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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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FLVCR2
FLVCR choline and putative heme transporter 2
Chromosome 14 Β· 14q24.3
NCBI Gene: 55640Ensembl: ENSG00000119686.11HGNC: HGNC:20105UniProt: Q9UPI3
30PubMed Papers
21Diseases
0Drugs
21Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
plasma membranecholine transportheme transmembrane transporter activitycholine transmembrane transporter activityFowler syndromegenetic disordersialolithiasisIncreased total eosinophil count
✦AI Summary

FLVCR2 (MFSD7C) is a major facilitator superfamily transporter with dual functions in choline and heme homeostasis. As a choline uniporter, FLVCR2 mediates the majority of choline uptake across the blood-brain barrier from circulation into the brain 12, a process driven exclusively by the choline concentration gradient rather than proton coupling 3. Cryo-electron microscopy has resolved inward-facing and outward-facing conformations, revealing that conserved tryptophan and tyrosine residues form an aromatic cage for substrate binding 13. FLVCR2 also transports ethanolamine 3 and mediates choline export from brain lysophosphatidylcholine 2. Beyond the BBB, FLVCR2 enables apical choline uptake in intestinal epithelium 4. Additionally, FLVCR2 acts as a heme transporter required for mitochondrial respiration and thermogenesis regulation 5. At low heme levels, FLVCR2 interacts with electron transfer chain complexes and ATP2A2, promoting their ubiquitin-mediated degradation to inhibit thermogenesis; heme binding causes dissociation to allow ATP synthesis switching 5. Mutations in FLVCR2 cause Fowler syndrome (proliferative vasculopathy and hydranencephaly-hydrocephaly), characterized by impaired CNS vascular development, microcephaly, and embryonic lethality 6. FLVCR2 deficiency also exacerbates hemolytic-induced lung injury through ferroptosis 7.

Sources cited
1
FLVCR2 is the major BBB choline transporter responsible for the majority of choline uptake into the brain; cryo-EM structures reveal choline binding in an aromatic cage
PMID: 38693257
2
MFSD7c (FLVCR2) functions as a facilitative choline transporter at the BBB; mutations in Fowler syndrome patients reduce choline transport activity
PMID: 38302740
3
FLVCR2 transports choline and ethanolamine via concentration-driven substrate translocation; tryptophan and tyrosine residues mediate substrate binding through cation-Ο€ interactions
PMID: 38778100
4
FLVCR2 enables choline uptake at the apical membrane of intestinal epithelium; works cumulatively with FLVCR1 to regulate intestinal choline absorption
PMID: 40320184
5
FLVCR2 functions as a heme transporter regulating mitochondrial respiration, ATP synthesis and thermogenesis; low heme levels promote ATP2A2 degradation via ubiquitin pathway
PMID: 32973183
6
MFSD7c deficiency causes microcephaly-associated vasculopathy; ablation inhibits CNS blood vessel angiogenic growth resulting in glomeruloid vessels, hypoxia, and neuronal cell death
PMID: 32369449
7
MFSD7C protects lungs from hemolytic-induced injury by preventing ferroptosis; deficiency leads to mitochondrial dysfunction and lipid peroxidation
PMID: 39300060
Disease Associationsβ“˜21
Fowler syndromeOpen Targets
0.82Strong
genetic disorderOpen Targets
0.41Moderate
sialolithiasisOpen Targets
0.28Weak
Increased total eosinophil countOpen Targets
0.25Weak
bilirubin metabolism diseaseOpen Targets
0.24Weak
posterior column ataxia-retinitis pigmentosa syndromeOpen Targets
0.19Weak
multiple sclerosisOpen Targets
0.11Weak
lung adenocarcinomaOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.07Suggestive
Parkinson diseaseOpen Targets
0.07Suggestive
hypertriglyceridemia 2Open Targets
0.07Suggestive
familial hypercholesterolemiaOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
cancerOpen Targets
0.06Suggestive
thyroid hormone metabolism, abnormal, 2Open Targets
0.06Suggestive
sitosterolemia 2Open Targets
0.05Suggestive
Combined hyperlipidemiaOpen Targets
0.05Suggestive
homozygous familial hypercholesterolemiaOpen Targets
0.05Suggestive
ProptosisOpen Targets
0.05Suggestive
hypercholesterolemia, autosomal dominant, 3Open Targets
0.04Suggestive
Proliferative vasculopathy and hydranencephaly-hydrocephaly syndromeUniProt
Pathogenic Variants21
NM_017791.3(FLVCR2):c.52dup (p.Glu18fs)Pathogenic
not provided|Fowler syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 18
NM_017791.3(FLVCR2):c.1289C>G (p.Thr430Arg)Pathogenic
Fowler syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 430
NM_017791.3(FLVCR2):c.1076T>C (p.Leu359Pro)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 359
NM_017791.3(FLVCR2):c.1509+1G>APathogenic
Cervical cancer|Melanoma|not provided
β˜…β˜†β˜†β˜†2025
NM_017791.3(FLVCR2):c.812-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_017791.3(FLVCR2):c.1101G>A (p.Trp367Ter)Pathogenic
Fowler syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 367
NM_017791.3(FLVCR2):c.1057_1060del (p.Ile353fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 353
NM_017791.3(FLVCR2):c.1011del (p.Trp337fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 337
NM_017791.3(FLVCR2):c.1024delLikely pathogenic
Fowler syndrome
β˜…β˜†β˜†β˜†2024
NM_017791.3(FLVCR2):c.1124+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_017791.3(FLVCR2):c.721_731del (p.Glu241fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024β†’ Residue 241
NM_017791.3(FLVCR2):c.191del (p.Leu64fs)Likely pathogenic
Fowler syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 64
NM_017791.3(FLVCR2):c.391dup (p.Met131fs)Likely pathogenic
Fowler syndrome
β˜…β˜†β˜†β˜†2018β†’ Residue 131
NM_017791.3(FLVCR2):c.1289C>T (p.Thr430Met)Pathogenic
Fowler syndrome
β˜†β˜†β˜†β˜†2024β†’ Residue 430
NM_017791.3(FLVCR2):c.402C>G (p.Tyr134Ter)Pathogenic
Fowler syndrome
β˜†β˜†β˜†β˜†2010β†’ Residue 134
NM_017791.3(FLVCR2):c.977C>T (p.Ala326Val)Pathogenic
Fowler syndrome
β˜†β˜†β˜†β˜†2010β†’ Residue 326
NM_017791.3(FLVCR2):c.329_334del (p.Asn110_Phe112delinsIle)Pathogenic
Fowler syndrome
β˜†β˜†β˜†β˜†2010β†’ Residue 110
NM_017791.3(FLVCR2):c.1341+2T>CPathogenic
Fowler syndrome
β˜†β˜†β˜†β˜†2010
NM_017791.3(FLVCR2):c.473C>A (p.Ser158Ter)Pathogenic
Fowler syndrome
β˜†β˜†β˜†β˜†2010β†’ Residue 158
NM_017791.3(FLVCR2):c.1192C>G (p.Leu398Val)Pathogenic
Fowler syndrome
β˜†β˜†β˜†β˜†2010β†’ Residue 398
View on ClinVar β†—
Related Genes
SLC44A1Shared pathway50%SLC35G4Shared pathway50%SLC16A12Shared pathway50%SLC35F4Shared pathway50%SLC35F3Shared pathway50%SLC35F5Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Lung
63%
Bone Marrow
37%
Ovary
14%
Heart
10%
Brain
8%
Gene Interaction Network
Click a node to explore
FLVCR2SLC44A1SLC35G4SLC16A12SLC35F4SLC35F3SLC35F5
PROTEIN STRUCTURE
Preparing viewer…
PDB8QD0 Β· 2.80 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.90LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.65 [0.47–0.90]
RankingsWhere FLVCR2 stands among ~20K protein-coding genes
  • #11,919of 20,598
    Most Researched30
  • #2,165of 5,498
    Most Pathogenic Variants21
  • #8,129of 17,882
    Most Constrained (LOEUF)0.90
Genes detectedFLVCR2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Structural and molecular basis of choline uptake into the brain by FLVCR2.
PMID: 38693257
Nature Β· 2024
1.00
2
Molecular mechanism of choline and ethanolamine transport in humans.
PMID: 38778100
Nature Β· 2024
0.90
3
FLVCR2: structure, substrate transport, and emerging roles in human disease.
PMID: 41672241
Life Sci Β· 2026
0.80
4
The role of FLVCR1 and FLVCR2 in choline transport in the Caco-2 intestinal epithelial cell model and rat small intestine.
PMID: 40320184
Biochim Biophys Acta Mol Basis Dis Β· 2025
0.70
5
Structural and molecular basis of choline uptake into the brain by FLVCR2.
PMID: 37873173
bioRxiv Β· 2023
0.60