MFSD1

Summary

MFSD1 (major facilitator superfamily domain containing 1, HGNC:25874) is a protein-coding gene on chromosome 3q25.32, encoding Lysosomal dipeptide transporter MFSD1 (Q9H3U5). Lysosomal dipeptide uniporter that selectively exports lysine, arginine or histidine-containing dipeptides with a net positive charge from the lysosome lumen into the cytosol.

Enables dipeptide uniporter activity. Involved in dipeptide transmembrane transport from lysosomal lumen to cytosol. Is active in lysosomal membrane.

Source: NCBI Gene 64747 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 120 total
• MANE Select transcript: NM_022736

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25874
Approved symbol	MFSD1
Name	major facilitator superfamily domain containing 1
Location	3q25.32
Locus type	gene with protein product
Status	Approved
Aliases	Minerva, SLC72A1, FLJ14153, UG0581B09
Ensembl gene	ENSG00000118855
Ensembl biotype	protein_coding
OMIM	619976
Entrez	64747

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 16 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay

ENST00000264266, ENST00000392813, ENST00000415822, ENST00000465235, ENST00000465624, ENST00000465739, ENST00000468409, ENST00000471266, ENST00000471500, ENST00000474670, ENST00000476860, ENST00000477743, ENST00000480292, ENST00000482835, ENST00000484166, ENST00000486568, ENST00000489639, ENST00000491804, ENST00000622669, ENST00000651862, ENST00000893305, ENST00000893306, ENST00000893307, ENST00000945280, ENST00000945281

RefSeq mRNA: 4 — MANE Select: NM_022736 NM_001167903, NM_001289406, NM_001289407, NM_022736

CCDS: CCDS3185, CCDS54666

Canonical transcript exons

ENST00000415822 — 16 exons

Exon	Start	End
ENSE00001821566	158802054	158802315
ENSE00003493263	158824124	158824236
ENSE00003507702	158809179	158809287
ENSE00003509305	158820215	158820326
ENSE00003525235	158821597	158821653
ENSE00003545740	158821984	158822140
ENSE00003554596	158819649	158819747
ENSE00003564792	158823428	158823525
ENSE00003608459	158826015	158826062
ENSE00003633520	158807040	158807082
ENSE00003635978	158827280	158827337
ENSE00003637209	158813965	158814067
ENSE00003660264	158805362	158805474
ENSE00003694329	158807396	158807463
ENSE00003788745	158804319	158804371
ENSE00003892740	158828979	158829716

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.0875 / max 841.4899, expressed in 1824 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39513	68.5194	1823
39510	1.2593	605
39518	0.7739	172
39515	0.6564	124
39509	0.3019	123
39517	0.1738	73
39514	0.1651	67
39516	0.1412	60
39519	0.0820	35
39511	0.0144	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.82	gold quality
mononuclear cell	CL:0000842	98.81	gold quality
leukocyte	CL:0000738	98.62	gold quality
esophagus squamous epithelium	UBERON:0006920	98.52	gold quality
trabecular bone tissue	UBERON:0002483	98.32	gold quality
palpebral conjunctiva	UBERON:0001812	98.20	gold quality
epithelium of esophagus	UBERON:0001976	98.17	gold quality
visceral pleura	UBERON:0002401	98.06	gold quality
pleura	UBERON:0000977	97.97	gold quality
squamous epithelium	UBERON:0006914	97.92	gold quality
epithelium of nasopharynx	UBERON:0001951	97.91	gold quality
parietal pleura	UBERON:0002400	97.90	gold quality
nasopharynx	UBERON:0001728	97.89	gold quality
gingiva	UBERON:0001828	97.69	gold quality
skin of hip	UBERON:0001554	97.65	gold quality
parotid gland	UBERON:0001831	97.45	gold quality
gingival epithelium	UBERON:0001949	97.43	gold quality
oral cavity	UBERON:0000167	97.41	gold quality
tibia	UBERON:0000979	97.34	gold quality
mammalian vulva	UBERON:0000997	97.33	gold quality
upper leg skin	UBERON:0004262	97.18	gold quality
germinal epithelium of ovary	UBERON:0001304	97.13	gold quality
calcaneal tendon	UBERON:0003701	97.09	gold quality
bone marrow	UBERON:0002371	97.04	gold quality
cervix squamous epithelium	UBERON:0006922	96.94	gold quality
bone marrow cell	CL:0002092	96.92	gold quality
layer of synovial tissue	UBERON:0007616	96.92	gold quality
synovial joint	UBERON:0002217	96.91	gold quality
eye	UBERON:0000970	96.90	gold quality
decidua	UBERON:0002450	96.88	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	40.35
E-MTAB-9543	yes	40.26
E-HCAD-13	yes	20.81
E-CURD-122	yes	20.01
E-CURD-112	yes	14.18
E-MTAB-9067	yes	13.89
E-GEOD-99795	no	274.49
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting MFSD1, 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-6499-3P	99.90	66.38	1212
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-7702	99.06	65.95	698
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-3144-3P	98.15	67.34	677
HSA-MIR-188-5P	97.89	67.01	756
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-618	97.62	67.46	861
HSA-MIR-4678	97.59	68.31	902
HSA-MIR-6866-3P	97.38	66.94	748
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-383-5P	96.86	67.55	820
HSA-MIR-331-5P	96.59	67.94	705
HSA-MIR-3157-3P	95.86	67.08	454
HSA-MIR-1178-5P	95.83	64.12	504

Literature-anchored findings (GeneRIF, showing 2)

• MFSD1 protein localizes in lysosomes in HeLa cells (PMID:21752829)
• Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport. (PMID:38507452)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfsd1	ENSDARG00000101379
mus_musculus	Mfsd1	ENSMUSG00000027775
rattus_norvegicus	Mfsd1	ENSRNOG00000013790
drosophila_melanogaster	CG12194	FBGN0031636
drosophila_melanogaster	mrva	FBGN0035763
caenorhabditis_elegans		WBGENE00010182
caenorhabditis_elegans		WBGENE00010282
caenorhabditis_elegans		WBGENE00012222
caenorhabditis_elegans		WBGENE00016093
caenorhabditis_elegans		WBGENE00016094
caenorhabditis_elegans		WBGENE00016095
caenorhabditis_elegans		WBGENE00017861
caenorhabditis_elegans		WBGENE00021814

Paralogs (6): MFSD10 (ENSG00000109736), MFSD9 (ENSG00000135953), MFSD14B (ENSG00000148110), MFSD14A (ENSG00000156875), MFSD8 (ENSG00000164073), MFSD5 (ENSG00000182544)

Protein

Protein identifiers

Lysosomal dipeptide transporter MFSD1 — Q9H3U5 (reviewed: Q9H3U5)

Alternative names: Major facilitator superfamily domain-containing protein 1, Smooth muscle cell-associated protein 4

All UniProt accessions (10): Q9H3U5, A0A494C105, C9J5G6, C9JAC3, C9JBA3, C9JCH3, C9JZW5, H7C4F4, H7C593, H7C5U3

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal dipeptide uniporter that selectively exports lysine, arginine or histidine-containing dipeptides with a net positive charge from the lysosome lumen into the cytosol. Could play a role in a specific type of protein O-glycosylation indirectly regulating macrophages migration and tissue invasion. Also essential for liver homeostasis.

Subunit / interactions. Homodimer. Interacts with lysosomal protein GLMP (via lumenal domain); the interaction starts while both proteins are still in the endoplasmic reticulum and is required for stabilization of MFSD1 in lysosomes but has no direct effect on its targeting to lysosomes or transporter activity.

Subcellular location. Lysosome membrane.

Domain organisation. The dileucine internalization motif is required for lysosomal localization.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the major facilitator superfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9H3U5-1	1	yes
Q9H3U5-2	2
Q9H3U5-3	3
Q9H3U5-4	4
Q9H3U5-5	5
Q9H3U5-6	6

RefSeq proteins (4): NP_001161375, NP_001276335, NP_001276336, NP_073573* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR052187	MFSD1	Family

Pfam: PF07690

Catalyzed reactions (Rhea), 12 shown:

• L-alpha-aminoacyl-L-arginine(out) = L-alpha-aminoacyl-L-arginine(in) (RHEA:79367)
• L-arginyl-L-alpha-amino acid(out) = L-arginyl-L-alpha-amino acid(in) (RHEA:79371)
• L-alpha-aminoacyl-L-histidine(out) = L-alpha-aminoacyl-L-histidine(in) (RHEA:79375)
• L-histidyl-L-alpha-amino acid(out) = L-histidyl-L-alpha-amino acid(in) (RHEA:79379)
• L-alpha-aminoacyl-L-lysine(out) = L-alpha-aminoacyl-L-lysine(in) (RHEA:79383)
• L-lysyl-L-alpha-amino acid(out) = L-lysyl-L-alpha-amino acid(in) (RHEA:79387)
• L-arginyl-glycine(out) = L-arginyl-glycine(in) (RHEA:79391)
• L-histidyl-glycine(out) = L-histidyl-glycine(in) (RHEA:79395)
• L-lysyl-L-alanine(out) = L-lysyl-L-alanine(in) (RHEA:79399)
• L-lysyl-L-lysine(out) = L-lysyl-L-lysine(in) (RHEA:79403)
• L-lysyl-glycine(out) = L-lysyl-glycine(in) (RHEA:79407)
• L-aspartyl-L-lysine(out) = L-aspartyl-L-lysine(in) (RHEA:79411)

UniProt features (27 total): transmembrane region 12, splice variant 6, sequence variant 4, chain 1, region of interest 1, short sequence motif 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3U5-F1	88.83	0.69

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 (1):

Position	Phenotype
11–12	loss of localization to lysosome. localizes to plasma membrane.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 211 (showing top): GOBP_LYSOSOMAL_TRANSPORT, MODULE_255, GOCC_VACUOLAR_MEMBRANE, MODULE_151, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MODULE_317, GOBP_VACUOLAR_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_LYSOSOME, GNF2_MCL1, GOBP_PROTEIN_LOCALIZATION_TO_VACUOLE, GOBP_PROTEIN_STABILIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, DOUGLAS_BMI1_TARGETS_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, TIEN_INTESTINE_PROBIOTICS_24HR_UP

GO Biological Process (5): protein stabilization (GO:0050821), protein localization to lysosome (GO:0061462), dipeptide transmembrane transport from lysosomal lumen to cytosol (GO:0141204), dipeptide transmembrane transport (GO:0035442), transmembrane transport (GO:0055085)

GO Molecular Function (3): protein homodimerization activity (GO:0042803), dipeptide uniporter activity (GO:0160178), transmembrane transporter activity (GO:0022857)

GO Cellular Component (4): lysosome (GO:0005764), lysosomal membrane (GO:0005765), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of protein stability	1
protein localization to vacuole	1
peptide transport	1
transmembrane transport from lysosomal lumen to cytosol	1
oligopeptide transmembrane transport	1
dipeptide transport	1
transport	1
cellular process	1
identical protein binding	1
protein dimerization activity	1
uniporter activity	1
dipeptide transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

806 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFSD1	SLC67A2	Q8NBP5	566
MFSD1	SLC49A3	Q6UXD7	512
MFSD1	SLC33A2	Q96ES6	509
MFSD1	MFSD11	O43934	493
MFSD1	UNC93A	Q86WB7	489
MFSD1	SLC75A1	Q14728	459
MFSD1	GFM1	Q96RP9	448
MFSD1	SLC71A1	Q96MC6	446
MFSD1	MFSD8	Q8NHS3	446
MFSD1	MLF1	P58340	430
MFSD1	MFSD6	Q6ZSS7	420
MFSD1	SLC61A1	Q6N075	407
MFSD1	SLC29A3	Q9BZD2	402
MFSD1	OR2F1	Q13607	399
MFSD1	SLC39A11	Q8N1S5	398
MFSD1	M0QYU9	M0QYU9	398

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TSPAN31	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CACNG1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
MFSD1	RP2	psi-mi:“MI:0914”(association)	0.350
MFSD1	RAB10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): MFSD1 (Affinity Capture-RNA), MFSD1 (Affinity Capture-RNA), MFSD1 (Affinity Capture-MS), MFSD1 (Affinity Capture-RNA), MFSD1 (Affinity Capture-MS), MFSD1 (Affinity Capture-MS), MFSD1 (Affinity Capture-MS), ABCA3 (Affinity Capture-MS), ACP2 (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), APP (Affinity Capture-MS), ATP13A2 (Affinity Capture-MS), ATP5L (Affinity Capture-MS), CC2D1A (Affinity Capture-MS), OSTC (Affinity Capture-MS)

ESM2 similar proteins: A6NFX1, A6QQL0, D2HKB0, D3ZG27, F1NCD6, F1NJ67, O09014, O70496, O82390, P51798, P51799, Q17QZ3, Q1JQC1, Q32LQ6, Q3T9M1, Q3T9X0, Q3TIT8, Q4PKH3, Q504N2, Q58CV5, Q5F3N0, Q5R8G5, Q5RB09, Q5T4D3, Q5ZIT9, Q5ZKS8, Q66H95, Q68F72, Q69YG0, Q6AY78, Q6PDE8, Q7SY29, Q8BFQ6, Q8BG19, Q8GX78, Q8IVW8, Q8IZD6, Q8N697, Q8NCC5, Q8NEB5

Diamond homologs: Q1JQC1, Q32LQ6, Q5R8G5, Q5ZIT9, Q9DC37, Q9H3U5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2833 predictions. Top by Δscore:

Variant	Effect	Δscore
3:158802171:G:GT	donor_gain	1.0000
3:158803320:G:GT	donor_gain	1.0000
3:158804318:GGCA:G	acceptor_gain	1.0000
3:158804368:ACGA:A	donor_gain	1.0000
3:158804369:CGA:C	donor_gain	1.0000
3:158804370:GA:G	donor_gain	1.0000
3:158804370:GAG:G	donor_gain	1.0000
3:158804371:AG:A	donor_loss	1.0000
3:158804372:G:GG	donor_gain	1.0000
3:158804372:GTAA:G	donor_loss	1.0000
3:158804373:T:A	donor_loss	1.0000
3:158804374:AAGTT:A	donor_loss	1.0000
3:158805472:ACGG:A	donor_loss	1.0000
3:158805473:CGGTA:C	donor_loss	1.0000
3:158805475:GTAAG:G	donor_loss	1.0000
3:158807390:TTATA:T	acceptor_loss	1.0000
3:158807391:TATA:T	acceptor_loss	1.0000
3:158807393:TA:T	acceptor_loss	1.0000
3:158807394:A:AT	acceptor_loss	1.0000
3:158807395:GGTT:G	acceptor_gain	1.0000
3:158807461:TGGG:T	donor_loss	1.0000
3:158807462:GG:G	donor_gain	1.0000
3:158807463:GG:G	donor_gain	1.0000
3:158807463:GGTA:G	donor_loss	1.0000
3:158807464:G:C	donor_loss	1.0000
3:158807464:G:GG	donor_gain	1.0000
3:158807465:T:A	donor_loss	1.0000
3:158809171:A:AG	acceptor_gain	1.0000
3:158809172:T:G	acceptor_gain	1.0000
3:158809174:TTTA:T	acceptor_loss	1.0000

AlphaMissense

3031 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:158809231:T:C	F165L	1.000
3:158809233:T:A	F165L	1.000
3:158809233:T:G	F165L	1.000
3:158809262:G:A	G175E	1.000
3:158809273:A:C	S179R	1.000
3:158809275:C:A	S179R	1.000
3:158809275:C:G	S179R	1.000
3:158822025:G:A	G321E	1.000
3:158823470:T:A	W374R	1.000
3:158823470:T:C	W374R	1.000
3:158823522:G:A	G391D	1.000
3:158824142:T:A	N398K	1.000
3:158824142:T:G	N398K	1.000
3:158805413:T:A	W90R	0.999
3:158805413:T:C	W90R	0.999
3:158805421:T:A	N92K	0.999
3:158805421:T:G	N92K	0.999
3:158805431:T:C	C96R	0.999
3:158805432:G:A	C96Y	0.999
3:158805433:T:G	C96W	0.999
3:158805443:G:C	G100R	0.999
3:158805444:G:A	G100D	0.999
3:158807044:G:C	G112R	0.999
3:158807462:G:T	G147W	0.999
3:158807463:G:A	G147E	0.999
3:158809184:G:A	G149D	0.999
3:158809190:A:T	E151V	0.999
3:158809202:T:A	V155D	0.999
3:158809205:C:A	A156D	0.999
3:158809212:T:A	N158K	0.999

dbSNP variants (sampled 300 via entrez): RS1000011986 (3:158807217 A>T), RS1000182979 (3:158807998 C>T), RS1000276334 (3:158800096 C>T), RS1000418555 (3:158823839 G>A,C), RS1000524773 (3:158814417 G>A,T), RS1000614192 (3:158803890 T>C), RS1000658374 (3:158820162 G>A), RS1000724663 (3:158827036 C>T), RS1000838022 (3:158827836 G>C,T), RS1000847728 (3:158811286 G>A), RS1000913160 (3:158812353 A>G,T), RS1000922039 (3:158805831 C>A), RS1001028848 (3:158822269 C>G), RS1001238012 (3:158824674 C>T), RS1001260370 (3:158816786 CTAACGTTTAAGTCTT>C)

Disease associations

OMIM: gene MIM:619976 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002126_21	Periodontitis (CDC/AAP)	3.000000e-07
GCST004251_5	Paneth cell defects in Crohn’s disease	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007963	abnormal paneth cell measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	9
sodium arsenite	decreases expression, increases expression	2
Tretinoin	increases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium bichromate	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Vitamin K 3	affects expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1X2	Abcam HeLa MFSD1 KO	Cancer cell line	Female
CVCL_D4EB	1321N1-MFSD1-KO-c12	Cancer cell line	Male
CVCL_D4EC	1321N1-MFSD1-KO-c5	Cancer cell line	Male
CVCL_D9K9	Ubigene HEK293 MFSD1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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