SLC13A3 solute carrier family 13 member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC13A3provided by HGNC
Official Full Name: solute carrier family 13 member 3provided by HGNC
Primary source: HGNC:HGNC:14430
See related: Ensembl:ENSG00000158296 MIM:606411; AllianceGenome:HGNC:14430
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NaC3; NADC3; SDCT2; ARLIAK
Summary: Mammalian sodium-dicarboxylate cotransporters transport succinate and other Krebs cycle intermediates. They fall into 2 categories based on their substrate affinity: low affinity and high affinity. Both the low- and high-affinity transporters play an important role in the handling of citrate by the kidneys. The protein encoded by this gene represents the high-affinity form. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, although the full-length nature of some of them have not been characterized yet. [provided by RefSeq, Jul 2008]
Expression: Biased expression in kidney (RPKM 195.8) and placenta (RPKM 14.9) See more
Orthologs: mouse all
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Genomic context

Location:: 20q13.12

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (46557828..46684485, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (48293974..48420764, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (45186467..45313124, complement)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SLC13A3 is a major effector downstream of activated beta-catenin in liver cancer pathogenesis.
Title: SLC13A3 is a major effector downstream of activated β-catenin in liver cancer pathogenesis.
Structural and functional implications of SLC13A3 and SLC9A6 mutations: an in silico approach to understanding intellectual disability.
Title: Structural and functional implications of SLC13A3 and SLC9A6 mutations: an in silico approach to understanding intellectual disability.
Association of Single Nucleotide Polymorphisms in KCNA10 and SLC13A3 Genes with the Susceptibility to Chronic Kidney Disease of Unknown Etiology in Central Indian Patients.
Title: Association of Single Nucleotide Polymorphisms in KCNA10 and SLC13A3 Genes with the Susceptibility to Chronic Kidney Disease of Unknown Etiology in Central Indian Patients.
NaDC3-related immunostaining was detected in the basolateral membrane of proximal tubules and in the basolateral membrane and/or luminal membrane of principal cells in connecting segments and collecting ducts
Title: Distribution of organic anion transporters NaDC3 and OAT1-3 along the human nephron.
OAT1 and NaDC3 in the basolateral membrane and OAT4 in the luminal membrane of proximal tubule cells are responsible for the avid renal secretion of N-carbamoylglutamate.
Title: Transporters involved in renal excretion of N-carbamoylglutamate, an orphan drug to treat inborn n-acetylglutamate synthase deficiency.
In a study addressing genetic, social, and environmental contributors of chronic kidney disease with tubulointerstitial damages in Sri Lanka, SNP rs6066043 of SLC13A3 was found attributable risk of 50%.
Title: An integrative study of the genetic, social and environmental determinants of chronic kidney disease characterized by tubulointerstitial damages in the North Central Region of Sri Lanka.
study concludes NaDC3 present at the basolateral membrane of proximal tubule cells mediates sodium-dependent glutathione (GSH) uptake; the kinetic data show that NaDC3 is a low-affinity GSH transporter
Title: Glutathione is a low-affinity substrate of the human sodium-dependent dicarboxylate transporter.
The data 1) reveal alpha-ketoglutarate as a common high-affinity substrate of NaDC3, OAT1, and OAT3
Title: Differential interaction of dicarboxylates with human sodium-dicarboxylate cotransporter 3 and organic anion transporters 1 and 3.
The results indicate that SLC13A3 is a direct downstream target of PITX2 transcriptional regulation and that levels of PITX2 and SLC13A3 modulate responses to oxidative stress in ocular cells.
Title: PITX2 is involved in stress response in cultured human trabecular meshwork cells through regulation of SLC13A3.
NaDC3 promotes cellular senescence probably by inhibiting NAD(+)-dependent SIRT1.
Title: High-affinity Na(+)-dependent dicarboxylate cotransporter promotes cellular senescence by inhibiting SIRT1.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate MedGen: C5193068 OMIM: 618384 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
An integrative study of the genetic, social and environmental determinants of chronic kidney disease characterized by tubulointerstitial damages in the North Central Region of Sri Lanka. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of solute carrier family 13, member 3 (SLC13A3; sodium-dependent dicarboxylate transporter) in primary human brain microvascular endothelial cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G27374 (e-PCR)
- UniSTS:46107

AFMB305XD9 (e-PCR)
- UniSTS:66100

SHGC-150948 (e-PCR)
- UniSTS:173629

WI-14322 (e-PCR)
- UniSTS:70757

AL031467 (e-PCR)
- UniSTS:66927

RH98928 (e-PCR)
- UniSTS:91303

D20S886 (e-PCR), detects polymorphism
- UniSTS:70062

A004V36 (e-PCR)
- UniSTS:42416

RH79978 (e-PCR)
- UniSTS:89781

D20S577E (e-PCR)
- UniSTS:31159

RH45751 (e-PCR)
- UniSTS:48837

RH66073 (e-PCR)
- UniSTS:38087

D20S565E (e-PCR)
- UniSTS:33227

D20S1114 (e-PCR)
- UniSTS:25042

G43492 (e-PCR)
- UniSTS:94952

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables alpha-ketoglutarate transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables citrate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables citrate transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables dicarboxylic acid transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables dicarboxylic acid transmembrane transporter activity	TAS Traceable Author Statement more info	PubMed
enables glutathione transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables high-affinity sodium:dicarboxylate symporter activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium:dicarboxylate symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables sodium:dicarboxylate symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium:dicarboxylate symporter activity	TAS Traceable Author Statement more info	PubMed
enables succinate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables succinate transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables succinate transmembrane transporter activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in alpha-ketoglutarate transport	IEA Inferred from Electronic Annotation more info
involved_in citrate transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in citrate transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in dicarboxylic acid transport	IDA Inferred from Direct Assay more info	PubMed
involved_in dicarboxylic acid transport	TAS Traceable Author Statement more info	PubMed
involved_in glutathione transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in lipid transport	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in succinate transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in succinate transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in succinate transmembrane transport	TAS Traceable Author Statement more info	PubMed
involved_in transport across blood-brain barrier	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: Na(+)/dicarboxylate cotransporter 3

Names: Na(+)-coupled carboxylate transporter 3; hNaDC3; naDC-3; sodium-dependent high affinity dicarboxylate transporter 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_047182.1 RefSeqGene

Range

38027..131658

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001011554.3 → NP_001011554.1 Na(+)/dicarboxylate cotransporter 3 isoform b

See identical proteins and their annotated locations for NP_001011554.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding region compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a.

Source sequence(s)

AL034424, AL442082, BM474324, CN310376, DA272524, DA503319

Consensus CDS

CCDS42886.1

UniProtKB/TrEMBL

B4DF27

Related

ENSP00000290317.5, ENST00000290317.9

Conserved Domains (2) summary

COG0471
Location:1 → 519

CitT; Di- and tricarboxylate transporter [Carbohydrate transport and metabolism]

cd01115
Location:1 → 511

SLC13_permease; Permease SLC13 (solute carrier 13). The sodium/dicarboxylate cotransporter NaDC-1 has been shown to translocate Krebs cycle intermediates such as succinate, citrate, and alpha-ketoglutarate across plasma membranes rabbit, human, and rat kidney. It is ...
NM_001193339.2 → NP_001180268.1 Na(+)/dicarboxylate cotransporter 3 isoform c

See identical proteins and their annotated locations for NP_001180268.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate segment which changes the reading frame, and uses a different splice site, which restores the reading frame, compared to variant 1. The resulting protein (isoform c) is shorter and has an internal distinct sequence when it is compared to isoform a.

Source sequence(s)

AK293902, AK295748, AL034424, DA334816

Consensus CDS

CCDS54470.1

UniProtKB/Swiss-Prot

Q8WWT9

UniProtKB/TrEMBL

B4DF27

Related

ENSP00000415852.2, ENST00000413164.6

Conserved Domains (2) summary

COG0471
Location:17 → 516

CitT; Di- and tricarboxylate transporter [Carbohydrate transport and metabolism]

cd01115
Location:42 → 508

SLC13_permease; Permease SLC13 (solute carrier 13). The sodium/dicarboxylate cotransporter NaDC-1 has been shown to translocate Krebs cycle intermediates such as succinate, citrate, and alpha-ketoglutarate across plasma membranes rabbit, human, and rat kidney. It is ...
NM_001193340.2 → NP_001180269.1 Na(+)/dicarboxylate cotransporter 3 isoform d

See identical proteins and their annotated locations for NP_001180269.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) has multiple differences in the 5' UTR and in the coding region which results in the use of a downstream start codon, compared to variant 1. The resulting protein (isoform d) is shorter when it is compared to isoform a.

Source sequence(s)

AK096658, AL034424, BP358260

Consensus CDS

CCDS54469.1

UniProtKB/TrEMBL

B4DF27

Related

ENSP00000420177.1, ENST00000472148.5

Conserved Domains (2) summary

COG0471
Location:1 → 484

CitT; Di- and tricarboxylate transporter [Carbohydrate transport and metabolism]

cd01115
Location:1 → 476

SLC13_permease; Permease SLC13 (solute carrier 13). The sodium/dicarboxylate cotransporter NaDC-1 has been shown to translocate Krebs cycle intermediates such as succinate, citrate, and alpha-ketoglutarate across plasma membranes rabbit, human, and rat kidney. It is ...
NM_001193342.2 → NP_001180271.1 Na(+)/dicarboxylate cotransporter 3 isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses a different splice site, which results in translation from a downstream, in-frame, start codon, compared to variant 1. The resulting isoform (e) is shorter at the N-terminus compared to isoform a.

Source sequence(s)

AK293902, AL034424, CB997336, DA636764

UniProtKB/TrEMBL

B4DF27

Conserved Domains (2) summary

COG0471
Location:1 → 468

CitT; Di- and tricarboxylate transporter [Carbohydrate transport and metabolism]

cd01115
Location:2 → 460

SLC13_permease; Permease SLC13 (solute carrier 13). The sodium/dicarboxylate cotransporter NaDC-1 has been shown to translocate Krebs cycle intermediates such as succinate, citrate, and alpha-ketoglutarate across plasma membranes rabbit, human, and rat kidney. It is ...
NM_022829.6 → NP_073740.2 Na(+)/dicarboxylate cotransporter 3 isoform a

See identical proteins and their annotated locations for NP_073740.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (a).

Source sequence(s)

AL034424, AY072810, DA636764

Consensus CDS

CCDS13400.1

UniProtKB/Swiss-Prot

B4DIR8, E1P5U4, F6WI18, Q5JYC9, Q5JYD0, Q5JYD1, Q5TCQ2, Q8IVB1, Q8N8K4, Q8WWT9, Q96MM5, Q9BR25, Q9H1G1, Q9H3W4, Q9NQN5, Q9NS04

UniProtKB/TrEMBL

B4DF27

Related

ENSP00000279027.4, ENST00000279027.9

Conserved Domains (2) summary

COG0471
Location:17 → 566

CitT; Di- and tricarboxylate transporter [Carbohydrate transport and metabolism]

cd01115
Location:42 → 558

SLC13_permease; Permease SLC13 (solute carrier 13). The sodium/dicarboxylate cotransporter NaDC-1 has been shown to translocate Krebs cycle intermediates such as succinate, citrate, and alpha-ketoglutarate across plasma membranes rabbit, human, and rat kidney. It is ...