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 (Strong), mode of inheritance: AR
• glucose-galactose malabsorption (Supportive), mode of inheritance: AR
• glucose-galactose malabsorption (Definitive), 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 (12 variants)
• SLC5A1-related disorder (1 variants)
• not provided (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	92	6	100
missense	3	4	125		4	136
nonsense	5	2	1			8
start loss						0
frameshift	3	1				4
inframe indel			4			4
splice donor/acceptor (+/-2bp)	1	3				4
splice region			10	17	4	31
non coding			33	52	20	105
Total	12	10	165	144	30

Highest pathogenic variant AF is 0.0000263

Variants in SLC5A1

This is a list of pathogenic ClinVar variants found in the SLC5A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-32043269-C-CA		Congenital glucose-galactose malabsorption	Uncertain significance (Jun 14, 2016)
22-32043287-C-T		Congenital glucose-galactose malabsorption	Benign (Jan 29, 2024)
22-32043287-C-CAGT		Congenital glucose-galactose malabsorption	Uncertain significance (Jun 18, 2017)
22-32043297-T-C		Congenital glucose-galactose malabsorption	Uncertain significance (Nov 15, 2022)
22-32043311-C-T		Congenital glucose-galactose malabsorption	Likely benign (Apr 28, 2022)
22-32043314-C-T		Congenital glucose-galactose malabsorption	Likely benign (Oct 08, 2023)
22-32043315-G-A		Congenital glucose-galactose malabsorption • Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
22-32043316-C-T		not specified • Congenital glucose-galactose malabsorption	Conflicting classifications of pathogenicity (Jan 31, 2024)
22-32043317-G-A		SLC5A1-related disorder • Congenital glucose-galactose malabsorption	Conflicting classifications of pathogenicity (Jan 18, 2024)
22-32043317-G-C		Congenital glucose-galactose malabsorption	Likely benign (Jan 02, 2021)
22-32043322-C-G		Inborn genetic diseases	Uncertain significance (Nov 29, 2023)
22-32043322-C-T		Congenital glucose-galactose malabsorption	Uncertain significance (Aug 23, 2021)
22-32043324-C-T		Congenital glucose-galactose malabsorption	Uncertain significance (Jul 05, 2022)
22-32043325-G-A		Congenital glucose-galactose malabsorption	Uncertain significance (Jul 19, 2022)
22-32043331-T-C		Congenital glucose-galactose malabsorption	Benign (Jan 29, 2024)
22-32043334-A-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
22-32043335-G-A		Congenital glucose-galactose malabsorption	Likely benign (Jul 17, 2023)
22-32043351-C-T		Congenital glucose-galactose malabsorption	Uncertain significance (Apr 14, 2022)
22-32043356-T-C		Congenital glucose-galactose malabsorption	Likely benign (Nov 08, 2022)
22-32043363-G-A		Congenital glucose-galactose malabsorption	Pathogenic (May 01, 1996)
22-32043364-A-G		Congenital glucose-galactose malabsorption	Uncertain significance (Aug 16, 2021)
22-32043370-C-T		Congenital glucose-galactose malabsorption	Uncertain significance (Jul 14, 2022)
22-32043378-G-A		Congenital glucose-galactose malabsorption	Conflicting classifications of pathogenicity (Oct 03, 2023)
22-32043382-T-C		Congenital glucose-galactose malabsorption	Uncertain significance (Sep 13, 2022)
22-32043383-C-T		Congenital glucose-galactose malabsorption	Likely benign (Jun 05, 2022)

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