SLC4A8

Summary

SLC4A8 (solute carrier family 4 member 8, HGNC:11034) is a protein-coding gene on chromosome 12q13.13, encoding Electroneutral sodium bicarbonate exchanger 1 (Q2Y0W8). Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1.

The protein encoded by this gene is a membrane protein that functions to transport sodium and bicarbonate ions across the cell membrane. The encoded protein is important for pH regulation in neurons. The activity of this protein can be inhibited by 4,4’-Di-isothiocyanatostilbene-2,2’-disulfonic acid (DIDS). Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9498 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_001039960

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11034
Approved symbol	SLC4A8
Name	solute carrier family 4 member 8
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	NBC3
Ensembl gene	ENSG00000050438
Ensembl biotype	protein_coding
OMIM	605024
Entrez	9498

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 9 retained_intron, 6 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000319957, ENST00000358657, ENST00000453097, ENST00000514353, ENST00000535225, ENST00000546497, ENST00000546663, ENST00000546872, ENST00000546875, ENST00000547697, ENST00000548352, ENST00000548616, ENST00000548811, ENST00000550211, ENST00000551071, ENST00000552001, ENST00000604314, ENST00000615370, ENST00000877857, ENST00000922421

RefSeq mRNA: 8 — MANE Select: NM_001039960 NM_001039960, NM_001258401, NM_001258402, NM_001258403, NM_001267615, NM_001405266, NM_001405268, NM_001405270

CCDS: CCDS44890, CCDS58232, CCDS58233, CCDS73470

Canonical transcript exons

ENST00000453097 — 25 exons

Exon	Start	End
ENSE00001720740	51496987	51497124
ENSE00002353988	51424831	51425035
ENSE00002400399	51507426	51515763
ENSE00003462515	51485787	51485900
ENSE00003469806	51463614	51463714
ENSE00003469881	51504029	51504120
ENSE00003475086	51494945	51495118
ENSE00003487261	51474342	51474447
ENSE00003494035	51462310	51462456
ENSE00003499122	51470392	51470525
ENSE00003508288	51489700	51489951
ENSE00003519960	51458559	51458650
ENSE00003549311	51457351	51457539
ENSE00003564989	51450876	51451022
ENSE00003565816	51452124	51452259
ENSE00003572619	51475045	51475206
ENSE00003592440	51459951	51460108
ENSE00003596315	51461204	51461291
ENSE00003635861	51488699	51488860
ENSE00003638009	51440708	51440789
ENSE00003645309	51471287	51471532
ENSE00003648207	51469614	51469788
ENSE00003655154	51493704	51493772
ENSE00003662855	51505835	51505930
ENSE00003682309	51453539	51453699

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 95.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.8832 / max 177.2011, expressed in 1130 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125497	4.0931	800
125493	0.7523	391
125498	0.6192	202
125492	0.1450	73
125494	0.0975	45
125500	0.0718	33
125496	0.0701	43
125499	0.0342	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	95.90	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.85	gold quality
superior vestibular nucleus	UBERON:0007227	93.77	gold quality
corpus callosum	UBERON:0002336	93.73	gold quality
middle temporal gyrus	UBERON:0002771	93.26	gold quality
ventral tegmental area	UBERON:0002691	92.96	gold quality
postcentral gyrus	UBERON:0002581	92.40	gold quality
parietal lobe	UBERON:0001872	92.13	gold quality
inferior vagus X ganglion	UBERON:0005363	91.80	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.17	gold quality
cerebellar vermis	UBERON:0004720	90.75	gold quality
primary visual cortex	UBERON:0002436	90.21	gold quality
subthalamic nucleus	UBERON:0001906	89.93	gold quality
superior frontal gyrus	UBERON:0002661	89.88	gold quality
occipital lobe	UBERON:0002021	89.47	gold quality
endothelial cell	CL:0000115	88.58	gold quality
cortical plate	UBERON:0005343	88.12	gold quality
lateral globus pallidus	UBERON:0002476	88.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.03	gold quality
globus pallidus	UBERON:0001875	88.03	gold quality
pituitary gland	UBERON:0000007	88.02	gold quality
sperm	CL:0000019	87.88	gold quality
medial globus pallidus	UBERON:0002477	87.66	gold quality
dorsal plus ventral thalamus	UBERON:0001897	87.64	gold quality
vena cava	UBERON:0004087	87.24	silver quality
left testis	UBERON:0004533	87.00	gold quality
right testis	UBERON:0004534	86.96	gold quality
medulla oblongata	UBERON:0001896	86.82	gold quality
entorhinal cortex	UBERON:0002728	86.63	gold quality
adenohypophysis	UBERON:0002196	86.43	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	9.47
E-ANND-3	yes	6.42
E-CURD-6	no	269.95
E-GEOD-81608	no	5.71
E-GEOD-137537	no	3.53
E-GEOD-83139	no	3.53

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• This study confirmed the presence in human cDNA of mouse NDCBE-like transcripts (human NDCBE-A) and three novel transcripts NDCBE-C, NDCBE-D, and NDCBE-D’. (PMID:18577713)
• The crystal structure at 2.8 A resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif. (PMID:28935959)
• Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE. (PMID:34584093)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc4a8	ENSDARG00000015531
mus_musculus	Slc4a8	ENSMUSG00000023032
rattus_norvegicus	Slc4a8	ENSRNOG00000028879
drosophila_melanogaster	Ae2	FBGN0036043
drosophila_melanogaster	Ndae1	FBGN0259111
caenorhabditis_elegans	abts-1	WBGENE00009920
caenorhabditis_elegans		WBGENE00019844

Paralogs (9): SLC4A1 (ENSG00000004939), SLC4A7 (ENSG00000033867), SLC4A4 (ENSG00000080493), SLC4A11 (ENSG00000088836), SLC4A9 (ENSG00000113073), SLC4A3 (ENSG00000114923), SLC4A10 (ENSG00000144290), SLC4A2 (ENSG00000164889), SLC4A5 (ENSG00000188687)

Protein

Protein identifiers

Electroneutral sodium bicarbonate exchanger 1 — Q2Y0W8 (reviewed: Q2Y0W8)

Alternative names: Electroneutral Na(+)-driven Cl-HCO3 exchanger, Solute carrier family 4 member 8, k-NBC3

All UniProt accessions (1): Q2Y0W8

UniProt curated annotations — full annotation on UniProt →

Function. Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1. Plays a major role in pH regulation in neurons. Mediates sodium reabsorption in the renal cortical collecting ducts.

Subunit / interactions. Homodimer. Homodimer.

Subcellular location. Apical cell membrane. Basolateral cell membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane Cell membrane Cell membrane Cell membrane Cell membrane.

Tissue specificity. Expressed in the pyramidal cells of the hippocampus (at protein level). Highly expressed in all major regions of the brain, spinal column and in testis, and moderate levels in trachea, thyroid and medulla region of kidney. Low expression levels observed in pancreas and kidney cortex. Expressed in the brain. Expressed in the brain, heart and kidney. Expressed in the brain, heart and kidney.

Activity regulation. Activity is inhibited by 4,4’-Di-isothiocyanatostilbene-2,2’-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters). Activity is inhibited by 4,4’-Di-isothiocyanatostilbene-2,2’-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters). Activity is inhibited by 4,4’-Di-isothiocyanatostilbene-2,2’-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters). Zinc-binding negatively regulates its activity. Activity is inhibited by 4,4’-Di-isothiocyanatostilbene-2,2’-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters).

Miscellaneous. May be due to an intron retention. May be due to an intron retention.

Similarity. Belongs to the anion exchanger (TC 2.A.31) family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q2Y0W8-1	1, NDCBE-A	yes
Q2Y0W8-2	2
Q2Y0W8-3	3, NDCBE-B
Q2Y0W8-4	4, NDCBE-D
Q2Y0W8-5	5, NDCBE-C
Q2Y0W8-6	6
Q2Y0W8-7	7
Q2Y0W8-8	8

RefSeq proteins (8): NP_001035049, NP_001245330, NP_001245331, NP_001245332, NP_001254544, NP_001392195, NP_001392197, NP_001392199 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003020	HCO3_transpt_euk	Family
IPR003024	Na/HCO3_transpt	Family
IPR011531	HCO3_transpt-like_TM_dom	Domain
IPR013769	Band3_cytoplasmic_dom	Domain
IPR016152	PTrfase/Anion_transptr	Homologous_superfamily

Pfam: PF00955, PF07565

Catalyzed reactions (Rhea), 1 shown:

• 2 hydrogencarbonate(out) + chloride(in) + Na(+)(out) = 2 hydrogencarbonate(in) + chloride(out) + Na(+)(in) (RHEA:72739)

UniProt features (70 total): topological domain 12, transmembrane region 11, helix 9, strand 9, splice variant 7, sequence conflict 4, mutagenesis site 3, region of interest 2, disulfide bond 2, sequence variant 2, turn 2, binding site 2, chain 1, coiled-coil region 1, compositionally biased region 1, glycosylation site 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5JHO	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2Y0W8-F1	72.70	0.17

Functional residue map

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

Ligand- & substrate-binding residues (2): 167; 169

Disulfide bonds (2): 636–684, 638–672

Glycosylation sites (1): 646

Mutagenesis-validated functional residues (3):

Position	Phenotype
80	significant reduction in zinc binding.
167	significant reduction in zinc binding.
169	significant reduction in zinc binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-425381	Bicarbonate transporters
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 324 (showing top): MORF_ITGA2, CAR_TNFRSF25, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GCANCTGNY_MYOD_Q6, MORF_BRCA1, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, MORF_RAD51L3, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS

GO Biological Process (14): bicarbonate transport (GO:0015701), sodium ion transmembrane transport (GO:0035725), regulation of membrane potential (GO:0042391), modulation of chemical synaptic transmission (GO:0050804), regulation of intracellular pH (GO:0051453), transmembrane transport (GO:0055085), basolateral protein secretion (GO:0110010), transport across blood-brain barrier (GO:0150104), chloride transmembrane transport (GO:1902476), positive regulation of synaptic vesicle exocytosis (GO:2000302), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), monoatomic anion transport (GO:0006820), regulation of synaptic vesicle exocytosis (GO:2000300)

GO Molecular Function (10): solute:inorganic anion antiporter activity (GO:0005452), zinc ion binding (GO:0008270), sodium:bicarbonate symporter activity (GO:0008510), sodium ion transmembrane transporter activity (GO:0015081), bicarbonate transmembrane transporter activity (GO:0015106), chloride transmembrane transporter activity (GO:0015108), identical protein binding (GO:0042802), sodium,bicarbonate:chloride antiporter activity (GO:0140892), monoatomic anion transmembrane transporter activity (GO:0008509), antiporter activity (GO:0015297)

GO Cellular Component (20): plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), dendrite (GO:0030425), synaptic vesicle membrane (GO:0030672), asymmetric synapse (GO:0032279), symmetric synapse (GO:0032280), neuronal cell body membrane (GO:0032809), presynaptic membrane (GO:0042734), neuron projection (GO:0043005), terminal bouton (GO:0043195), axon terminus (GO:0043679), glial cell projection (GO:0097386), hippocampal mossy fiber (GO:0097457), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transport of inorganic anions	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
presynapse	4
transport	3
regulation of biological quality	2
monoatomic anion transmembrane transport	2
synaptic vesicle exocytosis	2
cellular anatomical structure	2
plasma membrane region	2
neuron to neuron synapse	2
plasma membrane bounded cell projection	2
synapse	2
sodium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic ion transmembrane transport	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
regulation of pH	1
intracellular monoatomic cation homeostasis	1
cellular process	1
protein secretion	1
vascular transport	1
chloride transport	1
positive regulation of neurotransmitter secretion	1
positive regulation of regulated secretory pathway	1
regulation of synaptic vesicle exocytosis	1
metal ion transport	1
monoatomic ion transport	1
regulation of neurotransmitter secretion	1
regulation of regulated secretory pathway	1
antiporter activity	1
transition metal ion binding	1
solute:sodium symporter activity	1
monoatomic cation:bicarbonate symporter activity	1
sodium ion transmembrane transport	1
metal ion transmembrane transporter activity	1
bicarbonate transport	1
transmembrane transporter activity	1
monoatomic anion transmembrane transporter activity	1
chloride transmembrane transport	1
protein binding	1
sodium ion transmembrane transporter activity	1

Protein interactions and networks

STRING

989 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC4A8	ADGRV1	Q8WXG9	737
SLC4A8	SLC26A4	O43511	719
SLC4A8	CA2	P00918	695
SLC4A8	E9PNW1	E9PNW1	683
SLC4A8	USH2A	O75445	637
SLC4A8	SLC9A1	P19634	628
SLC4A8	SLC26A7	Q8TE54	614
SLC4A8	SLC9A3	P48764	605
SLC4A8	SLC12A2	P55011	576
SLC4A8	SLC12A3	P55017	570
SLC4A8	IFT172	Q9UG01	561
SLC4A8	SLC26A9	Q7LBE3	553
SLC4A8	SLC26A6	Q9BXS9	553
SLC4A8	SLC1A1	P43005	548
SLC4A8	SLC1A3	P43003	534

IntAct

11 interactions, top by confidence:

A	B	Type	Score
SLC4A8	CCT5	psi-mi:“MI:0915”(physical association)	0.400
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
SLC4A8	ABCC4	psi-mi:“MI:0914”(association)	0.350
SLC4A7	SAP18	psi-mi:“MI:0914”(association)	0.350
SLC4A8	PSMA7	psi-mi:“MI:0914”(association)	0.350
SLC4A8	JUN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (85): ADCK2 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), TMEM63B (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), C1orf43 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), GHDC (Affinity Capture-MS), ST7L (Affinity Capture-MS), SLC4A7 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), ATP13A2 (Affinity Capture-MS)

ESM2 similar proteins: A0A096X8J7, B1MTL0, E9Q3M5, G3X939, M5A7P9, O13134, O18917, O88343, P04919, P13808, P16283, P19334, P23347, P23348, P23562, P23685, P26433, P32418, P32847, P34586, P48746, P48751, P48765, P48766, P48767, P48994, P70414, P90895, Q01728, Q28362, Q2Y0W8, Q32LP4, Q4U116, Q5DTL9, Q5RB85, Q5RD44, Q6RI88, Q6RVG2, Q6SJP2, Q6U841

Diamond homologs: A0A096X8J7, A0A494BA31, B1MTL0, E9Q3M5, O13134, O18917, O88343, P02730, P04919, P04920, P13808, P15575, P16283, P23347, P23348, P23562, P32847, P48746, P48751, Q2Y0W8, Q32LP4, Q4U116, Q5DTL9, Q5RB85, Q5RD44, Q6RI88, Q6RVG2, Q6SJP2, Q6U841, Q80ZA5, Q8BTY2, Q8JZR6, Q8K4V2, Q96Q91, Q9BY07, Q9GKY1, Q9GL77, Q9JI66, Q9R1N3, Q9XSZ4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SLC4A8	“up-regulates quantity”	hydrogencarbonate	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4419 predictions. Top by Δscore:

Variant	Effect	Δscore
12:51425036:GTAGG:G	donor_loss	1.0000
12:51440788:AGG:A	donor_loss	1.0000
12:51440789:GGTAA:G	donor_loss	1.0000
12:51440791:T:A	donor_loss	1.0000
12:51450871:TCCA:T	acceptor_loss	1.0000
12:51450873:CA:C	acceptor_loss	1.0000
12:51450874:A:AC	acceptor_loss	1.0000
12:51450998:G:GT	donor_gain	1.0000
12:51451021:CGGT:C	donor_loss	1.0000
12:51451022:GGT:G	donor_loss	1.0000
12:51451023:G:GG	donor_gain	1.0000
12:51451023:GTAA:G	donor_loss	1.0000
12:51451024:T:A	donor_loss	1.0000
12:51452120:CTAG:C	acceptor_loss	1.0000
12:51452121:TAG:T	acceptor_loss	1.0000
12:51452122:A:AG	acceptor_gain	1.0000
12:51452122:A:C	acceptor_loss	1.0000
12:51452123:G:GA	acceptor_gain	1.0000
12:51452123:GACAC:G	acceptor_gain	1.0000
12:51452255:GCCAG:G	donor_gain	1.0000
12:51452256:CCAG:C	donor_loss	1.0000
12:51452258:AG:A	donor_loss	1.0000
12:51452259:GGTGA:G	donor_loss	1.0000
12:51452260:G:C	donor_loss	1.0000
12:51453538:G:GA	acceptor_loss	1.0000
12:51453630:C:G	donor_gain	1.0000
12:51453697:CAG:C	donor_loss	1.0000
12:51453698:AGG:A	donor_loss	1.0000
12:51453699:GGT:G	donor_loss	1.0000
12:51453700:G:A	donor_loss	1.0000

AlphaMissense

7242 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:51452205:T:C	L120P	1.000
12:51452243:T:A	W133R	1.000
12:51452243:T:C	W133R	1.000
12:51452244:G:C	W133S	1.000
12:51452245:G:C	W133C	1.000
12:51452245:G:T	W133C	1.000
12:51452259:G:C	R138T	1.000
12:51452259:G:T	R138M	1.000
12:51453539:G:C	R138S	1.000
12:51453539:G:T	R138S	1.000
12:51453540:T:A	W139R	1.000
12:51453540:T:C	W139R	1.000
12:51453542:G:C	W139C	1.000
12:51453542:G:T	W139C	1.000
12:51453544:T:C	L140P	1.000
12:51453549:T:C	F142L	1.000
12:51453550:T:C	F142S	1.000
12:51453550:T:G	F142C	1.000
12:51453551:T:A	F142L	1.000
12:51453551:T:G	F142L	1.000
12:51453562:T:A	V146D	1.000
12:51453579:C:A	R152S	1.000
12:51453582:T:A	W153R	1.000
12:51453582:T:C	W153R	1.000
12:51453583:G:C	W153S	1.000
12:51453584:G:C	W153C	1.000
12:51453584:G:T	W153C	1.000
12:51453585:A:C	S154R	1.000
12:51453587:C:A	S154R	1.000
12:51453587:C:G	S154R	1.000

dbSNP variants (sampled 300 via entrez): RS1000005909 (12:51512392 G>A), RS1000026822 (12:51417720 G>A,C,T), RS1000056696 (12:51512783 A>G,T), RS1000086005 (12:51410110 T>C), RS1000125851 (12:51405060 A>G), RS1000125928 (12:51466320 T>C), RS1000162985 (12:51506056 C>G,T), RS1000174674 (12:51461836 A>G), RS1000199610 (12:51458309 T>C), RS1000219861 (12:51465942 A>C), RS1000231494 (12:51513743 G>A), RS1000231899 (12:51429585 G>A), RS1000272169 (12:51498996 A>G), RS1000278390 (12:51403814 A>G), RS1000285450 (12:51449852 G>A)

Disease associations

OMIM: gene MIM:605024 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	Limited	Unknown

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001915_28	Alzheimer’s disease (cognitive decline)	3.000000e-07
GCST003151_1	White matter lesion progression	9.000000e-07
GCST003152_1	White matter lesion progression (adjusted for white matter lesion burden at baseline)	3.000000e-06
GCST003813_1	Response to antidepressants and depression	5.000000e-07
GCST010136_14	Fruit consumption	2.000000e-08
GCST010546_27	Problematic alcohol use	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007746	white matter lesion progression measurement
EFO:0008111	diet measurement
EFO:0009458	alcohol use disorder measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12296477	Toxicity	3	ethanol	Alcohol abuse

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12296477	SLC4A8	3	1.50	1	ethanol

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Sodium-dependent HCO₃^- transporters

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression	5
Benzo(a)pyrene	increases expression, increases methylation	4
bisphenol A	decreases expression, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
nutlin 3	increases expression, affects cotreatment	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Cytarabine	decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Nickel	increases expression	1
Tamoxifen	increases expression	1
Tobacco Smoke Pollution	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4FC	1321N1-SLC4A8-KO-c4	Cancer cell line	Male
CVCL_D4FD	1321N1-SLC4A8-KO-c6	Cancer cell line	Male
CVCL_TN93	HAP1 SLC4A8 (-) 1	Cancer cell line	Male
CVCL_TN94	HAP1 SLC4A8 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety