Gene Report

Basic Information

Approved Symbol	GNAL
Approved Name	guanine nucleotide binding protein (G protein), alpha activating activity polypeptide, olfactory type
Location	18p11.22-p11.21
Position	chr18:11689014-11885684 (+)
External Links	Entrez Gene: 2774 Ensembl: ENSG00000141404 UCSC: uc002kqc.2 HGNC ID: 4388
No. of Studies (Positive/Negative)	1(0/1)
Type	Literature-origin; Protein mapped

Positive relationships between GNAL and MDD (count: 0)

Positive relationships between GNAL and other components at different levels (count: 0)

Positive relationship network of GNAL in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between GNAL and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
GNAL	Zill P, 2002	Patients and nomal controls		In the control group, we found a significant increase in the...... In the control group, we found a significant increase in the G-allele frequency of the intron 3 polymorphism in females (P=0.0036, odds ratio=2.13, 95% confidence interval=1.29-3.54, Fisher's Exact Test). In patients, we found a similar tendency for higher G-allele frequencies in females. Concerning the intron 10 polymorphism, no differences in the genotype or allele frequencies were detectable for any of the separated gender groups. Also, the total patient and control groups showed no differences in allele or genotype frequencies for any of the investigated polymorphisms. More...

Negative relationships between GNAL and other components at different levels (count: 0)

GNAL related SNPs in MK4MDD (count: 0)

GNAL related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Guanine nucleotide-binding protein G(olf) subunit alpha	P38405	1(1/0)	Literature-origin

GNAL related GO terms (count: 24)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0007268	synaptic transmission	biological process	TAS

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0046872	metal ion binding	molecular function	IEA
GO:0007190	activation of adenylate cyclase activity	biological process	IEA
GO:0007608	sensory perception of smell	biological process	IBA
GO:0001664	G-protein coupled receptor binding	molecular function	IBA
GO:0005834	heterotrimeric G-protein complex	cellular component	IBA
GO:0001975	response to amphetamine	biological process	IEA
GO:0031000	response to caffeine	biological process	IEA
GO:0007165	signal transduction	biological process	TAS[8243272]
GO:0007189	adenylate cyclase-activating G-protein coupled receptor signaling pathway	biological process	TAS
GO:0031683	G-protein beta/gamma-subunit complex binding	molecular function	IBA
GO:0005525	GTP binding	molecular function	IEA
GO:0031234	extrinsic to internal side of plasma membrane	cellular component	IBA
GO:0004871	signal transducer activity	molecular function	IBA
GO:0006184	GTP catabolic process	biological process	TAS[8243272]
GO:0007193	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway	biological process	TAS
GO:0007191	adenylate cyclase-activating dopamine receptor signaling pathway	biological process	IBA
GO:0005886	plasma membrane	cellular component	TAS
GO:0003924	GTPase activity	molecular function	TAS[8243272]

GNAL related KEGG pathways (count: 2)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04020	calcium signaling_pathway	Calcium signaling pathway	Ca2+ that enters the cell from the outside is a principal so...... Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM). More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04740	olfactory transduction	Olfactory transduction	Within the compact cilia of the olfactory receptor neurons (...... Within the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be transmitted to the brain. Odorant molecules bind to a receptor protein (R) coupled to an olfactory specific Gs-protein (G) and activate a type III adenylyl cyclase (AC), increasing intracellular cAMP levels. cAMP targets an olfactory-specific cyclic-nucleotide gated ion channel (CNG), allowing cations, particularly Na and Ca, to flow down their electrochemical gradients into the cell, depolarizing the ORN. Furthermore, the Ca entering the cell is able to activate a Ca-activated Cl channel, which would allow Cl to flow out of the cell, thus further increasing the depolarization. Elevated intracellular Ca causes adaptation by at least two different molecular steps: inhibition of the activity of adenylyl cyclase via CAMKII-dependent phosphorylation and down-regulation of the affinity of the CNG channel to cAMP.Longer exposure to odorants can stimulate particulate guanylyl cyclase in cilia to produce cGMP and activate PKG, leading to a further increase in amount and duration of intracellular cAMP levels, which may serve to convert inactive forms of protein kinase A (PKA2) to active forms (PKA*). As part of a feedback loop, PKA can inhibit the activation of particulate guanylyl cyclase. More...

GNAL related BioCarta pathways (count: 0)

GNAL related Reactome pathways (count: 3)

ID	Name	Description
Gene mapped Reactome pathways
REACT_15312	adenylate cyclase_activating_pathway	Stimulatory G proteins activate adenylate cyclase, which dri...... Stimulatory G proteins activate adenylate cyclase, which drives the conversion of cAMP from ATP and in turn activates cAMP-dependent protein kinase and subsequent kinase pathways. More...
REACT_15295	opioid signalling	Opioids are chemical substances similar to opiates, the acti...... Opioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as the enkephalins, the endorphins or the dynorphins. Opioids possess powerful analgesic and sedative effects, and are widely used as pain-killers. Their main side-effect is the rapid establishment of a strong addiction. Opioids receptors are G-protein coupled receptors (GPCR). There are four classes of receptors: mu (MOR), kappa (KOR) and delta (DOR), and the nociceptin receptor (NOP). More...
REACT_15488	olfactory signaling_pathway	Mammalian Olfactory Receptor. Subsequent work in mice and ot...... Mammalian Olfactory Receptor. Subsequent work in mice and other vertebrates has confirmed that OR genes are comprised of a very large family of G Protein-Coupled Receptors }. Both models may be true for certain GPCRs in different contexts. Pre-coupling is likely to be functionally important, as pre-coupling of receptor and G Protein allows much more rapid kinetic response once ligand is bound, because the ligand-bound receptor is immediately able to transduce the signal, rather than having to diffuse around within the plasma membrane until it encounters a G Protein to interact with. The pre-coupling model is used here to characterise the reaction of the human ORs with G Proteins in the absence of ligand, because the ligands in humans are almost completely undocumented experimentally. In model genetic systems such as mice, many candidate OR genes have been shown experimentally to function in olfactory signaling {reviewed in }. For the human OR genes, experimental analysis has been much more limited, although some specific OR genes, such as OR7D4 and OR11H7P have been confirmed to mediate olfactory response and signaling in humans for specific chemical odorants. Mice and other rodents are believed to have about 1000 functional OR genes, as well as many additional pseudogenes. Based on sequence similarities, there are 960 human OR genes, but approximately half of these are pseudogenes {reviewed in }. In mice, essentially all olfactory signaling requires G-alpha-S. Thus, bona fide human OR genes identified by sequence similarity. These 357 olfactory-expressed OR genes are therefore expected to be functional in the Olfactory Signaling Pathway, and to interact directly with human G alpha olf in human olfactory cells. (Note: A subset of 200 of these 357 OR genes are shown as components of OR-G Protein reaction. The others will be added to Reactome later.) More...

GNAL related interactors from protein-protein interaction data in HPRD (count: 0)

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped Reactome pathways