SLC38A2

Summary

SLC38A2 (solute carrier family 38 member 2, HGNC:13448) is a protein-coding gene on chromosome 12q13.11, encoding Sodium-coupled neutral amino acid symporter 2 (Q96QD8). Symporter that cotransports neutral amino acids and sodium ions from the extracellular to the intracellular side of the cell membrane.

Enables neutral L-amino acid:sodium symporter activity. Involved in several processes, including cellular response to arsenite(3-); neutral amino acid transport; and positive regulation of RNA splicing. Located in cytoplasm and plasma membrane.

Source: NCBI Gene 54407 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 67 total
• Druggable target: yes
• MANE Select transcript: NM_018976

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13448
Approved symbol	SLC38A2
Name	solute carrier family 38 member 2
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	SAT2, ATA2, KIAA1382, SNAT2
Ensembl gene	ENSG00000134294
Ensembl biotype	protein_coding
OMIM	605180
Entrez	54407

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 9 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000256689, ENST00000546520, ENST00000547252, ENST00000548111, ENST00000548236, ENST00000548785, ENST00000548870, ENST00000549258, ENST00000551374, ENST00000551405, ENST00000552414, ENST00000552703, ENST00000553252, ENST00000612232, ENST00000901221, ENST00000914873, ENST00000914874, ENST00000914875, ENST00000914876, ENST00000951422

RefSeq mRNA: 2 — MANE Select: NM_018976 NM_001307936, NM_018976

CCDS: CCDS76551, CCDS8749

Canonical transcript exons

ENST00000256689 — 16 exons

Exon	Start	End
ENSE00000937138	46358188	46361209
ENSE00002348820	46372509	46372773
ENSE00003459885	46371178	46371379
ENSE00003462033	46363924	46364003
ENSE00003465028	46363726	46363826
ENSE00003473348	46363021	46363145
ENSE00003504608	46366864	46366945
ENSE00003525024	46370776	46370857
ENSE00003550378	46362284	46362381
ENSE00003562108	46367076	46367168
ENSE00003580304	46365107	46365189
ENSE00003587627	46364389	46364556
ENSE00003595318	46370512	46370627
ENSE00003599814	46367267	46367340
ENSE00003624469	46364644	46364702
ENSE00003647111	46362494	46362638

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 352.0841 / max 2988.5743, expressed in 1764 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130624	316.4483	1763
130623	12.9114	1729
130620	6.8183	1603
130625	4.1944	1289
130619	3.6580	1034
130618	1.0581	563
130608	1.0497	634
130617	1.0391	523
130616	0.9281	514
130610	0.8808	541

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.90	gold quality
visceral pleura	UBERON:0002401	99.87	gold quality
parietal pleura	UBERON:0002400	99.85	gold quality
pleura	UBERON:0000977	99.78	gold quality
gingival epithelium	UBERON:0001949	99.76	gold quality
upper leg skin	UBERON:0004262	99.73	gold quality
skin of hip	UBERON:0001554	99.70	gold quality
gingiva	UBERON:0001828	99.70	gold quality
endothelial cell	CL:0000115	99.65	gold quality
germinal epithelium of ovary	UBERON:0001304	99.64	gold quality
lower lobe of lung	UBERON:0008949	99.64	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.53	gold quality
oral cavity	UBERON:0000167	99.52	gold quality
parotid gland	UBERON:0001831	99.50	gold quality
epithelium of nasopharynx	UBERON:0001951	99.50	gold quality
esophagus squamous epithelium	UBERON:0006920	99.50	gold quality
superficial temporal artery	UBERON:0001614	99.49	gold quality
upper arm skin	UBERON:0004263	99.48	gold quality
mammalian vulva	UBERON:0000997	99.46	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.46	gold quality
trigeminal ganglion	UBERON:0001675	99.35	gold quality
penis	UBERON:0000989	99.34	gold quality
trabecular bone tissue	UBERON:0002483	99.33	gold quality
renal medulla	UBERON:0000362	99.31	gold quality
cauda epididymis	UBERON:0004360	99.28	gold quality
nipple	UBERON:0002030	99.26	gold quality
seminal vesicle	UBERON:0000998	99.25	gold quality
biceps brachii	UBERON:0001507	99.24	gold quality
dorsal root ganglion	UBERON:0000044	99.23	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-106540	yes	1124.50
E-CURD-119	yes	9.26
E-MTAB-8410	yes	8.61
E-GEOD-81547	yes	8.59
E-MTAB-9388	yes	7.78
E-GEOD-84465	yes	7.34
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, DDIT3, DNMT1, ESR1

miRNA regulators (miRDB)

293 targeting SLC38A2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
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-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821

Literature-anchored findings (GeneRIF, showing 38)

• SNAT2 amino acid response element, along with a nearby conserved CAAT box, has enhancer activity and it confers regulated transcription to a heterologous promoter (PMID:14623874)
• The synthesis of SNAT2 is required for the hypertonic stimulation of system A transport activity. (PMID:15581851)
• Up-regulation of SNAT2 is essential for the rapid restoration of cell volume after hypertonic stress. (PMID:15922329)
• Amino acid depletion was associated with an up-regulation of amino acid transport system A activity, largely mediated through an enhancement of SNAT2 expression at both the protein and mRNA level in BeWo cells. (PMID:16125834)
• deficient in the amino acid response pathway exhibited little or no induction of SNAT2 mRNA (PMID:16445384)
• The strong expression of Na(+)-coupled neutral amino acid transporter 2 in the somato-dendritic compartment and in non-neuronal elements that are integral parts of the blood-brain and brain-cerebrospinal fluid barrier. (PMID:16616430)
• SNAT2 expression can be modulated by specific signaling pathways in response to different stresses (PMID:16621798)
• Results suggest that cortisol may be involved in upregulation of system A (SNAT2)in the placenta to ensure sufficient amino acid supply to the developing fetus. (PMID:16621896)
• Therefore, we can speculate that such anion-conducting pathways are general features of Na+-transporting systems. (PMID:17237199)
• Despite increased ATF4 binding at the C/EBP-ATF composite site following activation of the unfolded protein response, system A transporter 2 (SNAT2) transcription activity is repressed (PMID:18697751)
• Report SNAT2 activity in fetal T lymphocytes in intrauterine growth restriction and with tumor necrosis factor-alpha treatment. (PMID:18703994)
• analysis of a conserved Na(+) binding site of the sodium-coupled neutral amino acid transporter 2 (PMID:19589777)
• we have identified a novel regulatory pathway involving increased gene expression of the SNAT2 isoform mediated by a STAT-dependent pathway, which links IL-6 to increased activity of amino acid transporter system A (PMID:19741197)
• Lower placental system A activity in women who reported strenuous exercise and had a lower arm muscle area may reflect an adaptation in placental function which protects maternal resources in those with lower nutrient reserves. (PMID:20206993)
• Proteomic analysis of TAP-tag purified SNAT2 fusion proteins identified two novel SNAT2-interacting proteins that may potentially function in conjunction with SNAT2 transceptor to regulate signalling pathways influencing protein turnover and cell growth (PMID:21622135)
• findings show methylation status of rRNA differentially influenced the mechanism of 80S complex formation on IRES elements from SNAT2)versus the hepatitis C virus mRNA (PMID:21930789)
• Placental mRNA expression of system A transporter isoforms SLC38A1 and -2 was lower in teenagers than in adults which may underlie their susceptibility to delivering small-for-gestational-age infants. (PMID:22028413)
• SLC38A1 and SLC38A2 transcript levels are altered in placental malaria with intervillositis. (PMID:23408887)
• SNAT2 mRNA levels were significantly decreased in intrauterine growth-restricted placentas with reduced umbilical blood flows. (PMID:23728383)
• Increased availability of unsaturated fatty acids can compromise the stress-induced induction/adaptation in SNAT2 expression. (PMID:25653282)
• GADD34 promotes cell survival and adaptation to increased extracellular osmolarity by increasing the uptake of small neutral amino acids via the amino acid transporter SNAT2. (PMID:26041779)
• Decreased placental mTOR activity causes down-regulation of placental system A activity by shifting SNAT-2 trafficking towards proteasomal degradation, thereby contributing to decreased fetal amino acid availability and restricted fetal growth in IUGR. (PMID:26374858)
• Propose regulation of placental SNAT2/LAT1 ubiquitination by mTORC1 and Nedd4-2. (PMID:26608079)
• In the absence of SLC1A5 there is a crucial role of SNAT1 in supplying glutamine for glutaminolysis with SNAT2 acting as a “backup” for glutamine transport. (PMID:27129276)
• there is a disulfide bond between Cys245 and Cys279 in SNAT2 which has no effect on cell surface trafficking, as well as transporter function (PMID:27355203)
• nutrient ingestion during repeated 30-s bouts of sprint exercise induces expression of the amino acid transporter SNAT2 and stimulates Akt/mTOR signaling and most likely the rate of muscle protein synthesis (PMID:28860165)
• findings show a switch in the regulation of SNAT2 between ERalpha and HIF-1alpha, leading to endocrine resistance in hypoxia (PMID:31152137)
• We describe how Slc38a2 senses amino acid availability and passes this onto intracellular signaling pathways and how it regulates protein synthesis, cellular proliferation and apoptosis through the mechanistic (mammalian) target of rapamycin (mTOR) and general control nonderepressible 2 (GCN2) pathways–{REVIEW} (PMID:31574264)
• Functional Consequences of Low Activity of Transport System A for Neutral Amino Acids in Human Bone Marrow Mesenchymal Stem Cells. (PMID:32164327)
• SLC38A2 Overexpression Induces a Cancer-like Metabolic Profile and Cooperates with SLC1A5 in Pan-cancer Prognosis. (PMID:32996252)
• Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer. (PMID:33028955)
• SNAT2/SLC38A2 Confers the Stemness of Gastric Cancer Cells via Regulating Glutamine Level. (PMID:34173116)
• LAT1 and SNAT2 Protein Expression and Membrane Localization of LAT1 Are Not Acutely Altered by Dietary Amino Acids or Resistance Exercise Nor Positively Associated with Leucine or Phenylalanine Incorporation in Human Skeletal Muscle. (PMID:34836160)
• Comprehensive analysis of the biological function and immune infiltration of SLC38A2 in gastric cancer. (PMID:36918802)
• Hsa_circRNA_001859 regulates pancreatic cancer progression and epithelial-mesenchymal transition through the miR-21-5p/SLC38A2 pathway. (PMID:37005877)
• Single-cell RNA sequencing reveals XBP1-SLC38A2 axis as a metabolic regulator in cytotoxic T lymphocytes in multiple myeloma. (PMID:37054944)
• CHOP upregulation and dysregulation of the mature form of the SNAT2 amino acid transporter in the placentas from small for gestational age newborns. (PMID:37957724)
• UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer. (PMID:38949026)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc38a2	ENSDARG00000045886
mus_musculus	Slc38a2	ENSMUSG00000022462
rattus_norvegicus	Slc38a2	ENSRNOG00000006305
drosophila_melanogaster	CG16700	FBGN0030816
drosophila_melanogaster	CG4991	FBGN0030817
drosophila_melanogaster	CG13384	FBGN0032036
drosophila_melanogaster	polyph	FBGN0033572
drosophila_melanogaster	VGAT	FBGN0033911
drosophila_melanogaster	acs	FBGN0035300
drosophila_melanogaster	CG7888	FBGN0036116
drosophila_melanogaster	CG32079	FBGN0052079
drosophila_melanogaster	CG32081	FBGN0052081
drosophila_melanogaster	mah	FBGN0285912
caenorhabditis_elegans		WBGENE00006783
caenorhabditis_elegans	slc-36.4	WBGENE00010421
caenorhabditis_elegans	Y18D10A.23	WBGENE00012487
caenorhabditis_elegans		WBGENE00012629
caenorhabditis_elegans		WBGENE00012804
caenorhabditis_elegans		WBGENE00019837
caenorhabditis_elegans		WBGENE00020837

Paralogs (15): SLC38A5 (ENSG00000017483), SLC32A1 (ENSG00000101438), SLC38A7 (ENSG00000103042), SLC38A1 (ENSG00000111371), SLC36A1 (ENSG00000123643), SLC38A4 (ENSG00000139209), SLC38A6 (ENSG00000139974), SLC38A10 (ENSG00000157637), SLC38A8 (ENSG00000166558), SLC38A11 (ENSG00000169507), SLC38A9 (ENSG00000177058), SLC36A4 (ENSG00000180773), SLC36A3 (ENSG00000186334), SLC36A2 (ENSG00000186335), SLC38A3 (ENSG00000188338)

Protein

Protein identifiers

Sodium-coupled neutral amino acid symporter 2 — Q96QD8 (reviewed: Q96QD8)

Alternative names: Amino acid transporter A2, Protein 40-9-1, Solute carrier family 38 member 2, System A amino acid transporter 2, System A transporter 1, System N amino acid transporter 2

All UniProt accessions (3): Q96QD8, F8VQW8, F8VUY8

UniProt curated annotations — full annotation on UniProt →

Function. Symporter that cotransports neutral amino acids and sodium ions from the extracellular to the intracellular side of the cell membrane. The transport is pH-sensitive, Li(+)-intolerant, electrogenic, driven by the Na(+) electrochemical gradient and cotransports of neutral amino acids and sodium ions with a stoichiometry of 1:1. May function in the transport of amino acids at the blood-brain barrier. May function in the transport of amino acids in the supply of maternal nutrients to the fetus through the placenta. Maintains a key metabolic glutamine/glutamate balance underpinning retrograde signaling by dendritic release of the neurotransmitter glutamate. Transports L-proline in differentiating osteoblasts for the efficient synthesis of proline-enriched proteins and provides proline essential for osteoblast differentiation and bone formation during bone development.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitously expressed. Expressed in neocortex. Widely expressed in the central nervous system with higher concentrations in caudal regions. Expressed by glutamatergic and GABAergic neurons together with astrocytes and other non-neuronal cells in the cerebral cortex (at protein level).

Post-translational modifications. Polyubiquitination by NEDD4L regulates the degradation and the activity of SLC38A2.

Activity regulation. Inhibited by N-methyl-D-glucamine. Inhibited by choline. Allosteric regulation of sodium ions binding by pH.

Domain organisation. The extracellular C-terminal domain controls the voltage dependence for amino acid transports activity.

Induction. Up-regulated upon amino acid deprivation. Up-regulated upon hypertonic conditions.

Similarity. Belongs to the amino acid/polyamine transporter 2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96QD8-1	1	yes
Q96QD8-2	2

RefSeq proteins (2): NP_001294865, NP_061849* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013057	AA_transpt_TM	Domain

Pfam: PF01490

Catalyzed reactions (Rhea), 11 shown:

• L-proline(in) + Na(+)(in) = L-proline(out) + Na(+)(out) (RHEA:28967)
• L-leucine(in) + Na(+)(in) = L-leucine(out) + Na(+)(out) (RHEA:29263)
• L-alanine(in) + Na(+)(in) = L-alanine(out) + Na(+)(out) (RHEA:29283)
• L-serine(in) + Na(+)(in) = L-serine(out) + Na(+)(out) (RHEA:29575)
• glycine(in) + Na(+)(in) = glycine(out) + Na(+)(out) (RHEA:68228)
• L-glutamine(in) + Na(+)(in) = L-glutamine(out) + Na(+)(out) (RHEA:68236)
• L-methionine(in) + Na(+)(in) = L-methionine(out) + Na(+)(out) (RHEA:68240)
• L-phenylalanine(in) + Na(+)(in) = L-phenylalanine(out) + Na(+)(out) (RHEA:68244)
• L-threonine(in) + Na(+)(in) = L-threonine(out) + Na(+)(out) (RHEA:69999)
• L-asparagine(in) + Na(+)(in) = L-asparagine(out) + Na(+)(out) (RHEA:71383)
• L-histidine(in) + Na(+)(in) = L-histidine(out) + Na(+)(out) (RHEA:71583)

UniProt features (41 total): topological domain 12, transmembrane region 11, modified residue 5, region of interest 2, binding site 2, glycosylation site 2, splice variant 2, sequence conflict 2, chain 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QD8-F1	79.11	0.53

Functional residue map

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

Ligand- & substrate-binding residues (2): 82; 386

Post-translational modifications (5): 10, 12, 21, 22, 55

Disulfide bonds (1): 245–281

Glycosylation sites (2): 258, 274

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-210500	Glutamate Neurotransmitter Release Cycle
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 510 (showing top): AP1_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_GLUTAMATE_SECRETION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, FISCHER_G1_S_CELL_CYCLE, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, MODULE_511, GOBP_NEUROTRANSMITTER_TRANSPORT, MITSIADES_RESPONSE_TO_APLIDIN_DN, CREBP1_Q2

GO Biological Process (29): amino acid transmembrane transport (GO:0003333), neurotransmitter transport (GO:0006836), amino acid transport (GO:0006865), L-glutamine transport (GO:0006868), female pregnancy (GO:0007565), positive regulation of gene expression (GO:0010628), response to muscle activity (GO:0014850), neutral amino acid transport (GO:0015804), proline transport (GO:0015824), L-serine transport (GO:0015825), cerebral cortex development (GO:0021987), glycine betaine transport (GO:0031460), alanine transport (GO:0032328), positive regulation of RNA splicing (GO:0033120), cellular response to amino acid starvation (GO:0034198), amino acid import (GO:0043090), cellular response to mechanical stimulus (GO:0071260), regulation of cellular response to stress (GO:0080135), transport across blood-brain barrier (GO:0150104), regulation of glutamate secretion, neurotransmission (GO:1903294), L-glutamine import across plasma membrane (GO:1903803), L-serine import across plasma membrane (GO:1903812), cellular response to arsenite(3-) (GO:1903841), L-proline import across plasma membrane (GO:1904271), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), acidic amino acid transport (GO:0015800), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085)

GO Molecular Function (11): amino acid:sodium symporter activity (GO:0005283), neutral L-amino acid:sodium symporter activity (GO:0005295), proline:sodium symporter activity (GO:0005298), amino acid transmembrane transporter activity (GO:0015171), acidic amino acid transmembrane transporter activity (GO:0015172), L-glutamine transmembrane transporter activity (GO:0015186), L-serine transmembrane transporter activity (GO:0015194), alanine:sodium symporter activity (GO:0015655), protein binding (GO:0005515), neutral L-amino acid transmembrane transporter activity (GO:0015175), symporter activity (GO:0015293)

GO Cellular Component (8): cytoplasm (GO:0005737), plasma membrane (GO:0005886), brush border (GO:0005903), axon (GO:0030424), dendrite (GO:0030425), sarcolemma (GO:0042383), neuronal cell body (GO:0043025), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Neurotransmitter release cycle	1
SLC-mediated transport of amino acids	1
Transmission across Chemical Synapses	1
Neuronal System	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neutral amino acid transport	4
amino acid transport	3
L-amino acid transport	3
amino acid:sodium symporter activity	3
transport	2
neutral L-amino acid transmembrane transporter activity	2
organic acid:sodium symporter activity	2
amino acid transmembrane transporter activity	2
L-amino acid transmembrane transporter activity	2
cellular anatomical structure	2
neuron projection	2
transmembrane transport	1
multi-organism reproductive process	1
multi-multicellular organism process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
response to activity	1
serine transport	1
pallium development	1
anatomical structure development	1
amino-acid betaine transport	1
carboxylic acid transport	1
nitrogen compound transport	1
RNA splicing	1
positive regulation of gene expression	1
regulation of RNA splicing	1
cellular response to starvation	1
response to amino acid starvation	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
cellular response to stress	1
regulation of cellular process	1
regulation of response to stress	1
vascular transport	1
regulation of glutamate secretion	1
regulation of neurotransmitter secretion	1
regulation of synaptic transmission, glutamatergic	1
glutamate secretion, neurotransmission	1

Protein interactions and networks

STRING

1832 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC38A2	SLC1A5	Q15758	790
SLC38A2	SLC7A5	Q01650	768
SLC38A2	SCN11A	Q9UI33	765
SLC38A2	PBX2	P40425	760
SLC38A2	AANAT	Q16613	720
SLC38A2	SLC3A2	P08195	705
SLC38A2	SLC7A6	Q92536	682
SLC38A2	SLC7A8	Q9UHI5	671
SLC38A2	SLC36A1	Q7Z2H8	655
SLC38A2	SLC38A9	Q8NBW4	651
SLC38A2	SLC2A1	P11166	647
SLC38A2	SLC43A2	Q8N370	641
SLC38A2	SLC1A4	P43007	632
SLC38A2	SLC7A1	P30825	629
SLC38A2	SLC1A1	P43005	629

IntAct

68 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RNF5	SLC1A5	psi-mi:“MI:0914”(association)	0.580
RNF5	SLC38A2	psi-mi:“MI:0915”(physical association)	0.580
SLC38A2	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
TMEM237	SLC38A2	psi-mi:“MI:0915”(physical association)	0.560
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
TEX29	TOR1A	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
ATP5F1B	SCAMP2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
Tuba3a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
CDC42	BBX	psi-mi:“MI:0914”(association)	0.350
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Rab5c		psi-mi:“MI:0914”(association)	0.350
GJB2	SNX3	psi-mi:“MI:0914”(association)	0.350
ATP6AP2	TMUB1	psi-mi:“MI:0914”(association)	0.350
Chmp4b		psi-mi:“MI:0914”(association)	0.350
KIF20B	ACSL3	psi-mi:“MI:0914”(association)	0.350
Tmed2		psi-mi:“MI:0914”(association)	0.350
Tgs1	EFCAB5	psi-mi:“MI:0914”(association)	0.350
CHMP4B	ELOC	psi-mi:“MI:0914”(association)	0.350
TMEM63B	CAV1	psi-mi:“MI:0914”(association)	0.350
GOLT1B		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
K8.1	EXOC5	psi-mi:“MI:0914”(association)	0.350
OCRL	MYO1C	psi-mi:“MI:0914”(association)	0.350
TSPAN5	KLHL2	psi-mi:“MI:0914”(association)	0.350
LPAR6	DEGS1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (208): SLC38A2 (Affinity Capture-RNA), SLC38A2 (Proximity Label-MS), SLC38A2 (Proximity Label-MS), SLC38A2 (Proximity Label-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS), SLC38A2 (Affinity Capture-MS)

ESM2 similar proteins: A1YG32, A2VCW5, A2VE31, D3Z813, F4KBM7, G3UVW3, O80668, P38176, P39981, P40074, P40501, P47082, Q08AI6, Q0WQJ3, Q17598, Q19425, Q28HE5, Q28I47, Q3U1J0, Q3USY0, Q503G8, Q54S12, Q5E9S9, Q5EA97, Q5F468, Q5R443, Q5RE87, Q5SPB1, Q5XH90, Q610N4, Q6DEL1, Q6DFE7, Q6WWW3, Q8CFE6, Q8HXI3, Q8IZM9, Q8K2P7, Q8R1S9, Q8WUX1, Q969I6

Diamond homologs: A1YG32, A2VCW5, A2VE31, G3UVW3, Q28HE5, Q3U1J0, Q503G8, Q5E9S9, Q5F468, Q5R443, Q5RE87, Q5SPB1, Q5XH90, Q6WWW3, Q8CFE6, Q8IZM9, Q8K2P7, Q8R1S9, Q8WUX1, Q969I6, Q96QD8, Q99624, Q9DCP2, Q9EQ25, Q9H2H9, Q9JHE5, Q9JHZ9, Q9JM15, F4J1Q9, A6NNN8, Q5HZH7, Q9LXF8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SLC38A2	“up-regulates quantity”	“L-glutamine zwitterion”	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHOJ GTPase cycle	6	22.3×	3e-05
RHOQ GTPase cycle	6	20.1×	3e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	14.3×	4e-04
RAC3 GTPase cycle	6	13.2×	2e-04
RAC1 GTPase cycle	7	7.9×	4e-04
CDC42 GTPase cycle	5	6.7×	5e-03
Membrane Trafficking	8	5.5×	9e-04
Vesicle-mediated transport	8	5.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein transport	10	6.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2821 predictions. Top by Δscore:

Variant	Effect	Δscore
12:46361205:AAAGC:A	acceptor_gain	1.0000
12:46361206:AAGC:A	acceptor_gain	1.0000
12:46361207:AGC:A	acceptor_gain	1.0000
12:46361207:AGCC:A	acceptor_loss	1.0000
12:46361210:C:CA	acceptor_loss	1.0000
12:46361210:C:CC	acceptor_gain	1.0000
12:46361211:T:A	acceptor_loss	1.0000
12:46362277:CACT:C	donor_loss	1.0000
12:46362278:ACTC:A	donor_loss	1.0000
12:46362279:CT:C	donor_loss	1.0000
12:46362282:A:AC	donor_gain	1.0000
12:46362282:A:T	donor_loss	1.0000
12:46362282:AC:A	donor_gain	1.0000
12:46362282:ACC:A	donor_gain	1.0000
12:46362283:C:CC	donor_gain	1.0000
12:46362283:CC:C	donor_gain	1.0000
12:46362283:CCC:C	donor_gain	1.0000
12:46362283:CCCCA:C	donor_gain	1.0000
12:46362378:GCACC:G	acceptor_loss	1.0000
12:46362382:C:T	acceptor_loss	1.0000
12:46362383:T:G	acceptor_loss	1.0000
12:46363014:TAC:T	donor_loss	1.0000
12:46363015:ACT:A	donor_loss	1.0000
12:46363016:CT:C	donor_loss	1.0000
12:46363017:TT:T	donor_loss	1.0000
12:46363018:TACT:T	donor_loss	1.0000
12:46363019:A:AC	donor_gain	1.0000
12:46363019:A:T	donor_loss	1.0000
12:46363020:C:CC	donor_gain	1.0000
12:46363020:CTGG:C	donor_gain	1.0000

AlphaMissense

3300 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:46363930:A:G	L316P	0.999
12:46367293:A:G	L121P	0.998
12:46370527:C:A	G100V	0.998
12:46370565:A:C	S87R	0.998
12:46370565:A:T	S87R	0.998
12:46370567:T:G	S87R	0.998
12:46366935:G:C	S164R	0.997
12:46366935:G:T	S164R	0.997
12:46366937:T:G	S164R	0.997
12:46370527:C:T	G100E	0.997
12:46370570:C:G	G86R	0.997
12:46370587:A:G	L80P	0.997
12:46362345:G:C	P454R	0.996
12:46362345:G:T	P454H	0.996
12:46363730:A:C	F350L	0.996
12:46363730:A:T	F350L	0.996
12:46363732:A:G	F350L	0.996
12:46364683:A:C	S222R	0.996
12:46364683:A:T	S222R	0.996
12:46364685:T:G	S222R	0.996
12:46367279:C:G	A126P	0.996
12:46367290:A:G	L122P	0.996
12:46370569:C:T	G86D	0.996
12:46363974:A:C	F301L	0.995
12:46363974:A:T	F301L	0.995
12:46363976:A:G	F301L	0.995
12:46361187:C:T	G482D	0.994
12:46361188:C:G	G482R	0.994
12:46362634:C:G	R395P	0.994
12:46363037:G:C	P388R	0.994

dbSNP variants (sampled 300 via entrez): RS1000065282 (12:46373207 T>C), RS1000112554 (12:46368338 G>A), RS1000144932 (12:46372697 G>A), RS1000214182 (12:46373784 C>G,T), RS1000519888 (12:46372440 C>A,T), RS1000739037 (12:46369801 C>G), RS1000792105 (12:46374575 G>C), RS1000845180 (12:46366619 G>A), RS1000864776 (12:46359181 C>G,T), RS1001388368 (12:46358614 A>G), RS1001769228 (12:46372171 A>T), RS1002039487 (12:46370073 A>C), RS1002153784 (12:46370305 C>T), RS1002225417 (12:46371553 C>T), RS1002801934 (12:46360510 G>C,T)

Disease associations

OMIM: gene MIM:605180 | 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
GCST006988_112	Blond vs. brown/black hair color	2.000000e-09
GCST009158_35	Uterine fibroids	2.000000e-18
GCST010796_3580	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-11
GCST010796_3581	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST90000025_962	Appendicular lean mass	2.000000e-25

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color
EFO:0004327	electrocardiography
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066238 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — System A-like transporters

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Air Pollutants	decreases expression, affects cotreatment, affects expression, increases abundance	3
Benzene	increases expression	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	3
arsenite	affects binding, decreases reaction, increases expression, increases phosphorylation, increases splicing	2
perfluorooctane sulfonic acid	increases expression, decreases expression	2
Arsenic	decreases expression, increases abundance, affects cotreatment, affects expression	2
Estradiol	increases expression, affects expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
bufotalin	increases expression	1
ethylbenzene	increases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
bisphenol A	affects expression	1
trichostatin A	decreases reaction, affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
2-xylene	increases expression	1
ferrous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, affects expression, increases abundance	1
pinosylvin	increases expression	1
celastrol	decreases expression	1
arsenic disulfide	increases expression	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5540568	Binding	Inhibition of SNAT2 (unknown origin) overexpressed in HEK293 cells assessed as reduction in [13C]-Gln uptake preincubated for 5 mins followed by substrate addition and measured after 15 mins	Discovery of Novel Aminobutanoic Acid-Based ASCT2 Inhibitors for the Treatment of Non-Small-Cell Lung Cancer. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4N2	HCT116-SLC38A2-KO-c1	Cancer cell line	Male
CVCL_D4N3	HCT116-SLC38A2-KO-c3	Cancer cell line	Male
CVCL_TN42	HAP1 SLC38A2 (-) 1	Cancer cell line	Male
CVCL_TN43	HAP1 SLC38A2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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