GNB2

Summary

GNB2 (G protein subunit beta 2, HGNC:4398) is a protein-coding gene on chromosome 7q22.1, encoding Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (P62879). Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems.

Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. This gene contains a trinucleotide (CCG) repeat length polymorphism in its 5’ UTR.

Source: NCBI Gene 2783 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with hypotonia and dysmorphic facies (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 106 total — 7 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 165
• MANE Select transcript: NM_005273

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4398
Approved symbol	GNB2
Name	G protein subunit beta 2
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172354
Ensembl biotype	protein_coding
OMIM	139390
Entrez	2783

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 20 protein_coding, 3 retained_intron

ENST00000303210, ENST00000393924, ENST00000393926, ENST00000412215, ENST00000419828, ENST00000424361, ENST00000427895, ENST00000431068, ENST00000436220, ENST00000451587, ENST00000469287, ENST00000470354, ENST00000480159, ENST00000879678, ENST00000879679, ENST00000879680, ENST00000879681, ENST00000879682, ENST00000879683, ENST00000879684, ENST00000922249, ENST00000922250, ENST00000966217

RefSeq mRNA: 1 — MANE Select: NM_005273 NM_005273

CCDS: CCDS5703

Canonical transcript exons

ENST00000303210 — 10 exons

Exon	Start	End
ENSE00001179662	100676177	100676322
ENSE00001791180	100673740	100673923
ENSE00003486848	100678398	100678614
ENSE00003490141	100677752	100677818
ENSE00003510034	100677352	100677415
ENSE00003537706	100678098	100678299
ENSE00003615589	100676693	100676799
ENSE00003631074	100677498	100677660
ENSE00003635649	100676535	100676573
ENSE00003842331	100678695	100679169

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 90.2291 / max 757.2379, expressed in 1827 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80040	31.7568	1821
80038	26.8105	1817
80041	20.3170	1805
80043	3.1866	1246
80039	2.3863	1386
80037	2.2653	1285
80046	1.6514	903
80045	0.8483	518
80044	0.8245	481
80042	0.1824	74

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.16	gold quality
ventricular zone	UBERON:0003053	99.15	gold quality
adenohypophysis	UBERON:0002196	99.13	gold quality
granulocyte	CL:0000094	99.05	gold quality
stromal cell of endometrium	CL:0002255	99.05	gold quality
skin of leg	UBERON:0001511	99.03	gold quality
ganglionic eminence	UBERON:0004023	98.99	gold quality
right uterine tube	UBERON:0001302	98.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.92	gold quality
skin of abdomen	UBERON:0001416	98.91	gold quality
cortical plate	UBERON:0005343	98.84	gold quality
ectocervix	UBERON:0012249	98.84	gold quality
mucosa of stomach	UBERON:0001199	98.82	gold quality
left uterine tube	UBERON:0001303	98.82	gold quality
right lung	UBERON:0002167	98.81	gold quality
endocervix	UBERON:0000458	98.76	gold quality
mucosa of transverse colon	UBERON:0004991	98.76	gold quality
right adrenal gland	UBERON:0001233	98.75	gold quality
pituitary gland	UBERON:0000007	98.73	gold quality
esophagus mucosa	UBERON:0002469	98.73	gold quality
left adrenal gland cortex	UBERON:0035825	98.73	gold quality
left adrenal gland	UBERON:0001234	98.72	gold quality
upper lobe of left lung	UBERON:0008952	98.70	gold quality
right adrenal gland cortex	UBERON:0035827	98.70	gold quality
right ovary	UBERON:0002118	98.65	gold quality
esophagus	UBERON:0001043	98.62	gold quality
body of stomach	UBERON:0001161	98.62	gold quality
body of uterus	UBERON:0009853	98.62	gold quality
minor salivary gland	UBERON:0001830	98.61	gold quality
metanephros cortex	UBERON:0010533	98.61	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	25.85
E-MTAB-6379	no	122.38
E-GEOD-124858	no	41.33
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting GNB2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4763-3P	99.10	67.83	2649

Literature-anchored findings (GeneRIF, showing 9)

• We conclude that the Gbetagamma complex interacts with the GR and suppresses its transcriptional activity by associating with the transcriptional complex formed on GR-responsive promoters. (PMID:15955845)
• Recombinant Gbetagamma subunits were used to establish that the Gbeta(2)gamma(2) dimer can selectively reconstitute the inhibition of alpha(1H) channels in isolated membrane patches. (PMID:16973746)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• Results indicate that G protein beta2 (Gbeta2) is required for starvation-induced NF-kappaB activation and constitutive NF-kappaB activity. (PMID:22917497)
• MIF and GNbeta2 interacted with influenza A H1N1 virus PB1-F2 protein. (PMID:23043599)
• GNB1 and GNB2 alterations confer transformed and resistance phenotypes across a range of human tumors and may be targetable with inhibitors of G protein signaling. (PMID:25485910)
• A GNB2 gene mutation is associated with familial sinus node and atrioventricular conduction dysfunction. (PMID:28219978)
• A novel somatic mutation in GNB2 provides new insights to the pathogenesis of Sturge-Weber syndrome. (PMID:34124757)
• A detailed multi-omics analysis of GNB2 gene in human cancers. (PMID:35730811)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnb2	ENSDARG00000035357
mus_musculus	Gnb2	ENSMUSG00000029713
rattus_norvegicus	Gnb2	ENSRNOG00000001409
drosophila_melanogaster	Gbeta13F	FBGN0001105
caenorhabditis_elegans		WBGENE00001679

Paralogs (4): GNB5 (ENSG00000069966), GNB1 (ENSG00000078369), GNB3 (ENSG00000111664), GNB4 (ENSG00000114450)

Protein

Protein identifiers

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 — P62879 (reviewed: P62879)

Alternative names: G protein subunit beta-2, Transducin beta chain 2

All UniProt accessions (6): C9JIS1, C9JXA5, C9JZN1, E7EP32, P62879, Q6FHM2

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. G proteins are composed of 3 units, alpha, beta and gamma. In this context, interacts with GNAI2 and GNG2. Interacts with ARHGEF18 and RASD2. Interacts with ATXN10. Interacts with SCN8A.

Subcellular location. Cytoplasm. Perinuclear region. Cell membrane.

Tissue specificity. Expressed in all cardiac subcompartments and in the brain, with highest levels in the atrioventricular node and brain.

Disease relevance. Neurodevelopmental disorder with hypotonia and dysmorphic facies (NEDHYDF) [MIM:619503] An autosomal dominant disorder characterized by global developmental delay, hypotonia, and variably impaired intellectual development, often with speech delay and delayed walking. Most patients have dysmorphic facial features. Clinical features are highly variable and may include congenital cardiac defects, non-specific renal anomalies, joint contractures or joint hyperextensibility, dry skin, and cryptorchidism. The disease is caused by variants affecting the gene represented in this entry. Sick sinus syndrome 4 (SSS4) [MIM:619464] The term ‘sick sinus syndrome’ encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia (’tachycardia-bradycardia syndrome’) are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS4 is characterized by early and progressive sinus node and atrioventricular conduction dysfunction. Some affected individuals are asymptomatic. SSS4 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat G protein beta family.

Isoforms (2)

UniProt ID	Names	Canonical?
P62879-1	1	yes
P62879-2	2

RefSeq proteins (1): NP_005264* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001632	WD40_G-protein_beta-like	Domain
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016346	G-protein_beta_1-5	Family
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF25391

UniProt features (20 total): sequence variant 7, repeat 7, modified residue 2, initiator methionine 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9AVL	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62879-F1	96.89	0.97

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 239, 2

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-1296041	Activation of G protein gated Potassium channels
R-HSA-163359	Glucagon signaling in metabolic regulation
R-HSA-202040	G-protein activation
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-392170	ADP signalling through P2Y purinoceptor 12
R-HSA-392451	G beta:gamma signalling through PI3Kgamma
R-HSA-392851	Prostacyclin signalling through prostacyclin receptor
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-4086398	Ca2+ pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-418217	G beta:gamma signalling through PLC beta
R-HSA-418555	G alpha (s) signalling events
R-HSA-418592	ADP signalling through P2Y purinoceptor 1
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events
R-HSA-420092	Glucagon-type ligand receptors
R-HSA-428930	Thromboxane signalling through TP receptor
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-500657	Presynaptic function of Kainate receptors
R-HSA-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
R-HSA-8964315	G beta:gamma signalling through BTK
R-HSA-8964616	G beta:gamma signalling through CDC42
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9634597	GPER1 signaling
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-997272	Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits

MSigDB gene sets: 743 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, PAX4_01, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, GOCC_VACUOLAR_MEMBRANE, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, ENK_UV_RESPONSE_KERATINOCYTE_UP, CMYB_01, MORF_UBE2I, MORF_HDAC1, TATTATA_MIR374

GO Biological Process (3): G protein-coupled receptor signaling pathway (GO:0007186), regulation of potassium ion transmembrane transport (GO:1901379), signal transduction (GO:0007165)

GO Molecular Function (5): GTPase activity (GO:0003924), signaling receptor complex adaptor activity (GO:0030159), protein-containing complex binding (GO:0044877), GTPase binding (GO:0051020), protein binding (GO:0005515)

GO Cellular Component (12): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829), heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020), vesicle (GO:0031982), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
GPCR downstream signalling	5
Signal amplification	3
Regulation of insulin secretion	2
G-protein beta:gamma signalling	2
G protein gated Potassium channels	1
Integration of energy metabolism	1
Opioid Signalling	1
Platelet homeostasis	1
Beta-catenin independent WNT signaling	1
Class B/2 (Secretin family receptors)	1
Aquaporin-mediated transport	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	2
cytoplasm	2
G protein-coupled receptor activity	1
signal transduction	1
regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
signaling receptor binding	1
signaling adaptor activity	1
enzyme binding	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
extrinsic component of cytoplasmic side of plasma membrane	1
plasma membrane protein complex	1
GTPase complex	1
membrane	1
cell periphery	1
cell-substrate junction	1
membrane-bounded organelle	1
cell junction	1
extracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

405 interactions, top by confidence:

A	B	Type	Score
PDE6D	ARL3	psi-mi:“MI:0914”(association)	0.920
AKR7A3	AKR7A2	psi-mi:“MI:0914”(association)	0.890
TUBG1	TUBG1	psi-mi:“MI:2364”(proximity)	0.760
GNGT1	Ntsr1	psi-mi:“MI:0914”(association)	0.750
GBP1	GBP2	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HTT	GNB2	psi-mi:“MI:0915”(physical association)	0.670
GNB2	TARDBP	psi-mi:“MI:0915”(physical association)	0.670
GNG5	GNB2	psi-mi:“MI:0914”(association)	0.640
GNG10	GNB2	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
GNGT1	GNB2	psi-mi:“MI:0914”(association)	0.620
CD81	EGFR	psi-mi:“MI:0914”(association)	0.600
Haus4	HAUS5	psi-mi:“MI:0915”(physical association)	0.560
UBE2K	GNB2	psi-mi:“MI:0915”(physical association)	0.560
GNB2		psi-mi:“MI:0915”(physical association)	0.560
GNB2	UBE2D1	psi-mi:“MI:0915”(physical association)	0.560
GNB2	UBE2D2	psi-mi:“MI:0915”(physical association)	0.560
GNB2	UBE2D3	psi-mi:“MI:0915”(physical association)	0.560
UBE2G1	GNB2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (795): GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A223GEB2, A1L271, G4MQX3, O14435, O14775, O24456, O35353, O45040, P11017, P16520, P17343, P23232, P26308, P29387, P29829, P36408, P52287, P54311, P54313, P62871, P62872, P62873, P62874, P62879, P62880, P62881, P62882, P79147, P79959, P93339, P93397, P93398, P93563, Q08706, Q20636, Q39336, Q39836, Q40507, Q5GIS3, Q5R5W8

Diamond homologs: A0A223GEB2, A1CJY4, A1D7I5, A1L271, A2QEV8, A4R3M4, A4RDD7, A6H603, A7THX0, A8ILK1, B0XYC8, B3MJV8, B4HWV6, B4Q9T6, B6QC56, B8AP31, B8M0Q1, E3LB80, G0SC29, O14435, O14775, O35353, O45040, P11017, P16520, P17343, P18851, P23232, P26308, P29387, P29829, P36408, P49177, P49178, P52287, P54311, P54313, P61480, P62871, P62872

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SMO	up-regulates	GNB2	binding
GNB2	up-regulates	PLCG1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 211 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
G beta:gamma signalling through BTK	12	52.1×	8e-17
Prostacyclin signalling through prostacyclin receptor	12	49.4×	1e-16
ADP signalling through P2Y purinoceptor 12	14	47.6×	1e-18
G beta:gamma signalling through PLC beta	12	46.9×	2e-16
G beta:gamma signalling through CDC42	12	46.9×	2e-16
Presynaptic function of Kainate receptors	12	44.7×	4e-16
ADP signalling through P2Y purinoceptor 1	13	40.7×	1e-16
G-protein activation	12	39.1×	2e-15

GO biological processes:

GO term	Partners	Fold	FDR
protein K6-linked ubiquitination	6	33.8×	5e-06
protein K11-linked ubiquitination	7	15.6×	8e-05
protein K63-linked ubiquitination	7	10.6×	8e-04
protein K48-linked ubiquitination	11	10.5×	4e-06
protein polyubiquitination	16	10.5×	4e-09
ubiquitin-dependent protein catabolic process	16	6.8×	2e-06
negative regulation of neuron apoptotic process	9	5.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

106 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	4
Uncertain significance	58
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1185051	NM_005273.4(GNB2):c.155G>T (p.Arg52Leu)	Pathogenic
1217306	NM_005273.4(GNB2):c.265A>G (p.Lys89Glu)	Pathogenic
1217307	NM_005273.4(GNB2):c.266A>C (p.Lys89Thr)	Pathogenic
2859535	NM_005273.4(GNB2):c.357C>A (p.Asn119Lys)	Pathogenic
3776371	NM_005273.4(GNB2):c.230G>A (p.Gly77Glu)	Pathogenic
4685512	NM_005273.4(GNB2):c.227A>G (p.Asp76Gly)	Pathogenic
977754	NM_005273.4(GNB2):c.229G>A (p.Gly77Arg)	Pathogenic
1013609	NM_005273.4(GNB2):c.229G>T (p.Gly77Trp)	Likely pathogenic
2429882	NM_005273.4(GNB2):c.284T>C (p.Leu95Pro)	Likely pathogenic
3028901	NM_005273.4(GNB2):c.803A>T (p.Asn268Ile)	Likely pathogenic
3378079	NM_005273.4(GNB2):c.143G>A (p.Arg48Gln)	Likely pathogenic

SpliceAI

1388 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100676321:GGGT:G	donor_loss	1.0000
7:100676524:A:AG	acceptor_gain	1.0000
7:100676525:T:G	acceptor_gain	1.0000
7:100677335:A:AG	acceptor_gain	1.0000
7:100677335:ACACC:A	acceptor_gain	1.0000
7:100677336:C:G	acceptor_gain	1.0000
7:100677337:A:AG	acceptor_gain	1.0000
7:100677337:ACC:A	acceptor_gain	1.0000
7:100677338:C:G	acceptor_gain	1.0000
7:100677339:C:CA	acceptor_gain	1.0000
7:100677347:ACCAG:A	acceptor_gain	1.0000
7:100677348:CCA:C	acceptor_loss	1.0000
7:100677349:CAG:C	acceptor_loss	1.0000
7:100677350:A:AG	acceptor_gain	1.0000
7:100677350:AG:A	acceptor_gain	1.0000
7:100677350:AGGCT:A	acceptor_gain	1.0000
7:100677351:G:GA	acceptor_gain	1.0000
7:100677351:G:GC	acceptor_loss	1.0000
7:100677351:GG:G	acceptor_gain	1.0000
7:100677351:GGC:G	acceptor_gain	1.0000
7:100677351:GGCT:G	acceptor_gain	1.0000
7:100677351:GGCTG:G	acceptor_gain	1.0000
7:100677416:G:GA	donor_loss	1.0000
7:100677416:G:GG	donor_gain	1.0000
7:100677417:T:A	donor_loss	1.0000
7:100677488:T:A	acceptor_gain	1.0000
7:100677492:CCGCA:C	acceptor_loss	1.0000
7:100677493:CGCA:C	acceptor_loss	1.0000
7:100677494:GCAG:G	acceptor_loss	1.0000
7:100677495:CAG:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000302566 (7:100676586 G>A), RS1000360190 (7:100672421 CA>C,CAA), RS1001625407 (7:100677306 T>C), RS1001849793 (7:100679067 CAGGAGGT>C), RS1001863285 (7:100673312 T>G), RS1001964230 (7:100678389 G>A,T), RS1002465053 (7:100674901 A>C), RS1002755749 (7:100675160 C>G), RS1002796066 (7:100674739 G>A,C), RS1002886781 (7:100673497 G>A,T), RS1003349959 (7:100674154 CGACCCCA>C), RS1003620621 (7:100679212 T>C), RS1003803097 (7:100675872 C>T), RS1003918308 (7:100675175 C>T), RS1003934982 (7:100679083 C>T)

Disease associations

OMIM: gene MIM:139390 | disease phenotypes: MIM:619503, MIM:619464

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with hypotonia and dysmorphic facies	Definitive	Autosomal dominant
sick sinus syndrome 4	Limited	Unknown

Mondo (2): neurodevelopmental disorder with hypotonia and dysmorphic facies (MONDO:0859185), sick sinus syndrome 4 (MONDO:0859173)

Orphanet (0):

HPO phenotypes

165 total (30 of 165 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000122	Unilateral renal agenesis
HP:0000125	Pelvic kidney
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000185	Cleft soft palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000293	Full cheeks
HP:0000303	Mandibular prognathia
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000389	Chronic otitis media
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000448	Prominent nose
HP:0000490	Deeply set eye
HP:0000506	Telecanthus
HP:0000527	Long eyelashes
HP:0000540	Hypermetropia
HP:0000574	Thick eyebrow

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004604_123	Hematocrit	3.000000e-15
GCST004615_49	Hemoglobin concentration	2.000000e-12
GCST010083_118	Hemoglobin levels	2.000000e-71

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	4
bisphenol A	increases expression, decreases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Valproic Acid	affects expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
4-hydroxy-2-nonenal	decreases expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bromovanin	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Gefitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Aspirin	decreases expression	1
Atrazine	increases expression	1
Barium	decreases reaction, increases transport, affects binding	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2XU	Abcam HEK293T GNB2 KO	Transformed cell line	Female
CVCL_D7QR	Ubigene A-549 GNB2 KO	Cancer cell line	Male
CVCL_E0DX	Ubigene HeLa GNB2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.