MFSD2A

Chr 1AR

MFSD2 lysolipid transporter A, lysophospholipid

Also known as: HsMFSD2A, MCPH15, MFSD2, NEDMISBA, NLS1, SLC59A1

NCBI Gene: 84879ENSG00000168389UniProt: Q8NA29

The protein encoded by this gene is a transmembrane protein and sodium-dependent lysophosphatidylcholine transporter. The encoded protein is involved in the establishment of the blood-brain barrier and is required for brain growth and function. Defects in this gene are a cause of a progressive microcephaly syndrome. [provided by RefSeq, Mar 2017]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain abnormalitiesMIM #616486
AR
232
ClinVar variants
16
Pathogenic / LP
0.01
pLI score
1
Active trials
Clinical Summary— MFSD2A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 89 VUS of 232 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.54LOEUF
pLI 0.011
Z-score 3.47
OE 0.31 (0.18–0.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.04Z-score
OE missense 0.68 (0.60–0.76)
211 obs / 312.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.18–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.60–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 9 / 29.2Missense obs/exp: 211 / 312.2Syn Z: 1.31

ClinVar Variant Classifications

232 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS89
Likely Benign95
Benign13
Conflicting6
13
Pathogenic
3
Likely Pathogenic
89
VUS
95
Likely Benign
13
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
8
0
13
Likely Pathogenic
0
1
2
0
3
VUS
3
77
7
2
89
Likely Benign
0
2
38
55
95
Benign
0
2
9
2
13
Conflicting
—6
Total6846459219

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MFSD2A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MFSD2A-related primary microcephaly

definitive
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain abnormalities

MIM #616486

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MFSD2A potentiates gastric cancer response to anti-PD-1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response.
Zhang B et al.·Cancer Commun (Lond)
2023
Mfsd2a suppresses colorectal cancer progression and liver metastasis via the S100A14/STAT3 axis.
Sun L et al.·J Transl Med
2025
MFSD2A: a molecular nexus linking blood-brain barrier, lipid metabolism, and ischemia-reperfusion injury.
Li C et al.·Cell Mol Biol Lett
2025Review
MFSD2A expression predicts better prognosis in gastric cancer.
Shi X et al.·Biochem Biophys Res Commun
2018
MFSD2A frameshift variant in Kerry Hill sheep with microcephaly.
Rudd Garces G et al.·Anim Genet
2024
MFSD2A-associated primary microcephaly - Expanding the clinical and mutational spectrum of this ultra-rare disease.
Khuller K et al.·Eur J Med Genet
2021Case report
Mfsd2a-based pharmacological strategies for drug delivery across the blood-brain barrier.
Wang JZ et al.·Pharmacol Res
2016
Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features.
Scala M et al.·Eur J Hum Genet
2020Case report
Mfsd2a is important for maintaining epidermal homeostasis.
Wong BH et al.·Proc Natl Acad Sci U S A
2026
Zika virus degrades the ω-3 fatty acid transporter Mfsd2a in brain microvascular endothelial cells and impairs lipid homeostasis.
Zhou J et al.·Sci Adv
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Colorectal Cancer

The Role of Lipid Transporter MFSD2A in the Resolution of Colorectal Cancer-associated Inflammation

RECRUITING
NCT06071598IRCCS San RaffaeleStarted 2023-03-15
Surgical specimens of CRC-affected patients

External Resources

Links to major genomics databases and tools