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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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SLC5A6
solute carrier family 5 member 6
Chromosome 2 Β· 2p23.3
NCBI Gene: 8884Ensembl: ENSG00000138074.15HGNC: HGNC:11041UniProt: Q9HD19
66PubMed Papers
22Diseases
0Drugs
13Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingiodide transmembrane transporter activitybiotin transmembrane transporter activitypantothenate transmembrane transporter activityneurodegeneration, infantile-onset, biotin-responsiveperipheral motor neuropathy, childhood-onset, biotin-responsivegenetic disorderNeurodevelopmental disorder
✦AI Summary

SLC5A6 encodes a sodium-dependent multivitamin transporter (SMVT) that mediates electrogenic transport of pantothenate, biotin, lipoate, and iodide across cell membranes 1. The transporter functions as a Na+-coupled symporter with 2:1 Na+:substrate stoichiometry, utilizing the electrochemical sodium gradient to drive substrate uptake 2. SLC5A6 is essential for intestinal absorption of biotin and pantothenic acid across the brush border membrane and critically supplies these vitamins to the brain across the blood-brain barrier, accounting for 88.7% of biotin and 98.6% of pantothenic acid uptake in cerebral microvascular endothelial cells 2. These vitamins serve as cofactors for coenzyme A (CoA) biosynthesis, which is required for cellular metabolism including the tricarboxylic acid cycle, lipid synthesis, and histone acetylation 1. Mutations in SLC5A6 cause severe multivitamin deficiency disorders presenting with neurological symptoms, developmental delay, sensory polyneuropathy, and immunodeficiency 34. Early supplementation with biotin and pantothenic acid can stabilize or reverse these manifestations 43. Additionally, SLC5A6 upregulation by the MYC oncogene promotes tumor metabolic reprogramming toward anabolic pathways, making it a potential therapeutic target in cancer 5.

Sources cited
1
SLC5A6 transports pantothenate and biotin; pantothenate is an essential nutrient for CoA biosynthesis which regulates multiple metabolic pathways
PMID: 38871981
2
SLC5A6 accounts for 88.7% of biotin and 98.6% of pantothenic acid uptake at the blood-brain barrier; functions as Na+-coupled symporter
PMID: 25809983
3
SLC5A6 mutations cause multivitamin-dependent neurometabolic disorder with developmental delay, polyneuropathy, and optic atrophy; multivitamin supplementation can stabilize disease
PMID: 37391029
4
SLC5A6 mutations cause biotin deficiency leading to B cell maturation defects and immunodeficiency; biotin replenishment rescues plasma cell function
PMID: 38036278
5
MYC upregulates SLC5A6 to increase pantothenic acid uptake and CoA biosynthesis, promoting tumor growth and metabolic reprogramming
PMID: 37946084
6
SLC5A6 mutations are linked to severe neurological disorders due to impaired blood-brain barrier vitamin supply; current treatment involves vitamin supplementation
PMID: 39234898
Disease Associationsβ“˜22
neurodegeneration, infantile-onset, biotin-responsiveOpen Targets
0.75Strong
peripheral motor neuropathy, childhood-onset, biotin-responsiveOpen Targets
0.62Moderate
genetic disorderOpen Targets
0.19Weak
Neurodevelopmental disorderOpen Targets
0.18Weak
Crigler-Najjar syndrome type 2Open Targets
0.06Suggestive
maple syrup urine disease, mild variantOpen Targets
0.06Suggestive
sarcosinemiaOpen Targets
0.06Suggestive
schizophreniaOpen Targets
0.06Suggestive
transient familial neonatal hyperbilirubinemiaOpen Targets
0.05Suggestive
methylmalonic acidemia due to transcobalamin receptor defectOpen Targets
0.05Suggestive
Methylmalonic aciduria due to transcobalamin receptor defectOpen Targets
0.05Suggestive
polycythemiaOpen Targets
0.05Suggestive
gastric cancerOpen Targets
0.04Suggestive
gluthathione peroxidase deficiencyOpen Targets
0.04Suggestive
Rotor syndromeOpen Targets
0.04Suggestive
Dubin-Johnson syndromeOpen Targets
0.04Suggestive
metabolic diseaseOpen Targets
0.04Suggestive
hypercholanemia, familial, 2Open Targets
0.04Suggestive
hyperlipidemiaOpen Targets
0.04Suggestive
hemolytic anemia due to glutathione reductase deficiencyOpen Targets
0.03Suggestive
Peripheral motor neuropathy, childhood-onset, biotin-responsiveUniProt
Sodium-dependent multivitamin transporter deficiencyUniProt
Pathogenic Variants13
NM_021095.4(SLC5A6):c.280C>T (p.Arg94Ter)Pathogenic
Neurodegeneration, infantile-onset, biotin-responsive|Peripheral motor neuropathy, childhood-onset, biotin-responsive|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 94
NM_021095.4(SLC5A6):c.1285A>G (p.Ser429Gly)Pathogenic
Neurodegeneration, infantile-onset, biotin-responsive|Peripheral motor neuropathy, childhood-onset, biotin-responsive
β˜…β˜…β˜†β˜†2024β†’ Residue 429
NM_021095.4(SLC5A6):c.422_423del (p.Val141fs)Pathogenic
Neurodegeneration, infantile-onset, biotin-responsive|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 141
NM_021095.4(SLC5A6):c.1865_1866del (p.Gln622fs)Likely pathogenic
Neurodegeneration, infantile-onset, biotin-responsive|not provided|SLC5A6-related disorder|Peripheral motor neuropathy, childhood-onset, biotin-responsive
β˜…β˜…β˜†β˜†2023β†’ Residue 622
NM_021095.4(SLC5A6):c.393+2T>CPathogenic
Neurodegeneration, infantile-onset, biotin-responsive
β˜…β˜…β˜†β˜†2022
NM_021095.4(SLC5A6):c.1648+2T>GLikely pathogenic
Neurodegeneration, infantile-onset, biotin-responsive
β˜…β˜†β˜†β˜†2024
NM_021095.4(SLC5A6):c.1403del (p.Phe468fs)Likely pathogenic
Neurodegeneration, infantile-onset, biotin-responsive
β˜…β˜†β˜†β˜†2023β†’ Residue 468
NM_021095.4(SLC5A6):c.424C>T (p.Arg142Ter)Pathogenic
not provided|Squamous cell lung carcinoma|Cervical cancer
β˜…β˜†β˜†β˜†2022β†’ Residue 142
NM_021095.4(SLC5A6):c.829C>T (p.Gln277Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 277
NM_021095.4(SLC5A6):c.1005+1G>APathogenic
Neurodegeneration, infantile-onset, biotin-responsive
β˜…β˜†β˜†β˜†2021
NM_021095.4(SLC5A6):c.460-19T>GLikely pathogenic
Neurodegeneration, infantile-onset, biotin-responsive
β˜…β˜†β˜†β˜†
NM_021095.4(SLC5A6):c.368G>T (p.Arg123Leu)Pathogenic
Neurodegeneration, infantile-onset, biotin-responsive
β˜†β˜†β˜†β˜†2022β†’ Residue 123
NM_021095.4(SLC5A6):c.1199G>C (p.Arg400Thr)Pathogenic
Neurodegeneration, infantile-onset, biotin-responsive
β˜†β˜†β˜†β˜†2022β†’ Residue 400
View on ClinVar β†—
Related Genes
PDZD11Protein interaction97%ASIC5Shared pathway33%SLC16A12Shared pathway33%PANK3Co-mentioned in literature30%SLC5A1Shared pathway25%SLC2A13Shared pathway25%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
30%
Ovary
16%
Lung
11%
Heart
6%
Brain
6%
Gene Interaction Network
Click a node to explore
SLC5A6PDZD11ASIC5SLC16A12PANK3SLC5A1SLC2A13
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9HD19
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.61LoF Tolerant
pLIβ“˜
0.02Tolerant
Observed/Expected LoF0.45 [0.34–0.61]
RankingsWhere SLC5A6 stands among ~20K protein-coding genes
  • #7,124of 20,598
    Most Researched66
  • #2,601of 5,498
    Most Pathogenic Variants13
  • #4,223of 17,882
    Most Constrained (LOEUF)0.61 Β· top quartile
Genes detectedSLC5A6
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Coenzyme A biosynthesis: mechanisms of regulation, function and disease.
PMID: 38871981
Nat Metab Β· 2024
1.00
2
Vitamin B
PMID: 37946084
Nat Metab Β· 2023
0.90
3
Acetyl-CoA biosynthesis drives resistance to histone acetyltransferase inhibition.
PMID: 37127754
Nat Chem Biol Β· 2023
0.80
4
Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells.
PMID: 25809983
J Neurochem Β· 2015
0.70
5
Novel SLC5A6 mutations lead to B lymphocyte maturation defects with metabolic abnormality rescuable by biotin replenishment.
PMID: 38036278
Clin Immunol Β· 2023
0.60