SLC6A18

Chr 5

solute carrier family 6 member 18

Also known as: Xtrp2

NCBI Gene: 348932ENSG00000164363UniProt: Q96N87

The SLC6 family of proteins, which includes SLC6A18, act as specific transporters for neurotransmitters, amino acids, and osmolytes like betaine, taurine, and creatine. SLC6 proteins are sodium cotransporters that derive the energy for solute transport from the electrochemical gradient for sodium ions (Hoglund et al., 2005 [PubMed 16125675]).[supplied by OMIM, Apr 2010]

316
ClinVar variants
134
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC6A18
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
134 Pathogenic / Likely Pathogenic· 144 VUS of 316 total submissions

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.
1.47LOEUF
pLI 0.000
Z-score -0.42
OE 1.09 (0.81–1.47)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.19Z-score
OE missense 0.97 (0.90–1.06)
395 obs / 406.0 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.1.09 (0.81–1.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.90–1.06)
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.0.95
0≤1.21.6
LoF obs/exp: 31 / 28.5Missense obs/exp: 395 / 406.0Syn Z: 0.53

ClinVar Variant Classifications

316 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic132
Likely Pathogenic2
VUS144
Likely Benign24
Benign14
132
Pathogenic
2
Likely Pathogenic
144
VUS
24
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
132
0
132
Likely Pathogenic
0
0
2
0
2
VUS
1
118
25
0
144
Likely Benign
0
18
3
3
24
Benign
0
7
2
5
14
Total11431648316

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC6A18 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The SLC6A18 Transporter Is Most Likely a Na-Dependent Glycine/Urea Antiporter Responsible for Urea Secretion in the Proximal Straight Tubule: Influence of This Urea Secretion on Glomerular Filtration Rate.
Bankir L et al.·Nephron
2024🔓 Open Access
Spatial mRNA Expression and Response to Fasting and Refeeding of Neutral Amino Acid Transporters slc6a18 and slc6a19a in the Intestinal Epithelium of Mozambique tilapia.
Orozco ZGA et al.·Front Physiol
2018🔓 Open Access
Association study: SLC6A18 gene and myocardial infarction.
Matsumoto K et al.·Clin Biochem
2011
Orphan transporter SLC6A18 is renal neutral amino acid transporter B0AT3.
Singer D et al.·J Biol Chem
2009
Analysis of VNTRs in the solute carrier family 6, member 18 (SLC6A18) and lack of association with hypertension.
Yoon YH et al.·DNA Cell Biol
2008
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools