SLC17A3

protein-coding

solute carrier family 17 member 3, the group of Solute carrier family 17

Gene summary

The protein encoded by this gene is a voltage-driven transporter that excretes intracellular urate and organic anions from the blood into renal tubule cells. Two transcript variants encoding different isoforms have been found for this gene. The longer isoform is a plasma membrane protein with transporter activity while the shorter isoform localizes to the endoplasmic reticulum. [provided by RefSeq, Aug 2012]

MANE transcript

NM_001098486.2

Inheritance

ClinVar variants

U:58B:5

Top phenotype

SLC17A3-related disorder

gnomAD constraint

pLI —, LoF o/e 1.1

Max pathogenic AF

—

Genomic locus

chr6:25,833,066-25,882,286

External References & Databases

Ensembl (ENSG00000124564)

Transcript & Mutation Effects

hg38 • Region Span ~49.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

uric acid concentration, serum, quantitative trait locus 4LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0044277

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC17A3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 52

SLC17A3-related disorderTotal: 4

Uric acid concentration, serum, quantitative trait locus 4Total: 2

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001098486.2. 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			1 clinvar		2 clinvar	3
missense			53 clinvar	2 clinvar	1 clinvar	56
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	58	2	3	63

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001098486.2	RefSeq	NP_001091956.1	11	MANE Select
ENST00000397060.8	Ensembl	ENSP00000380250.4	11	MANE Select
NM_006632.4	RefSeq	NP_006623.2	10	Standard
ENST00000360657.7	Ensembl	ENSP00000353873.3	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Uricosurics Pathway, Pharmacodynamics
Stimuli-sensing channels
Ion channel transport
Transport of small molecules

Biological Process

sodium ion transport
phosphate ion transport
drug transmembrane transport
organic anion transport
sialic acid transport

Molecular Function

sodium:phosphate symporter activity
voltage-gated anion channel activity
organic anion transmembrane transporter activity
sialic acid transmembrane transporter activity
urate transmembrane transporter activity

Cellular Component

cytoplasm
lysosome
endoplasmic reticulum membrane
plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397060
Coding exons: 11
Length: 49221
Individuals with no LoFs: 125611
Homozygous LoFs: 0
Heterozygous LoFs: 137
Defined: 125748
p: 0.000545

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.298	272	259	1.05	0.0000127	3200
Missense (PolyPhen)		68	63.467	1.0714		835
Synonymous	-0.0527	94	93.4	1.01	0.00000477	1023
Loss of Function	-0.489	31	28.2	1.10	0.00000157	309

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00070	0.00068	rare
Latino/Admixed American	0.00075	0.00075	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00054	0.00054	rare
South Asian	0.00095	0.00095	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 2: voltage-driven, multispecific, organic anion transporter able to transport para-aminohippurate (PAH), estrone sulfate, estradiol-17-beta-glucuronide, bumetanide, and ochratoxin A. Isoform 2 functions as urate efflux transporter on the apical side of renal proximal tubule and is likely to act as an exit path for organic anionic drugs as well as urate in vivo. May be involved in actively transporting phosphate into cells via Na(+) cotransport.;

Recessive Scores

pRec: 0.0945

Intolerance Scores

LoFtool: 0.983
RVIS EVS: 0.11
RVIS percentile EVS: 62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0557

Gene Damage Prediction

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