MFSD6

Summary

MFSD6 (major facilitator superfamily domain containing 6, HGNC:24711) is a protein-coding gene on chromosome 2q32.2, encoding Major facilitator superfamily domain-containing protein 6 (Q6ZSS7). (Microbial infection) Acts as a receptor for respiratory enterovirus D68.

Predicted to enable MHC class I protein binding activity and MHC class I receptor activity. Predicted to be involved in antigen processing and presentation of exogenous peptide antigen via MHC class I. Located in membrane.

Source: NCBI Gene 54842 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 111 total
• MANE Select transcript: NM_017694

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24711
Approved symbol	MFSD6
Name	major facilitator superfamily domain containing 6
Location	2q32.2
Locus type	gene with protein product
Status	Approved
Aliases	SLC73A1, FLJ20160
Ensembl gene	ENSG00000151690
Ensembl biotype	protein_coding
OMIM	613476
Entrez	54842

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000281416, ENST00000392328, ENST00000412482, ENST00000417958, ENST00000432036, ENST00000434582, ENST00000444317, ENST00000445546, ENST00000486123, ENST00000489793, ENST00000861426, ENST00000861427, ENST00000861428, ENST00000861429, ENST00000861430, ENST00000962434, ENST00000962435

RefSeq mRNA: 9 — MANE Select: NM_017694 NM_001375986, NM_001375987, NM_001375988, NM_001375989, NM_001375990, NM_001375992, NM_001375993, NM_001375994, NM_017694

CCDS: CCDS2306

Canonical transcript exons

ENST00000392328 — 8 exons

Exon	Start	End
ENSE00001001167	190489768	190489866
ENSE00001001168	190497439	190497719
ENSE00001001170	190488657	190488818
ENSE00001511471	190408355	190408503
ENSE00003645623	190469758	190469855
ENSE00003979864	190415292	190415413
ENSE00003979866	190435977	190437561
ENSE00003979869	190500015	190502314

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0413 / max 307.4960, expressed in 1576 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24302	9.1525	1371
24300	1.6332	637
24296	0.9787	363
24298	0.7996	366
24295	0.7875	315
24301	0.5899	297
24299	0.4676	243
24291	0.3642	65
24303	0.2891	67
24305	0.1802	82

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
substantia nigra pars reticulata	UBERON:0001966	99.01	gold quality
substantia nigra pars compacta	UBERON:0001965	98.96	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.62	gold quality
pons	UBERON:0000988	98.13	gold quality
middle temporal gyrus	UBERON:0002771	98.06	gold quality
esophagus squamous epithelium	UBERON:0006920	97.96	gold quality
bronchial epithelial cell	CL:0002328	97.65	gold quality
subthalamic nucleus	UBERON:0001906	97.13	gold quality
lateral globus pallidus	UBERON:0002476	96.88	gold quality
superior vestibular nucleus	UBERON:0007227	96.82	gold quality
inferior vagus X ganglion	UBERON:0005363	96.52	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.40	gold quality
globus pallidus	UBERON:0001875	96.25	gold quality
dorsal root ganglion	UBERON:0000044	96.22	gold quality
medial globus pallidus	UBERON:0002477	96.11	gold quality
postcentral gyrus	UBERON:0002581	96.08	gold quality
parotid gland	UBERON:0001831	95.95	gold quality
parietal lobe	UBERON:0001872	95.94	gold quality
corpus callosum	UBERON:0002336	95.64	gold quality
gingival epithelium	UBERON:0001949	95.45	gold quality
mammalian vulva	UBERON:0000997	95.42	gold quality
gingiva	UBERON:0001828	95.41	gold quality
epithelium of nasopharynx	UBERON:0001951	95.16	gold quality
ventral tegmental area	UBERON:0002691	95.12	gold quality
superior frontal gyrus	UBERON:0002661	95.07	gold quality
penis	UBERON:0000989	94.82	gold quality
entorhinal cortex	UBERON:0002728	94.82	gold quality
prefrontal cortex	UBERON:0000451	94.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.70	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.41

Regulation

Is transcription factor: no

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfsd6a	ENSDARG00000032318
danio_rerio	mfsd6b	ENSDARG00000054583
mus_musculus	Mfsd6	ENSMUSG00000041439
rattus_norvegicus	Mfsd6	ENSRNOG00000012663
drosophila_melanogaster	jef	FBGN0033958
caenorhabditis_elegans		WBGENE00020051

Paralogs (1): MFSD6L (ENSG00000185156)

Protein

Protein identifiers

Major facilitator superfamily domain-containing protein 6 — Q6ZSS7 (reviewed: Q6ZSS7)

Alternative names: Macrophage MHC class I receptor 2 homolog

All UniProt accessions (7): Q6ZSS7, C9IYL1, C9J134, C9JAZ7, C9JJH2, H7C0X2, H7C284

UniProt curated annotations — full annotation on UniProt →

Function. (Microbial infection) Acts as a receptor for respiratory enterovirus D68. Mechanistically, binds to viral particles and is required for viral cell entry while initial attachment to cells is mainly mediated by interactions with sialic acid.

Subunit / interactions. May interact with HLA-B62. (Microbial infection) Interacts with enterovirus D68 protein VP1.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed. Expression levels in peripheral blood mononuclear cells are highly variable between individuals, including no expression at all.

Similarity. Belongs to the major facilitator superfamily. MFSD6 family.

RefSeq proteins (9): NP_001362915, NP_001362916, NP_001362917, NP_001362918, NP_001362919, NP_001362921, NP_001362922, NP_001362923, NP_060164* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024989	MFS_assoc_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR051717	MFS_MFSD6	Family

Pfam: PF12832

UniProt features (26 total): transmembrane region 12, region of interest 4, compositionally biased region 4, modified residue 2, initiator methionine 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9MXC	ELECTRON MICROSCOPY	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZSS7-F1	66.05	0.31

Functional residue map

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

Post-translational modifications (2): 2, 10

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN_VIA_MHC_CLASS_I, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_EXOGENOUS_PEPTIDE_ANTIGEN_VIA_MHC_CLASS_I, KIM_GERMINAL_CENTER_T_HELPER_UP, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, TTTGCAC_MIR19A_MIR19B, NUYTTEN_EZH2_TARGETS_DN, ATGTACA_MIR493, MARSON_BOUND_BY_FOXP3_STIMULATED, GAL_LEUKEMIC_STEM_CELL_UP

GO Biological Process (2): antigen processing and presentation of exogenous peptide antigen via MHC class I (GO:0042590), transmembrane transport (GO:0055085)

GO Molecular Function (2): protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
antigen processing and presentation of peptide antigen via MHC class I	1
antigen processing and presentation of exogenous peptide antigen	1
transport	1
cellular process	1
binding	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFSD6	SLC67A2	Q8NBP5	703
MFSD6	SLC75A1	Q14728	677
MFSD6	MFSD11	O43934	607
MFSD6	SLC68A1	Q14CX5	603
MFSD6	MFSD12	Q6NUT3	578
MFSD6	UNC93A	Q86WB7	560
MFSD6	SLC61A1	Q6N075	558
MFSD6	MFSD8	Q8NHS3	555
MFSD6	NEMP2	A6NFY4	526
MFSD6	SLC71A2	Q5SR56	516
MFSD6	SLC71A1	Q96MC6	506
MFSD6	MIGA1	Q8NAN2	487
MFSD6	SVOPL	Q8N434	486
MFSD6	SLC37A3	Q8NCC5	466
MFSD6	SVOP	Q8N4V2	463

IntAct

119 interactions, top by confidence:

A	B	Type	Score
MFSD6	SDC3	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	TMPRSS2	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	TMEM242	psi-mi:“MI:0915”(physical association)	0.560
SDC3	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
AQP7	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	TMEM179B	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	SYNDIG1	psi-mi:“MI:0915”(physical association)	0.560
	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
SHISAL1	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	APH1A	psi-mi:“MI:0915”(physical association)	0.560
SMIM1	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
GJA8	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	SELENOK	psi-mi:“MI:0915”(physical association)	0.560
SGPL1	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
GJB2	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	STX12	psi-mi:“MI:0915”(physical association)	0.560
TMEM258	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
MFSD6	C19orf18	psi-mi:“MI:0915”(physical association)	0.560
EBP	MFSD6	psi-mi:“MI:0915”(physical association)	0.560
APOL3	MFSD6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (65): MFSD6 (Affinity Capture-RNA), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid), MFSD6 (Two-hybrid)

ESM2 similar proteins: A0JPH4, A1DWM3, A4QN56, A6H8H5, B0UYT5, B3MG58, B3NSE1, B4GAP7, B4KR05, B4LPX5, B4QBN2, O18868, O60741, P08911, P11483, P15387, P20309, P41984, P59995, Q03717, Q0P5V9, Q14721, Q1LUC3, Q1LUQ4, Q291H8, Q4V887, Q4ZHA6, Q5BKX6, Q5VW38, Q62897, Q63099, Q63881, Q6ZSS7, Q8C145, Q8CBH5, Q8HYZ1, Q91WD0, Q92953, Q95167, Q95L11

Diamond homologs: A0A1C7E424, A1A9U9, A1DWM3, A1JN04, A7ZKF6, A7ZZ10, A8AI28, A8GCZ5, A9MH10, A9N5Q9, B1IV49, B1LIV8, B1X9G6, B4EYY4, B4T2Y5, B4TES5, B4TSR5, B5BBD5, B5F954, B5FL11, B5QY11, B5XXK2, B6I9D0, B7LFG4, B7LT82, B7M928, B7MIJ4, B7MTI5, B7NAS9, B7NL82, B7UP67, C0Q855, C4ZRZ3, D2BX50, D8MQN9, E3GC98, E8XY75, G4MWA9, P0A4K4, P0A4K5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1701 predictions. Top by Δscore:

Variant	Effect	Δscore
2:190408501:CAGGT:C	donor_loss	1.0000
2:190408502:AGG:A	donor_loss	1.0000
2:190435974:CAGA:C	acceptor_loss	1.0000
2:190435975:A:AG	acceptor_gain	1.0000
2:190435975:AGAT:A	acceptor_loss	1.0000
2:190435976:G:GG	acceptor_gain	1.0000
2:190435976:GAT:G	acceptor_gain	1.0000
2:190469854:AGGT:A	donor_loss	1.0000
2:190469855:GGTA:G	donor_loss	1.0000
2:190469856:G:GG	donor_gain	1.0000
2:190469857:T:A	donor_loss	1.0000
2:190488656:GGA:G	acceptor_gain	1.0000
2:190489763:TATA:T	acceptor_loss	1.0000
2:190489765:TA:T	acceptor_loss	1.0000
2:190489766:A:AG	acceptor_gain	1.0000
2:190489766:AG:A	acceptor_gain	1.0000
2:190489766:AGG:A	acceptor_gain	1.0000
2:190489767:G:C	acceptor_loss	1.0000
2:190489767:G:GG	acceptor_gain	1.0000
2:190489767:GG:G	acceptor_gain	1.0000
2:190489767:GGG:G	acceptor_gain	1.0000
2:190489860:G:GT	donor_gain	1.0000
2:190489863:GAAG:G	donor_gain	1.0000
2:190489864:AAGGT:A	donor_loss	1.0000
2:190489865:AGG:A	donor_loss	1.0000
2:190489867:GT:G	donor_loss	1.0000
2:190489868:T:A	donor_loss	1.0000
2:190497437:A:AG	acceptor_gain	1.0000
2:190497438:G:GG	acceptor_gain	1.0000
2:190497715:TACAG:T	donor_loss	1.0000

AlphaMissense

5189 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:190436340:G:A	G104E	1.000
2:190436351:G:C	G108R	1.000
2:190436352:G:A	G108D	1.000
2:190436378:A:C	S117R	1.000
2:190436380:T:A	S117R	1.000
2:190436380:T:G	S117R	1.000
2:190436390:T:A	W121R	1.000
2:190436390:T:C	W121R	1.000
2:190436393:G:C	G122R	1.000
2:190436430:T:A	V134D	1.000
2:190436433:T:C	L135P	1.000
2:190436957:G:C	D310H	1.000
2:190436957:G:T	D310Y	1.000
2:190436958:A:C	D310A	1.000
2:190436958:A:G	D310G	1.000
2:190436958:A:T	D310V	1.000
2:190436967:C:A	T313K	1.000
2:190436970:T:A	L314H	1.000
2:190436970:T:C	L314P	1.000
2:190436979:T:C	L317P	1.000
2:190436999:T:C	Y324H	1.000
2:190437000:A:G	Y324C	1.000
2:190437002:G:A	G325R	1.000
2:190437002:G:C	G325R	1.000
2:190437002:G:T	G325W	1.000
2:190437003:G:A	G325E	1.000
2:190437011:C:A	R328S	1.000
2:190437020:G:C	G331R	1.000
2:190437021:G:A	G331D	1.000
2:190437195:T:C	F389S	1.000

dbSNP variants (sampled 300 via entrez): RS1000018158 (2:190499584 C>G), RS1000026890 (2:190460331 T>A), RS1000065536 (2:190413624 AAGG>A), RS1000078690 (2:190460536 T>C), RS1000088689 (2:190499208 A>G), RS1000092279 (2:190492028 C>A,G,T), RS1000146913 (2:190426559 T>C), RS1000163178 (2:190500635 G>A), RS1000166944 (2:190486775 AT>A), RS1000177605 (2:190454961 T>C), RS1000235225 (2:190467998 T>C), RS1000270332 (2:190448176 A>G), RS1000292373 (2:190420213 T>A,C), RS1000299033 (2:190484776 G>T), RS1000343922 (2:190427796 A>G)

Disease associations

OMIM: gene MIM:613476 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003518_14	Daytime sleep phenotypes	3.000000e-06
GCST007387_32	Insomnia symptoms (never/rarely vs. sometimes/usually)	9.000000e-09
GCST007388_25	Insomnia symptoms (never/rarely vs. usually)	1.000000e-09
GCST007876_46	Estimated glomerular filtration rate	3.000000e-08
GCST007932_108	Medication use (thyroid preparations)	3.000000e-09
GCST90002402_283	Platelet count	4.000000e-11
GCST90010715_5	Arthritis (juvenile idiopathic)	1.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0007876	insomnia measurement
EFO:0009933	Thyroid preparation use measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
Cyclosporine	decreases expression, increases expression	4
trichostatin A	increases expression, affects cotreatment	3
Arsenic	affects cotreatment, decreases expression, increases abundance	2
Calcitriol	increases expression, affects cotreatment	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Demecolcine	decreases expression	1
Doxorubicin	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4GS	HCT116-MFSD6-KO-c15	Cancer cell line	Male
CVCL_D4GT	HCT116-MFSD6-KO-c5	Cancer cell line	Male
CVCL_E0HY	Ubigene HeLa MFSD6 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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