SLC13A5

Chr 17AR

solute carrier family 13 member 5

Also known as: DEE25, EIEE25, INDY, NACT, mIndy

NCBI Gene: 284111ENSG00000141485UniProt: Q86YT5

This gene encodes a protein belonging to the solute carrier family 13 group of proteins. This family member is a sodium-dependent citrate cotransporter that may regulate metabolic processes. Mutations in this gene cause early infantile epileptic encephalopathy 25. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 25, with amelogenesis imperfectaMIM #615905
AR
597
ClinVar variants
55
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— SLC13A5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 199 VUS of 597 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.001
Z-score 2.83
OE 0.39 (0.24–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.14Z-score
OE missense 0.83 (0.75–0.91)
288 obs / 347.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.24–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.75–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 10 / 25.4Missense obs/exp: 288 / 347.9Syn Z: -0.16

ClinVar Variant Classifications

597 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic17
VUS199
Likely Benign315
Benign19
Conflicting9
38
Pathogenic
17
Likely Pathogenic
199
VUS
315
Likely Benign
19
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
24
0
38
Likely Pathogenic
14
2
1
0
17
VUS
2
174
21
2
199
Likely Benign
0
2
144
169
315
Benign
0
0
19
0
19
Conflicting
—9
Total30178209171597

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC13A5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLC13A5-related epileptic encephalopathy with seizure onset in the first days of life

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta

MIM #615905

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Plasma Membrane Na⁺-Coupled Citrate Transporter (SLC13A5) and Neonatal Epileptic Encephalopathy.
Bhutia YD et al.·Molecules
2017Review
SLC13A5 Deficiency Disorder: From Genetics to Gene Therapy.
Goodspeed K et al.·Genes (Basel)
2022Review
The citrate transporter SLC13A5 as a therapeutic target for kidney disease: evidence from Mendelian randomization to inform drug development.
Gill D et al.·BMC Med
2023
Consequences of NaCT/SLC13A5/mINDY deficiency: good versus evil, separated only by the blood-brain barrier.
Kopel JJ et al.·Biochem J
2021Review
Opportunities and Challenges for Inhibitors Targeting Citrate Transport and Metabolism in Drug Discovery.
Zhang L et al.·J Med Chem
2023Review
The neuroimaging spectrum of SLC13A5 related developmental and epileptic encephalopathy.
Whitney R et al.·Seizure
2023Review
Neonatal developmental and epileptic encephalopathy due to autosomal recessive variants in SLC13A5 gene.
Matricardi S et al.·Epilepsia
2020Review
Developmental phenotype and quality of life in SLC13A5 citrate transporter disorder.
Ozlu C et al.·Dev Med Child Neurol
2025
SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population.
Mir A et al.·Hum Genet
2022
Unraveling neuroimaging insights in developmental epileptic encephalopathy type 25: a comprehensive review of reported cases and a novel SLC13A5 variant.
Mohammadi MF et al.·Acta Neurol Belg
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Citrate Transporter DeficiencyEpilepsyRare Diseases

SLC13A5 Deficiency Natural History Study - Remote Only

ENROLLING BY INVITATION
NCT04681781TESS Research FoundationStarted 2021-03-01
Citrate Transporter DeficiencyEpilepsyRare Diseases

SLC13A5 Deficiency Natural History Study - United States Only

ENROLLING BY INVITATION
NCT06144957TESS Research FoundationStarted 2021-12-01
SLC13A5 Citrate Transporter Disorder

Intrathecal Gene Therapy For SLC13A5 Citrate Transporter Disorder

NOT YET RECRUITING
NCT07102524Phase PHASE1, PHASE2TESS Research FoundationStarted 2025-12-01
TSHA-105

External Resources

Links to major genomics databases and tools