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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC6A18
solute carrier family 6 member 18
Chromosome 5 · 5p15.33
NCBI Gene: 348932Ensembl: ENSG00000164363.10HGNC: HGNC:26441UniProt: Q96N87
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
amino acid transmembrane transporter activityamino acid transportplasma membranesodium ion transmembrane transportprostate carcinomabenign colon neoplasmnephrotic syndromecolorectal adenocarcinoma
✦AI Summary

SLC6A18 is a sodium-dependent amino acid transporter belonging to the solute carrier family 6, primarily expressed in the proximal straight tubule of the kidney 1. While initially characterized as a glycine transporter based on knockout mouse studies, recent evidence suggests SLC6A18 functions as a glycine/urea antiporter that secretes urea into the tubular lumen in exchange for glycine and sodium 1. This transporter requires an accessory protein for surface expression, similar to other SLC6 family members 2. The urea secretion mediated by SLC6A18 contributes to efficient nitrogen excretion and influences glomerular filtration rate regulation through the tubulo-glomerular feedback mechanism 1. Disease relevance includes mutations in SLC6A18 associated with iminoglycinuria and/or hyperglycinuria 3, though genetic testing may not always detect mutations, particularly in underrepresented populations 4. Clinical significance extends beyond renal function, as genetic variants have been associated with myocardial infarction susceptibility in some populations 5, though not with hypertension 67. The transporter's dual role in amino acid transport and urea handling makes it important for understanding kidney physiology and nitrogen metabolism disorders.

Sources cited
1
SLC6A18 is expressed exclusively in the proximal straight tubule and functions as a glycine/urea antiporter
PMID: 38824912
2
SLC6A18 requires an accessory protein for surface expression like other SLC6 family transporters
PMID: 19184091
3
Mutations of SLC6A18 cause iminoglycinuria and/or hyperglycinuria
PMID: 37940347
4
Genetic testing may not detect mutations in underrepresented populations
PMID: 35236679
5
SLC6A18 genetic variants associated with myocardial infarction susceptibility
PMID: 21420947
6
Y319X polymorphism not associated with hypertension in Japanese population
PMID: 16340170
7
VNTRs in SLC6A18 not associated with hypertension in Korean population
PMID: 18554081
Disease Associationsⓘ20
prostate carcinomaOpen Targets
0.35Weak
benign colon neoplasmOpen Targets
0.35Weak
nephrotic syndromeOpen Targets
0.30Weak
colorectal adenocarcinomaOpen Targets
0.30Weak
colorectal cancerOpen Targets
0.27Weak
colon adenocarcinomaOpen Targets
0.26Weak
malignant colon neoplasmOpen Targets
0.26Weak
focal segmental glomerulosclerosisOpen Targets
0.08Suggestive
skin diseaseOpen Targets
0.08Suggestive
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.08Suggestive
IGA glomerulonephritisOpen Targets
0.07Suggestive
frozen shoulderOpen Targets
0.07Suggestive
nail-patella-like renal diseaseOpen Targets
0.06Suggestive
glomerulopathy with fibronectin deposits 2Open Targets
0.06Suggestive
polycystic kidney disease 7Open Targets
0.06Suggestive
glomerulopathy with fibronectin deposits 1Open Targets
0.06Suggestive
autosomal dominant progressive nephropathy with hypertensionOpen Targets
0.05Suggestive
Autosomal dominant polycystic kidney diseaseOpen Targets
0.05Suggestive
focal segmental glomerulosclerosis 5Open Targets
0.05Suggestive
Denys-Drash syndromeOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SLC36A2Protein interaction74%SLC6A16Shared pathway67%SLC6A8Shared pathway50%SLC6A12Shared pathway40%SLC38A4Shared pathway40%SLC6A19Shared pathway33%
Tissue Expression6 tissues
Lung
0%
Liver
0%
Brain
0%
Ovary
0%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
SLC6A18SLC36A2SLC6A16SLC6A8SLC6A12SLC38A4SLC6A19
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q96N87
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.14LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.91 [0.73–1.14]
RankingsWhere SLC6A18 stands among ~20K protein-coding genes
  • #13,743of 20,598
    Most Researched22
  • #11,875of 17,882
    Most Constrained (LOEUF)1.14
Genes detectedSLC6A18
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Association study: SLC6A18 gene and myocardial infarction.
PMID: 21420947
Clin Biochem · 2011
1.00
2
The SLC6A15-SLC6A20 Neutral Amino Acid Transporter Subfamily: Functions, Diseases, and Their Therapeutic Relevance.
PMID: 37940347
Pharmacol Rev · 2023
0.90
3
Energy-Dependent Urea Transports in Mammals and their Functional Consequences.
PMID: 40637983
Subcell Biochem · 2025
0.80
4
A nonsense polymorphism (Y319X) of the solute carrier family 6 member 18 (SLC6A18) gene is not associated with hypertension and blood pressure in Japanese.
PMID: 16340170
Tohoku J Exp Med · 2006
0.70
5
Hyperglycinuria: diagnosis in middle age.
PMID: 35236679
BMJ Case Rep · 2022
0.60