SLC38A6

Summary

SLC38A6 (solute carrier family 38 member 6, HGNC:19863) is a protein-coding gene on chromosome 14q23.1, encoding Solute carrier family 38 member 6 (Q8IZM9). Amino acid transporter with an apparent selectivity for L-glutamine and L-glutamate.

Predicted to enable L-glutamate transmembrane transporter activity and L-glutamine transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and glutamine transport. Predicted to be located in membrane and synapse. Predicted to be active in plasma membrane.

Source: NCBI Gene 145389 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_153811

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19863
Approved symbol	SLC38A6
Name	solute carrier family 38 member 6
Location	14q23.1
Locus type	gene with protein product
Status	Approved
Aliases	NAT-1, SNAT6
Ensembl gene	ENSG00000139974
Ensembl biotype	protein_coding
OMIM	616518
Entrez	145389

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 8 protein_coding, 8 nonsense_mediated_decay, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000267488, ENST00000354886, ENST00000451406, ENST00000491344, ENST00000524402, ENST00000525585, ENST00000525723, ENST00000526105, ENST00000526539, ENST00000527591, ENST00000528350, ENST00000529212, ENST00000529345, ENST00000532148, ENST00000533744, ENST00000534758, ENST00000554072, ENST00000554304, ENST00000554498, ENST00000556938, ENST00000703134, ENST00000878035

RefSeq mRNA: 2 — MANE Select: NM_153811 NM_001172702, NM_153811

CCDS: CCDS53900, CCDS9751

Canonical transcript exons

ENST00000267488 — 16 exons

Exon	Start	End
ENSE00001709211	61052349	61052630
ENSE00002140710	60981245	60981382
ENSE00003496580	61037625	61037683
ENSE00003502962	61019541	61019580
ENSE00003509571	61043450	61043503
ENSE00003510687	60982508	60982638
ENSE00003535277	61052041	61052135
ENSE00003563154	61046067	61046167
ENSE00003577584	61050512	61050636
ENSE00003597564	61037059	61037141
ENSE00003639340	61043147	61043212
ENSE00003662341	61051787	61051931
ENSE00003677323	61030445	61030523
ENSE00003680708	60984730	60984803
ENSE00003692744	61015904	61015956
ENSE00003692968	61045346	61045425

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 93.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4049 / max 452.5874, expressed in 1781 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139894	18.3532	1752
139893	2.3948	1381
139895	1.2736	266
139896	0.1989	77
139898	0.0825	36
139897	0.0572	33
139899	0.0448	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.38	gold quality
bronchial epithelial cell	CL:0002328	90.34	gold quality
adrenal tissue	UBERON:0018303	90.29	gold quality
right adrenal gland cortex	UBERON:0035827	87.97	gold quality
gall bladder	UBERON:0002110	87.84	gold quality
stromal cell of endometrium	CL:0002255	87.32	gold quality
right adrenal gland	UBERON:0001233	87.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.11	gold quality
choroid plexus epithelium	UBERON:0003911	87.05	gold quality
secondary oocyte	CL:0000655	86.91	gold quality
left adrenal gland	UBERON:0001234	86.63	gold quality
left adrenal gland cortex	UBERON:0035825	86.30	gold quality
right uterine tube	UBERON:0001302	85.59	gold quality
right ovary	UBERON:0002118	85.43	gold quality
descending thoracic aorta	UBERON:0002345	85.36	gold quality
left testis	UBERON:0004533	85.36	gold quality
sperm	CL:0000019	85.33	gold quality
sural nerve	UBERON:0015488	85.30	gold quality
tibia	UBERON:0000979	85.21	gold quality
adenohypophysis	UBERON:0002196	85.16	gold quality
right testis	UBERON:0004534	85.07	gold quality
adrenal gland	UBERON:0002369	85.06	gold quality
omental fat pad	UBERON:0010414	84.79	gold quality
right coronary artery	UBERON:0001625	84.77	gold quality
tibial nerve	UBERON:0001323	84.68	gold quality
peritoneum	UBERON:0002358	84.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.48	gold quality
adrenal cortex	UBERON:0001235	84.42	gold quality
ascending aorta	UBERON:0001496	84.38	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.98

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• SLC38A6 is primarily expressed in excitatory neurons and is not expressed in the astrocytes. (PMID:24752331)
• SLC38A6, regulated by EP300-mediated modifications of H3K27ac, promotes cell proliferation, glutamine metabolism and mitochondrial respiration in hepatocellular carcinoma. (PMID:35901507)
• New Transcriptomic Biomarkers of 5-Fluorouracil Resistance. (PMID:36675023)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc38a6	ENSDARG00000054312
mus_musculus	Slc38a6	ENSMUSG00000044712
rattus_norvegicus	Slc38a6	ENSRNOG00000022622
drosophila_melanogaster	CG16700	FBGN0030816
drosophila_melanogaster	CG4991	FBGN0030817
drosophila_melanogaster	polyph	FBGN0033572
drosophila_melanogaster	acs	FBGN0035300
drosophila_melanogaster	CG7888	FBGN0036116
drosophila_melanogaster	CG32079	FBGN0052079
drosophila_melanogaster	CG32081	FBGN0052081
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), SLC38A2 (ENSG00000134294), SLC38A4 (ENSG00000139209), SLC38A10 (ENSG00000157637), SLC38A8 (ENSG00000166558), SLC38A11 (ENSG00000169507), SLC38A9 (ENSG00000177058), SLC36A4 (ENSG00000180773), SLC36A3 (ENSG00000186334), SLC36A2 (ENSG00000186335), SLC38A3 (ENSG00000188338)

Protein

Protein identifiers

Solute carrier family 38 member 6 — Q8IZM9 (reviewed: Q8IZM9)

Alternative names: Amino acid transporter SLC38A6, N-system amino acid transporter 1

All UniProt accessions (14): Q8IZM9, A0A087WZP5, A0A0C4DG39, A0A8V8TRG7, E9PM79, E9PMA3, G3V3H5, H0YDY0, H0YE10, H0YEH3, H0YF42, H0YJ85, H0YJG2, H0YJU1

UniProt curated annotations — full annotation on UniProt →

Function. Amino acid transporter with an apparent selectivity for L-glutamine and L-glutamate. May facilitate glutamine uptake in excitatory neurons. The transport mechanism remains to be elucidated.

Subcellular location. Cell membrane. Synapse.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IZM9-1	1	yes
Q8IZM9-2	2

RefSeq proteins (2): NP_001166173, NP_722518* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013057	AA_transpt_TM	Domain

Pfam: PF01490

Catalyzed reactions (Rhea), 2 shown:

• L-glutamate(out) = L-glutamate(in) (RHEA:66336)
• L-glutamine(out) = L-glutamine(in) (RHEA:73419)

UniProt features (21 total): transmembrane region 11, modified residue 3, glycosylation site 2, sequence variant 2, chain 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZM9-F1	83.77	0.61

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 (3): 1, 4, 7

Disulfide bonds (1): 218–238

Glycosylation sites (2): 233, 283

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, PATIL_LIVER_CANCER, NKX61_01, ONKEN_UVEAL_MELANOMA_UP, WTGAAAT_UNKNOWN, CASORELLI_APL_SECONDARY_VS_DE_NOVO_UP, GOBP_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, TGANTCA_AP1_C, TGACATY_UNKNOWN, GOBP_DICARBOXYLIC_ACID_TRANSPORT, GOBP_ACIDIC_AMINO_ACID_TRANSPORT, PETROVA_ENDOTHELIUM_LYMPHATIC_VS_BLOOD_DN

GO Biological Process (4): amino acid transmembrane transport (GO:0003333), L-glutamine transport (GO:0006868), amino acid transport (GO:0006865), L-glutamate transmembrane transport (GO:0015813)

GO Molecular Function (3): L-glutamate transmembrane transporter activity (GO:0005313), L-glutamine transmembrane transporter activity (GO:0015186), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), synapse (GO:0045202), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
L-amino acid transmembrane transporter activity	2
amino acid transport	1
transmembrane transport	1
neutral amino acid transport	1
L-amino acid transport	1
transport	1
L-glutamate import	1
L-alpha-amino acid transmembrane transport	1
dicarboxylic acid transmembrane transporter activity	1
acidic amino acid transmembrane transporter activity	1
L-glutamate transmembrane transport	1
L-glutamine transport	1
neutral L-amino acid transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

717 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC38A6	SLC43A2	Q8N370	475
SLC38A6	SLC35H1	Q9NQQ7	468
SLC38A6	SLC1A4	P43007	465
SLC38A6	SLC41A2	Q96JW4	458
SLC38A6	SLC38A9	Q8NBW4	458
SLC38A6	SLC7A8	Q9UHI5	451
SLC38A6	SLC7A6	Q92536	446
SLC38A6	SLC31A2	O15432	429
SLC38A6	PREPL	Q4J6C6	418
SLC38A6	SLC3A1	Q07837	417
SLC38A6	SLC7A7	Q9UM01	407
SLC38A6	ARHGAP28	Q9P2N2	404
SLC38A6	SLC6A14	Q9UN76	404
SLC38A6	SLC36A1	Q7Z2H8	386
SLC38A6	RD3L	P0DJH9	383

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TUSC5	SLC38A6	psi-mi:“MI:0915”(physical association)	0.560
SLC38A6	EDIL3	psi-mi:“MI:0914”(association)	0.350
SLC38A6	AP3D1	psi-mi:“MI:0914”(association)	0.350
TUSC5	SLC38A6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): TF (Affinity Capture-MS), NPLOC4 (Affinity Capture-MS), MUCL1 (Affinity Capture-MS), APOB (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), CYB5A (Affinity Capture-MS), RBFOX3 (Affinity Capture-MS), TF (Affinity Capture-MS), TUSC5 (Two-hybrid), TF (Affinity Capture-MS), EDIL3 (Affinity Capture-MS), MUCL1 (Affinity Capture-MS), GDA (Affinity Capture-MS), SLC38A6 (Reconstituted Complex)

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2986 predictions. Top by Δscore:

Variant	Effect	Δscore
14:60981362:T:G	donor_gain	1.0000
14:60981378:GCAAC:G	donor_gain	1.0000
14:60981383:G:GG	donor_gain	1.0000
14:60982636:TAGG:T	donor_loss	1.0000
14:60982638:GGTGA:G	donor_loss	1.0000
14:60982639:GT:G	donor_loss	1.0000
14:60982640:T:G	donor_loss	1.0000
14:60982641:GA:G	donor_loss	1.0000
14:60984728:A:AG	acceptor_gain	1.0000
14:60984729:G:GG	acceptor_gain	1.0000
14:60984799:GACAG:G	donor_gain	1.0000
14:60984800:ACAGG:A	donor_loss	1.0000
14:60984801:CAGG:C	donor_loss	1.0000
14:60984802:AGG:A	donor_loss	1.0000
14:60984803:GGTG:G	donor_loss	1.0000
14:60984804:G:T	donor_loss	1.0000
14:60984805:T:A	donor_loss	1.0000
14:61015902:A:AG	acceptor_gain	1.0000
14:61015903:G:GG	acceptor_gain	1.0000
14:61015903:GCT:G	acceptor_gain	1.0000
14:61046065:A:AG	acceptor_gain	1.0000
14:61046066:G:GG	acceptor_gain	1.0000
14:60981374:C:G	donor_gain	0.9900
14:60981379:CAAC:C	donor_gain	0.9900
14:60981380:AACG:A	donor_loss	0.9900
14:60981381:AC:A	donor_gain	0.9900
14:60981382:CGTA:C	donor_loss	0.9900
14:60981383:G:C	donor_loss	0.9900
14:60981384:T:A	donor_loss	0.9900
14:60982502:TTACA:T	acceptor_loss	0.9900

AlphaMissense

2974 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:61051792:A:C	R352S	0.997
14:61051792:A:T	R352S	0.997
14:61045373:T:C	F258L	0.996
14:61045375:T:A	F258L	0.996
14:61045375:T:G	F258L	0.996
14:61045419:T:C	L273P	0.996
14:61046116:A:C	S292R	0.996
14:61046118:T:A	S292R	0.996
14:61046118:T:G	S292R	0.996
14:61037642:A:C	S195R	0.995
14:61037644:T:A	S195R	0.995
14:61037644:T:G	S195R	0.995
14:61050620:C:G	P345R	0.994
14:60982580:G:A	G60R	0.993
14:60982580:G:C	G60R	0.993
14:61046161:T:C	F307L	0.993
14:61046163:T:A	F307L	0.993
14:61046163:T:G	F307L	0.993
14:61050620:C:A	P345H	0.993
14:61051791:G:C	R352T	0.993
14:60982583:A:C	S61R	0.992
14:60982585:T:A	S61R	0.992
14:60982585:T:G	S61R	0.992
14:61015925:T:C	L111P	0.992
14:61045407:T:A	I269K	0.992
14:61046150:G:A	G303E	0.992
14:61052046:A:C	S401R	0.992
14:61052048:T:A	S401R	0.992
14:61052048:T:G	S401R	0.992
14:61045385:T:C	C262R	0.991

dbSNP variants (sampled 300 via entrez): RS1000008085 (14:61004864 G>T), RS1000010118 (14:61040618 T>C), RS1000026648 (14:61083041 GT>G), RS1000094054 (14:61036706 C>G), RS1000097014 (14:61002403 G>A,C), RS1000118954 (14:61047607 G>C), RS1000194899 (14:61043983 A>G), RS1000227459 (14:61044165 T>C), RS1000234961 (14:61041261 G>A), RS1000280334 (14:61076164 A>C,G), RS1000281081 (14:61054664 C>A,G), RS1000293604 (14:60990036 T>G), RS1000296054 (14:61034375 C>T), RS1000313326 (14:61006655 C>T), RS1000325660 (14:61010979 G>A)

Disease associations

OMIM: gene MIM:616518 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002928_8	Nickel levels	8.000000e-06
GCST003564_4	Waist-to-hip ratio adjusted for body mass index	2.000000e-06
GCST004049_1	Cough in response to angiotensin-converting enzyme inhibitor drugs	3.000000e-06
GCST010002_153	Refractive error	2.000000e-40

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0005325	response to angiotensin-converting enzyme inhibitor

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 — Orphan SLC38 transporters

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
Cyclosporine	increases expression	3
bisphenol A	decreases methylation, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
belinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium bichromate	decreases expression	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, 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
dorsomorphin	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4TJ	HuH7-SLC38A6-KO-c1	Cancer cell line	Male
CVCL_D4TK	HuH7-SLC38A6-KO-c12	Cancer cell line	Male
CVCL_D4TL	HuH7-SLC38A6-KO-c14	Cancer cell line	Male
CVCL_TN46	HAP1 SLC38A6 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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