SLC46A2

Summary

SLC46A2 (solute carrier family 46 member 2, HGNC:16055) is a protein-coding gene on chromosome 9q32, encoding Solute carrier family 46 member 2 (Q9BY10). Proton-coupled transporter that delivers pathogen-associated or danger-associated molecular patterns to cytosolic pattern recognition receptors as part of the innate immune response to microbes or tissue injury.

Enables cyclic-GMP-AMP transmembrane transporter activity. Involved in cyclic-GMP-AMP transmembrane import across plasma membrane and positive regulation of nucleotide-binding activity oligomerization domain containing 1 signaling pathway. Located in plasma membrane.

Source: NCBI Gene 57864 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_033051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16055
Approved symbol	SLC46A2
Name	solute carrier family 46 member 2
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	Ly110
Ensembl gene	ENSG00000119457
Ensembl biotype	protein_coding
OMIM	608956
Entrez	57864

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000374228, ENST00000491462, ENST00000868988

RefSeq mRNA: 1 — MANE Select: NM_033051 NM_033051

CCDS: CCDS6786

Canonical transcript exons

ENST00000374228 — 4 exons

Exon	Start	End
ENSE00001462844	112889553	112890876
ENSE00003269679	112878920	112879819
ENSE00003468054	112886460	112886616
ENSE00003589125	112887330	112887413

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 92.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4947 / max 40.6607, expressed in 120 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102075	0.2098	78
102076	0.1508	60
102074	0.0675	35
102073	0.0666	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	92.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.42	gold quality
monocyte	CL:0000576	85.84	gold quality
leukocyte	CL:0000738	85.47	gold quality
skin of leg	UBERON:0001511	84.80	gold quality
zone of skin	UBERON:0000014	83.00	gold quality
granulocyte	CL:0000094	82.55	gold quality
skin of abdomen	UBERON:0001416	82.29	gold quality
upper leg skin	UBERON:0004262	81.76	gold quality
thymus	UBERON:0002370	75.15	gold quality
blood	UBERON:0000178	74.94	gold quality
nipple	UBERON:0002030	73.28	gold quality
mammalian vulva	UBERON:0000997	71.02	gold quality
upper lobe of left lung	UBERON:0008952	69.95	gold quality
upper lobe of lung	UBERON:0008948	69.64	gold quality
lower esophagus mucosa	UBERON:0035834	69.36	gold quality
skin of hip	UBERON:0001554	67.82	gold quality
lower lobe of lung	UBERON:0008949	67.17	silver quality
lung	UBERON:0002048	67.06	gold quality
esophagus squamous epithelium	UBERON:0006920	66.12	silver quality
penis	UBERON:0000989	65.86	gold quality
epithelial cell of pancreas	CL:0000083	65.25	gold quality
seminal vesicle	UBERON:0000998	63.14	gold quality
right lung	UBERON:0002167	62.67	gold quality
urinary bladder	UBERON:0001255	61.66	gold quality
corpus epididymis	UBERON:0004359	61.42	gold quality
pancreatic ductal cell	CL:0002079	60.35	silver quality
esophagus mucosa	UBERON:0002469	59.23	gold quality
vermiform appendix	UBERON:0001154	58.55	gold quality
bone marrow cell	CL:0002092	57.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting SLC46A2, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-154-5P	98.92	66.65	733

Literature-anchored findings (GeneRIF, showing 3)

• Affected sib-pairs with cervical cancer susceptibility and high mean age at diagnosis show increased sharing at all microsatellite markers at 9q31.1-33.1 and linkage signals of up to maximum lod-score of 2.74 for TSCOT single nucleotide polymorphisms. (PMID:18392855)
• Mammalian SLC46A2s promote tracheal cytotoxin -triggered NOD1 activation in human epithelial cell lines, indicating that SLC46As is a conserved group of peptidoglycan transporter contributing to cytosolic immune recognition (PMID:28539433)
• When SLC46A2 delivers cargo into keratinocytes. (PMID:37163988)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc46a2	ENSDARG00000075229
mus_musculus	Slc46a2	ENSMUSG00000028386
rattus_norvegicus	Slc46a2	ENSRNOG00000017324
drosophila_melanogaster	CG15890	FBGN0030576
drosophila_melanogaster	CG8008	FBGN0033387
drosophila_melanogaster	CG8046	FBGN0033388
drosophila_melanogaster	CG15553	FBGN0039817
drosophila_melanogaster	CG30344	FBGN0050344
drosophila_melanogaster	CG30345	FBGN0050345
drosophila_melanogaster	CG31321	FBGN0051321
drosophila_melanogaster	CG42514	FBGN0260388
caenorhabditis_elegans		WBGENE00021159

Paralogs (2): SLC46A1 (ENSG00000076351), SLC46A3 (ENSG00000139508)

Protein

Protein identifiers

Solute carrier family 46 member 2 — Q9BY10 (reviewed: Q9BY10)

Alternative names: Thymic stromal cotransporter homolog

All UniProt accessions (2): Q9BY10, S4R3Y2

UniProt curated annotations — full annotation on UniProt →

Function. Proton-coupled transporter that delivers pathogen-associated or danger-associated molecular patterns to cytosolic pattern recognition receptors as part of the innate immune response to microbes or tissue injury. Has selectivity toward muropeptides that contain the amino acid diaminopimelic acid (DAP-type peptidoglycan muropeptides) including Tri-DAP and tracheal toxin (TCT), common in Gram-negative bacteria and Gram-positive bacilli. In the context of immune recognition of skin microbiota, shuttles bacterial muropeptides across the endolysosomal membranes into the cytosol for recognition by NOD1, triggering MYD88-dependent secretion of IL1A and neutrophil recruitment in a pyroptosis-type inflammatory process. To a lesser extent and redundantly, transports muramyl dipeptides derived from most bacterial proteoglycans, eliciting NOD2 receptor activation and downstream inflammatory responses. Postulated to function as a dominant importer of cyclic GMP-AMP dinucleotides (cGAMPs) in monocyte and macrophage cell lineages. Selectively imports cGAMPs derived from pathogenic bacteria such as 3'3’-cGAMP thus providing for differential immune recognition of pathogenic versus commensal bacteria. During tumorigenesis may transport extracellular tumor-derived 2'3’-cGAMP across the plasma membrane of M1-polarized macrophages to activate the anti-tumoral stimulator of interferon genes (STING) pathway. The transport mechanism, its electrogenicity and stoichiometry remain to be elucidated.

Subcellular location. Endosome membrane. Cell membrane.

Tissue specificity. Strongly expressed in the adult thymus. Expressed in spleen, lymph nodes, thymus, PBL, bone marrow and fetal liver. Expressed in monocytes and pre-dendridic cells.

Post-translational modifications. Glycosylated.

Induction. Up-regulated in keratinocytes upon differentiation.

Similarity. Belongs to the major facilitator superfamily. SLC46A family.

RefSeq proteins (1): NP_149040* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001958	Tet-R_TetA/multi-R_MdtG-like	Family
IPR011701	MFS	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF07690

Catalyzed reactions (Rhea), 5 shown:

• L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimelate(out) + n H(+)(out) = L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimelate(in) + n H(+)(in) (RHEA:64412)
• N-acetyl-beta-D-glucosaminyl-(1->4)-1,6-anhydro-N-acetyl-beta-D-muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanine(out) + n H(+)(out) = N-acetyl-beta-D-glucosaminyl-(1->4)-1,6-anhydro-N-acetyl-beta-D-muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanine(in) + n H(+)(in) (RHEA:76355)
• N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine(out) + n H(+)(out) = N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine(in) + n H(+)(in) (RHEA:76371)
• 2’,3’-cGAMP(out) + n H(+)(out) = 2’,3’-cGAMP(in) + n H(+)(in) (RHEA:76411)
• 3’,3’-cGAMP(out) + n H(+)(out) = 3’,3’-cGAMP(in) + n H(+)(in) (RHEA:76415)

UniProt features (30 total): topological domain 13, transmembrane region 12, sequence conflict 2, chain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY10-F1	80.66	0.56

Functional residue map

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

Glycosylation sites (1): 55

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_SIGNALING_PATHWAY, GOBP_T_CELL_HOMEOSTASIS, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_THYMUS_DEVELOPMENT, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_REGULATION_OF_HEMOPOIESIS

GO Biological Process (9): T cell homeostasis (GO:0043029), innate immune response (GO:0045087), regulation of T cell differentiation (GO:0045580), thymus development (GO:0048538), transmembrane transport (GO:0055085), negative regulation of T cell apoptotic process (GO:0070233), positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070430), cyclic-GMP-AMP transmembrane import across plasma membrane (GO:0140361), immune system process (GO:0002376)

GO Molecular Function (3): symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), cyclic-GMP-AMP transmembrane transporter activity (GO:0140360)

GO Cellular Component (5): plasma membrane (GO:0005886), cell surface (GO:0009986), endosome membrane (GO:0010008), membrane (GO:0016020), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
lymphocyte homeostasis	1
immune response	1
defense response to symbiont	1
T cell differentiation	1
regulation of lymphocyte differentiation	1
regulation of T cell activation	1
hematopoietic or lymphoid organ development	1
gland development	1
transport	1
cellular process	1
negative regulation of lymphocyte apoptotic process	1
T cell apoptotic process	1
regulation of T cell apoptotic process	1
positive regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	1
nucleotide-binding oligomerization domain containing 1 signaling pathway	1
regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway	1
purine ribonucleotide transport	1
adenine nucleotide transport	1
cyclic nucleotide transport	1
import across plasma membrane	1
guanine nucleotide transmembrane transport	1
biological_process	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
adenine nucleotide transmembrane transporter activity	1
guanine nucleotide transmembrane transporter activity	1
purine ribonucleotide transmembrane transporter activity	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC46A2	GTF3A	Q92664	631
SLC46A2	ZFP37	Q9Y6Q3	617
SLC46A2	CTSC	P53634	549
SLC46A2	SLC67A2	Q8NBP5	543
SLC46A2	SUSD1	Q6UWL2	507
SLC46A2	ZFP3	Q96NJ6	503
SLC46A2	SLC75A1	Q14728	490
SLC46A2	IFNA7	P01567	481
SLC46A2	IFNA8	P01565	481
SLC46A2	IFNA21	P01568	481
SLC46A2	IFNA16	P05015	481
SLC46A2	IFNA5	P01569	480
SLC46A2	IFNA14	P01570	480
SLC46A2	IFNA10	P01566	479
SLC46A2	IFNA6	P05013	472

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SLC46A2	SNAP23	psi-mi:“MI:0914”(association)	0.350

BioGRID (47): ABCA3 (Affinity Capture-MS), ABCB1 (Affinity Capture-MS), ACBD3 (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ATP11B (Affinity Capture-MS), ATP1B3 (Affinity Capture-MS), ATP6AP1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), ATP6V1A (Affinity Capture-MS), ATP6V1B2 (Affinity Capture-MS), ATP6V1D (Affinity Capture-MS), ATP9A (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS)

ESM2 similar proteins: A1Z7R6, A2AWR3, A4IF94, A4IHK6, A5D7V7, B2RXV4, B2RYH9, O75387, P34711, P42557, P58355, P70187, Q09428, Q0P5V9, Q0VCM6, Q4LE88, Q5BK75, Q5BKX6, Q5F4B8, Q5RBM3, Q5RF58, Q5SR56, Q7Z3Q1, Q866G7, Q8BIV7, Q8BSM7, Q8C0T7, Q8CA03, Q8CGA3, Q8CIA9, Q8HYW2, Q8K0H7, Q8K4S3, Q8N370, Q8NBP5, Q8R3L5, Q96MC6, Q99624, Q99N02, Q9BY10

Diamond homologs: Q866G7, Q8CA03, Q9BY10

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

508 predictions. Top by Δscore:

Variant	Effect	Δscore
9:112886612:CTTTC:C	acceptor_gain	0.9900
9:112886617:C:CC	acceptor_gain	0.9900
9:112889889:A:AC	donor_gain	0.9900
9:112889890:C:CC	donor_gain	0.9900
9:112886526:T:TA	donor_gain	0.9800
9:112887325:CTCA:C	donor_loss	0.9800
9:112887326:T:TA	donor_loss	0.9800
9:112887327:C:CC	donor_loss	0.9800
9:112887328:A:C	donor_loss	0.9800
9:112887410:CGAG:C	acceptor_gain	0.9800
9:112887414:C:CC	acceptor_gain	0.9800
9:112889546:GACT:G	donor_loss	0.9800
9:112889547:AC:A	donor_loss	0.9800
9:112889548:C:G	donor_loss	0.9800
9:112889549:T:TA	donor_loss	0.9800
9:112889550:C:CA	donor_loss	0.9800
9:112889551:A:AC	donor_gain	0.9800
9:112889551:ACCAA:A	donor_loss	0.9800
9:112889552:C:CC	donor_gain	0.9800
9:112879815:CGATG:C	acceptor_gain	0.9700
9:112883385:T:TA	donor_gain	0.9700
9:112886454:TCCTA:T	donor_loss	0.9700
9:112886455:CCTA:C	donor_loss	0.9700
9:112886456:CTACC:C	donor_loss	0.9700
9:112886457:TAC:T	donor_loss	0.9700
9:112886458:ACCT:A	donor_loss	0.9700
9:112886463:A:C	donor_gain	0.9700
9:112886614:TTCCT:T	acceptor_loss	0.9700
9:112886615:TCC:T	acceptor_loss	0.9700
9:112886617:CTGT:C	acceptor_loss	0.9700

AlphaMissense

3032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:112889680:G:C	S334R	0.998
9:112889680:G:T	S334R	0.998
9:112889682:T:G	S334R	0.998
9:112890046:G:C	S212R	0.996
9:112890046:G:T	S212R	0.996
9:112890048:T:G	S212R	0.996
9:112889739:A:G	W315R	0.995
9:112889739:A:T	W315R	0.995
9:112889737:C:A	W315C	0.993
9:112889737:C:G	W315C	0.993
9:112890013:G:C	S223R	0.991
9:112890013:G:T	S223R	0.991
9:112890015:T:G	S223R	0.991
9:112890242:C:T	G147D	0.990
9:112889622:C:A	G354W	0.988
9:112887383:G:C	P387R	0.987
9:112889621:C:T	G354E	0.987
9:112889689:G:C	F331L	0.987
9:112889689:G:T	F331L	0.987
9:112889691:A:G	F331L	0.987
9:112890339:C:G	G115R	0.987
9:112889622:C:G	G354R	0.986
9:112889622:C:T	G354R	0.986
9:112890141:C:G	G181R	0.986
9:112890338:C:T	G115D	0.985
9:112887368:C:G	R392P	0.983
9:112887383:G:T	P387H	0.983
9:112890122:C:T	G187E	0.983
9:112889738:C:G	W315S	0.982
9:112890118:G:C	S188R	0.982

dbSNP variants (sampled 300 via entrez): RS1000474313 (9:112883068 C>T), RS1000529327 (9:112892528 A>C,G), RS1000703755 (9:112888781 T>A), RS1000767641 (9:112890062 A>G,T), RS1001135592 (9:112888526 T>C), RS1001190101 (9:112890178 G>T), RS1001258927 (9:112884970 T>C), RS1001388869 (9:112883751 G>A), RS1001421216 (9:112883366 T>G), RS1002038381 (9:112886514 C>T), RS1002096630 (9:112880510 C>T), RS1002146390 (9:112891413 C>G), RS1002150844 (9:112880128 C>G,T), RS1002653651 (9:112883825 A>G), RS1003330910 (9:112883467 T>A,G)

Disease associations

OMIM: gene MIM:608956 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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 — SLC46 family of folate transporters

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
pirinixic acid	increases activity, affects binding, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
pinostrobin	increases expression	1
bisphenol S	increases methylation	1
Calcitriol	increases expression	1
Diazinon	increases methylation	1
Estradiol	increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Nickel	decreases expression	1
Medroxyprogesterone Acetate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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