGAG-C			Uncertain significance (Jan 31, 2024)
7-100676569-C-G			Uncertain significance (Nov 01, 2023)
7-100676700-C-T		Inborn genetic diseases	Uncertain significance (Jan 02, 2025)
7-100676739-G-A			Likely pathogenic (Feb 25, 2025)
7-100676742-G-A		Inborn genetic diseases	Uncertain significance (Dec 28, 2024)
7-100676745-C-T			Uncertain significance (Jul 28, 2022)
7-100676747-C-A			Uncertain significance (May 26, 2023)
7-100676751-G-A			Uncertain significance (Aug 31, 2024)
7-100676751-G-T		Sick sinus syndrome 4	Pathogenic (Apr 25, 2022)
7-100677365-G-A		Neurodevelopmental disorder with hypotonia and dysmorphic facies	Pathogenic/Likely pathogenic (Mar 14, 2024)
7-100677377-G-A		GNB2-related disorder • Neurodevelopmental disorder with hypotonia and dysmorphic facies	Pathogenic (Jul 03, 2024)
7-100677377-G-C			Uncertain significance (Aug 21, 2020)
7-100677377-G-T		Global developmental delay • Neurodevelopmental disorder with hypotonia and dysmorphic facies	Likely pathogenic (Mar 09, 2021)
7-100677378-G-A			Pathogenic (Oct 04, 2024)
7-100677408-CCAA-C			Uncertain significance (Sep 01, 2022)
7-100677413-A-G		Neurodevelopmental disorder with hypotonia and dysmorphic facies	Pathogenic (Aug 03, 2021)
7-100677414-A-C		Neurodevelopmental disorder with hypotonia and dysmorphic facies	Pathogenic (Apr 25, 2022)
7-100677487-C-G			Likely benign (Mar 05, 2019)
7-100677498-G-A		Inborn genetic diseases	Uncertain significance (Jun 22, 2021)
7-100677501-C-G			Uncertain significance (Aug 07, 2024)
7-100677514-T-C		Neurodevelopmental disorder with hypotonia and dysmorphic facies	Likely pathogenic (Aug 12, 2022)
7-100677546-G-A		Inborn genetic diseases	Uncertain significance (Jan 17, 2023)
7-100677556-G-A			Uncertain significance (Aug 13, 2021)
7-100677580-T-C			Uncertain significance (Nov 08, 2024)
7-100677587-C-A			Pathogenic (Apr 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNB2	protein_coding	protein_coding	ENST00000303210	9	5644

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0112	125687	0	2	125689	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.21	87	222	0.393	0.0000147	2221
Missense in Polyphen		14	76.522	0.18295		794
Synonymous	-2.58	129	96.7	1.33	0.00000727	678
Loss of Function	3.71	1	17.9	0.0558	9.53e-7	183

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000881	0.00000880
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

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.
• 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);Morphine addiction - Homo sapiens (human);Alcoholism - Homo sapiens (human);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;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;Thromboxane signalling through TP receptor;Metabolism of proteins;ADP signalling through P2Y purinoceptor 12;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;Platelet activation, signaling and aggregation;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;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 (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.36

Haploinsufficiency Scores

• pHI: 0.380
• hipred: Y
• hipred_score: 0.685
• ghis: 0.607

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gnb2

Gene ontology

• Biological process: protein folding;G protein-coupled receptor signaling pathway
• Cellular component: extracellular space;lysosomal membrane;cytosol;plasma membrane;focal adhesion;membrane;vesicle;protein-containing complex;myelin sheath;cell body;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: GTPase activity;calcium channel regulator activity;protein binding;protein-containing complex binding;GTPase binding