MFSD2B

Summary

MFSD2B (MFSD2 lysolipid transporter B, sphingolipid, HGNC:37207) is a protein-coding gene on chromosome 2p23.3, encoding Sphingosine-1-phosphate transporter MFSD2B (A6NFX1). Lipid transporter that specifically mediates export of sphingosine-1-phosphate in red blood cells and platelets.

Enables sphingolipid transporter activity. Involved in lipid transport. Is active in plasma membrane.

Source: NCBI Gene 388931 — RefSeq curated summary.

At a glance

• GWAS associations: 32
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_001346880

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37207
Approved symbol	MFSD2B
Name	MFSD2 lysolipid transporter B, sphingolipid
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	SLC59A2
Ensembl gene	ENSG00000205639
Ensembl biotype	protein_coding
OMIM	617845
Entrez	388931

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000338315, ENST00000406420, ENST00000453731, ENST00000469562, ENST00000495018, ENST00000669179

RefSeq mRNA: 1 — MANE Select: NM_001346880 NM_001346880

CCDS: CCDS86824

Canonical transcript exons

ENST00000338315 — 14 exons

Exon	Start	End
ENSE00001183098	24023583	24023726
ENSE00001183102	24023130	24023239
ENSE00001536140	24021648	24021738
ENSE00001536152	24017286	24017364
ENSE00003471072	24016845	24016968
ENSE00003475643	24022433	24022516
ENSE00003514827	24013285	24013410
ENSE00003593745	24017458	24017588
ENSE00003595367	24024095	24024271
ENSE00003615530	24021849	24021970
ENSE00003634247	24022822	24022902
ENSE00003641842	24016156	24016280
ENSE00003692851	24025432	24026775
ENSE00003901033	24010085	24010192

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 81.88.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.4601 / max 180.1310, expressed in 135 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19166	1.2457	133
19167	0.2144	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	81.88	gold quality
monocyte	CL:0000576	79.18	gold quality
bone marrow	UBERON:0002371	78.34	gold quality
leukocyte	CL:0000738	78.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.46	silver quality
bone marrow cell	CL:0002092	73.43	gold quality
thymus	UBERON:0002370	69.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.52	silver quality
stromal cell of endometrium	CL:0002255	68.42	gold quality
placenta	UBERON:0001987	66.38	gold quality
quadriceps femoris	UBERON:0001377	65.49	gold quality
granulocyte	CL:0000094	65.33	gold quality
cerebellar vermis	UBERON:0004720	64.61	gold quality
sural nerve	UBERON:0015488	64.08	gold quality
nucleus accumbens	UBERON:0001882	63.03	gold quality
skeletal muscle tissue	UBERON:0001134	59.76	gold quality
putamen	UBERON:0001874	59.11	gold quality
ganglionic eminence	UBERON:0004023	58.76	gold quality
caudate nucleus	UBERON:0001873	58.66	gold quality
cortical plate	UBERON:0005343	58.30	gold quality
right lung	UBERON:0002167	57.88	gold quality
right coronary artery	UBERON:0001625	57.77	gold quality
gastrocnemius	UBERON:0001388	57.69	gold quality
muscle of leg	UBERON:0001383	57.61	gold quality
muscle tissue	UBERON:0002385	57.60	gold quality
colonic epithelium	UBERON:0000397	57.19	silver quality
adrenal tissue	UBERON:0018303	56.67	gold quality
tibial nerve	UBERON:0001323	55.78	gold quality
myometrium	UBERON:0001296	55.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	55.15	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.35
E-GEOD-124858	no	3.32

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• 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)
• MFSD2B, CCL20 and STAT1, or STARD7 and ZNF512 genes may be risk or protect factors in prognosis of ADC; HTR2B, DPP4, and TGFBRAP1 genes may be risk factors in prognosis of SQC. (PMID:27301951)
• Using microarray analysis of erythroid cell lines overexpressing human and mouse MFSD2B study showed sphingosine 1-phosphate (S1P) transport activity. The properties of S1P release by MFSD2B were similar to those in erythrocytes. Moreover, knockout of MFSD2B in MEDEP-E14 cells decreased S1P export from the cells. These results strongly suggest that MFSD2B is a novel S1P transporter in erythroid cells. (PMID:29563527)
• Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction. (PMID:37100836)
• An erythrocyte-centric view on the MFSD2B sphingosine-1-phosphate transporter. (PMID:37390971)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfsd2b	ENSDARG00000030263
mus_musculus	Mfsd2b	ENSMUSG00000037336
rattus_norvegicus	Mfsd2b	ENSRNOG00000023508
caenorhabditis_elegans		WBGENE00017530

Paralogs (2): MFSD12 (ENSG00000161091), MFSD2A (ENSG00000168389)

Protein

Protein identifiers

Sphingosine-1-phosphate transporter MFSD2B — A6NFX1 (reviewed: A6NFX1)

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

All UniProt accessions (4): A0A2I3JL00, A6NFX1, A0A590UK14, H7BZN4

UniProt curated annotations — full annotation on UniProt →

Function. Lipid transporter that specifically mediates export of sphingosine-1-phosphate in red blood cells and platelets. Sphingosine-1-phosphate is a signaling sphingolipid and its export from red blood cells into in the plasma is required for red blood cell morphology. Sphingosine-1-phosphate export from platelets is required for platelet aggregation and thrombus formation. Mediates the export of different sphingosine-1-phosphate (S1P) species, including S1P(d18:0) (sphinganine 1-phosphate), S1P (d18:1) (sphing-4-enine 1-phosphate) and S1P (d18:2) (sphinga-4E,14Z-dienine-1-phosphate). Release of sphingosine-1-phosphate is facilitated by a proton gradient. In contrast, cations, such as sodium, are not required to drive sphingosine-1-phosphate transport. In addition to export, also able to mediate S1P import. Does not transport lysophosphatidylcholine (LPC).

Subcellular location. Cell membrane.

Similarity. Belongs to the major facilitator superfamily.

RefSeq proteins (1): NP_001333809* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR039672	MFS_2	Family

Pfam: PF13347

Catalyzed reactions (Rhea), 3 shown:

• sphing-4-enine 1-phosphate(in) = sphing-4-enine 1-phosphate(out) (RHEA:38667)
• sphinganine 1-phosphate(in) = sphinganine 1-phosphate(out) (RHEA:38671)
• sphinga-4E,14Z-dienine-1-phosphate(in) = sphinga-4E,14Z-dienine-1-phosphate(out) (RHEA:70207)

UniProt features (18 total): transmembrane region 10, mutagenesis site 3, region of interest 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NFX1-F1	80.82	0.46

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
95	abolishes export of sphingosine-1-phosphate.
157	abolishes export of sphingosine-1-phosphate.
423	does not affect export of sphingosine-1-phosphate.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1660661	Sphingolipid de novo biosynthesis
R-HSA-1430728	Metabolism
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 86 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_SPHINGOLIPID_MEDIATED_SIGNALING_PATHWAY, GOBP_PLATELET_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_WOUND_HEALING, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_PLATELET_AGGREGATION, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_REGULATION_OF_HOMOTYPIC_CELL_CELL_ADHESION, REACTOME_SPHINGOLIPID_METABOLISM, GOBP_HOMOTYPIC_CELL_CELL_ADHESION

GO Biological Process (6): sphingosine-1-phosphate receptor signaling pathway (GO:0003376), lipid transport (GO:0006869), carbohydrate transport (GO:0008643), sphingolipid biosynthetic process (GO:0030148), transmembrane transport (GO:0055085), positive regulation of platelet aggregation (GO:1901731)

GO Molecular Function (2): symporter activity (GO:0015293), sphingolipid intramembrane carrier activity (GO:0046624)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
G protein-coupled receptor signaling pathway	1
sphingolipid mediated signaling pathway	1
lipid localization	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
cellular process	1
positive regulation of homotypic cell-cell adhesion	1
platelet aggregation	1
regulation of platelet aggregation	1
secondary active transmembrane transporter activity	1
intramembrane lipid carrier activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFSD2B	SPNS2	Q8IVW8	990
MFSD2B	SPNS1	Q9H2V7	857
MFSD2B	SPHK1	Q9NYA1	718
MFSD2B	SPHK2	Q9NRA0	696
MFSD2B	S1PR2	O95136	691
MFSD2B	S1PR3	Q99500	658
MFSD2B	S1PR5	Q9H228	603
MFSD2B	S1PR4	O95977	582
MFSD2B	APOM	O95445	571
MFSD2B	SLC33A2	Q96ES6	560
MFSD2B	SGPL1	O95470	541
MFSD2B	SPNS3	Q6ZMD2	541
MFSD2B	SLC67A2	Q8NBP5	540
MFSD2B	MFSD11	O43934	521
MFSD2B	SLC75A1	Q14728	513

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MFSD2B	USP33	psi-mi:“MI:0915”(physical association)	0.400
HIF1A	MFSD2B	psi-mi:“MI:0915”(physical association)	0.400
MFSD2B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): MFSD2B (Affinity Capture-RNA), ARHGEF1 (Affinity Capture-MS), ATP11C (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), CR2 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), ERLIN2 (Affinity Capture-MS), KDM5C (Affinity Capture-MS), MARCH5 (Affinity Capture-MS), MARVELD2 (Affinity Capture-MS), PTPRJ (Affinity Capture-MS), RETSAT (Affinity Capture-MS), TMEM33 (Affinity Capture-MS), TNFRSF10B (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3730 predictions. Top by Δscore:

Variant	Effect	Δscore
2:24010192:GGTG:G	donor_loss	1.0000
2:24010193:G:GA	donor_loss	1.0000
2:24010194:T:G	donor_loss	1.0000
2:24017365:G:GG	donor_gain	1.0000
2:24017589:G:GG	donor_gain	1.0000
2:24022817:CACA:C	acceptor_loss	1.0000
2:24022820:AGGT:A	acceptor_loss	1.0000
2:24022901:TT:T	donor_gain	1.0000
2:24022901:TTGTG:T	donor_loss	1.0000
2:24022903:G:GG	donor_gain	1.0000
2:24022903:G:T	donor_loss	1.0000
2:24022907:G:GG	donor_gain	1.0000
2:24023578:CGCA:C	acceptor_loss	1.0000
2:24023579:GCA:G	acceptor_loss	1.0000
2:24023580:CAGG:C	acceptor_loss	1.0000
2:24023581:AGGT:A	acceptor_loss	1.0000
2:24023582:GGTCC:G	acceptor_gain	1.0000
2:24023724:GGA:G	donor_gain	1.0000
2:24023725:GA:G	donor_gain	1.0000
2:24023725:GAG:G	donor_gain	1.0000
2:24023727:G:GG	donor_gain	1.0000
2:24023738:GGT:G	donor_gain	1.0000
2:24024090:TCCA:T	acceptor_loss	1.0000
2:24024092:CAGG:C	acceptor_loss	1.0000
2:24024093:A:AG	acceptor_gain	1.0000
2:24024093:A:C	acceptor_loss	1.0000
2:24024093:AG:A	acceptor_gain	1.0000
2:24024094:G:GA	acceptor_gain	1.0000
2:24024094:GG:G	acceptor_gain	1.0000
2:24024094:GGTT:G	acceptor_gain	1.0000

AlphaMissense

3203 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:24017458:G:C	R184P	0.993
2:24013390:T:C	F68L	0.991
2:24013392:C:A	F68L	0.991
2:24013392:C:G	F68L	0.991
2:24023211:A:C	S381R	0.991
2:24023213:C:A	S381R	0.991
2:24023213:C:G	S381R	0.991
2:24022837:A:C	S332R	0.988
2:24022839:C:A	S332R	0.988
2:24022839:C:G	S332R	0.988
2:24023206:G:A	G379D	0.986
2:24016891:T:A	W132R	0.985
2:24016891:T:C	W132R	0.985
2:24022849:T:A	W336R	0.985
2:24022849:T:C	W336R	0.985
2:24023205:G:C	G379R	0.983
2:24022457:T:C	F307L	0.982
2:24022459:C:A	F307L	0.982
2:24022459:C:G	F307L	0.982
2:24013331:G:A	G48D	0.981
2:24013330:G:C	G48R	0.980
2:24013363:A:C	S59R	0.980
2:24013365:C:A	S59R	0.980
2:24013365:C:G	S59R	0.980
2:24021963:C:A	A296D	0.980
2:24017490:G:A	G195R	0.978
2:24017490:G:C	G195R	0.978
2:24024195:G:A	G472R	0.978
2:24024195:G:C	G472R	0.978
2:24013391:T:C	F68S	0.977

dbSNP variants (sampled 300 via entrez): RS1000012917 (2:24025943 C>A,T), RS1000066663 (2:24020894 T>A), RS1000234531 (2:24018215 G>A), RS1000287005 (2:24018000 A>G), RS1000442489 (2:24024011 G>A,C,T), RS1000567147 (2:24019685 T>C,G), RS1000741968 (2:24016731 C>T), RS1001198494 (2:24010243 A>G), RS1001239095 (2:24016936 A>T), RS1001394910 (2:24022964 T>C), RS1001605012 (2:24016739 A>G), RS1001780971 (2:24022716 G>C), RS1002215889 (2:24010022 G>A,C,T), RS1002287741 (2:24018062 T>G), RS1002682295 (2:24020968 C>T)

Disease associations

OMIM: gene MIM:617845 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST004609_136	Monocyte percentage of white cells	4.000000e-21
GCST004611_7	High light scatter reticulocyte count	4.000000e-26
GCST004612_164	High light scatter reticulocyte percentage of red cells	1.000000e-29
GCST004619_48	Reticulocyte fraction of red cells	9.000000e-20
GCST004622_148	Reticulocyte count	2.000000e-15
GCST004627_136	Lymphocyte count	9.000000e-40
GCST004628_142	Immature fraction of reticulocytes	5.000000e-27
GCST004632_126	Lymphocyte percentage of white cells	7.000000e-13
GCST006268_492	Reaction time	5.000000e-08
GCST008163_219	Height	3.000000e-07
GCST012126_2	hemolysis of donated blood (osmotic)	5.000000e-08
GCST012135_2	hemolysis of donated blood (osmotic)	1.000000e-13
GCST90002385_118	High light scatter reticulocyte count	9.000000e-31
GCST90002386_236	High light scatter reticulocyte percentage of red cells	8.000000e-25
GCST90002386_237	High light scatter reticulocyte percentage of red cells	4.000000e-16
GCST90002387_251	Immature fraction of reticulocytes	2.000000e-11
GCST90002387_252	Immature fraction of reticulocytes	3.000000e-27
GCST90002388_64	Lymphocyte count	1.000000e-60
GCST90002388_65	Lymphocyte count	2.000000e-10
GCST90002389_103	Lymphocyte percentage of white cells	7.000000e-16
GCST90002397_765	Mean spheric corpuscular volume	2.000000e-59
GCST90002397_791	Mean spheric corpuscular volume	4.000000e-09
GCST90002399_158	Neutrophil percentage of white cells	3.000000e-17
GCST90002400_557	Plateletcrit	2.000000e-11
GCST90002400_558	Plateletcrit	2.000000e-09
GCST90002403_75	Red blood cell count	3.000000e-41
GCST90002405_112	Reticulocyte count	3.000000e-16
GCST90002405_113	Reticulocyte count	1.000000e-10
GCST90002406_7	Reticulocyte fraction of red cells	6.000000e-19
GCST90002406_8	Reticulocyte fraction of red cells	7.000000e-12

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0008393	reaction time measurement
EFO:0009473	hemolysis
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0004305	erythrocyte count
EFO:0007788	BMI-adjusted waist-hip ratio

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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
abrine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4GL	HCT116-MFSD2B-KO-c17	Cancer cell line	Male
CVCL_D4GM	HCT116-MFSD2B-KO-c21	Cancer cell line	Male

Clinical trials (associated diseases)

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