MFSD2A

Summary

MFSD2A (MFSD2 lysolipid transporter A, lysophospholipid, HGNC:25897) is a protein-coding gene on chromosome 1p34.2, encoding Sodium-dependent lysophosphatidylcholine symporter 1 (Q8NA29). Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function.

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.

Source: NCBI Gene 84879 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly 15, primary, autosomal recessive (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 222 total — 7 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 36
• MANE Select transcript: NM_032793

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25897
Approved symbol	MFSD2A
Name	MFSD2 lysolipid transporter A, lysophospholipid
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14490, SLC59A1
Ensembl gene	ENSG00000168389
Ensembl biotype	protein_coding
OMIM	614397
Entrez	84879

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000372809, ENST00000372811, ENST00000420632, ENST00000434861, ENST00000459917, ENST00000469745, ENST00000480630, ENST00000481612, ENST00000483824, ENST00000491515, ENST00000857590, ENST00000857591, ENST00000857592, ENST00000918782, ENST00000942984, ENST00000942985

RefSeq mRNA: 7 — MANE Select: NM_032793 NM_001136493, NM_001287808, NM_001287809, NM_001349821, NM_001349822, NM_001349823, NM_032793

CCDS: CCDS44118, CCDS446, CCDS72762

Canonical transcript exons

ENST00000372811 — 14 exons

Exon	Start	End
ENSE00000000148	39969505	39969956
ENSE00001634576	39955145	39955385
ENSE00003471020	39965211	39965334
ENSE00003482267	39957087	39957221
ENSE00003511063	39965471	39965549
ENSE00003585504	39967086	39967169
ENSE00003589358	39965857	39966014
ENSE00003604819	39967628	39967711
ENSE00003638871	39967804	39967916
ENSE00003650530	39968334	39968477
ENSE00003680620	39958701	39958825
ENSE00003687320	39968569	39968745
ENSE00003692574	39966811	39966932
ENSE00003787275	39966601	39966691

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 97.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.9722 / max 1391.9220, expressed in 1545 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2326	21.9722	1545

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.80	gold quality
skin of abdomen	UBERON:0001416	97.61	gold quality
ileal mucosa	UBERON:0000331	96.18	gold quality
skin of leg	UBERON:0001511	96.09	gold quality
seminal vesicle	UBERON:0000998	95.25	gold quality
zone of skin	UBERON:0000014	95.21	gold quality
upper arm skin	UBERON:0004263	95.08	gold quality
liver	UBERON:0002107	94.40	gold quality
corpus epididymis	UBERON:0004359	93.41	gold quality
right testis	UBERON:0004534	93.16	gold quality
left testis	UBERON:0004533	92.54	gold quality
testis	UBERON:0000473	91.65	gold quality
upper lobe of left lung	UBERON:0008952	91.34	gold quality
upper lobe of lung	UBERON:0008948	91.27	gold quality
upper leg skin	UBERON:0004262	91.07	gold quality
caput epididymis	UBERON:0004358	90.21	gold quality
placenta	UBERON:0001987	90.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.04	gold quality
penis	UBERON:0000989	89.91	gold quality
lower lobe of lung	UBERON:0008949	89.38	gold quality
spinal cord	UBERON:0002240	89.19	gold quality
lower esophagus mucosa	UBERON:0035834	88.98	gold quality
nipple	UBERON:0002030	88.61	gold quality
nasal cavity epithelium	UBERON:0005384	88.26	silver quality
lung	UBERON:0002048	88.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.95	gold quality
amygdala	UBERON:0001876	87.89	gold quality
substantia nigra	UBERON:0002038	87.68	gold quality
hypothalamus	UBERON:0001898	87.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.49	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ENAD-21	yes	416.29
E-CURD-7	yes	354.67
E-HCAD-1	yes	91.53
E-MTAB-6678	yes	8.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, ARNT, GCGR, GCM1, PPARA

miRNA regulators (miRDB)

26 targeting MFSD2A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-7705	98.69	67.47	543
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-4747-3P	87.34	61.83	60

Literature-anchored findings (GeneRIF, showing 28)

• three additional SNPs in the MFSD2 genes showed ethnic differences in allelic frequencies (PMID:17145094)
• Results identify Mfsd2a (major facilitator superfamily domain-containing protein 2a) and an additional closely related protein Mfsd2b, and suggest that Mfsd2a plays a role in adaptive thermogenesis. (PMID:18694395)
• MFSD2 is a placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2, and plays a role in placenta morphogenesis. (PMID:18988732)
• MFSD2A is a novel lung cancer tumor suppressor gene that regulates cell cycle progression and matrix attachment. (PMID:20236515)
• MFSD2A is a putative Tunicamycin transporter at the plasma membrane. (PMID:21677192)
• SNP rs12072037 modulates MFSD2A promoter activity and thus might affect MFSD2A levels in normal lung and in lung tumors. (PMID:21736709)
• Importance of MFSD2a in trophoblast fusion and placenta development. (PMID:23177091)
• Several tagging SNPs and haplotypes in TRIT1, MYCL1 and MFSD2A region are significantly associated with risk and clinicopathological features of gastric cancer in a Chinese population. (PMID:23349019)
• A homozygous mutation affecting a highly conserved MFSD2A residue (p.Ser339Leu) is associated with a progressive microcephaly syndrome characterized by intellectual disability, spasticity and absent speech. (PMID:26005865)
• MFSD2A mutations impair brain lipid transport activity. (PMID:26005868)
• The regulatory role of Mfsd2a deepens our knowledge of the function of the BBB, potentially contributing to the effective drug delivery in the treatments for neurodegenerative diseases, brain tumors, and life-threatening infections in the CNS (PMID:26747400)
• In offspring of women with gestational diabetes mellitus treated either with diet or insulin, higher fetal fat accretion and lower placental MFSD2a contribute to reduce docosahexaenoic acid availability. (PMID:26869380)
• MFSD2A transported structurally related acylcarnitines but not a lysolipid without a negative charge, demonstrating the necessity of a negatively charged headgroup interaction with Lys-436 for transport. (PMID:26945070)
• Levels of DHA-derived epoxides are lower in colon tissues from patients with ulcerative colitis than healthy and resolving mucosa. Production of these metabolites by gut endothelium requires MFSD2A; endothelial progenitor cells that overexpress MFSD2A reduce colitis in mice. (PMID:28827082)
• When compared with placental expression of other genes, alkaline phosphatase expression was positively related to genes including the lysophosphatidylcholine transporter MFSD2A (major facilitator superfamily domain containing 2A, P < 0.001) and negatively related to genes including the fatty acid transport proteins 2 and 3 (P = 0.001, P < 0.001). (PMID:29899523)
• Two siblings with shared parental ancestry, in whom we identified a homozygous missense mutation (c.1205C > A; p.Pro402His) in MFSD2A. Both affected individuals had microcephaly, hypotonia, appendicular spasticity, dystonia, strabismus, and global developmental delay. (PMID:30043326)
• Results suggest that major facilitator superfamily domain containing-2A (MFSD2A) might affect angiogenesis and inhibit gastric cancer (GC) development and progression, and may help predict prognosis and could be a therapeutic target in GC. (PMID:30292405)
• The prognostic value of major facilitator superfamily domain-containing protein 2A in patients with hepatocellular carcinoma. (PMID:31584009)
• These findings suggest endothelial Mfsd2a as an important pathogenic mediator and supplementation with docosahexaenoic acid as a potential therapeutic option for Zika virus infection. (PMID:31681849)
• This study found a significant and progressive decline of MFSD2a levels in blood of Alzheimer’s Disease patients (Control 0.83 +/- 0.13, GDS4 0.72 +/- 0.09, GDS6 0.48 +/- 0.05*, p < 0.01). (PMID:31861865)
• Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy. (PMID:32117064)
• Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features. (PMID:32572202)
• Mfsd2a: A Physiologically Important Lysolipid Transporter in the Brain and Eye. (PMID:32705603)
• Mfsd2a overexpression alleviates vascular dysfunction in diabetic retinopathy. (PMID:34229049)
• MFSD2A-associated primary microcephaly - Expanding the clinical and mutational spectrum of this ultra-rare disease. (PMID:34400370)
• Structural insights into the lysophospholipid brain uptake mechanism and its inhibition by syncytin-2. (PMID:35710838)
• Investigation of the Binding Interaction of Mfsd2a with NEDD4-2 via Molecular Dynamics Simulations. (PMID:38155530)
• Placental MFSD2A expression in fetal growth restriction and maternal and fetal DHA status. (PMID:38583303)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfsd2aa	ENSDARG00000030630
danio_rerio	mfsd2ab	ENSDARG00000035909
mus_musculus	Mfsd2a	ENSMUSG00000028655
rattus_norvegicus	Mfsd2a	ENSRNOG00000014008
caenorhabditis_elegans		WBGENE00017530

Paralogs (2): MFSD12 (ENSG00000161091), MFSD2B (ENSG00000205639)

Protein

Protein identifiers

Sodium-dependent lysophosphatidylcholine symporter 1 — Q8NA29 (reviewed: Q8NA29)

Alternative names: Major facilitator superfamily domain-containing protein 2A

All UniProt accessions (3): Q8NA29, E7EPI8, Q5SSK0

UniProt curated annotations — full annotation on UniProt →

Function. Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function. Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain. Transport of LPC is essential because it constitutes the major mechanism by which docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for normal brain growth and cognitive function, enters the brain. Transports LPC carrying long-chain fatty acids such LPC oleate and LPC palmitate with a minimum acyl chain length of 14 carbons. Does not transport docosahexaenoic acid in unesterified fatty acid. Specifically required for blood-brain barrier formation and function, probably by mediating lipid transport. Not required for central nervous system vascular morphogenesis. Acts as a transporter for tunicamycin, an inhibitor of asparagine-linked glycosylation. In placenta, acts as a receptor for ERVFRD-1/syncytin-2 and is required for trophoblast fusion.

Subunit / interactions. Interacts with ERVFRD-1/syncytin-2.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane.

Tissue specificity. In placenta, associated with trophoblast cells.

Disease relevance. Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (NEDMISBA) [MIM:616486] An autosomal recessive disorder characterized by impaired intellectual development with poor speech, progressive microcephaly, and appendicular spasticity. Brain imaging usually shows abnormalities, including enlarged ventricles, white matter defects, and atrophy or hypoplasia of brain tissue. Some patients have a more severe phenotype with seizures, lack of developmental milestones, and early death. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the major facilitator superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NA29-1	1	yes
Q8NA29-2	2
Q8NA29-3	3

RefSeq proteins (7): NP_001129965, NP_001274737, NP_001274738, NP_001336750, NP_001336751, NP_001336752, NP_116182* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR039672	MFS_2	Family

Pfam: PF13347

Catalyzed reactions (Rhea), 5 shown:

• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine(in) + Na(+)(in) = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine(out) + Na(+)(out) (RHEA:43856)
• 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine(in) + Na(+)(in) = 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine(out) + Na(+)(out) (RHEA:43860)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine(in) + Na(+)(in) = 1-hexadecanoyl-sn-glycero-3-phosphocholine(out) + Na(+)(out) (RHEA:43864)
• a 1-acyl-sn-glycero-3-phosphoethanolamine(in) + Na(+)(in) = a 1-acyl-sn-glycero-3-phosphoethanolamine(out) + Na(+)(out) (RHEA:43868)
• a 1-acyl-sn-glycero-3-phosphocholine(in) + Na(+)(in) = a 1-acyl-sn-glycero-3-phosphocholine(out) + Na(+)(out) (RHEA:44376)

UniProt features (74 total): mutagenesis site 32, topological domain 13, transmembrane region 12, sequence variant 8, glycosylation site 2, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7OIX	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NA29-F1	81.03	0.48

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 225–473

Glycosylation sites (2): 230, 240

Mutagenesis-validated functional residues (32):

Position	Phenotype
57	does not affect lysophosphatidylcholine (lpc) transport.
57	abolished lysophosphatidylcholine (lpc) transport.
65	abolished lysophosphatidylcholine (lpc) transport.
66	abolished lysophosphatidylcholine (lpc) transport.
73	abolished lysophosphatidylcholine (lpc) transport.
103	reduced lysophosphatidylcholine (lpc) transport.
103	no effect on cell sensitivity toward tunicamycin.
106	no effect on cell sensitivity toward tunicamycin.
110	drastic loss of cell sensitivity toward tunicamycin. abolished lysophosphatidylcholine (lpc) transport.
177	reduced expression; no effect on cell membrane localization; decreased lpc transport activity.
200	reduced lysophosphatidylcholine (lpc) transport.
225	reduced lysophosphatidylcholine (lpc) transport.
230	loss of glycosylation; when associated with q-240.
240	loss of glycosylation; when associated with q-230.
325	abolished lysophosphatidylcholine (lpc) transport.
328	reduced lysophosphatidylcholine (lpc) transport.
334	does not affect lysophosphatidylcholine (lpc) transport.
339	reduced lysophosphatidylcholine (lpc) transport.
342	abolished lysophosphatidylcholine (lpc) transport.
346	abolished lysophosphatidylcholine (lpc) transport.
349	reduced lysophosphatidylcholine (lpc) transport.
350	reduced lysophosphatidylcholine (lpc) transport.
357	does not affect lysophosphatidylcholine (lpc) transport.
357	abolished lysophosphatidylcholine (lpc) transport.
361	reduced lysophosphatidylcholine (lpc) transport.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483191	Synthesis of PC

MSigDB gene sets: 390 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, CCAWYNNGAAR_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS

GO Biological Process (34): retinal pigment epithelium development (GO:0003406), phosphatidylcholine biosynthetic process (GO:0006656), brain development (GO:0007420), photoreceptor cell morphogenesis (GO:0008594), carbohydrate transport (GO:0008643), cellular response to starvation (GO:0009267), positive regulation of triglyceride biosynthetic process (GO:0010867), fatty acid transport (GO:0015908), long-chain fatty acid transport (GO:0015909), hippocampus development (GO:0021766), positive regulation of cell growth (GO:0030307), negative regulation of fatty acid beta-oxidation (GO:0031999), very-low-density lipoprotein particle assembly (GO:0034379), maintenance of blood-brain barrier (GO:0035633), photoreceptor cell outer segment organization (GO:0035845), regulation of multicellular organism growth (GO:0040014), transcytosis (GO:0045056), regulation of dendrite development (GO:0050773), cognition (GO:0050890), lysophospholipid transport (GO:0051977), transmembrane transport (GO:0055085), retina morphogenesis in camera-type eye (GO:0060042), establishment of blood-brain barrier (GO:0060856), motor behavior (GO:0061744), energy homeostasis (GO:0097009), lysophospholipid translocation (GO:0140329), regulation of neuron projection arborization (GO:0150011), transport across blood-brain barrier (GO:0150104), regulation of phosphatidylcholine metabolic process (GO:0150172), regulation of phosphatidylethanolamine metabolic process (GO:0150175), obsolete regulation of phosphatidylserine metabolic process (GO:0150178), lipid transport across blood-brain barrier (GO:1990379), lipid transport (GO:0006869), lipid translocation (GO:0034204)

GO Molecular Function (8): long-chain fatty acid transmembrane transporter activity (GO:0005324), obsolete phospholipid transporter activity (GO:0005548), fatty acid transmembrane transporter activity (GO:0015245), lysophospholipid:sodium symporter activity (GO:0051978), lysophosphatidylcholine flippase activity (GO:0140348), oleate transmembrane transporter activity (GO:1901480), protein binding (GO:0005515), symporter activity (GO:0015293)

GO Cellular Component (7): lysosome (GO:0005764), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic ribonucleoprotein granule (GO:0036464), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
photoreceptor cell development	2
fatty acid transport	2
lipid transmembrane transporter activity	2
cellular anatomical structure	2
retina development in camera-type eye	1
epithelium development	1
phosphatidylcholine metabolic process	1
glycerophospholipid biosynthetic process	1
central nervous system development	1
animal organ development	1
head development	1
cell morphogenesis involved in neuron differentiation	1
transport	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
regulation of triglyceride biosynthetic process	1
triglyceride biosynthetic process	1
positive regulation of lipid biosynthetic process	1
positive regulation of triglyceride metabolic process	1
lipid transport	1
monocarboxylic acid transport	1
pallium development	1
limbic system development	1
anatomical structure development	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
fatty acid beta-oxidation	1
regulation of fatty acid beta-oxidation	1
negative regulation of fatty acid oxidation	1
negative regulation of lipid catabolic process	1
plasma lipoprotein particle assembly	1
tissue homeostasis	1
cellular component organization	1
multicellular organism growth	1
regulation of developmental growth	1
regulation of multicellular organismal process	1

Protein interactions and networks

STRING

1018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFSD2A	ERVFRD-1	P60508	987
MFSD2A	ERVW-1	Q9UQF0	949
MFSD2A	ZNF335	Q9H4Z2	681
MFSD2A	SYN2	Q92777	640
MFSD2A	SLC1A5	Q15758	625
MFSD2A	SASS6	Q6UVJ0	619
MFSD2A	CLDN5	O00501	613
MFSD2A	ANKLE2	Q86XL3	507
MFSD2A	OCLN	Q16625	501
MFSD2A	KIF14	Q15058	486
MFSD2A	MFSD11	O43934	469
MFSD2A	WDR62	O43379	460
MFSD2A	SLC39A10	Q9ULF5	458
MFSD2A	CEP135	Q66GS9	453
MFSD2A	ADGRA2	Q96PE1	446

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MFSD2A	ERVFRD-1	psi-mi:“MI:0915”(physical association)	0.400
MFSD2A	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
MFSD2A	CAND2	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): TMEM242 (Two-hybrid), MFSD2A (Two-hybrid), MFSD2A (Negative Genetic), GBAS (Co-fractionation), MFSD2A (Co-fractionation), MFSD2A (Co-fractionation), NUCB2 (Co-fractionation), UEVLD (Co-fractionation), ARFGEF1 (Affinity Capture-MS), BAG6 (Affinity Capture-MS), CAND2 (Affinity Capture-MS), CORO1B (Affinity Capture-MS), DDX20 (Affinity Capture-MS), DDX50 (Affinity Capture-MS), GCN1L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2HW92, A6NDV4, A6NFX1, A6QLK4, B1AWJ5, F1NCD6, F1NJ67, F1PZV2, O35308, O35595, O70461, O95907, Q08DX7, Q0IHM1, Q0P5C0, Q0P5M9, Q13286, Q14728, Q29611, Q2YDU8, Q3T9M1, Q3U481, Q501I9, Q5R8G5, Q5R9A1, Q5U419, Q60HH0, Q61124, Q66H95, Q6NUT3, Q6UXD7, Q6ZMD2, Q7RTT9, Q8BFQ6, Q8CE47, Q8NA29, Q8R0G7, Q8R139, Q8TB61, Q8VCW4

Diamond homologs: A4IH46, A6NFX1, F1NCD6, Q0IHM1, Q3T9M1, Q5U3U7, Q6DEJ6, Q8NA29, Q9DA75

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

222 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	87
Likely benign	91
Benign	12

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1700576	NM_032793.5(MFSD2A):c.1386_1435del (p.Gln462fs)	Pathogenic
1700577	NM_032793.5(MFSD2A):c.750_753del (p.Cys251fs)	Pathogenic
1700578	NM_032793.5(MFSD2A):c.556+1G>A	Pathogenic
2265225	NM_032793.5(MFSD2A):c.456C>A (p.Cys152Ter)	Pathogenic
372260	NM_032793.5(MFSD2A):c.476C>T (p.Thr159Met)	Pathogenic
372262	NM_032793.5(MFSD2A):c.1016C>T (p.Ser339Leu)	Pathogenic
684729	NM_032793.5(MFSD2A):c.229-25_229-23del	Pathogenic
4845352	NM_032793.5(MFSD2A):c.432_437del (p.Trp146_Tyr147del)	Likely pathogenic

SpliceAI

2027 predictions. Top by Δscore:

Variant	Effect	Δscore
1:39955385:GGTGA:G	donor_loss	1.0000
1:39955386:GTGA:G	donor_loss	1.0000
1:39955387:T:G	donor_loss	1.0000
1:39965205:CCTCA:C	acceptor_loss	1.0000
1:39965206:CTCA:C	acceptor_loss	1.0000
1:39965207:TCAG:T	acceptor_loss	1.0000
1:39965208:CAGG:C	acceptor_loss	1.0000
1:39965209:A:AG	acceptor_gain	1.0000
1:39965209:AG:A	acceptor_gain	1.0000
1:39965210:G:GT	acceptor_gain	1.0000
1:39965210:GG:G	acceptor_gain	1.0000
1:39965210:GGATC:G	acceptor_gain	1.0000
1:39965335:GTG:G	donor_loss	1.0000
1:39965336:T:A	donor_loss	1.0000
1:39965469:A:AG	acceptor_gain	1.0000
1:39965470:G:GG	acceptor_gain	1.0000
1:39965470:GT:G	acceptor_gain	1.0000
1:39965550:G:GG	donor_gain	1.0000
1:39966599:A:AG	acceptor_gain	1.0000
1:39966600:G:GG	acceptor_gain	1.0000
1:39966806:CCCA:C	acceptor_loss	1.0000
1:39966808:CAG:C	acceptor_loss	1.0000
1:39966809:A:AG	acceptor_gain	1.0000
1:39966810:G:GA	acceptor_gain	1.0000
1:39966810:GA:G	acceptor_gain	1.0000
1:39966810:GAA:G	acceptor_gain	1.0000
1:39966810:GAAC:G	acceptor_gain	1.0000
1:39966810:GAACC:G	acceptor_gain	1.0000
1:39966931:TG:T	donor_gain	1.0000
1:39966932:GG:G	donor_gain	1.0000

AlphaMissense

3437 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:39965857:G:C	R199P	0.999
1:39965529:G:C	R192P	0.998
1:39966895:T:C	L310P	0.997
1:39967684:G:C	K369N	0.996
1:39967684:G:T	K369N	0.996
1:39957142:C:A	A50E	0.995
1:39958746:T:A	W105R	0.995
1:39958746:T:C	W105R	0.995
1:39965496:T:C	L181P	0.995
1:39965510:A:C	S186R	0.995
1:39965512:C:A	S186R	0.995
1:39965512:C:G	S186R	0.995
1:39967915:T:A	W416R	0.995
1:39967915:T:C	W416R	0.995
1:39968342:T:C	L419P	0.995
1:39968712:G:C	R512P	0.995
1:39958824:T:A	W131R	0.994
1:39958824:T:C	W131R	0.994
1:39965257:T:A	W147R	0.994
1:39965257:T:C	W147R	0.994
1:39965538:C:A	A195D	0.994
1:39967655:T:A	W360R	0.994
1:39967655:T:C	W360R	0.994
1:39958761:G:C	D110H	0.993
1:39965471:T:C	C173R	0.993
1:39965531:G:C	D193H	0.993
1:39967888:A:C	S407R	0.993
1:39967890:T:A	S407R	0.993
1:39967890:T:G	S407R	0.993
1:39968470:A:C	S462R	0.993

dbSNP variants (sampled 300 via entrez): RS1000494353 (1:39966508 T>C,G), RS1001164168 (1:39954819 C>T), RS1001266882 (1:39966157 C>A,T), RS1001407673 (1:39954457 G>A), RS1002142435 (1:39964277 G>A), RS1002443784 (1:39953658 G>A,C,T), RS1002674765 (1:39959254 T>C,G), RS1002827611 (1:39964555 T>C), RS1002940469 (1:39964828 C>T), RS1003008509 (1:39963066 A>G,T), RS1003082008 (1:39963287 C>G,T), RS1003145883 (1:39962888 G>A), RS1003240945 (1:39959593 A>T), RS1003275886 (1:39963326 A>C,G), RS1003847527 (1:39969781 G>C)

Disease associations

OMIM: gene MIM:614397 | disease phenotypes: MIM:616486, MIM:252160, MIM:219050

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly 15, primary, autosomal recessive	Definitive	Autosomal recessive
autosomal recessive primary microcephaly	Supportive	Autosomal recessive

Mondo (7): microcephaly 15, primary, autosomal recessive (MONDO:0014660), sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (MONDO:0009644), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), fetal growth restriction (MONDO:0005030), cryptorchidism (MONDO:0009047), autosomal recessive primary microcephaly (MONDO:0016660)

Orphanet (4): Autosomal recessive primary microcephaly (Orphanet:2512), Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (Orphanet:308393), Encephalopathy due to sulfite oxidase deficiency (Orphanet:833), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000340	Sloping forehead
HP:0000582	Upslanted palpebral fissure
HP:0000729	Autistic behavior
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001285	Spastic tetraparesis
HP:0001302	Pachygyria
HP:0001321	Cerebellar hypoplasia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001510	Growth delay
HP:0001776	Bilateral talipes equinovarus
HP:0002064	Spastic gait
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002282	Gray matter heterotopia
HP:0002365	Hypoplasia of the brainstem
HP:0002421	Poor head control
HP:0002540	Inability to walk
HP:0003103	Abnormal cortical bone morphology
HP:0003577	Congenital onset

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001925_8	PR interval	9.000000e-06
GCST006804_161	Red cell distribution width	2.000000e-09
GCST008547_1	Time to smoke first cigarette in the morning	4.000000e-07
GCST010002_380	Refractive error	4.000000e-10
GCST010244_346	Triglyceride levels	3.000000e-08
GCST90002383_131	Hematocrit	9.000000e-12
GCST90002384_535	Hemoglobin	5.000000e-15
GCST90002395_301	Mean platelet volume	2.000000e-20
GCST90002397_626	Mean spheric corpuscular volume	1.000000e-13
GCST90002403_42	Red blood cell count	6.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0009188	Red cell distribution width
EFO:0010126	time to first cigarette measurement
EFO:0004530	triglyceride measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D003456	Cryptorchidism	C12.100.500.829.258; C12.200.294.829.258; C12.200.706.258; C12.800.258; C16.131.939.258; C19.391.829.258
D005317	Fetal Growth Retardation	C12.050.703.277.370; C16.300.390; C23.550.393.450
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C579935	Autosomal Recessive Primary Microcephaly (supp.)
C565373	Molybdenum Cofactor Deficiency, Complementation Group B (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC59 Sodium-dependent lysophosphatidylcholine symporter family

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Benzo(a)pyrene	increases expression, increases methylation, decreases expression, decreases methylation	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	2
Calcitriol	increases expression	2
Estradiol	decreases expression, increases expression	2
Nickel	increases expression	2
Valproic Acid	increases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ferrous chloride	increases expression	1
pentanal	increases expression	1
15-acetyldeoxynivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
docosahexaenoyl lysophosphatidylcholine	decreases transport, increases transport	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
obeticholic acid	increases expression	1
Rosiglitazone	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4GJ	HCT116-MFSD2A-KO-c1	Cancer cell line	Male
CVCL_D4GK	HCT116-MFSD2A-KO-c2	Cancer cell line	Male
CVCL_F1PZ	HyCyte Hep 3B2.1-7 KO-hMFSD2A	Cancer cell line	Male
CVCL_SY19	HAP1 MFSD2A (-)	Cancer cell line	Male

Clinical trials (associated diseases)

297 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00347867	PHASE4	UNKNOWN	Viagra for the Treatment of IUGR
NCT00909974	PHASE4	COMPLETED	Effect of Prenatal Nutritional Supplementation on Birth Outcome in Hounde District, Burkina Faso
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01390051	PHASE4	COMPLETED	Can Low Molecular Weight Heparin During Pregnancy With Intrauterine Growth Restriction Increase Birth Weight?
NCT01695070	PHASE4	COMPLETED	Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT05029778	PHASE4	UNKNOWN	Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve
NCT05800938	PHASE4	COMPLETED	The Effect of Oral Isosorbide Mononitrate Therapy on Umbilical Artery Doppler Resistance Index in Pregnancies With Intrauterine Growth Restriction: Prospective Randomized Control Trial
NCT07171086	PHASE4	NOT_YET_RECRUITING	AI-POCUS for Maternal and Neonatal Health in Ethiopia
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00174252	PHASE3	COMPLETED	Study Aimed At Improving Height With Genotonorm In Children Born Little And/Or Light With Growth Retardation At The Age
NCT00197340	PHASE3	COMPLETED	Antepartum Chronic Epidural Therapy (ACET) to Improve Blood Flow to the Uterus, Placenta and Baby in Pre-Eclampsia and Intrauterine Growth Restriction
NCT00452491	PHASE3	COMPLETED	MAXOMAT ® in the Treatment of Severe Early Onset Intrauterine Growth Retardation on Pre-pubertal Children
NCT01073605	PHASE3	COMPLETED	Genotropin Treatment in Short Prepubertal Children With Intra-Uterine Growth Retardation
NCT02336243	PHASE3	UNKNOWN	A Randomized Trial of Docosahexaenoic Acid Supplementation During Pregnancy to Prevent Deep Placentation Disorders
NCT02590536	PHASE3	COMPLETED	A Trial Evaluating the Role of Sildenafil in the Treatment of Fetal Growth Restriction
NCT02672566	PHASE3	COMPLETED	Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction
NCT03177824	PHASE3	UNKNOWN	Sildenafil Citrate for Treatment of Growth-restricted Fetuses
NCT03230162	PHASE3	UNKNOWN	Sildenafil Versus Low Molecular Weight Heparin in Fetal Growth Restriction Treatment
NCT03324139	PHASE3	COMPLETED	Treatment of Intrauterine Growth Restriction With Low Molecular Heparin.
NCT03669185	PHASE3	UNKNOWN	Pentaerithrityl Tetranitrate (PETN) for Secondary Prevention of Intrauterine Growth Restriction
NCT04084990	PHASE3	TERMINATED	Sleep Apnea and Fetal Growth Restriction
NCT04356326	PHASE3	RECRUITING	Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy
NCT04557475	PHASE3	WITHDRAWN	Transplacental Aspirin Therapy for Early Onset Fetal Growth Restriction
NCT04762992	PHASE3	ENROLLING_BY_INVITATION	LMWH for Treatment of Early Fetal Growth Restriction (HepaGrowth)
NCT05253781	PHASE3	COMPLETED	Low Dose Aspirin for Preventing Intrauterine Growth Restriction and Preeclampsia in Sickle Cell Pregnancy (PIPSICKLE)
NCT05651347	PHASE3	RECRUITING	Antenatal Melatonin Supplementation for Neuroprotection in Fetal Growth Restriction
NCT05774236	PHASE3	COMPLETED	Cook´s Balloon Versus Dinoprostone for Labor Induction of Term Pregnancies With Fetal Growth Restriction
NCT06497959	PHASE3	RECRUITING	Study of Placental Vascularization Using Contrast Ultrasound
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02280031	PHASE2	COMPLETED	Effect of Low Dose Aspirin on Birthweight in Twins: The GAP Trial.
NCT02425436	PHASE2	COMPLETED	Role of Ginkgo Biloba Extract in IUGR