SLC5A1

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

Basic information

Region (hg38): 22:32043261-32113029

Previous symbols: [ "SGLT1" ]

Links

ENSG00000100170

∙ NCBI:6523 ∙ OMIM:182380 ∙ HGNC:11036 ∙ Uniprot:P13866 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

glucose-galactose malabsorption (Strong), mode of inheritance: AR
glucose-galactose malabsorption (Supportive), mode of inheritance: AR
glucose-galactose malabsorption (Definitive), mode of inheritance: AR
glucose-galactose malabsorption (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glucose/galactose malabsorption	AR	Gastrointestinal	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)	Gastrointestinal	11406349; 2008213; 8985845; 8844006; 9815014; 12139397; 17169300; 18288487; 20486940; 22843301; 23107089; 24048166

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC5A1 gene.

Congenital_glucose-galactose_malabsorption (398 variants)
Inborn_genetic_diseases (47 variants)
not_provided (24 variants)
SLC5A1-related_disorder (14 variants)
Renal_glycosuria (1 variants)
not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC5A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000343.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	116 clinvar	2 clinvar	123
missense	3 clinvar	12 clinvar	159 clinvar	11 clinvar	1 clinvar	186
nonsense	8 clinvar	4 clinvar	1 clinvar			13
start loss		1				1
frameshift	4 clinvar	4 clinvar				8
splice donor/acceptor (+/-2bp)	1 clinvar	9 clinvar				10
Total	16	30	165	127	3

Highest pathogenic variant AF is 0.0000403625

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC5A1	protein_coding	protein_coding	ENST00000266088	15	69998

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.75e-8	0.996	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	274	374	0.733	0.0000226	4322
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000297	0.000297
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000109	0.000109
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

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.;
Pathway: Bile secretion - Homo sapiens (human);Carbohydrate digestion and absorption - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Trehalose Degradation;Lactose Degradation;Lactose Intolerance;Nuclear Receptors Meta-Pathway;NRF2 pathway;Purine metabolism;SLC-mediated transmembrane transport;Transport of small molecules;Fructose and mannose metabolism;Galactose metabolism;Cellular hexose transport;Intestinal hexose absorption;Intestinal absorption;Digestion and absorption (Consensus)

Recessive Scores

pRec: 0.405

Intolerance Scores

loftool: 0.0773
rvis_EVS: 0.33
rvis_percentile_EVS: 73.61

Haploinsufficiency Scores

pHI: 0.164
hipred: Y
hipred_score: 0.684
ghis: 0.410

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.649

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Slc5a1
Phenotype: digestive/alimentary phenotype; limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);

Gene ontology

Biological process: sodium ion transport;intestinal hexose absorption;glucose transmembrane transport
Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;extracellular exosome
Molecular function: glucose:sodium symporter activity;protein binding