MFSD2A

Chr 1AR

MFSD2 lysolipid transporter A, lysophospholipid

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

The encoded protein is a sodium-dependent lysophosphatidylcholine transporter that is essential for blood-brain barrier formation and function, specifically transporting docosahexaenoic acid (DHA) and other long-chain fatty acids into the brain. Mutations cause neurodevelopmental disorder with progressive microcephaly, spasticity, and brain abnormalities with autosomal recessive inheritance. The progressive nature of the microcephaly reflects the protein's critical role in ongoing brain growth and cognitive function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.541 OMIM phenotype
Clinical SummaryMFSD2A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.011
Z-score 3.47
OE 0.31 (0.180.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.04Z-score
OE missense 0.68 (0.600.76)
211 obs / 312.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.31 (0.180.54)
00.351.4
Missense OE0.68 (0.600.76)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 9 / 29.2Missense obs/exp: 211 / 312.2Syn Z: 1.31
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMFSD2A-related primary microcephalyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.74top 25%
GOF
0.7027th %ile
LOF
0.2092th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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