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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SLC13A5
solute carrier family 13 member 5
Chromosome 17 Β· 17p13.1
NCBI Gene: 284111Ensembl: ENSG00000141485.18HGNC: HGNC:23089UniProt: Q86YT5
52PubMed Papers
21Diseases
0Drugs
61Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
organic acid:sodium symporter activityprotein bindingcitrate transmembrane transporter activityoxaloacetate transportgenetic developmental and epileptic encephalopathyundetermined early-onset epileptic encephalopathygenetic disorderamelocerebrohypohidrotic syndrome
✦AI Summary

SLC13A5 encodes a high-affinity sodium/citrate cotransporter that mediates Na(+)-dependent entry of citrate into cells 1. The transporter recognizes the physiologically relevant trivalent form of citrate with a stoichiometry of 4 Na(+) per citrate molecule, making it an electrogenic transporter 1. SLC13A5 supports critical metabolic pathways including the Krebs cycle, fatty acid synthesis, cholesterol synthesis, glycolysis, and gluconeogenesis 2. The transporter is expressed in hepatocyte sinusoidal membranes, spermatozoa mitochondria, and neuronal plasma membranes, where it facilitates citrate uptake for energy production and cellular metabolism 1. Biallelic loss-of-function variants in SLC13A5 cause developmental and epileptic encephalopathy 25 (DEE25), characterized by neonatal-onset seizures evolving into status epilepticus in 57% of patients 3. Clinical features include severe developmental delay, hypotonia, and distinctive tooth hypoplasia or hypodontia 3. Notably, seizures often become controlled by late childhood, with ~60% seizure-free between ages 3-12 years 3. Neuroimaging abnormalities occur in approximately one-third of cases, with white matter lesions being most common 4. The molecular mechanisms linking citrate transporter deficiency to epilepsy likely involve dysfunction of GABA signaling and NMDA receptor hyperfunction 1. Current antiseizure medications partially control seizures, though gene therapy approaches show promise 5.

Sources cited
1
SLC13A5 is a Na(+)-coupled citrate transporter with 4:1 Na(+):citrate stoichiometry, electrogenic properties, and tissue-specific expression; human variant shows 30-fold lower citrate affinity than rodent; dysfunction implicates GABA and NMDA signaling in epilepsy
PMID: 28264506
2
SLC13A5 (NaC2) is a Na(+)-carboxylate cotransporter with 3:1 Na(+):anion coupling ratio supporting Krebs cycle intermediates and other metabolic functions
PMID: 23177988
3
Autosomal recessive SLC13A5 variants cause neonatal epileptic encephalopathy with seizures in first days of life, developmental delay, hypotonia, tooth hypoplasia/hypodontia; 57% develop status epilepticus; seizure frequency improves significantly after age 3
PMID: 33063863
4
SLC13A5-related DEE shows neuroimaging abnormalities in ~34% of cases, with white matter abnormalities and punctate white matter lesions being most common
PMID: 36701889
5
SLC13A5 deficiency disorder causes seizure onset within first week of life with developmental delay and intellectual disability; current antiseizure medications reduce seizure frequency but more targeted treatments needed; AAV9-based gene replacement therapy shows promise
PMID: 36140822
Disease Associationsβ“˜21
genetic developmental and epileptic encephalopathyOpen Targets
0.69Moderate
undetermined early-onset epileptic encephalopathyOpen Targets
0.66Moderate
genetic disorderOpen Targets
0.47Moderate
amelocerebrohypohidrotic syndromeOpen Targets
0.37Weak
Amelo-cerebro-hypohidrotic syndromeOpen Targets
0.37Weak
Hypoplastic amelogenesis imperfectaOpen Targets
0.37Weak
Epileptic encephalopathyOpen Targets
0.33Weak
insomniaOpen Targets
0.31Weak
alcohol drinkingOpen Targets
0.31Weak
Intellectual disabilityOpen Targets
0.27Weak
Global developmental delayOpen Targets
0.27Weak
chronic kidney diseaseOpen Targets
0.26Weak
SeizureOpen Targets
0.26Weak
microcephalyOpen Targets
0.11Weak
bipolar disorderOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
esophageal squamous cell carcinomaOpen Targets
0.07Suggestive
Absent tibia - polydactylyOpen Targets
0.05Suggestive
tibia, hypoplasia or aplasia of, with polydactylyOpen Targets
0.05Suggestive
AcheiropodiaOpen Targets
0.05Suggestive
Developmental and epileptic encephalopathy 25, with amelogenesis imperfectaUniProt
Pathogenic Variants61
NM_177550.5(SLC13A5):c.655G>A (p.Gly219Arg)Pathogenic
Developmental and epileptic encephalopathy, 25|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2026β†’ Residue 219
NM_177550.5(SLC13A5):c.680C>T (p.Thr227Met)Pathogenic
Developmental and epileptic encephalopathy, 25|Undetermined early-onset epileptic encephalopathy|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 227
NM_177550.5(SLC13A5):c.548-2A>GLikely pathogenic
not provided|Developmental and epileptic encephalopathy, 25
β˜…β˜…β˜†β˜†2025
NM_177550.5(SLC13A5):c.1280C>T (p.Ser427Leu)Pathogenic
Developmental and epileptic encephalopathy, 25|SLC13A5-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 427
NM_177550.5(SLC13A5):c.1276-1G>APathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜…β˜†β˜†2024
NM_177550.5(SLC13A5):c.425C>T (p.Thr142Met)Pathogenic
Developmental and epileptic encephalopathy, 25|not provided|Intellectual disability
β˜…β˜…β˜†β˜†2024β†’ Residue 142
NM_177550.5(SLC13A5):c.548-1G>ALikely pathogenic
Developmental and epileptic encephalopathy, 25|Inborn genetic diseases
β˜…β˜…β˜†β˜†2024
NM_177550.5(SLC13A5):c.997C>T (p.Arg333Ter)Pathogenic
not provided|Developmental and epileptic encephalopathy, 25|Inborn genetic diseases
β˜…β˜…β˜†β˜†2024β†’ Residue 333
NM_177550.5(SLC13A5):c.1022G>A (p.Trp341Ter)Pathogenic
Developmental and epileptic encephalopathy, 25|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 341
NM_177550.5(SLC13A5):c.1141del (p.Ser381fs)Pathogenic
not provided|Developmental and epileptic encephalopathy, 25
β˜…β˜…β˜†β˜†2021β†’ Residue 381
NM_177550.5(SLC13A5):c.202C>T (p.Pro68Ser)Likely pathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2026β†’ Residue 68
NM_177550.5(SLC13A5):c.1379C>A (p.Thr460Asn)Likely pathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2026β†’ Residue 460
NM_177550.5(SLC13A5):c.1056-1G>CPathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2026
NM_177550.5(SLC13A5):c.1487_1502del (p.Leu496fs)Pathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2025β†’ Residue 496
NM_177550.5(SLC13A5):c.232-2A>GPathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2025
NM_177550.5(SLC13A5):c.1437+1G>ALikely pathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2025
NM_177550.5(SLC13A5):c.238_239del (p.Val80fs)Pathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2025β†’ Residue 80
NM_177550.5(SLC13A5):c.1501dup (p.Ala501fs)Pathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2025β†’ Residue 501
NM_177550.5(SLC13A5):c.1118del (p.Gln373fs)Pathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2025β†’ Residue 373
NM_177550.5(SLC13A5):c.1496C>T (p.Ser499Phe)Likely pathogenic
Developmental and epileptic encephalopathy, 25
β˜…β˜†β˜†β˜†2025β†’ Residue 499
View on ClinVar β†—
Related Genes
SLC13A2Shared pathway100%SLC15A5Protein interaction95%MINDY1Protein interaction79%DYRK1AProtein interaction70%SLC13A3Shared pathway57%SLC25A10Shared pathway25%
Tissue Expression6 tissues
Liver
100%
Brain
0%
Ovary
0%
Lung
0%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
SLC13A5SLC13A2SLC15A5MINDY1DYRK1ASLC13A3SLC25A10
PROTEIN STRUCTURE
Preparing viewer…
PDB8UVB Β· 2.13 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.55Moderately Constrained
pLIβ“˜
0.70Intermediate
Observed/Expected LoF0.38 [0.27–0.55]
RankingsWhere SLC13A5 stands among ~20K protein-coding genes
  • #8,611of 20,598
    Most Researched52
  • #1,158of 5,498
    Most Pathogenic Variants61 Β· top quartile
  • #3,525of 17,882
    Most Constrained (LOEUF)0.55 Β· top quartile
Genes detectedSLC13A5
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Neonatal developmental and epileptic encephalopathy due to autosomal recessive variants in SLC13A5 gene.
PMID: 33063863
Epilepsia Β· 2020
1.00
2
SLC13A5 Deficiency Disorder: From Genetics to Gene Therapy.
PMID: 36140822
Genes (Basel) Β· 2022
0.90
3
Sodium-sulfate/carboxylate cotransporters (SLC13).
PMID: 23177988
Curr Top Membr Β· 2012
0.80
4
Plasma Membrane Na⁺-Coupled Citrate Transporter (SLC13A5) and Neonatal Epileptic Encephalopathy.
PMID: 28264506
Molecules Β· 2017
0.70
5
Novel Approaches to Studying SLC13A5 Disease.
PMID: 38392976
Metabolites Β· 2024
0.60