SLC5A2

protein-coding

solute carrier family 5 member 2, the group of Solute carrier family 5

Gene summary

This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene. [provided by RefSeq, Feb 2015]

Previous symbols:

SGLT2

MANE transcript

NM_003041.4

Inheritance

AR, AD, SD

ClinVar variants

P:67U:291B:28

Top phenotype

Renal glucosuria

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr16:31,483,002-31,490,860

External References & Databases

Ensembl (ENSG00000140675)

Transcript & Mutation Effects

hg38 • Region Span ~7.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial renal glucosuriaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009297

Submitter: Ambry Genetics

familial renal glucosuriaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0009297

Submitter: Labcorp Genetics (formerly Invitae)

familial renal glucosuriaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009297

Submitter: Labcorp Genetics (formerly Invitae)

familial renal glucosuriaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0009297

Submitter: Ambry Genetics

familial renal glucosuriaSTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0009297

Submitter: PanelApp Australia

familial renal glucosuriaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0009297

Submitter: Orphanet

Clinical Genomic Database (CGD)

Renal glucosuriaAD/AR

Manifestation: Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 12436245; 21165652

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC5A2 variants in ClinVar

11 Conditions Cataloged

Familial renal glucosuriaTotal: 269

Inborn genetic diseasesTotal: 114

not providedTotal: 73

SLC5A2-related disorderTotal: 43

not specifiedTotal: 17

Prostate cancerTotal: 1

Hypophosphatemic nephrolithiasis/osteoporosis 1Total: 1

Renal tubulopathiesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003041.4. 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			20 clinvar	16 clinvar	2 clinvar	38
missense	3 clinvar	27 clinvar	264 clinvar	9 clinvar	1 clinvar	304
nonsense	3 clinvar	9 clinvar				12
start loss			1 clinvar			1
frameshift	3 clinvar	13 clinvar	3 clinvar			19
splice donor/acceptor (+/-2bp)	2 clinvar	7 clinvar	3 clinvar			12
Total	11	56	291	25	3	386

Highest pathogenic variant AF is 0.00025782024

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003041.4	RefSeq	NP_003032.1	14	MANE Select
ENST00000330498.4	Ensembl	ENSP00000327943.3	14	MANE Select
ENST00000419665.6	Ensembl	ENSP00000410601.2	11	Standard
ENST00000569576.5	Ensembl	ENSP00000455143.1	4	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
Fructose and mannose metabolism

Biological Process

carbohydrate metabolic process
sodium ion transport
hexose transmembrane transport
glucose transmembrane transport

Molecular Function

low-affinity glucose:sodium symporter activity
glucose:sodium symporter activity

Cellular Component

plasma membrane
integral component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000330498
Coding exons: 14
Length: 7859
Individuals with no LoFs: 125639
Homozygous LoFs: 0
Heterozygous LoFs: 109
Defined: 125748
p: 0.000434

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.16	472	406	1.16	0.0000258	4262
Missense (PolyPhen)		208	197.17	1.0549		2064
Synonymous	-2.18	218	181	1.21	0.0000126	1440
Loss of Function	1.02	24	30.0	0.799	0.00000143	323

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.0010	notable
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00015	0.00014	rare
European (Non-Finnish)	0.00058	0.00057	rare
South Asian	0.00029	0.00029	rare
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Sodium-dependent glucose transporter. Has a Na(+) to glucose coupling ratio of 1:1.;
Disease: DISEASE: Renal glucosuria (GLYS) [MIM:233100]: A disorder characterized by persistent isolated glucosuria, normal fasting serum glucose concentration, decreased renal tubular resorption of glucose from the urine, and absence of any other signs of tubular dysfunction. {ECO:0000269|PubMed:14614622}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.192

Intolerance Scores

LoFtool: 0.140
RVIS EVS: -0.86
RVIS percentile EVS: 10.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.169

Gene Damage Prediction

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