SLC5A8

protein-coding

solute carrier family 5 member 8, the group of Solute carrier family 5

Gene summary

SLC5A8 has been shown to transport iodide by a passive mechanism (Rodriguez et al., 2002 [PubMed 12107270]) and monocarboxylates and short-chain fatty acids by a sodium-coupled mechanism (Gopal et al., 2004 [PubMed 15322102]). In kidney, SLC5A8 functions as a high-affinity sodium-coupled lactate transporter involved in reabsorption of lactate and maintenance of blood lactate levels (Thangaraju et al., 2006 [PubMed 16873376]).[supplied by OMIM, Dec 2008]

MANE transcript

NM_145913.5

Inheritance

—

ClinVar variants

U:93B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr12:101,155,493-101,210,238

External References & Databases

Ensembl (ENSG00000256870)

Transcript & Mutation Effects

hg38 • Region Span ~54.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC5A8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 97

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145913.5. 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				1 clinvar	1 clinvar	2
missense			93 clinvar	4 clinvar	2 clinvar	99
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	93	5	3	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145913.5	RefSeq	NP_666018.3	15	MANE Select
ENST00000536262.3	Ensembl	ENSP00000445340.2	15	MANE Select
ENST00000957672.1	Ensembl	ENSP00000627731.1	12	Standard
ENST00000957672.2	Ensembl	ENSP00000627731.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Nuclear Receptors Meta-Pathway
NRF2 pathway
Tyrosine metabolism
Metabolism
Organic anion transporters

Biological Process

ion transport
sodium ion transport
apoptotic process
propanoate transport
short-chain fatty acid import

Molecular Function

monocarboxylic acid transmembrane transporter activity
lactate transmembrane transporter activity
propionate transmembrane transporter activity
passive transmembrane transporter activity
monocarboxylate:sodium symporter activity

Cellular Component

plasma membrane
integral component of membrane
apical plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000536262
Coding exons: 15
Length: 54915
Individuals with no LoFs: 125652
Homozygous LoFs: 0
Heterozygous LoFs: 96
Defined: 125748
p: 0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.285	315	330	0.956	0.0000160	3924
Missense (PolyPhen)		92	111.73	0.82341		1317
Synonymous	-1.55	150	128	1.17	0.00000691	1226
Loss of Function	0.701	26	30.2	0.862	0.00000133	386

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00064	0.00062	rare
Latino/Admixed American	0.0010	0.00081	notable
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.00055	0.00054	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00027	0.00025	rare
South Asian	0.00048	0.00046	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactate, pyruvate, acetate, propionate, valerate and butyrate), lactate, mocarboxylate drugs (nicotinate, benzoate, salicylate and 5-aminosalicylate) and ketone bodies (beta-D- hydroxybutyrate, acetoacetate and alpha-ketoisocaproate), with a Na(+):substrate stoichiometry of between 4:1 and 2:1. Catalyzes passive carrier mediated diffusion of iodide. Mediates iodide transport from the thyrocyte into the colloid lumen through the apical membrane. May be responsible for the absorption of D- lactate and monocarboxylate drugs from the intestinal tract. Acts as a tumor suppressor, suppressing colony formation in colon cancer, prostate cancer and glioma cell lines. May play a critical role in the entry of L-lactate and ketone bodies into neurons by a process driven by an electrochemical Na(+) gradient and hence contribute to the maintenance of the energy status and function of neurons. {ECO:0000269|PubMed:12107270, ECO:0000269|PubMed:12829793, ECO:0000269|PubMed:14966140, ECO:0000269|PubMed:15090606, ECO:0000269|PubMed:15361710, ECO:0000269|PubMed:15867356, ECO:0000269|PubMed:16729224, ECO:0000269|PubMed:16805814, ECO:0000269|PubMed:17178845, ECO:0000269|PubMed:17245649, ECO:0000269|PubMed:18037591}.;

Recessive Scores

pRec: 0.196

Intolerance Scores

LoFtool: 0.221
RVIS EVS: 0.4
RVIS percentile EVS: 76.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.213

Gene Damage Prediction

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