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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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MFSD2A
MFSD2 lysolipid transporter A, lysophospholipid
Chromosome 1 Β· 1p34.2
NCBI Gene: 84879Ensembl: ENSG00000168389.18HGNC: HGNC:25897UniProt: B4DNN7
51PubMed Papers
21Diseases
0Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of phosphatidylcholine metabolic processplasma membranelysophospholipid:sodium symporter activitylysosomemicrocephaly 15, primary, autosomal recessivegenetic disorderautosomal recessive primary microcephalyPrimary microcephaly
✦AI Summary

MFSD2A is a sodium-dependent lysophosphatidylcholine (LPC) symporter essential for blood-brain barrier formation and function 1. The protein specifically transports LPC-conjugated docosahexaenoic acid (DHA) across the blood-brain barrier, representing the primary mechanism by which this omega-3 fatty acid enters the brain for normal development and cognitive function 1. Structurally, MFSD2A contains a unique extracellular domain and conserved sodium-binding site that facilitates its transport mechanism 1. The transporter is specifically expressed in brain endothelial cells and plays a critical role in maintaining blood-brain barrier integrity by inhibiting transcytosis 23. Beyond brain function, MFSD2A exhibits tumor suppressor properties in various cancers, including gastric and colorectal cancer, where it suppresses proliferation, migration, and metastasis through multiple pathways including S100A14/STAT3 signaling 45. In diabetic retinopathy, reduced MFSD2A expression contributes to vascular dysfunction, and its overexpression combined with DHA supplementation shows therapeutic potential 6. MFSD2A mutations cause microcephaly syndromes, highlighting its essential role in neurodevelopment 1. The protein's dual functions in lipid transport and blood-brain barrier regulation make it an attractive target for therapeutic modulation.

Sources cited
1
MFSD2A is a sodium-dependent lysophosphatidylcholine symporter with unique structural features and role in blood-brain barrier function
PMID: 34349262
2
MFSD2A is expressed in brain endothelial cells and maintains blood-brain barrier integrity
PMID: 38957991
3
MFSD2A is involved in blood-brain barrier permeability regulation
PMID: 34979902
4
MFSD2A acts as tumor suppressor in gastric cancer by reprogramming tumor microenvironment
PMID: 37539769
5
MFSD2A suppresses colorectal cancer progression through S100A14/STAT3 signaling pathway
PMID: 39806334
6
MFSD2A overexpression alleviates vascular dysfunction in diabetic retinopathy and enhances DHA therapy effectiveness
PMID: 34229049
Disease Associationsβ“˜21
microcephaly 15, primary, autosomal recessiveOpen Targets
0.71Strong
genetic disorderOpen Targets
0.41Moderate
autosomal recessive primary microcephalyOpen Targets
0.37Weak
Primary microcephalyOpen Targets
0.37Weak
microcephalyOpen Targets
0.37Weak
cryptorchidismOpen Targets
0.35Weak
fetal growth restrictionOpen Targets
0.33Weak
Intellectual disabilityOpen Targets
0.33Weak
Delayed gross motor developmentOpen Targets
0.33Weak
Febrile seizure (within the age range of 3 months to 6 years)Open Targets
0.33Weak
Functional abnormality of male internal genitaliaOpen Targets
0.33Weak
HyperammonemiaOpen Targets
0.33Weak
IMAGe syndromeOpen Targets
0.33Weak
Abnormality of refractionOpen Targets
0.30Weak
placental retentionOpen Targets
0.25Weak
hypothyroidismOpen Targets
0.20Weak
hepatocellular carcinomaOpen Targets
0.10Weak
neoplasmOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
Alzheimer diseaseOpen Targets
0.08Suggestive
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalitiesUniProt
Pathogenic Variants8
NM_032793.5(MFSD2A):c.476C>T (p.Thr159Met)Pathogenic
Microcephaly 15, primary, autosomal recessive
β˜…β˜†β˜†β˜†2024β†’ Residue 159
NM_032793.5(MFSD2A):c.456C>A (p.Cys152Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2022β†’ Residue 152
NM_032793.5(MFSD2A):c.750_753del (p.Cys251fs)Pathogenic
Microcephaly 15, primary, autosomal recessive
β˜†β˜†β˜†β˜†2022β†’ Residue 251
NM_032793.5(MFSD2A):c.556+1G>APathogenic
Microcephaly 15, primary, autosomal recessive
β˜†β˜†β˜†β˜†2022
NM_032793.5(MFSD2A):c.1386_1435del (p.Gln462fs)Pathogenic
Microcephaly 15, primary, autosomal recessive
β˜†β˜†β˜†β˜†2022β†’ Residue 462
NM_032793.5(MFSD2A):c.1016C>T (p.Ser339Leu)Pathogenic
Microcephaly 15, primary, autosomal recessive
β˜†β˜†β˜†β˜†2022β†’ Residue 339
NM_032793.5(MFSD2A):c.1205C>A (p.Pro402His)Pathogenic
Microcephaly 15, primary, autosomal recessive
β˜†β˜†β˜†β˜†2020β†’ Residue 402
NM_032793.5(MFSD2A):c.229-25_229-23delPathogenic
8 conditions
β˜†β˜†β˜†β˜†
View on ClinVar β†—
Related Genes
ERVFRD-1Protein interaction100%ERVW-1Protein interaction95%SLC27A1Shared pathway14%SLC27A4Shared pathway13%FABP5Shared pathway10%SLC44A4Shared pathway8%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
24%
Lung
14%
Brain
4%
Ovary
1%
Heart
0%
Gene Interaction Network
Click a node to explore
MFSD2AERVFRD-1ERVW-1SLC27A1SLC27A4FABP5SLC44A4
PROTEIN STRUCTURE
Preparing viewer…
PDB7OIX Β· 3.60 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.57Moderately Constrained
pLIβ“˜
0.21Tolerant
Observed/Expected LoF0.41 [0.30–0.57]
RankingsWhere MFSD2A stands among ~20K protein-coding genes
  • #8,700of 20,598
    Most Researched51
  • #3,091of 5,498
    Most Pathogenic Variants8
  • #3,774of 17,882
    Most Constrained (LOEUF)0.57 Β· top quartile
Genes detectedMFSD2A
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Decoding m
PMID: 36574771
Cell Stem Cell Β· 2023
1.00
2
MFSD2A potentiates gastric cancer response to anti-PD-1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response.
PMID: 37539769
Cancer Commun (Lond) Β· 2023
0.90
3
Mfsd2a suppresses colorectal cancer progression and liver metastasis via the S100A14/STAT3 axis.
PMID: 39806334
J Transl Med Β· 2025
0.80
4
Structure and mechanism of blood-brain-barrier lipid transporter MFSD2A.
PMID: 34349262
Nature Β· 2021
0.70
5
mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis.
PMID: 38957991
Circ Res Β· 2024
0.60