SLC38A9

Summary

SLC38A9 (solute carrier family 38 member 9, HGNC:26907) is a protein-coding gene on chromosome 5q11.2, encoding Neutral amino acid transporter 9 (Q8NBW4). Lysosomal amino acid transporter involved in the activation of mTORC1 in response to amino acid levels.

Enables several functions, including L-amino acid transmembrane transporter activity; cholesterol binding activity; and guanyl-nucleotide exchange factor activity. Involved in carboxylic acid transport; cellular response to amino acid stimulus; and positive regulation of TORC1 signaling. Located in Ragulator complex; late endosome; and lysosomal membrane. Part of FNIP-folliculin RagC/D GAP.

Source: NCBI Gene 153129 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lysosomal storage disease (No Known Disease Relationship, ClinGen)
• GWAS associations: 20
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_173514

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26907
Approved symbol	SLC38A9
Name	solute carrier family 38 member 9
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90709, SNAT9
Ensembl gene	ENSG00000177058
Ensembl biotype	protein_coding
OMIM	616203
Entrez	153129

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 44 protein_coding, 5 protein_coding_CDS_not_defined, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000318672, ENST00000396865, ENST00000416547, ENST00000502247, ENST00000502416, ENST00000503817, ENST00000503891, ENST00000504880, ENST00000505563, ENST00000505708, ENST00000506624, ENST00000507109, ENST00000507216, ENST00000507447, ENST00000508124, ENST00000511233, ENST00000512208, ENST00000512595, ENST00000513275, ENST00000513993, ENST00000514806, ENST00000515159, ENST00000515629, ENST00000515754, ENST00000524030, ENST00000524154, ENST00000870429, ENST00000870430, ENST00000870431, ENST00000870432, ENST00000870433, ENST00000870434, ENST00000870435, ENST00000870436, ENST00000870437, ENST00000917078, ENST00000917079, ENST00000917080, ENST00000917081, ENST00000917082, ENST00000917083, ENST00000917084, ENST00000917085, ENST00000917086, ENST00000917087, ENST00000917088, ENST00000917089, ENST00000917090, ENST00000917091, ENST00000917092, ENST00000917093, ENST00000917094, ENST00000945400, ENST00000945401, ENST00000945402, ENST00000945403

RefSeq mRNA: 8 — MANE Select: NM_173514 NM_001258286, NM_001258287, NM_001282429, NM_001349382, NM_001349383, NM_001349384, NM_001349385, NM_173514

CCDS: CCDS3968, CCDS58947, CCDS58948, CCDS75243

Canonical transcript exons

ENST00000396865 — 16 exons

Exon	Start	End
ENSE00001526538	55711452	55711499
ENSE00003499575	55672563	55672695
ENSE00003500464	55633754	55633902
ENSE00003502321	55649207	55649314
ENSE00003506462	55697846	55697992
ENSE00003523449	55652529	55652723
ENSE00003525997	55669758	55669879
ENSE00003534109	55627891	55627980
ENSE00003542302	55656715	55656774
ENSE00003594767	55664693	55664863
ENSE00003609531	55669228	55669321
ENSE00003611644	55625848	55626659
ENSE00003667883	55669557	55669620
ENSE00003675340	55645789	55645895
ENSE00003688323	55635544	55635657
ENSE00003850837	55712217	55712324

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 97.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2349 / max 156.1556, expressed in 1759 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61711	5.4448	1679
61710	3.0247	1471
61709	1.6969	963
61706	0.0209	3
61712	0.0167	9
61705	0.0165	5
61707	0.0143	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.65	gold quality
placenta	UBERON:0001987	94.06	gold quality
oocyte	CL:0000023	92.89	gold quality
epithelial cell of pancreas	CL:0000083	92.57	gold quality
buccal mucosa cell	CL:0002336	91.96	gold quality
esophagus squamous epithelium	UBERON:0006920	91.49	gold quality
adrenal tissue	UBERON:0018303	89.38	gold quality
calcaneal tendon	UBERON:0003701	89.09	gold quality
tibia	UBERON:0000979	88.17	gold quality
body of pancreas	UBERON:0001150	87.91	gold quality
germinal epithelium of ovary	UBERON:0001304	87.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.37	gold quality
bone marrow cell	CL:0002092	87.04	gold quality
sperm	CL:0000019	86.95	gold quality
visceral pleura	UBERON:0002401	86.80	gold quality
pancreas	UBERON:0001264	86.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.21	gold quality
gingival epithelium	UBERON:0001949	86.13	gold quality
monocyte	CL:0000576	86.04	gold quality
leukocyte	CL:0000738	85.97	gold quality
epithelium of nasopharynx	UBERON:0001951	85.22	gold quality
palpebral conjunctiva	UBERON:0001812	85.12	gold quality
colonic epithelium	UBERON:0000397	84.94	gold quality
tonsil	UBERON:0002372	84.73	gold quality
left testis	UBERON:0004533	84.56	gold quality
parietal pleura	UBERON:0002400	84.43	gold quality
oviduct epithelium	UBERON:0004804	84.36	gold quality
gingiva	UBERON:0001828	84.11	gold quality
right testis	UBERON:0004534	84.00	gold quality
testis	UBERON:0000473	83.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	44.36
E-ANND-3	no	5.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting SLC38A9, 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-3646	100.00	73.56	5283
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4803	99.98	71.99	3117
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-12129	99.72	67.45	1311

Literature-anchored findings (GeneRIF, showing 7)

• SNPs within SLC38A9 are correlated with inflammatory bowel disease patients’ 6-thioguanine nucleotide blood concentrations. (PMID:24762746)
• SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR (PMID:25561175)
• SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway. (PMID:25567906)
• Data suggest that amino acid transporter SLC38A9 controls mTORC1 activity through binding to the Rag-Ragulator complex at the lysosome upon amino acid availability. (PMID:25963655)
• Study validates that SLC38A9 is an arginine sensor for the mTORC1 pathway, and we uncover an unexpectedly central role for SLC38A9 in amino acid homeostasis. SLC38A9 mediates the transport, in an arginine-regulated fashion, of many essential amino acids out of lysosomes, including leucine, which mTORC1 senses through the cytosolic Sestrin proteins. (PMID:29053970)
• Ragulator and SLC38A9 act on the Rag GTPases to activate the mTORC1 pathway in response to nutrient sufficiency. (PMID:30181260)
• Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9. (PMID:32868926)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc38a9	ENSDARG00000032769
mus_musculus	Slc38a9	ENSMUSG00000047789
rattus_norvegicus	Slc38a9	ENSRNOG00000009851
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		WBGENE00008774

Paralogs (15): SLC38A5 (ENSG00000017483), SLC32A1 (ENSG00000101438), SLC38A7 (ENSG00000103042), SLC38A1 (ENSG00000111371), SLC36A1 (ENSG00000123643), SLC38A2 (ENSG00000134294), SLC38A4 (ENSG00000139209), SLC38A6 (ENSG00000139974), SLC38A10 (ENSG00000157637), SLC38A8 (ENSG00000166558), SLC38A11 (ENSG00000169507), SLC36A4 (ENSG00000180773), SLC36A3 (ENSG00000186334), SLC36A2 (ENSG00000186335), SLC38A3 (ENSG00000188338)

Protein

Protein identifiers

Neutral amino acid transporter 9 — Q8NBW4 (reviewed: Q8NBW4)

Alternative names: Solute carrier family 38 member 9, Up-regulated in lung cancer 11

All UniProt accessions (13): Q8NBW4, B3KVK8, D6R9Q7, D6R9X0, D6RBB9, D6RDH2, D6RE72, D6RER8, D6RG31, D6RHF5, D6RHW0, D6RIW7, E7ESU6

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal amino acid transporter involved in the activation of mTORC1 in response to amino acid levels. Probably acts as an amino acid sensor of the Rag GTPases and Ragulator complexes, 2 complexes involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Following activation by amino acids, the Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. SLC38A9 mediates transport of amino acids with low capacity and specificity with a slight preference for polar amino acids. Acts as an arginine sensor. Following activation by arginine binding, mediates transport of L-glutamine, leucine and tyrosine with high efficiency, and is required for the efficient utilization of these amino acids after lysosomal protein degradation. However, the transport mechanism is not well defined and the role of sodium is not clear. Can disassemble the lysosomal folliculin complex (LFC), and thereby triggers GAP activity of FLCN:FNIP2 toward RRAGC. Acts as an cholesterol sensor that conveys increases in lysosomal cholesterol, leading to lysosomal recruitment and activation of mTORC1 via the Rag GTPases. Guanine exchange factor (GEF) that, upon arginine binding, stimulates GDP release from RRAGA and therefore activates the Rag GTPase heterodimer and the mTORC1 pathway in response to nutrient sufficiency.

Subunit / interactions. Associated component of the Ragulator complex (composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5). Associated component of the Rag GTPases heterodimers (composed of RRAGA, RRAGB, RRAGC and RRAGD); this interaction is independent of the Ragulator complex but depends on the nucleotide loading state of the Rag GTPase heterodimer. Interacts with TM4SF5. Interacts with NPC1; this interaction inhibits cholesterol-mediated mTORC1 activation via its sterol transport activity.

Subcellular location. Lysosome membrane. Late endosome membrane.

Post-translational modifications. Glycosylated.

Activity regulation. Amino acid transport activity is increased by sodium and is most active at acidic pH. Transport of L-glutamine, leucine and tyrosine is increased by arginine binding.

Domain organisation. The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex. The cytosolic N-terminus part of the protein destabilizes the LFC and thereby triggers GAP activity of FLCN:FNIP2 toward RRAGC. The cytosolic N-terminus part of the protein mediates interaction with the Rag GTPase heterodimer in a RRAGA GDP-loaded state dependent and upon arginine binding, leading to the GDP release and SLC38A9 dissociation from the activated Rag GTPase heterodimer. The cytosolic N-terminus part of the protein exists at least in two distinct conformations; The first is when the N-terminus is bound snugly in the arginine binding site (in the absence of arginine, low luminal arginine state) and the second is where the N-terminus is released and the substrate-binding site is occupied by arginine (in the presence of arginine, high luminal arginine state). The CARC and CRAC motifs mediate binding to cholesterol.

Similarity. Belongs to the amino acid/polyamine transporter 2 family. SLC38A9 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NBW4-1	1	yes
Q8NBW4-2	2
Q8NBW4-3	3
Q8NBW4-4	4

RefSeq proteins (8): NP_001245215, NP_001245216, NP_001269358, NP_001336311, NP_001336312, NP_001336313, NP_001336314, NP_775785* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013057	AA_transpt_TM	Domain

Pfam: PF01490

Catalyzed reactions (Rhea), 4 shown:

• L-tyrosine(in) = L-tyrosine(out) (RHEA:68572)
• L-leucine(in) = L-leucine(out) (RHEA:73011)
• L-glutamine(out) = L-glutamine(in) (RHEA:73419)
• L-asparagine(out) = L-asparagine(in) (RHEA:73423)

UniProt features (59 total): mutagenesis site 15, topological domain 11, transmembrane region 11, glycosylation site 4, splice variant 4, region of interest 2, short sequence motif 2, turn 2, chain 1, compositionally biased region 1, binding site 1, disulfide bond 1, sequence variant 1, sequence conflict 1, strand 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6WJ2	ELECTRON MICROSCOPY	3.2
8DHB	ELECTRON MICROSCOPY	3.53
6WJ3	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBW4-F1	76.87	0.31

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 (1): 134

Disulfide bonds (1): 255–424

Glycosylation sites (4): 239, 248, 266, 274

Mutagenesis-validated functional residues (15):

Position	Phenotype
38–40	abolishes interaction with the ragulator and rag gtpases complexes.
60	does not affect association with the ragulator complex. abolishes the interaction with the rag gtpases heterodimer compl
68	abolishes association with the ragulator complex. no effect on amino acid transport activity. abolishes the interaction
70–73	abolishes interaction with the ragulator and rag gtpases complexes.
71	abolishes association with the ragulator complex. abolishes the interaction with the rag gtpases heterodimer complex.
74	abolishes association with the ragulator complex. abolishes the interaction with the rag gtpases heterodimer complex.
85–87	abolishes interaction with the ragulator and rag gtpases complexes.
85	abolishes association with the ragulator complex.
90	abolishes association with the ragulator complex.
98–101	does not affect interaction with the ragulator and rag gtpases complexes.
128	moderately affects amino acid transport.
133	abolishes arginine transport. no effect on subcellular location and interaction with ragulator complex.
449	abolishes cholesterol binding; when associated with i-460. does not affect disrupted arginine-mediated activation of mto
453	does not affect l-glutamine transport activity.
460	decreases cholesterol binding. abolishes cholesterol binding; when associated with i-449. does not affect disrupted argi

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-165159	MTOR signalling
R-HSA-166208	mTORC1-mediated signalling
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-6807070	PTEN Regulation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9612973	Autophagy
R-HSA-9711097	Cellular response to starvation

MSigDB gene sets: 179 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, RRAGTTGT_UNKNOWN, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOCC_VACUOLAR_MEMBRANE, ATACCTC_MIR202, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_AMINO_ACID_TRANSPORT, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOBP_BASIC_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (9): amino acid transmembrane transport (GO:0003333), asparagine transport (GO:0006867), L-glutamine transport (GO:0006868), positive regulation of TOR signaling (GO:0032008), cellular response to amino acid stimulus (GO:0071230), L-arginine transmembrane transport (GO:1903826), positive regulation of TORC1 signaling (GO:1904263), amino acid transport (GO:0006865), branched-chain amino acid transport (GO:0015803)

GO Molecular Function (12): guanyl-nucleotide exchange factor activity (GO:0005085), amino acid transmembrane transporter activity (GO:0015171), L-amino acid transmembrane transporter activity (GO:0015179), L-asparagine transmembrane transporter activity (GO:0015182), L-glutamine transmembrane transporter activity (GO:0015186), L-leucine transmembrane transporter activity (GO:0015190), cholesterol binding (GO:0015485), sterol sensor activity (GO:0032935), arginine binding (GO:0034618), metal ion binding (GO:0046872), L-arginine transmembrane transporter activity (GO:0061459), protein binding (GO:0005515)

GO Cellular Component (8): lysosome (GO:0005764), lysosomal membrane (GO:0005765), late endosome (GO:0005770), late endosome membrane (GO:0031902), FNIP-folliculin RagC/D GAP (GO:1990877), endosome (GO:0005768), membrane (GO:0016020), Ragulator complex (GO:0071986)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Signal Transduction	2
MTOR signalling	2
Autophagy	1
Transcriptional Regulation by TP53	1
PTEN Regulation	1
Cellular response to starvation	1
Intracellular signaling by second messengers	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Generic Transcription Pathway	1
PIP3 activates AKT signaling	1
Gene expression (Transcription)	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
L-amino acid transmembrane transporter activity	4
neutral L-amino acid transmembrane transporter activity	3
neutral amino acid transport	2
carboxylic acid transport	2
nitrogen compound transport	2
L-alpha-amino acid transmembrane transport	2
sterol binding	2
cation binding	2
amino acid transport	1
transmembrane transport	1
L-amino acid transport	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
response to amino acid	1
cellular response to acid chemical	1
basic amino acid transmembrane transport	1
positive regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
transport	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
amino acid transmembrane transport	1
transmembrane transporter activity	1
amino acid transmembrane transporter activity	1
carboxylic acid transmembrane transporter activity	1
asparagine transport	1
L-glutamine transport	1
branched-chain amino acid transmembrane transporter activity	1
alcohol binding	1
lipid sensor activity	1
amino acid binding	1
carboxylic acid binding	1
basic amino acid transmembrane transporter activity	1
L-arginine transmembrane transport	1
binding	1
lytic vacuole	1
lysosome	1

Protein interactions and networks

STRING

1012 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC38A9	NPC1	O15118	964
SLC38A9	CASTOR1	Q8WTX7	876
SLC38A9	RRAGA	Q7L523	836
SLC38A9	EFNA5	P52803	770
SLC38A9	LAMTOR1	Q6IAA8	769
SLC38A9	LAMTOR4	Q0VGL1	760
SLC38A9	RRAGC	Q9HB90	731
SLC38A9	LARS1	Q9P2J5	729
SLC38A9	FLCN	Q8NFG4	724
SLC38A9	RRAGB	Q5VZM2	715
SLC38A9	MTOR	P42345	710
SLC38A9	LARS2	Q15031	707
SLC38A9	FNIP2	Q9P278	689
SLC38A9	SLC36A1	Q7Z2H8	680
SLC38A9	SAMTOR	Q1RMZ1	678

IntAct

77 interactions, top by confidence:

A	B	Type	Score
LAMTOR4	LAMTOR5	psi-mi:“MI:0914”(association)	0.960
LAMTOR5	LAMTOR4	psi-mi:“MI:0914”(association)	0.960
RRAGC	RRAGA	psi-mi:“MI:0914”(association)	0.950
RRAGA	SLC38A9	psi-mi:“MI:0915”(physical association)	0.870
SLC38A9	RRAGA	psi-mi:“MI:0915”(physical association)	0.870
RRAGC	RRAGB	psi-mi:“MI:0914”(association)	0.870
LAMTOR1	LAMTOR5	psi-mi:“MI:0914”(association)	0.870
LAMTOR1	SLC38A9	psi-mi:“MI:0915”(physical association)	0.860
LAMTOR1	SLC38A9	psi-mi:“MI:0914”(association)	0.860
SLC38A9	LAMTOR1	psi-mi:“MI:0914”(association)	0.860
SLC38A9	LAMTOR1	psi-mi:“MI:0915”(physical association)	0.860
LAMTOR2	LAMTOR5	psi-mi:“MI:0914”(association)	0.860
LAMTOR5	SLC38A9	psi-mi:“MI:0915”(physical association)	0.830
SLC38A9	LAMTOR5	psi-mi:“MI:0915”(physical association)	0.830

BioGRID (143): SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Proximity Label-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS), SLC38A9 (Affinity Capture-MS)

ESM2 similar proteins: A1L272, A2VCW5, A7E3U5, F4IUW3, F4IZW8, F4JE35, O35458, O35633, O54902, P34579, P41251, P49279, P49280, P49281, P49282, P49283, P51027, P56436, P70553, Q08BA4, Q10R54, Q1PER9, Q27946, Q27981, Q2M3M2, Q3B8Q3, Q3U1J0, Q5E9S9, Q5M7S0, Q5R9F5, Q6DEL1, Q6DFE7, Q6DFK0, Q6DIV6, Q6JWR2, Q6PF45, Q7XGU4, Q8BGD6, Q8BWH0, Q8GYS4

Diamond homologs: Q08BA4, Q19425, Q3B8Q3, Q5M7S0, Q6DFK0, Q8BGD6, Q8NBW4, O80668

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
L-arginine	“up-regulates activity”	SLC38A9	“chemical activation”
SLC38A9	“up-regulates activity”	mTORC1
SLC38A9	“up-regulates quantity”	leucine	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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
mTORC1-mediated signalling	8	122.8×	2e-13
Energy dependent regulation of mTOR by LKB1-AMPK	8	101.6×	5e-13
MTOR signalling	8	68.5×	8e-12
PTEN Regulation	8	58.9×	2e-11
Amino acids regulate mTORC1	9	58.2×	1e-12
Regulation of PTEN gene transcription	8	46.0×	1e-10
Autophagy	9	43.1×	1e-11
Cellular response to starvation	8	42.7×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
TORC1 signaling	5	97.9×	1e-07
positive regulation of TOR signaling	7	84.6×	2e-10
cellular response to amino acid stimulus	8	59.8×	2e-10
positive regulation of TORC1 signaling	8	57.7×	2e-10
intracellular protein localization	6	15.3×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3729 predictions. Top by Δscore:

Variant	Effect	Δscore
5:55633852:CCT:C	acceptor_gain	1.0000
5:55633854:T:C	acceptor_gain	1.0000
5:55645783:ACTC:A	donor_loss	1.0000
5:55645785:T:TC	donor_loss	1.0000
5:55645786:CAC:C	donor_loss	1.0000
5:55645787:A:AC	donor_gain	1.0000
5:55645788:C:CT	donor_gain	1.0000
5:55645788:CA:C	donor_gain	1.0000
5:55645788:CAT:C	donor_gain	1.0000
5:55645788:CATT:C	donor_gain	1.0000
5:55645788:CATTG:C	donor_gain	1.0000
5:55645835:T:TC	acceptor_gain	1.0000
5:55645894:CT:C	acceptor_gain	1.0000
5:55645895:TC:T	acceptor_loss	1.0000
5:55645896:C:CC	acceptor_gain	1.0000
5:55645897:T:A	acceptor_loss	1.0000
5:55651793:T:A	donor_gain	1.0000
5:55656775:C:CC	acceptor_gain	1.0000
5:55669226:A:AC	donor_gain	1.0000
5:55669227:C:CC	donor_gain	1.0000
5:55669551:TATTA:T	donor_loss	1.0000
5:55669552:ATTAC:A	donor_loss	1.0000
5:55669553:TTAC:T	donor_loss	1.0000
5:55669554:TA:T	donor_loss	1.0000
5:55669555:AC:A	donor_loss	1.0000
5:55669616:TAAAA:T	acceptor_gain	1.0000
5:55669621:C:CC	acceptor_gain	1.0000
5:55669756:A:AC	donor_gain	1.0000
5:55669757:C:CC	donor_gain	1.0000
5:55669769:A:C	donor_gain	1.0000

AlphaMissense

3740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:55669595:C:G	G132R	0.999
5:55669595:C:T	G132R	0.999
5:55669610:A:G	W127R	0.999
5:55669610:A:T	W127R	0.999
5:55626529:C:G	G551R	0.998
5:55633796:C:G	R463P	0.998
5:55669259:G:C	C165W	0.998
5:55669578:G:C	S137R	0.998
5:55669578:G:T	S137R	0.998
5:55669580:T:G	S137R	0.998
5:55669594:C:T	G132E	0.998
5:55626528:C:T	G551D	0.997
5:55626651:C:T	G510E	0.997
5:55635638:G:T	A396D	0.997
5:55645850:G:T	A369D	0.997
5:55669321:C:G	A145P	0.997
5:55669605:A:C	N128K	0.997
5:55669605:A:T	N128K	0.997
5:55626652:C:G	G510R	0.996
5:55626652:C:T	G510R	0.996
5:55645834:A:C	N374K	0.996
5:55645834:A:T	N374K	0.996
5:55645859:A:G	L366P	0.996
5:55645865:C:T	G364E	0.996
5:55645866:C:G	G364R	0.996
5:55645866:C:T	G364R	0.996
5:55664734:A:G	L219P	0.996
5:55664741:A:G	W217R	0.996
5:55664741:A:T	W217R	0.996
5:55664759:C:G	G211R	0.996

dbSNP variants (sampled 300 via entrez): RS1000016038 (5:55707723 T>C), RS1000063940 (5:55694789 T>C), RS1000146290 (5:55694720 C>A,G,T), RS1000147353 (5:55673778 C>T), RS1000180417 (5:55673450 T>C), RS1000183146 (5:55652851 A>G), RS1000236492 (5:55662826 A>G), RS1000252440 (5:55656554 CT>C,CTT), RS1000289690 (5:55633338 C>G), RS1000303928 (5:55640485 G>T), RS1000435696 (5:55688340 T>C), RS1000499386 (5:55661302 A>G), RS1000514744 (5:55675180 G>C), RS1000547285 (5:55674750 T>C), RS1000627295 (5:55635232 C>T)

Disease associations

OMIM: gene MIM:616203 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
lysosomal storage disease	No Known Disease Relationship	UD

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000817_10	Height	2.000000e-12
GCST002647_147	Height	7.000000e-22
GCST002702_52	Height	3.000000e-11
GCST006979_102	Heel bone mineral density	3.000000e-14
GCST008163_426	Height	3.000000e-06
GCST008839_362	Height	3.000000e-21
GCST90020024_722	A body shape index	6.000000e-09
GCST90020025_484	Waist-to-hip ratio adjusted for BMI	2.000000e-15
GCST90020025_485	Waist-to-hip ratio adjusted for BMI	9.000000e-09
GCST90020025_486	Waist-to-hip ratio adjusted for BMI	2.000000e-11
GCST90020026_329	Hip index	8.000000e-13
GCST90020026_330	Hip index	5.000000e-09
GCST90020027_1964	Waist-hip index	4.000000e-17
GCST90020027_1965	Waist-hip index	8.000000e-10
GCST90020027_1966	Waist-hip index	2.000000e-12
GCST90020027_887	Waist-hip index	2.000000e-08
GCST90020029_1514	Waist circumference adjusted for body mass index	8.000000e-17
GCST90020029_1515	Waist circumference adjusted for body mass index	9.000000e-12
GCST90020029_1516	Waist circumference adjusted for body mass index	3.000000e-09
GCST90020029_1517	Waist circumference adjusted for body mass index	2.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

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

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
salinomycin	decreases expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
clothianidin	decreases expression	1
abrine	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	increases expression	1
Vanadates	increases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

10 cell lines: 8 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2G4	Abcam HeLa SLC38A9 KO	Cancer cell line	Female
CVCL_D4N8	HCT116-SLC38A9-KO-c1	Cancer cell line	Male
CVCL_D4N9	HCT116-SLC38A9-KO-c8	Cancer cell line	Male
CVCL_D7HJ	Ubigene HEK293T SLC38A9 KO	Transformed cell line	Female
CVCL_D8AG	Ubigene A-549 SLC38A9 KO	Cancer cell line	Male
CVCL_D8VD	Ubigene HCT 116 SLC38A9 KO	Cancer cell line	Male
CVCL_D9S0	Ubigene HEK293 SLC38A9 KO	Transformed cell line	Female
CVCL_E0NY	Ubigene HeLa SLC38A9 KO	Cancer cell line	Female
CVCL_TN48	HAP1 SLC38A9 (-) 1	Cancer cell line	Male
CVCL_TN49	HAP1 SLC38A9 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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