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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC6A20
solute carrier family 6 member 20
Chromosome 3 · 3p21.31
NCBI Gene: 54716Ensembl: ENSG00000163817.17HGNC: HGNC:30927UniProt: A0A8V8TQV4
36PubMed Papers
22Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
proline:sodium symporter activityprotein bindingamino acid transmembrane transporter activityneutral L-amino acid transmembrane transporter activityCOVID-19response to COVID-19 vaccineHyperglycinuriamacular telangiectasia type 2
✦AI Summary

SLC6A20 is a sodium- and chloride-dependent membrane transporter that mediates uptake of imino acids including L-proline and N-methylated amino acids, as well as glycine 1. In the brain, SLC6A20 regulates proline and glycine homeostasis, modulating NMDA receptor (NMDAR) currents through glycine transport 2. The transporter is widely distributed across the central nervous, renal, and intestinal systems, where it facilitates amino acid absorption and reabsorption 1. Mutations in SLC6A20 cause iminoglycinuria and hyperglycinuria, metabolic disorders affecting amino acid excretion 1. SLC6A20 variants have been associated with Type 2 diabetes susceptibility across multiple populations, with rs13062383 showing highly significant association 3. Additionally, polymorphisms in SLC6A20 correlate with Hirschsprung disease susceptibility, particularly long-segment forms 4. Clinically, SLC6A20 has emerged as a therapeutic target. The gene maps to the 3p21.31 locus identified in genome-wide association studies of COVID-19 severity with respiratory failure 5, and elevated SLC6A20 expression may increase cancer patients' COVID-19 susceptibility 6. SLC6A20 inhibition shows therapeutic promise for brain disorders involving NMDAR hypofunction, such as schizophrenia 2.

Sources cited
1
SLC6A20 mediates Na+ and Cl--dependent transport of imino acids and neutral amino acids; mutations cause iminoglycinuria/hyperglycinuria; broadly distributed in CNS, renal, and intestinal systems
PMID: 37940347
2
SLC6A20 regulates brain proline and glycine homeostasis and modulates NMDAR currents; inhibition has therapeutic potential for NMDAR hypofunction disorders
PMID: 33428810
3
SLC6A20 variant rs13062383 is significantly associated with Type 2 diabetes susceptibility across white-European and Chinese populations
PMID: 24958070
4
SLC6A20 is located at the 3p21.31 genetic susceptibility locus for COVID-19 severity with respiratory failure
PMID: 32558485
5
SLC6A20 polymorphisms are associated with Hirschsprung disease susceptibility, particularly long-segment HSCR
PMID: 26049783
6
Elevated SLC6A20 expression is positively correlated with SARS-CoV-2-associated genes and may increase cancer patients' COVID-19 susceptibility
PMID: 37041751
Disease Associationsⓘ22
COVID-19Open Targets
0.54Moderate
response to COVID-19 vaccineOpen Targets
0.44Moderate
HyperglycinuriaOpen Targets
0.42Moderate
macular telangiectasia type 2Open Targets
0.42Moderate
iminoglycinuriaOpen Targets
0.42Moderate
Sensorineural hearing impairmentOpen Targets
0.37Weak
age-related macular degenerationOpen Targets
0.33Weak
musculoskeletal system diseaseOpen Targets
0.31Weak
hereditary ataxiaOpen Targets
0.12Weak
Intellectual disabilityOpen Targets
0.12Weak
Barrett's esophagusOpen Targets
0.08Suggestive
pneumoniaOpen Targets
0.07Suggestive
esophageal adenocarcinomaOpen Targets
0.05Suggestive
cancerOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.04Suggestive
dehydrated hereditary stomatocytosisOpen Targets
0.04Suggestive
hemolytic anemia due to glutathione reductase deficiencyOpen Targets
0.04Suggestive
Hemolytic anemia due to red cell pyruvate kinase deficiencyOpen Targets
0.04Suggestive
dominant beta-thalassemiaOpen Targets
0.03Suggestive
granular corneal dystrophy type IIOpen Targets
0.03Suggestive
HyperglycinuriaUniProt
IminoglycinuriaUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ACE2Protein interaction100%XYLT2Protein interaction92%LZTFL1Protein interaction86%FYCO1Protein interaction84%SLC36A2Protein interaction67%SLC6A9Shared pathway50%
Tissue Expression6 tissues
Brain
100%
Lung
66%
Liver
23%
Ovary
18%
Bone Marrow
17%
Heart
5%
Gene Interaction Network
Click a node to explore
SLC6A20ACE2XYLT2LZTFL1FYCO1SLC36A2SLC6A9
PROTEIN STRUCTURE
Preparing viewer…
PDB7Y75 · 3.10 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.32LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.09 [0.90–1.32]
RankingsWhere SLC6A20 stands among ~20K protein-coding genes
  • #10,869of 20,598
    Most Researched36
  • #13,855of 17,882
    Most Constrained (LOEUF)1.32
Genes detectedSLC6A20
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The SLC6A15-SLC6A20 Neutral Amino Acid Transporter Subfamily: Functions, Diseases, and Their Therapeutic Relevance.
PMID: 37940347
Pharmacol Rev · 2023
1.00
2
Genomewide Association Study of Severe Covid-19 with Respiratory Failure.
PMID: 32558485
N Engl J Med · 2020
0.90
3
A genetic variant in SLC6A20 is associated with Type 2 diabetes in white-European and Chinese populations.
PMID: 24958070
Diabet Med · 2014
0.80
4
Association Analysis of SLC6A20 Polymorphisms With Hirschsprung Disease.
PMID: 26049783
J Pediatr Gastroenterol Nutr · 2016
0.70
5
Pan-Cancer Analysis of the COVID-19 Causal Gene
PMID: 37041751
ACS Omega · 2023
0.60