SLC4A8

protein-coding

solute carrier family 4 member 8, the group of Solute carrier family 4

Gene summary

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. [provided by RefSeq, Apr 2012]

MANE transcript

NM_001039960.3

Inheritance

—

ClinVar variants

U:76B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr12:51,391,317-51,515,763

External References & Databases

Ensembl (ENSG00000050438)

Transcript & Mutation Effects

hg38 • Region Span ~124.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC4A8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039960.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			65 clinvar	1 clinvar		66
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	76	1	0	77

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001039960.3	RefSeq	NP_001035049.1	25	MANE Select
ENST00000453097.7	Ensembl	ENSP00000405812.2	25	MANE Select
NM_001258401.3	RefSeq	NP_001245330.1	23	Standard
NM_001258402.2	RefSeq	NP_001245331.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transport of inorganic cations/anions and amino acids/oligopeptides
SLC-mediated transmembrane transport
Transport of small molecules
Bicarbonate transporters

Biological Process

sodium ion transport
inorganic anion transport
bicarbonate transport
regulation of intracellular pH
anion transmembrane transport

Molecular Function

inorganic anion exchanger activity
sodium:bicarbonate symporter activity
anion:anion antiporter activity

Cellular Component

plasma membrane
integral component of plasma membrane
neuronal cell body membrane
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000453097
Coding exons: 25
Length: 117880
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.06	319	598	0.533	0.0000315	7209
Missense (PolyPhen)		115	284.42	0.40433		3377
Synonymous	0.672	201	213	0.941	0.0000110	2105
Loss of Function	5.81	8	54.2	0.148	0.00000273	658

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000070	0.000070	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. May be involved in cell pH regulation by transporting HCO3(-) from blood to cell. Enhanced expression in severe acid stress could be important for cell survival by mediating the influx of HCO3(-) into the cells. Also mediates lithium-dependent HCO3(-) cotransport. May be regulated by osmolarity. {ECO:0000269|PubMed:10362779, ECO:0000269|PubMed:11133997}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.114
RVIS EVS: -0.8
RVIS percentile EVS: 12.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.493

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium