SLC5A1

protein-coding

solute carrier family 5 member 1, the group of Solute carrier family 5

Gene summary

This gene encodes a member of the sodium-dependent glucose transporter (SGLT) family. The encoded integral membrane protein is the primary mediator of dietary glucose and galactose uptake from the intestinal lumen. Mutations in this gene have been associated with glucose-galactose malabsorption. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Previous symbols:

SGLT1

MANE transcript

NM_000343.4

Inheritance

ClinVar variants

P:54U:175B:144

Top phenotype

Glucose/galactose malabsorption

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr22:32,043,261-32,113,029

External References & Databases

Ensembl (ENSG00000100170)

Transcript & Mutation Effects

hg38 • Region Span ~69.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

glucose-galactose malabsorptionSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011731

Submitter: Orphanet

glucose-galactose malabsorptionSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011731

Submitter: PanelApp Australia

glucose-galactose malabsorptionDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011731

Submitter: Ambry Genetics

glucose-galactose malabsorptionSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011731

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Glucose/galactose malabsorptionAR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: Individuals typically present in infancy with severe osmotic diarrhea and consequent dehydration, which can be fatal without dietary elimination of glucose and galactose (ie, individuals demonstrate dramatic improvement on fructose-based formula)

Refs: 11406349; 2008213; 8985845; 8844006; 9815014; 12139397; 17169300; 18288487; 20486940; 22843301; 23107089; 24048166

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC5A1 variants in ClinVar

7 Conditions Cataloged

Congenital glucose-galactose malabsorptionTotal: 424

Inborn genetic diseasesTotal: 55

not providedTotal: 32

SLC5A1-related disorderTotal: 25

not specifiedTotal: 19

SLC5A1-related glucose/galactose malabsorptionTotal: 1

Renal glycosuriaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000343.4. 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			6 clinvar	130 clinvar	2 clinvar	138
missense	3 clinvar	15 clinvar	168 clinvar	11 clinvar	1 clinvar	198
nonsense	9 clinvar	5 clinvar				14
start loss		1 clinvar				1
frameshift	5 clinvar	5 clinvar				10
splice donor/acceptor (+/-2bp)	1 clinvar	10 clinvar	1 clinvar			12
Total	18	36	175	141	3	373

Highest pathogenic variant AF is 0.00004036247

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000343.4	RefSeq	NP_000334.1	15	MANE Select
ENST00000266088.9	Ensembl	ENSP00000266088.4	15	MANE Select
NM_001256314.2	RefSeq	NP_001243243.1	11	Standard
ENST00000543737.2	Ensembl	ENSP00000444898.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Bile secretion - Homo sapiens (human)
Carbohydrate digestion and absorption - Homo sapiens (human)
Mineral absorption - Homo sapiens (human)
Trehalose Degradation
Lactose Degradation

Biological Process

sodium ion transport
intestinal hexose absorption
glucose transmembrane transport

Molecular Function

glucose:sodium symporter activity
protein binding

Cellular Component

plasma membrane
integral component of plasma membrane
integral component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000266088
Coding exons: 15
Length: 69998
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 125748
p: 0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.83	274	374	0.733	0.0000226	4322
Missense (PolyPhen)		62	130.55	0.47492		1524
Synonymous	-0.385	151	145	1.04	0.00000960	1328
Loss of Function	2.59	17	33.1	0.514	0.00000171	387

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Actively transports glucose into cells by Na(+) cotransport with a Na(+) to glucose coupling ratio of 2:1. Efficient substrate transport in mammalian kidney is provided by the concerted action of a low affinity high capacity and a high affinity low capacity Na(+)/glucose cotransporter arranged in series along kidney proximal tubules.;
Disease: DISEASE: Congenital glucose/galactose malabsorption (GGM) [MIM:606824]: Intestinal monosaccharide transporter deficiency. It is an autosomal recessive disorder manifesting itself within the first weeks of life. It is characterized by severe diarrhea and dehydration which are usually fatal unless glucose and galactose are eliminated from the diet. {ECO:0000269|PubMed:10036327, ECO:0000269|PubMed:11406349, ECO:0000269|PubMed:2008213, ECO:0000269|PubMed:8195156}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.405

Intolerance Scores

LoFtool: 0.0773
RVIS EVS: 0.33
RVIS percentile EVS: 73.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.649

Gene Damage Prediction

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