SLC33A2

Summary

SLC33A2 (solute carrier family 33 member 2, HGNC:25157) is a protein-coding gene on chromosome 8q24.3, encoding Solute carrier family 33 member 2 (Q96ES6).

Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in membrane.

Source: NCBI Gene 113655 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_138431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25157
Approved symbol	SLC33A2
Name	solute carrier family 33 member 2
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167700
Ensembl biotype	protein_coding
OMIM	620308
Entrez	113655

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 retained_intron, 2 protein_coding

ENST00000301327, ENST00000526749, ENST00000528047, ENST00000534427, ENST00000883534

RefSeq mRNA: 1 — MANE Select: NM_138431 NM_138431

CCDS: CCDS6431

Canonical transcript exons

ENST00000301327 — 5 exons

Exon	Start	End
ENSE00001115757	144510360	144510507
ENSE00001115759	144510991	144511213
ENSE00001115763	144510794	144510903
ENSE00001115765	144510598	144510722
ENSE00002181483	144509070	144510015

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 95.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.9766 / max 98.5822, expressed in 1736 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91527	10.2576	1724
91526	0.7190	464

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.25	gold quality
apex of heart	UBERON:0002098	93.79	gold quality
right lobe of liver	UBERON:0001114	91.14	gold quality
right frontal lobe	UBERON:0002810	89.74	gold quality
right lobe of thyroid gland	UBERON:0001119	89.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.17	gold quality
left lobe of thyroid gland	UBERON:0001120	88.78	gold quality
transverse colon	UBERON:0001157	88.77	gold quality
right adrenal gland cortex	UBERON:0035827	88.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.70	gold quality
right adrenal gland	UBERON:0001233	88.69	gold quality
prefrontal cortex	UBERON:0000451	88.46	gold quality
anterior cingulate cortex	UBERON:0009835	88.45	gold quality
left adrenal gland	UBERON:0001234	88.03	gold quality
left adrenal gland cortex	UBERON:0035825	87.99	gold quality
metanephros cortex	UBERON:0010533	87.75	gold quality
cerebellar hemisphere	UBERON:0002245	87.70	gold quality
cerebellar cortex	UBERON:0002129	87.34	gold quality
right atrium auricular region	UBERON:0006631	87.19	gold quality
pancreatic ductal cell	CL:0002079	86.97	silver quality
thyroid gland	UBERON:0002046	86.94	gold quality
gastrocnemius	UBERON:0001388	86.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.73	gold quality
heart left ventricle	UBERON:0002084	86.37	gold quality
adenohypophysis	UBERON:0002196	86.17	gold quality
adrenal cortex	UBERON:0001235	85.91	gold quality
cardiac atrium	UBERON:0002081	85.56	gold quality
lower esophagus mucosa	UBERON:0035834	85.44	gold quality
cerebellum	UBERON:0002037	85.41	gold quality
cardiac ventricle	UBERON:0002082	85.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.53
E-MTAB-6142	no	99.53

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Association of MFSD3 promoter methylation level and weight regain after gastric bypass: Assessment for 3 y after surgery. (PMID:31655468)
• Network-based meta-analysis and the candidate gene association studies reveal novel ethnicity-specific variants in MFSD3 and MRPL43 associated with dementia with Lewy bodies. (PMID:35765761)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfsd3	ENSDARG00000093253
mus_musculus	Mfsd3	ENSMUSG00000019080
rattus_norvegicus	Mfsd3	ENSRNOG00000015685
drosophila_melanogaster	CG9706	FBGN0036662
caenorhabditis_elegans		WBGENE00012033

Paralogs (1): SLC33A1 (ENSG00000169359)

Protein

Protein identifiers

Solute carrier family 33 member 2 — Q96ES6 (reviewed: Q96ES6)

Alternative names: Major facilitator superfamily domain-containing protein 3

All UniProt accessions (1): Q96ES6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Similarity. Belongs to the SLC33A transporter family.

RefSeq proteins (1): NP_612440* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004752	AmpG_permease/AT-1	Family
IPR011701	MFS	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF07690

UniProt features (14 total): transmembrane region 12, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96ES6-F1	89.67	0.66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_TRANSMEMBRANE_TRANSPORT, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GOMF_TRANSPORTER_ACTIVITY, YAUCH_HEDGEHOG_SIGNALING_PARACRINE_UP, MARTENS_TRETINOIN_RESPONSE_DN, LU_EZH2_TARGETS_UP, chr8q24, FORTSCHEGGER_PHF8_TARGETS_DN, STK33_DN, STK33_NOMO_DN, FOXD2_TARGET_GENES, ID2_TARGET_GENES, KAT5_TARGET_GENES, PTPRA_TARGET_GENES, SNRNP70_TARGET_GENES

GO Biological Process (1): transmembrane transport (GO:0055085)

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

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
cellular process	1
transporter activity	1
transmembrane transport	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1012 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC33A2	SLC61A1	Q6N075	716
SLC33A2	MFSD11	O43934	645
SLC33A2	SLC67A2	Q8NBP5	624
SLC33A2	SLC71A1	Q96MC6	623
SLC33A2	SPNS3	Q6ZMD2	567
SLC33A2	MFSD2B	A6NFX1	560
SLC33A2	SLC75A1	Q14728	557
SLC33A2	ADCK5	Q3MIX3	556
SLC33A2	LRRC24	Q50LG9	541
SLC33A2	UNC93A	Q86WB7	521
SLC33A2	SLC68A1	Q14CX5	519
SLC33A2	LRRC14	Q15048	513
SLC33A2	SVOPL	Q8N434	512
SLC33A2	MFSD6L	Q8IWD5	509
SLC33A2	MFSD1	Q9H3U5	509

IntAct

32 interactions, top by confidence:

A	B	Type	Score
MFSD3	AQP6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	MFSD3	psi-mi:“MI:0915”(physical association)	0.560
MFSD3	UBE2J1	psi-mi:“MI:0915”(physical association)	0.560
MFSD3	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
AQP6	MFSD3	psi-mi:“MI:0915”(physical association)	0.560
MMGT1	MFSD3	psi-mi:“MI:0915”(physical association)	0.560
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
MFSD3	PTAFR	psi-mi:“MI:0915”(physical association)	0.370
MFSD3	DPAGT1	psi-mi:“MI:0915”(physical association)	0.370
MFSD3	PCDHGC3	psi-mi:“MI:0915”(physical association)	0.370
APPBP2	MFSD3	psi-mi:“MI:0915”(physical association)	0.370
MDFI	MFSD3	psi-mi:“MI:0915”(physical association)	0.370
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
KLRB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC22A9	TMEM131L	psi-mi:“MI:0914”(association)	0.350
MFSD4A	UBXN8	psi-mi:“MI:0914”(association)	0.350
GPR35	SLC33A1	psi-mi:“MI:0914”(association)	0.350
ICAM2	RAB29	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
MFSD3	NME4	psi-mi:“MI:0914”(association)	0.350
SLC2A7	GPR89A	psi-mi:“MI:0914”(association)	0.350
MFSD3	KRTAP10-6	psi-mi:“MI:0915”(physical association)	0.000
MFSD3	UBE2J1	psi-mi:“MI:0915”(physical association)	0.000
MFSD3	SLC7A8	psi-mi:“MI:0915”(physical association)	0.000
MFSD3	MMGT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (47): MFSD3 (Two-hybrid), MFSD3 (Two-hybrid), MFSD3 (Two-hybrid), MFSD3 (Two-hybrid), MMGT1 (Two-hybrid), KRTAP10-6 (Two-hybrid), UBE2J1 (Two-hybrid), MFSD3 (Affinity Capture-MS), MFSD3 (Two-hybrid), MFSD3 (Affinity Capture-MS), MFSD3 (Affinity Capture-MS), MFSD3 (Affinity Capture-MS), MFSD3 (Affinity Capture-MS), MFSD3 (Affinity Capture-MS), MFSD3 (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: O00400, P24326, P38317, P38318, Q4V8E5, Q5U419, Q6AYY8, Q96ES6, Q99J27, Q9USW4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

506 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144510591:A:AG	acceptor_gain	1.0000
8:144510592:T:G	acceptor_gain	1.0000
8:144510594:CCA:C	acceptor_loss	1.0000
8:144510596:A:AG	acceptor_gain	1.0000
8:144510596:AG:A	acceptor_gain	1.0000
8:144510597:G:A	acceptor_gain	1.0000
8:144510597:G:GC	acceptor_gain	1.0000
8:144510597:GGA:G	acceptor_gain	1.0000
8:144510597:GGAA:G	acceptor_gain	1.0000
8:144510597:GGAAA:G	acceptor_gain	1.0000
8:144510719:AGAG:A	donor_loss	1.0000
8:144510720:GAG:G	donor_gain	1.0000
8:144510720:GAGGT:G	donor_loss	1.0000
8:144510721:AG:A	donor_loss	1.0000
8:144510722:GGT:G	donor_loss	1.0000
8:144510723:GT:G	donor_loss	1.0000
8:144510724:T:A	donor_loss	1.0000
8:144510792:AG:A	acceptor_gain	1.0000
8:144510793:GG:G	acceptor_gain	1.0000
8:144510900:GCAG:G	donor_gain	1.0000
8:144510904:G:GA	donor_loss	1.0000
8:144510905:T:A	donor_loss	1.0000
8:144510011:GCTGG:G	donor_gain	0.9900
8:144510399:T:A	acceptor_gain	0.9900
8:144510792:A:AG	acceptor_gain	0.9900
8:144510793:G:GG	acceptor_gain	0.9900
8:144510904:G:GG	donor_gain	0.9900
8:144510012:C:G	donor_gain	0.9800
8:144510013:TGGGT:T	donor_loss	0.9800
8:144510014:GG:G	donor_gain	0.9800

AlphaMissense

2522 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144510856:T:C	F340L	0.992
8:144510858:C:A	F340L	0.992
8:144510858:C:G	F340L	0.992
8:144511003:A:C	S360R	0.988
8:144511005:C:A	S360R	0.988
8:144511005:C:G	S360R	0.988
8:144510011:G:C	K226N	0.987
8:144510011:G:T	K226N	0.987
8:144510877:A:C	S347R	0.985
8:144510879:C:A	S347R	0.985
8:144510879:C:G	S347R	0.985
8:144509565:G:C	G78R	0.984
8:144509660:C:A	N109K	0.984
8:144509660:C:G	N109K	0.984
8:144509679:G:C	D116H	0.981
8:144509566:G:A	G78D	0.980
8:144510471:G:A	G265D	0.980
8:144509765:G:C	K144N	0.978
8:144509765:G:T	K144N	0.978
8:144509492:G:C	K53N	0.976
8:144509492:G:T	K53N	0.976
8:144509741:T:A	N136K	0.976
8:144509741:T:G	N136K	0.976
8:144510808:A:C	S324R	0.976
8:144510810:C:A	S324R	0.976
8:144510810:C:G	S324R	0.976
8:144509481:T:A	W50R	0.975
8:144509481:T:C	W50R	0.975
8:144509692:A:T	D120V	0.975
8:144510458:T:C	C261R	0.974

dbSNP variants (sampled 300 via entrez): RS1000804275 (8:144508689 G>A,T), RS1001106308 (8:144508836 C>T), RS1001181823 (8:144509006 C>T), RS1001531004 (8:144510350 A>C,G), RS1002424790 (8:144508301 C>G,T), RS1002659570 (8:144508638 T>G), RS1003183868 (8:144507097 G>A), RS1003353703 (8:144507384 G>A), RS1003500353 (8:144511407 C>A,T), RS1003658037 (8:144507673 C>T), RS1004335477 (8:144509460 G>A), RS1005705525 (8:144510112 C>G,T), RS1005731353 (8:144511548 G>A), RS1006008507 (8:144510294 G>A,C), RS1006223623 (8:144507846 T>A)

Disease associations

OMIM: gene MIM:620308 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002598_30	Educational attainment	9.000000e-06
GCST006879_12	Blood metabolite levels	4.000000e-10
GCST006879_13	Blood metabolite levels	2.000000e-09
GCST006879_14	Blood metabolite levels	2.000000e-11
GCST006879_5	Blood metabolite levels	2.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
sodium arsenite	decreases expression, increases abundance, increases expression	3
Cyclosporine	decreases expression, decreases methylation	3
Benzo(a)pyrene	decreases expression	2
Copper	affects binding, increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
monomethylarsonous acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4V2	LS180-MFSD3-KO-c4	Cancer cell line	Female
CVCL_D4V3	LS180-MFSD3-KO-c6	Cancer cell line	Female

Clinical trials (associated diseases)

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