SLC5A4

protein-coding

solute carrier family 5 member 4, the group of Solute carrier family 5

Gene summary

Predicted to enable low-affinity D-glucose:sodium symporter activity and proton transmembrane transporter activity. Predicted to be involved in D-glucose import across plasma membrane and renal D-glucose absorption. Predicted to act upstream of or within proton transmembrane transport. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_014227.3

Inheritance

—

ClinVar variants

U:100B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr22:32,218,464-32,255,347

External References & Databases

Ensembl (ENSG00000100191)

Transcript & Mutation Effects

hg38 • Region Span ~36.9 kb

Loading mutation effect viewer...

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 SLC5A4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 101

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014227.3. 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	3 clinvar		5
missense			95 clinvar	6 clinvar		101
nonsense			1 clinvar			1
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	100	10	0	110

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_014227.3	RefSeq	NP_055042.1	15	MANE Select
ENST00000266086.6	Ensembl	ENSP00000266086.3	15	MANE Select
ENST00001132148.1	Ensembl	ENSP00000803834.1	15	Standard
XM_006724308.4	RefSeq	XP_006724371.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Nuclear Receptors Meta-Pathway
NRF2 pathway
SLC-mediated transmembrane transport
Transport of small molecules
Cellular hexose transport

Biological Process

sodium ion transport
glucose transmembrane transport

Molecular Function

glucose:sodium symporter activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000266086
Coding exons: 15
Length: 36864
Individuals with no LoFs: 121728
Homozygous LoFs: 47
Heterozygous LoFs: 3973
Defined: 125748
p: 0.0161

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.839	342	389	0.880	0.0000215	4271
Missense (PolyPhen)		113	147.33	0.76696		1668
Synonymous	0.793	137	149	0.917	0.00000913	1330
Loss of Function	0.936	28	33.9	0.826	0.00000187	360

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0067	0.0047	notable
Latino/Admixed American	0.016	0.0087	notable
Ashkenazi Jewish	0.0070	0.0042	notable
East Asian	0.032	0.030	notable
Finnish	0.0079	0.0045	notable
European (Non-Finnish)	0.023	0.014	notable
South Asian	0.045	0.042	notable
Other	0.025	0.015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has electrogenic activity in response to glucose, and may function as a glucose sensor (PubMed:13130073, PubMed:17110502, PubMed:20421923, PubMed:22766068). Mediates influx of sodium ions into the cell but does not transport sugars (PubMed:13130073, PubMed:22766068). Also potently activated by imino sugars such as deoxynojirimycin (DNJ) (PubMed:17110502, PubMed:20421923, PubMed:22766068). {ECO:0000269|PubMed:13130073, ECO:0000269|PubMed:17110502, ECO:0000269|PubMed:20421923, ECO:0000269|PubMed:22766068}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.187
RVIS EVS: 0.74
RVIS percentile EVS: 86.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.157

Gene Damage Prediction

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