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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RFT1
RFT1 glycolipid translocator homolog
Chromosome 3 · 3p21.1
NCBI Gene: 91869Ensembl: ENSG00000163933.12HGNC: HGNC:30220UniProt: Q96AA3
51PubMed Papers
21Diseases
0Drugs
17Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingglycolipid floppase activityprotein N-linked glycosylationdolichol-linked oligosaccharide biosynthetic processRFT1-congenital disorder of glycosylationcongenital disorder of glycosylation type Icongenital disorder of glycosylationCrohn's disease
✦AI Summary

RFT1 (glycolipid translocator homolog) is a multispanning endoplasmic reticulum (ER) membrane protein with N and C termini facing the cytoplasm 1. Its primary function is mediating transbilayer translocation of the heptasaccharide lipid intermediate Man₅GlcNAc₂-PP-dolichol across the ER membrane during N-linked glycosylation 23. This translocation is essential for completing assembly of the Glc₃Man₉GlcNAc₂-PP-dolichol oligosaccharide precursor, which is subsequently transferred to asparagine residues in nascent proteins by oligosaccharyltransferases 2. RFT1 is essential for cell viability in yeast and mammalian systems 1. Mutations in RFT1 cause Congenital Disorder of Glycosylation type 1N (RFT1-CDG), characterized by intracellular accumulation of incomplete dolichol-linked oligosaccharide intermediates and profound N-glycosylation defects 2. RFT1-CDG clinical presentations include typical CDG symptoms and sensorineural deafness 3. Additionally, RFT1 translation is regulated by leucyl-tRNA synthetase 1 in a codon-biased manner; reduced RFT1 expression impairs N-glycosylation and contributes to chemoresistance in intrahepatic cholangiocarcinoma 4. The majority of disease-causing mutations map to highly conserved protein regions 1. Note: RFT1 should be distinguished from riboflavin transporters also designated RFT, which are SLC52 family members 5.

Sources cited
1
RFT1 is a multispanning ER membrane protein with N and C termini in cytoplasm; essential for N-glycosylation and cell viability; RFT1-CDG mutations map to conserved regions
PMID: 39025454
2
RFT1 mediates translocation of Man₅GlcNAc₂-PP-dolichol across ER membrane; RFT1 mutations cause CDG with accumulation of incomplete oligosaccharide intermediates; functional conservation between yeast and human RFT1
PMID: 18313027
3
RFT1 facilitates translocation of Man₅GlcNAc₂-PP-dolichol; RFT1-CDG patients present with N-glycosylation disorder and sensorineural deafness; multiple disease-causing mutations identified
PMID: 19701946
4
RFT1 translation is codon-biased and regulated by LARS1; reduced RFT1 expression impairs N-glycosylation and promotes chemoresistance in intrahepatic cholangiocarcinoma
PMID: 40683603
5
RFT1/SLC52A1 nomenclature clarification distinguishing glycolipid translocator RFT1 from riboflavin transporters RFVT/SLC52
PMID: 23506902
Disease Associationsⓘ21
RFT1-congenital disorder of glycosylationOpen Targets
0.82Strong
congenital disorder of glycosylation type IOpen Targets
0.67Moderate
congenital disorder of glycosylationOpen Targets
0.41Moderate
Crohn's diseaseOpen Targets
0.35Weak
Abnormality of the skeletal systemOpen Targets
0.32Weak
neurodegenerative diseaseOpen Targets
0.28Weak
ovarian dysfunctionOpen Targets
0.27Weak
metabolic syndromeOpen Targets
0.24Weak
type 2 diabetes mellitusOpen Targets
0.23Weak
response to vaccineOpen Targets
0.23Weak
osteoarthritisOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
hypertrophic cardiomyopathyOpen Targets
0.13Weak
otosclerosisOpen Targets
0.09Suggestive
Blackfan-Diamond anemiaOpen Targets
0.06Suggestive
goutOpen Targets
0.06Suggestive
Alpha-thalassemia - myelodysplastic syndromeOpen Targets
0.05Suggestive
alpha-thalassemia-myelodysplastic syndromeOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
Congenital disorder of glycosylation 1NUniProt
Pathogenic Variants17
NM_052859.4(RFT1):c.199C>T (p.Arg67Cys)Pathogenic
RFT1-congenital disorder of glycosylation|not provided
★★☆☆2025→ Residue 67
NM_052859.4(RFT1):c.1195G>T (p.Glu399Ter)Likely pathogenic
RFT1-congenital disorder of glycosylation
★★☆☆2025→ Residue 399
NM_052859.4(RFT1):c.1325G>A (p.Arg442Gln)Likely pathogenic
RFT1-congenital disorder of glycosylation
★★☆☆2025→ Residue 442
NM_052859.4(RFT1):c.454A>G (p.Lys152Glu)Pathogenic
RFT1-congenital disorder of glycosylation|not provided
★★☆☆2024→ Residue 152
NM_052859.4(RFT1):c.1208+1G>TLikely pathogenic
RFT1-congenital disorder of glycosylation
★☆☆☆2023
NM_052859.4(RFT1):c.306G>A (p.Trp102Ter)Likely pathogenic
RFT1-congenital disorder of glycosylation
★☆☆☆2021→ Residue 102
NM_052859.4(RFT1):c.740dup (p.Lys248fs)Likely pathogenic
RFT1-congenital disorder of glycosylation
★☆☆☆2020→ Residue 248
NM_052859.4(RFT1):c.775G>A (p.Gly259Ser)Pathogenic
RFT1-congenital disorder of glycosylation
★☆☆☆2019→ Residue 259
NM_052859.4(RFT1):c.545del (p.Phe182fs)Likely pathogenic
not provided
★☆☆☆2019→ Residue 182
NM_052859.4(RFT1):c.902A>G (p.Tyr301Cys)Likely pathogenic
RFT1-congenital disorder of glycosylation
★☆☆☆2017→ Residue 301
NM_052859.4(RFT1):c.36_37delinsA (p.Leu13fs)Likely pathogenic
not provided
★☆☆☆2016→ Residue 13
NM_052859.4(RFT1):c.229C>T (p.Arg77Ter)Likely pathogenic
RFT1-congenital disorder of glycosylation
★☆☆☆→ Residue 77
NM_052859.4(RFT1):c.775+1G>CLikely pathogenic
RFT1-congenital disorder of glycosylation
☆☆☆☆2024
NM_052859.4(RFT1):c.1222A>G (p.Met408Val)Pathogenic
RFT1-congenital disorder of glycosylation
☆☆☆☆2012→ Residue 408
NM_052859.4(RFT1):c.887T>A (p.Ile296Lys)Pathogenic
RFT1-congenital disorder of glycosylation
☆☆☆☆2009→ Residue 296
NM_052859.4(RFT1):c.887T>G (p.Ile296Arg)Pathogenic
RFT1-congenital disorder of glycosylation
☆☆☆☆2009→ Residue 296
NM_052859.4(RFT1):c.892G>A (p.Glu298Lys)Pathogenic
RFT1-congenital disorder of glycosylation
☆☆☆☆2009→ Residue 298
View on ClinVar ↗
Related Genes
DPAGT1Shared pathway100%ALG5Shared pathway100%ALG6Shared pathway100%ALG8Shared pathway100%ALG9Shared pathway100%ALG13Shared pathway100%
Tissue Expression6 tissues
Ovary
100%
Liver
86%
Brain
79%
Lung
76%
Heart
63%
Bone Marrow
60%
Gene Interaction Network
Click a node to explore
RFT1DPAGT1ALG5ALG6ALG8ALG9ALG13
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96AA3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.89LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.68 [0.53–0.89]
RankingsWhere RFT1 stands among ~20K protein-coding genes
  • #8,722of 20,598
    Most Researched51
  • #2,359of 5,498
    Most Pathogenic Variants17
  • #8,036of 17,882
    Most Constrained (LOEUF)0.89
Genes detectedRFT1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Molecular characterization of Rft1, an ER membrane protein associated with congenital disorder of glycosylation RFT1-CDG.
PMID: 39025454
J Biol Chem · 2024
1.00
2
Restoration of N-glycosylation via leucine-activated leucyl-tRNA synthetase 1 overcomes chemoresistance in intrahepatic cholangiocarcinoma.
PMID: 40683603
J Hepatol · 2026
0.90
3
PMID: 20301507
0.80
4
Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1.
PMID: 18632736
Am J Physiol Cell Physiol · 2008
0.70
5
Molecular characterization of Rft1, an ER membrane protein associated with congenital disorder of glycosylation RFT1-CDG.
PMID: 38617304
bioRxiv · 2024
0.60