SLC38A1

Summary

SLC38A1 (solute carrier family 38 member 1, HGNC:13447) is a protein-coding gene on chromosome 12q13.11, encoding Sodium-coupled neutral amino acid symporter 1 (Q9H2H9). Symporter that cotransports short-chain neutral amino acids and sodium ions from the extracellular to the intracellular side of the cell membrane.

Amino acid transporters play essential roles in the uptake of nutrients, production of energy, chemical metabolism, detoxification, and neurotransmitter cycling. SLC38A1 is an important transporter of glutamine, an intermediate in the detoxification of ammonia and the production of urea. Glutamine serves as a precursor for the synaptic transmitter, glutamate (Gu et al., 2001 [PubMed 11325958]).

Source: NCBI Gene 81539 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 76
• Clinical variants (ClinVar): 142 total
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_030674

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13447
Approved symbol	SLC38A1
Name	solute carrier family 38 member 1
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	ATA1, NAT2, SAT1, SNAT1
Ensembl gene	ENSG00000111371
Ensembl biotype	protein_coding
OMIM	608490
Entrez	81539

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 36 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000398637, ENST00000439706, ENST00000546519, ENST00000546893, ENST00000548979, ENST00000549049, ENST00000549633, ENST00000550173, ENST00000551506, ENST00000552197, ENST00000612161, ENST00000851697, ENST00000851698, ENST00000851699, ENST00000851700, ENST00000851701, ENST00000851702, ENST00000851703, ENST00000851704, ENST00000851705, ENST00000851706, ENST00000851707, ENST00000851708, ENST00000851709, ENST00000851710, ENST00000851711, ENST00000851712, ENST00000851713, ENST00000851714, ENST00000851715, ENST00000851716, ENST00000851717, ENST00000922815, ENST00000922816, ENST00000922817, ENST00000922818, ENST00000922819, ENST00000922820, ENST00000955604, ENST00000955605

RefSeq mRNA: 6 — MANE Select: NM_030674 NM_001077484, NM_001278387, NM_001278388, NM_001278389, NM_001278390, NM_030674

CCDS: CCDS41774, CCDS61106

Canonical transcript exons

ENST00000398637 — 17 exons

Exon	Start	End
ENSE00000887986	46197919	46198060
ENSE00000914027	46239679	46239893
ENSE00001223014	46198625	46198743
ENSE00001534088	46183063	46189071
ENSE00001534097	46197720	46197817
ENSE00001534247	46243200	46243314
ENSE00002253932	46268526	46269043
ENSE00003477333	46207155	46207236
ENSE00003575457	46204532	46204590
ENSE00003594251	46229564	46229639
ENSE00003598792	46201098	46201198
ENSE00003603327	46204301	46204417
ENSE00003603917	46229153	46229268
ENSE00003619807	46209054	46209127
ENSE00003636986	46203010	46203089
ENSE00003670288	46207529	46207621
ENSE00003691673	46206080	46206162

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.5604 / max 701.7617, expressed in 1744 samples.

FANTOM5 promoters (26 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130600	20.6024	1640
130595	12.1656	1613
130592	5.3256	1309
130601	5.2500	1362
130599	4.7808	1142
130593	3.6905	1236
130594	3.6426	1192
130596	3.0580	1311
130602	2.9801	1179
130603	1.9299	977

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.06	gold quality
seminal vesicle	UBERON:0000998	98.53	gold quality
superficial temporal artery	UBERON:0001614	98.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.24	gold quality
middle temporal gyrus	UBERON:0002771	98.16	gold quality
colonic mucosa	UBERON:0000317	97.98	gold quality
substantia nigra pars compacta	UBERON:0001965	97.76	gold quality
body of tongue	UBERON:0011876	97.75	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.74	gold quality
cortical plate	UBERON:0005343	97.68	gold quality
cerebellar vermis	UBERON:0004720	97.65	gold quality
lateral globus pallidus	UBERON:0002476	97.56	gold quality
heart right ventricle	UBERON:0002080	97.51	gold quality
postcentral gyrus	UBERON:0002581	97.47	gold quality
pons	UBERON:0000988	97.45	gold quality
superior surface of tongue	UBERON:0007371	97.42	gold quality
superior vestibular nucleus	UBERON:0007227	97.40	gold quality
medulla oblongata	UBERON:0001896	97.13	gold quality
tongue	UBERON:0001723	97.11	gold quality
germinal epithelium of ovary	UBERON:0001304	97.10	gold quality
penis	UBERON:0000989	97.07	gold quality
parietal lobe	UBERON:0001872	97.05	gold quality
epithelium of nasopharynx	UBERON:0001951	97.05	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.01	gold quality
nipple	UBERON:0002030	96.68	gold quality
endothelial cell	CL:0000115	96.57	gold quality
oral cavity	UBERON:0000167	96.56	gold quality
left ventricle myocardium	UBERON:0006566	96.46	gold quality
entorhinal cortex	UBERON:0002728	96.22	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.21	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1606.78
E-MTAB-11121	yes	1114.37
E-MTAB-3929	yes	327.09
E-MTAB-5061	yes	310.61
E-GEOD-81608	yes	220.70
E-MTAB-7316	yes	42.97
E-MTAB-6678	yes	27.11
E-CURD-119	yes	26.90
E-GEOD-135922	yes	25.31
E-HCAD-10	yes	17.57
E-MTAB-7249	yes	11.10
E-MTAB-9388	yes	7.16
E-ENAD-27	yes	6.20
E-CURD-112	yes	5.28
E-GEOD-150728	no	761.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, JUN, NR1I2

miRNA regulators (miRDB)

248 targeting SLC38A1, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-146A-5P	99.96	68.93	988

Literature-anchored findings (GeneRIF, showing 21)

• Theses data demonstrate the physiological importance of ATA1 in hepatocarcinogenesis. (PMID:17549407)
• Report SNAT1 activity in fetal T lymphocytes in intrauterine growth restriction and with tumor necrosis factor-alpha treatment. (PMID:18703994)
• A possible association between low expression of SNAT1 and suicidal behavior is suggested. (PMID:19442705)
• The results of this study provided that RAB2A and SLC38A1, were associated with the density of calbindin-positive neurons and the number of perineuronal oligodendrocytes in psychiatric disorders. (PMID:20308991)
• SNAT1 is a key contributor to system A activity at term. (PMID:20599747)
• Increased expression of ATA1 is frequent in human hilar cholangiocarcinoma and significantly correlated with the progression of cholangiocarcinoma, suggesting the importance of ATA1 in cancer development and progression. (PMID:20605601)
• results suggest that slc38a1 may play a role in the mechanisms underlying the determination of cellular viability in astrocytes through modulation of intracellular ROS generation (PMID:21219957)
• SLC38A1 and SLC38A2 transcript levels are altered in placental malaria with intervillositis. (PMID:23408887)
• The cross-talk between Akt signaling and SNAT1 might play a critical role in the development and progression of breast cancer (PMID:23848995)
• The SLC38A1 protein was very low or undetectable in healthy gastric mucosa but strong staining of SLC38A1 protein was found in the cytoplasm in more than half of gastric cancer samples. SLC38A1 knockdown decreased tumor cell proliferation and migration. (PMID:24712400)
• High SNAT1 expression is associated with increased cell migration in breast neoplasms. (PMID:27048259)
• 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)
• this study indicates that inhibition of miRNA-593-3p by insulin promotes glucose metabolism through the regulation of Slc38a1 and CLIP3 expression, and provides a new insight into the role and mechanism of insulin-induced glycolysis. (PMID:27613819)
• Results found that SLC38A1 was up-regulated in colorectal cancer cells (CRC) and significantly associated with tumor invasion and advanced disease stage. Its overexpression enhanced growth and migration of HCT116 cells providing evidence that activation of SLC38A1 may play a critical role in CRC development and progression. (PMID:28224429)
• revealed SLC38A1 as a valuable prognostic and predictive marker for acute myeloid leukemia (PMID:31344987)
• Functional Consequences of Low Activity of Transport System A for Neutral Amino Acids in Human Bone Marrow Mesenchymal Stem Cells. (PMID:32164327)
• CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR-485-5p/SLC38A1 axis. (PMID:33769559)
• miRNA-432 and SLC38A1 as Predictors of Hepatocellular Carcinoma Complicated with Alcoholic Steatohepatitis. (PMID:35663198)
• CENPA promotes glutamine metabolism and tumor progression by up-regulating SLC38A1 in endometrial cancer. (PMID:38382691)
• OTUD5 promotes the growth of hepatocellular carcinoma by deubiquitinating and stabilizing SLC38A1. (PMID:38658981)
• METTL3-mediated m[6]A methylation of SLC38A1 stimulates cervical cancer growth. (PMID:38701556)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc38a1	ENSMUSG00000023169
rattus_norvegicus	Slc38a1	ENSRNOG00000005291
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), SLC36A1 (ENSG00000123643), SLC38A2 (ENSG00000134294), 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 1 — Q9H2H9 (reviewed: Q9H2H9)

Alternative names: Amino acid transporter A1, N-system amino acid transporter 2, Solute carrier family 38 member 1, System A amino acid transporter 1, System N amino acid transporter 1

All UniProt accessions (3): Q9H2H9, F8VX04, F8VX12

UniProt curated annotations — full annotation on UniProt →

Function. Symporter that cotransports short-chain neutral amino acids and sodium ions from the extracellular to the intracellular side of the cell membrane. The transport is elctrogenic, pH dependent and driven by the Na(+) electrochemical gradient. Participates in the astroglia-derived glutamine transport into GABAergic interneurons for neurotransmitter GABA de novo synthesis. May also contributes to amino acid transport in placental trophoblasts. Also regulates synaptic plasticity.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the cerebral cortex by pyramidal and GABAergic neurons, astrocytes and other non-neuronal cells (at protein level). Expressed in placenta, heart, lung, skeletal muscle, spleen, stomach and testis. Highly expressed in cytotrophoblast cells from term placenta.

Post-translational modifications. N-glycosylation plays an important role in the L-glutamine transport.

Activity regulation. Inhibited by alpha-(methylamino)isobutyric acid (MeAIB). Inhibited by lithium, potassium, choline ions, N-methylglucamine. The pH dependence has an allosteric effect on the transport.

Induction. Down-regulated by bacterial lipopolysaccharides (LPS) in glial cells. Down-regulated upon hypoxia.

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

RefSeq proteins (6): NP_001070952, NP_001265316, NP_001265317, NP_001265318, NP_001265319, NP_109599* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013057	AA_transpt_TM	Domain

Pfam: PF01490

Catalyzed reactions (Rhea), 10 shown:

• L-proline(in) + Na(+)(in) = L-proline(out) + Na(+)(out) (RHEA:28967)
• 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-cysteine(in) + Na(+)(in) = L-cysteine(out) + Na(+)(out) (RHEA:68232)
• 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-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 (39 total): topological domain 12, transmembrane region 11, modified residue 8, sequence conflict 4, glycosylation site 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2H9-F1	79.81	0.45

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 (8): 6, 11, 25, 28, 49, 52, 54, 56

Disulfide bonds (1): 245–264

Glycosylation sites (2): 251, 257

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-210455	Astrocytic Glutamate-Glutamine Uptake And Metabolism
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-112313	Neurotransmitter uptake and metabolism In glial cells
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: 1025 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, E2F_Q4, VERHAAK_AML_WITH_NPM1_MUTATED_DN, E2F_Q4_01, RRAGTTGT_UNKNOWN, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, LEE_NEURAL_CREST_STEM_CELL_DN, REACTOME_BIOLOGICAL_OXIDATIONS, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, MCLACHLAN_DENTAL_CARIES_UP, XU_HGF_TARGETS_REPRESSED_BY_AKT1_UP, HARRIS_HYPOXIA, GOBP_CIRCULATORY_SYSTEM_PROCESS

GO Biological Process (18): neurotransmitter uptake (GO:0001504), amino acid transmembrane transport (GO:0003333), amino acid transport (GO:0006865), L-glutamine transport (GO:0006868), female pregnancy (GO:0007565), GABA biosynthetic process (GO:0009449), neutral amino acid transport (GO:0015804), regulation of synaptic transmission, GABAergic (GO:0032228), amino acid import (GO:0043090), regulation of synaptic plasticity (GO:0048167), transport across blood-brain barrier (GO:0150104), L-alpha-amino acid transmembrane transport (GO:1902475), L-glutamine import across plasma membrane (GO:1903803), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), glycine transport (GO:0015816), alanine transport (GO:0032328), sodium ion transmembrane transport (GO:0035725)

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), neutral L-amino acid transmembrane transporter activity (GO:0015175), L-amino acid transmembrane transporter activity (GO:0015179), L-glutamine transmembrane transporter activity (GO:0015186), glycine:sodium symporter activity (GO:0015375), alanine:sodium symporter activity (GO:0015655), protein binding (GO:0005515), symporter activity (GO:0015293)

GO Cellular Component (7): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), axon (GO:0030424), neuronal cell body (GO:0043025), extracellular exosome (GO:0070062), external side of apical plasma membrane (GO:0098591)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Neurotransmitter uptake and metabolism In glial cells	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
amino acid:sodium symporter activity	3
organic acid:sodium symporter activity	3
transport	2
L-amino acid transport	2
modulation of chemical synaptic transmission	2
amino acid transmembrane transport	2
L-glutamine transport	2
L-alpha-amino acid transmembrane transport	2
carboxylic acid transport	2
nitrogen compound transport	2
neutral L-amino acid transmembrane transporter activity	2
carboxylic acid transmembrane transporter activity	2
amino acid transmembrane transporter activity	2
neurotransmitter transport	1
import into cell	1
transmembrane transport	1
multi-organism reproductive process	1
multi-multicellular organism process	1
amino acid biosynthetic process	1
non-proteinogenic amino acid biosynthetic process	1
synaptic transmission, GABAergic	1
regulation of biological quality	1
vascular transport	1
carboxylic acid transmembrane transport	1
amino acid import across plasma membrane	1
metal ion transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
amino acid:monoatomic cation symporter activity	1
solute:sodium symporter activity	1
transmembrane transporter activity	1
L-amino acid transmembrane transporter activity	1
neutral L-amino acid:sodium symporter activity	1
glycine transmembrane transporter activity	1
alanine transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
membrane	1

Protein interactions and networks

STRING

1240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC38A1	SCN11A	Q9UI33	765
SLC38A1	SLC1A5	Q15758	763
SLC38A1	PBX2	P40425	719
SLC38A1	SLC7A5	Q01650	707
SLC38A1	AANAT	Q16613	696
SLC38A1	SLC7A8	Q9UHI5	633
SLC38A1	SLC3A2	P08195	622
SLC38A1	SLC1A4	P43007	606
SLC38A1	SLC43A2	Q8N370	605
SLC38A1	SLC7A6	Q92536	605
SLC38A1	SLC1A1	P43005	573
SLC38A1	SLC38A9	Q8NBW4	562
SLC38A1	SLC7A7	Q9UM01	543
SLC38A1	SLC7A1	P30825	536
SLC38A1	SLC2A3	P11169	527
SLC38A1	GLS	O94925	527

IntAct

144 interactions, top by confidence:

A	B	Type	Score
SLC38A1	FATE1	psi-mi:“MI:0915”(physical association)	0.720
FATE1	SLC38A1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
IGFBP5	SLC38A1	psi-mi:“MI:0915”(physical association)	0.600
SSMEM1	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
SERP2	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
SLC38A1	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
BMP10	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
SLC38A1	RPRM	psi-mi:“MI:0915”(physical association)	0.560
IL1RL1	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
CD79A	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
SMIM3	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
SCGB1D1	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
GRM2	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
SLC38A1	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
PMP22	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
PDCD1LG2	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
GPR152	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (229): FATE1 (Two-hybrid), SLC38A1 (Affinity Capture-RNA), SLC38A1 (Proximity Label-MS), SLC38A1 (Proximity Label-MS), SLC38A1 (Two-hybrid), SLC38A1 (Affinity Capture-MS), SLC38A1 (Proximity Label-MS), SLC38A1 (Proximity Label-MS), SLC38A1 (Proximity Label-MS), SLC38A1 (Affinity Capture-RNA), SLC38A1 (Two-hybrid), SLC38A1 (Proximity Label-MS), SLC38A1 (Proximity Label-MS), SLC38A1 (Proximity Label-MS), SLC38A1 (Proximity Label-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
SLC38A1	“up-regulates quantity”	“L-glutamine zwitterion”	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 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
FRS-mediated FGFR4 signaling	5	44.3×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2854 predictions. Top by Δscore:

Variant	Effect	Δscore
12:46196818:C:A	donor_gain	1.0000
12:46197913:CCATA:C	donor_loss	1.0000
12:46197914:CATAC:C	donor_loss	1.0000
12:46197915:ATACC:A	donor_loss	1.0000
12:46197916:TA:T	donor_loss	1.0000
12:46197917:A:C	donor_loss	1.0000
12:46197918:C:A	donor_loss	1.0000
12:46197918:CCTA:C	donor_gain	1.0000
12:46197921:A:AC	donor_gain	1.0000
12:46197922:C:CC	donor_gain	1.0000
12:46197922:CGA:C	donor_gain	1.0000
12:46197922:CGACT:C	donor_gain	1.0000
12:46198056:CGAAC:C	acceptor_gain	1.0000
12:46198057:GAAC:G	acceptor_gain	1.0000
12:46198058:AAC:A	acceptor_gain	1.0000
12:46198059:AC:A	acceptor_gain	1.0000
12:46198059:ACCTG:A	acceptor_loss	1.0000
12:46198060:CC:C	acceptor_gain	1.0000
12:46198061:C:CC	acceptor_gain	1.0000
12:46198061:CTGCA:C	acceptor_loss	1.0000
12:46198064:C:CT	acceptor_gain	1.0000
12:46198065:A:T	acceptor_gain	1.0000
12:46198621:TCAC:T	donor_loss	1.0000
12:46198622:CAC:C	donor_loss	1.0000
12:46198623:A:AC	donor_gain	1.0000
12:46198623:ACCGT:A	donor_loss	1.0000
12:46198624:C:CC	donor_gain	1.0000
12:46198739:GTTGT:G	acceptor_gain	1.0000
12:46198740:TTGT:T	acceptor_gain	1.0000
12:46198741:TGT:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000036008 (12:46243133 T>C), RS1000055679 (12:46218508 G>A), RS1000071082 (12:46215209 A>C), RS1000085585 (12:46249316 T>A), RS1000125403 (12:46207303 G>T), RS1000231587 (12:46268504 C>G,T), RS1000278012 (12:46267439 G>A,C), RS1000282054 (12:46191327 G>A,C), RS1000313944 (12:46255249 C>G,T), RS1000333752 (12:46191129 T>C), RS1000356005 (12:46184873 C>T), RS1000365559 (12:46225877 G>A,T), RS1000405 (12:46262739 C>A,G,T), RS1000412364 (12:46261156 T>C), RS1000419251 (12:46226163 G>A)

Disease associations

OMIM: gene MIM:608490 | disease phenotypes: MIM:243400

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic lupus erythematosus	Strong	X-linked
acetylation, slow	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pediatric systemic lupus erythematosus	Limited	XL

Mondo (2): acetylation, slow (MONDO:0009472), systemic lupus erythematosus (MONDO:0007915)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001939	Abnormality of metabolism/homeostasis

GWAS associations

76 associations (top):

Study	Trait	p-value
GCST000758_17	Triglycerides	4.000000e-14
GCST000760_16	Cholesterol, total	2.000000e-09
GCST000842_2	Bladder cancer	4.000000e-11
GCST001073_3	Urinary metabolites	1.000000e-28
GCST001217_19	Metabolic traits	2.000000e-40
GCST002074_8	Paclitaxel-induced neuropathy	4.000000e-06
GCST002216_39	Triglycerides	3.000000e-12
GCST002221_70	Cholesterol, total	3.000000e-08
GCST002240_5	Bladder cancer	2.000000e-10
GCST002364_15	Urinary metabolites (H-NMR features)	4.000000e-32
GCST002678_5	Iron status biomarkers (transferrin levels)	7.000000e-19
GCST002825_1	Insulin resistance/response	3.000000e-06
GCST003119_16	Urinary metabolites	3.000000e-202
GCST003542_5	Night sleep phenotypes	3.000000e-06
GCST004235_63	Total cholesterol levels	7.000000e-17
GCST004237_33	Triglyceride levels	2.000000e-20
GCST005194_137	Coronary artery disease	2.000000e-07
GCST006003_15	Triglyceride levels	1.000000e-08
GCST007565_39	Morning person	1.000000e-15
GCST007897_1	Liver injury in anti-tuberculosis drug treatment	7.000000e-11
GCST007929_62	Medication use (calcium channel blockers)	3.000000e-08
GCST007931_3	Medication use (HMG CoA reductase inhibitors)	1.000000e-17
GCST008074_111	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-16
GCST008074_40	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-28
GCST008074_5	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-11
GCST008076_2	Triglyceride levels	5.000000e-09
GCST008076_29	Triglyceride levels	7.000000e-15
GCST008076_67	Triglyceride levels	2.000000e-07
GCST008078_141	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-07
GCST008078_43	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-07

EFO canonical traits (23, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004725	metabolite measurement
EFO:0005116	urinary metabolite measurement
EFO:0004461	iron biomarker measurement
EFO:0006341	transferrin measurement
EFO:0008328	chronotype measurement
EFO:0007918	response to anti-tuberculosis drug
EFO:0009930	Calcium channel blocker use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0010534	suberic acid measurement
EFO:0000195	metabolic syndrome
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0007874	gut microbiome measurement
EFO:0006334	total iron binding capacity
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066229 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

23 annotations.

Variant	Type	Level	Drugs	Phenotypes
NAT21, NAT24, NAT25, NAT26, NAT26J, NAT27, NAT27G, NAT214, NAT216, NAT239	Metabolism/PK	2A	isoniazid	Tuberculosis
NAT21, NAT24, NAT25, NAT26, NAT27, NAT214, NAT2*16	Toxicity	1B	Drugs For Treatment Of Tuberculosis;isoniazid	Drug-induced liver injury;Toxic liver disease;Tuberculosis
NAT21, NAT24, NAT26, NAT27, NAT214, NAT216	Efficacy	1A	hydralazine	Hypertension
NAT21, NAT24, NAT26, NAT27, NAT2*16	Toxicity	3	Antivirals for treatment of HIV infections;combinations;Drugs For Treatment Of Tuberculosis	Drug-induced liver injury;HIV infectious disease;Tuberculosis
NAT24, NAT25, NAT26, NAT27, NAT214, NAT216	Toxicity	3	sulfamethoxazole / trimethoprim	adverse events;Hypersensitivity;Severe Cutaneous Adverse Reactions
NAT24, NAT25, NAT26, NAT27, NAT2*16	Metabolism/PK	1A	hydralazine
NAT24, NAT26, NAT27, NAT214, NAT2*16	Metabolism/PK	3	dipyrone
NAT26, NAT27, NAT214, NAT216	Toxicity	1A	hydralazine	Hypertension
rs1041983	Toxicity	3	isoniazid;phenytoin	Drug interaction with drug;Drug Toxicity
rs1041983	Toxicity	3	ethambutol;isoniazid;pyrazinamide;rifampin	Toxic liver disease;Tuberculosis
rs1041983	Toxicity	3	isoniazid;pyrazinamide;rifampin	Toxic liver disease;Tuberculosis
rs1208	Toxicity	3	isoniazid;phenytoin	Drug interaction with drug;Drug Toxicity
rs1799929	Toxicity	3	Drugs For Treatment Of Tuberculosis	Tuberculosis
rs1799929	Toxicity	3	isoniazid;phenytoin	Drug interaction with drug;Drug Toxicity
rs1799930	Toxicity	3	isoniazid;phenytoin	Drug interaction with drug;Drug Toxicity
rs1799930	Toxicity	3	sulfamethoxazole / trimethoprim	adverse events;Hypersensitivity
rs1799931	Toxicity	3	docetaxel;thalidomide	Prostatic Neoplasms
rs1799931	Toxicity	3	isoniazid;phenytoin	Drug interaction with drug;Drug Toxicity
rs1799931	Toxicity	3	sulfamethoxazole / trimethoprim	adverse events;Hypersensitivity
rs1801280	Toxicity	3	cisplatin;cyclophosphamide	Ovarian Neoplasms
rs1801280	Toxicity	3	isoniazid;phenytoin	Drug interaction with drug;Drug Toxicity
rs4271002	Toxicity	3	aspirin	Asthma
rs4646244	Toxicity,Metabolism/PK	3	ethambutol;isoniazid;pyrazinamide;rifampin	Tuberculosis

PharmGKB variants

14 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1208	NAT2	3	2.25	9	isoniazid;phenytoin
rs1041983	NAT2	3	3.00	4	isoniazid;pyrazinamide;rifampin;isoniazid;phenytoin;ethambutol;isoniazid;pyrazinamide;rifampin
rs1799929	NAT2	3	6.75	2	isoniazid;phenytoin;Drugs For Treatment Of Tuberculosis
rs1799930	NAT2	3	2.25	10	isoniazid;phenytoin;sulfamethoxazole / trimethoprim
rs1799931	NAT2	3	2.25	11	docetaxel;thalidomide;sulfamethoxazole / trimethoprim;isoniazid;phenytoin
rs1801279	NAT2		0.00	6
rs1801280	NAT2	3	2.25	10	isoniazid;phenytoin;cisplatin;cyclophosphamide
rs1805158	NAT2		0.00	0
rs4271002	NAT2	3	2.25	1	aspirin
rs4646244	NAT2	3	4.75	1	ethambutol;isoniazid;pyrazinamide;rifampin
rs4646267	NAT2		0.00	0
rs45607939	NAT2		0.00	0
rs56393504	NAT2		0.00	1
rs72554616	NAT2		0.00	0

PharmGKB dosing guidelines

1 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	hydralazine	Annotation of CPIC Guideline for hydralazine and NAT2	yes	yes

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — System A-like transporters

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	4
perfluorooctane sulfonic acid	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	3
Tretinoin	increases expression, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
Cyclosporine	increases expression	3
perfluorooctanoic acid	affects cotreatment, increases expression, decreases expression	2
cadmium sulfate	increases expression	2
Acetaminophen	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
nickel chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
deguelin	increases expression	1
corosolic acid	increases expression	1
monomethylarsonous acid	increases expression	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
CHEMBL5540567	Binding	Inhibition of SNAT1 (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

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4MY	HCT116-SLC38A1-KO-c5	Cancer cell line	Male
CVCL_D4MZ	HCT116-SLC38A1-KO-c7	Cancer cell line	Male
CVCL_TN39	HAP1 SLC38A1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients