MFSD2A

Chr 1AR

MFSD2 lysolipid transporter A, lysophospholipid

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

NCBI Gene: 84879 ENSG00000168389 UniProt: Q8NA29 OMIM: 614397

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.541 OMIM phenotype

Clinical Summary— MFSD2A

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 87 VUS of 223 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.31 (0.18–0.54)

0≤0.351.4

Missense OE?0.68 (0.60–0.76)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 9 / 29.2Missense obs/exp: 211 / 312.2Syn Z: 1.31

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMFSD2A-related primary microcephalyOTHERAR

This gene — mechanism propensity

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

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

223 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic2

VUS87

Likely Benign95

Benign13

Conflicting6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	3	0	0	7
Likely Pathogenic	0	2	0	0	2
VUS	3	78	4	2	87
Likely Benign	0	2	38	55	95
Benign	0	2	9	2	13
Conflicting	—				6
Total	7	87	51	59	210

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap MFSD2A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →