GNB3 (G protein subunit beta 3)

Gene

• Entrez ID: 2784
• Gene name: G protein subunit beta 3
• Gene symbol: GNB3
• Synonyms: CSNB1H
• Chromosome: 12
• Chromosome location: 12p13.31
• Summary: 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 which belongs to the WD repeat G protein beta family. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. A single-nucleotide polymorphism (C825T) in this gene is associated with essential hypertension and obesity. This polymorphism is also associated with the occurrence of the splice variant GNB3-s, which appears to have increased activity. GNB3-s is an example of alternative splicing caused by a nucleotide change outside of the splice donor and acceptor sites. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs140263599	C>T	Pathogenic	Missense variant, coding sequence variant
rs879253774	AGA>-	Pathogenic	Coding sequence variant, inframe deletion

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029954	hsa-miR-26b-5p	Microarray	19088304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003924	Function	GTPase activity	TAS	9425898
GO:0005515	Function	Protein binding	IPI	23773523
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0005834	Component	Heterotrimeric G-protein complex	IBA	21873635
GO:0005886	Component	Plasma membrane	TAS
GO:0006457	Process	Protein folding	TAS
GO:0006884	Process	Cell volume homeostasis	IGI	29206867
GO:0007186	Process	G protein-coupled receptor signaling pathway	IBA	21873635
GO:0008217	Process	Regulation of blood pressure	TAS	9425898
GO:0010468	Process	Regulation of gene expression	IGI	29206867
GO:0010906	Process	Regulation of glucose metabolic process	IGI	29206867
GO:0030425	Component	Dendrite	IEA
GO:0030507	Function	Spectrin binding	IEA
GO:0031682	Function	G-protein gamma-subunit binding	IBA	21873635
GO:0032350	Process	Regulation of hormone metabolic process	IGI	29206867
GO:0044297	Component	Cell body	IEA
GO:0045598	Process	Regulation of fat cell differentiation	IGI	29206867
GO:0051020	Function	GTPase binding	IPI	19255495
GO:0060259	Process	Regulation of feeding behavior	IGI	29206867
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0090181	Process	Regulation of cholesterol metabolic process	IGI	29206867
GO:0090207	Process	Regulation of triglyceride metabolic process	IGI	29206867
GO:0090325	Process	Regulation of locomotion involved in locomotory behavior	IGI	29206867
GO:1903725	Process	Regulation of phospholipid metabolic process	IGI	29206867

Other IDs

• MIM: 139130
• HGNC: 4400
• e!Ensembl: ENSG00000111664

Protein

• UniProt ID: P16520
• Protein name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (Transducin beta chain 3)
• Protein 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.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00400	WD40	45 → 83	WD domain, G-beta repeat	Repeat
  PF00400	WD40	86 → 125	WD domain, G-beta repeat	Repeat
  PF00400	WD40	133 → 170	WD domain, G-beta repeat	Repeat
  PF00400	WD40	174 → 212	WD domain, G-beta repeat	Repeat
  PF00400	WD40	216 → 254	WD domain, G-beta repeat	Repeat
  PF00400	WD40	259 → 298	WD domain, G-beta repeat	Repeat
  PF00400	WD40	302 → 340	WD domain, G-beta repeat	Repeat

• Sequence:

  MGEMEQLRQEAEQLKKQIADARKACADVTLAELVSGLEVVGRVQMRTRRTLRGHLAKIYA
  MHWATDSKLLVSASQDGKLIVWDSYTTNKVHAIPLRSSWVMTCAYAPSGNFVACGGLDNM
  CSIYNLKSREGNVKVSRELSAHTGYLSCCRFLDDNNIVTSSGDTTCALWDIETGQQKTVF
  VGHTGDCMSLAVSPDFNLFISGACDASAKLWDVREGTCRQTFTGHESDINAICFFPNGEA
  ICTGSDDASCRLFDLRADQELICFSHESIICGITSVAFSLSGRLLFAGYDDFNCNVWDSM
  KSERVGILSGHDNRVSCLGVTADGMAVATGSWDSFLKIWN

• Sequence length: 340

Pathways

KEGG:

Ras signaling pathway
Chemokine signaling pathway
Hormone signaling
PI3K-Akt signaling pathway
Apelin signaling pathway
Circadian entrainment
Retrograde endocannabinoid signaling
Glutamatergic synapse
Cholinergic synapse
Serotonergic synapse
GABAergic synapse
Dopaminergic synapse
Taste transduction
Relaxin signaling pathway
Morphine addiction
Alcoholism
Human cytomegalovirus infection
Kaposi sarcoma-associated herpesvirus infection
Human immunodeficiency virus 1 infection
Pathways in cancer

Reactome:

Activation of G protein gated Potassium channels
Glucagon signaling in metabolic regulation
G-protein activation
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
ADP signalling through P2Y purinoceptor 12
G beta:gamma signalling through PI3Kgamma
Prostacyclin signalling through prostacyclin receptor
Adrenaline,noradrenaline inhibits insulin secretion
Ca2+ pathway
G alpha (q) signalling events
G alpha (12/13) signalling events
G beta:gamma signalling through PLC beta
G alpha (s) signalling events
ADP signalling through P2Y purinoceptor 1
G alpha (i) signalling events
G alpha (z) signalling events
Glucagon-type ligand receptors
Thromboxane signalling through TP receptor
Vasopressin regulates renal water homeostasis via Aquaporins
Thrombin signalling through proteinase activated receptors (PARs)
Presynaptic function of Kainate receptors
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
G beta:gamma signalling through BTK
G beta:gamma signalling through CDC42
Extra-nuclear estrogen signaling
ADORA2B mediated anti-inflammatory cytokines production
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Diabetes mellitus	Diabetes Mellitus, Non-Insulin-Dependent	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs-1, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs371977235, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261	12511541
Congenital stationary night blindness	Cone-rod synaptic disorder, congenital nonprogressive, Congenital stationary night blindness	rs786205249, rs80338903, rs62638214, rs62638624, rs62638202, rs62638197, rs766862238, rs267607140, rs267607141, rs-1, rs62638191, rs62638193, rs62637021, rs62637027, rs104894910, rs104894911, rs122456133, rs122456134, rs122456135, rs2147483647, rs104893789, rs104893790, rs104893796, rs121918582, rs104893740, rs80359870, rs387906862, rs786205113, rs772011426, rs281875234, rs794726685, rs387907138, rs773126191, rs770066665, rs794726686, rs397509379, rs397509380, rs61750168, rs281865186, rs281865194, rs150115958, rs786205852, rs786205853, rs786205854, rs778390089, rs869312176, rs879253773, rs879253774, rs886039559, rs886039560, rs886043488, rs1057518829, rs104893793, rs1553186509, rs61751398, rs781463257, rs531851447, rs770380556, rs748046539, rs1555418784, rs1555424166, rs781610444, rs1555424849, rs1555966753, rs1555967281, rs1557106008, rs1557107192, rs1557107417, rs1557108147, rs1557109796, rs1557109912, rs1557110046, rs1557110192, rs1557110499, rs1557110988, rs372529012, rs374913800, rs1410075831, rs766780281, rs1555967031, rs1566945534, rs777989874, rs782581701, rs1485132228, rs1567728372, rs1567725425, rs150441866, rs1358925739, rs779821510, rs1590998813, rs1594580431, rs777168556, rs763546583, rs1290420698, rs765645888, rs1596029830, rs1602180478, rs1602180791, rs1602181006, rs1602181043, rs1602181253, rs1602627593, rs782740998, rs1602630650, rs1602639607, rs1602641426, rs1602644716, rs1602658505, rs1602628429, rs2065841382, rs1596017653, rs769355168, rs1578278438, rs984572250, rs775166854, rs2065717735
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs-1, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	16139171
Seizure	Complex partial seizures, Generalized seizures, Visual seizure, Tonic - clonic seizures, Single Seizure	rs587784365, rs28939683, rs74315390, rs28939684, rs74315391, rs267607198, rs74315392, rs118192244, rs118192250, rs121917749, rs121917750, rs121917751, rs121917752, rs-1, rs267606670, rs267607061, rs121912707, rs118192249, rs118192251, rs118192217, rs118192218, rs118192219, rs118192222, rs118192226, rs118192228, rs118192234, rs118192236, rs118192235, rs118192241, rs118192242, rs118192185, rs118192188, rs118192245, rs118192246, rs118192186, rs118192194, rs118192197, rs118192199, rs118192201, rs118192202, rs118192203, rs118192204, rs118192205, rs118192206, rs118192208, rs118192211, rs118192216, rs118192239, rs387906684, rs387906686, rs387906687, rs1596893185, rs387907126, rs387907281, rs397515405, rs587778771, rs730882067, rs730882073, rs397514579, rs397514582, rs587776976, rs398122394, rs121918784, rs121918751, rs121918735, rs398123588, rs587780450, rs61749751, rs587777620, rs727503974, rs730882124, rs794726710, rs794726697, rs794726799, rs794727444, rs794727740, rs796053166, rs794726825, rs796052676, rs796053219, rs796053220, rs796053228, rs796052653, rs759584387, rs796052650, rs796052641, rs796052626, rs796052623, rs796052663, rs796052615, rs796052802, rs797044999, rs797045047, rs797045942, rs797045941, rs118192212, rs797044938, rs777257591, rs864321712, rs879255652, rs886039268, rs886039517, rs886039529, rs199497486, rs886039496, rs886039903, rs886041300, rs769827124, rs886041339, rs886041591, rs587783092, rs1555850151, rs1057516123, rs1057516121, rs1057516115, rs1057516111, rs1057516106, rs1057516105, rs756921902, rs1057516089, rs1057516087, rs1057516080, rs1057516076, rs1060499544, rs1555850512, rs1057517919, rs118192231, rs1057520413, rs1060503101, rs1064796294, rs1064794981, rs1064794632, rs1064797245, rs1131691830, rs1131692231, rs1131691936, rs1554626549, rs1553579225, rs1553531385, rs121918736, rs1554898088, rs1553579282, rs763353895, rs1553463119, rs1554093891, rs77838305, rs1555408401, rs1554627439, rs1554097873, rs1555850403, rs1064794719, rs1315483224, rs1567134495, rs770187706, rs1057518555, rs1576983339, rs1574192005, rs1459374430, rs1586800133, rs1574641522, rs1572096837, rs1572630269, rs1574554892, rs1574556643, rs1574571769, rs1574641605, rs1574697769, rs1574716524, rs1574746733, rs1574746935, rs1574752700, rs1574754680, rs863225030, rs1601545088, rs1600714727, rs1371059392, rs1600767259, rs1339542565, rs1600785769, rs2065899210, rs1600732174, rs1162306056, rs879255709, rs1900111672, rs2066910297, rs1554122080, rs796052941, rs1600789325, rs2082695884, rs1737677036, rs1737495759, rs868389022, rs1737685202, rs1737672350, rs762737130	18855531
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	16141801
Obesity	Obesity	rs34911341, rs74315349, rs1474810899, rs121918111, rs796065034, rs753856820, rs796065035, rs121918112, rs-1, rs104894023, rs137852821, rs1580764441, rs137852822, rs137852823, rs137852824, rs13447324, rs121913562, rs121913564, rs74315393, rs121913556, rs2989924, rs193922650, rs193922685, rs193922687, rs751160202, rs1421085, rs747681609, rs1553400259, rs13447339, rs370479598, rs1554394014, rs1553174844, rs756232889, rs369841551, rs1557670950, rs1571321748, rs148538980, rs1572820988, rs1591461970, rs1419374563, rs745921568, rs144159890, rs1570714352, rs779783209, rs1573250294, rs1573254045, rs1580744791, rs1580746829, rs6548238, rs7138803, rs7754840	16141801, 15961981
Hypertension	Hypertensive disease, Essential Hypertension	rs13306026	16141801, 15961981
Nystagmus	Nystagmus	rs137852207, rs137852208, rs1928435502, rs137852209, rs137852210, rs1929191668, rs137852211, rs137852212, rs2124209414, rs387906720, rs387906721, rs1602791884, rs786205896
Myopia	Myopia, Severe myopia	rs387907109, rs146936371, rs587776903, rs786205127, rs398122836, rs199624584, rs587777625, rs786205216, rs758872875, rs764211125, rs1135402746, rs765658563, rs1555941129, rs1555941116, rs199923805, rs782555528, rs1554862601, rs1586620121, rs1387950081, rs2051026773, rs1422332023	27182965

Unknown
Disease name	Disease term	dbSNP ID	References
Mental depression	Mental Depression, Depressive disorder, Unipolar Depression, Major Depressive Disorder	rs587778876, rs587778877	25037115, 24882179, 21709600, 15057736, 16897596, 17943025, 22222462, 18325652, 20826553
Congenital stationary night blindness, x-linked	X-Linked Csnb	rs201620180, rs762960396
Bipolar disorder	Bipolar Disorder		20814328
Clonic seizures	Clonic Seizures		18855531
Coronary arteriosclerosis	Coronary Arteriosclerosis		16141801
Hypoplasia of optic disc	Hypoplasia of optic disc
Hypotonic seizures	Epileptic drop attack		18855531
Jacksonian seizure	Jacksonian Seizure		18855531
Mood disorder	Mood Disorders		11586049, 11992559
Night blindness	Night blindness, congenital stationary, NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 2A, NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1B, NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 2B (disorder), Night Blindness, Congenital Stationary, Type 1A, Night blindness, congenital stationary, type 1		27063057
Night blindness, congenital stationary	NIGHT BLINDNESS, CONGENITAL STATIONARY, TYPE 1H		27063057
Nyctalopia	Nyctalopia
Strabismus	Strabismus