Gene Report

Basic Information

Approved Symbol	SLC4A4
Approved Name	solute carrier family 4 (sodium bicarbonate cotransporter), member 4
Previous Symbol	SLC4A5
Previous Name	"solute carrier family 4, sodium bicarbonate cotransporter, member 4"
Symbol Alias	NBC1, HNBC1, NBC2, pNBC, hhNMC
Location	4q13.3
Position	chr4:72433611-72437804 (+)
External Links	Entrez Gene: 8671 Ensembl: ENSG00000080493 UCSC: uc010iic.3 HGNC ID: 11030
No. of Studies (Positive/Negative)	2(1/1)
Type	Literature-origin

Positive relationships between SLC4A4 and MDD (count: 0)

Positive relationships between SLC4A4 and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
SLC4A5		Depression-like behaviors from animal model(depressive-like behavior)	cognition and behavior	Andrus, 2010	animal model		Differentially expressed depression genes hippocampus, (fold...... Differentially expressed depression genes hippocampus, (fold change > 2). More...

Positive relationship network of SLC4A4 in MK4MDD

Network loading ...

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 SLC4A4 and MDD (count: 0)

Negative relationships between SLC4A4 and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description
Name in Literature	Related Components
SLC4A4		suicide attempt (SA)(suicide attempt (SA))	symptoms	Mullins N, 2014	Patients and nomal controls		From the meta-analysis, a candidate association study of 19 ...... From the meta-analysis, a candidate association study of 19 genes previously associated with suicide was also performed though no SNPs were significant after a Bonferroni correction was applied (Supplementary material). A SNP in ABI3BP had reached GWAS significance in a previous study of SA in depression, however the finding did not replicate in this analysis. More...

SLC4A4 related SNPs in MK4MDD (count: 0)

SLC4A4 related proteins in MK4MDD (count: 0)

SLC4A4 related GO terms (count: 14)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0015701	bicarbonate transport	biological process	TAS
GO:0005886	plasma membrane	cellular component	TAS
GO:0008510	sodium:bicarbonate symporter activity	molecular function	IMP[17661077]
GO:0005887	integral component of plasma membrane	cellular component	TAS[9235899]
GO:0016323	basolateral plasma membrane	cellular component	IDA[17661077]
GO:0070062	extracellular exosome	cellular component	IDA[19056867\|23376485]
GO:0006814	sodium ion transport	biological process	IDA[16769890]
GO:0005452	inorganic anion exchanger activity	molecular function	IEA
GO:0055085	transmembrane transport	biological process	TAS
GO:0005515	protein binding	molecular function	IPI[14567693\|15563508\|16769890]
GO:0006810	transport	biological process	TAS[9235899]
GO:0006811	ion transport	biological process	TAS
GO:0098656	anion transmembrane transport	biological process	IEA
GO:0035725	sodium ion transmembrane transport	biological process	IMP[17661077]

SLC4A4 related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04964	proximal tubule_bicarbonate_reclamation	Proximal tubule bicarbonate reclamation	One of the major tasks of the renal proximal tubule (PT) is ...... One of the major tasks of the renal proximal tubule (PT) is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered bicarbonate (HCO3(-)), as well as generating new HCO3(-) for regulating blood pH. In the tubular lumen, filtered HCO3(-) combines with H(+) in a reaction catalyzed by CA IV. The CO2 thus produced rapidly diffuses into the tubular cells and is combined with water to produce intracellular H(+) and HCO3(-), catalyzed by soluble cytoplasmic CA II. HCO3(-) is then cotransported with Na(+) into blood via the NBC-1. The intracellular H(+) produced by CA II is secreted into the tubular lumen predominantly via the NHE-3. The PT creates the new HCO3(-) by taking glutamine and metabolizing it to two molecules each of NH4(+) and HCO3(-). The NH4(+) is excreted into the tubular lumen, and the HCO3(-) , which is new HCO3(-) , is returned to the blood, where it replaces the HCO3(-) lost earlier in the titration of nonvolatile acids. More...

SLC4A4 related BioCarta pathways (count: 0)

SLC4A4 related Reactome pathways (count: 3)

ID	Name	Description
Gene mapped Reactome pathways
REACT_15518	transmembrane transport_of_small_molecules
REACT_19397	inorganic cation_anion_slc_transporters	Teleologically, one might argue that inorganic cation and an...... Teleologically, one might argue that inorganic cation and anion transport would be evolutionarily among the oldest transport functions. Eight families comprise the group that transports exclusively inorganic cations and anions across membranes : SLC4 plays a pivotal role in mediating Na+- and/or Cl-dependent transport of basic anions [e.g. HCO3, ; SLC8 is a group of Na+/Ca2+ exchangers ; SLC24 is a group of Na+/Ca2+ or Na+/K+ exchangers ; SLC9 comprises Na+/H+ exchanger proteins involved in the electroneutral exchange of sodium ion and protons ; SLC12 functions as Na+, K+ and Cl ion electroneutral symporters ; SLC26 is the trans-epithelial multifunctional anion. SLC34 is an important Type II Na+/; SLC20 was originally identified as a viral receptor, and functions as a Type III Na+/. Eight SLC gene families are involved in the transport of amino acids and oligopeptides. More...
REACT_19118	slc mediated_transmembrane_transport	Proteins with transporting functions can be roughly classifi...... Proteins with transporting functions can be roughly classified into 3 categories: ATP-powered pumps, ion channels, and transporters. Pumps utilize the energy released by ATP hydrolysis to power the movement of the substrates across the membrane, against their electrochemical gradient. Channels at the open state can transfer the substrates. At least 20-25% amino-acid sequence identity is shared by members belonging to the same SLC family. No homology is shared between different SLC families. While the HUGO nomenclature system by definition only includes human genes, the nomenclature system has been informally extended to include rodent species through the use of lower cases letters (e.g., Slc1a1 denotes the rodent ortholog of the human SLC1A1 gene). And it's worthwhile to mention that pumps, channels and aquporins are not included in SLC superfamily. More...

SLC4A4 related interactors from protein-protein interaction data in HPRD (count: 4)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
SLC4A4	PRKACA	No	in vitro	11744745
SLC4A4	SLC4A7	No	in vivo	10600945
SLC4A4	CA2	No	in vitro	12411514
SLC4A4	CA4	No	in vitro;in vivo	14567693

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped Reactome pathways