SLC7A5

Summary

SLC7A5 (solute carrier family 7 member 5, HGNC:11063) is a protein-coding gene on chromosome 16q24.2, encoding Large neutral amino acids transporter small subunit 1 (Q01650). The heterodimer with SLC3A2 functions as a sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, leucine, histidine, methionine, tryptophan, valine, isoleucine and alanine. It is a selective cancer dependency (DepMap: 25.8% of cell lines).

Enables L-amino acid transmembrane transporter activity and secondary active transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in several cellular components, including apical plasma membrane; cytosol; and microvillus membrane. Part of amino acid transport complex. Implicated in cholangiocarcinoma; colon cancer; hepatocellular carcinoma; and lung squamous cell carcinoma. Biomarker of esophagitis; gastrointestinal system cancer (multiple); malignant astrocytoma (multiple); and respiratory system cancer (multiple).

Source: NCBI Gene 8140 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, ClinGen)
• GWAS associations: 12
• Clinical variants (ClinVar): 99 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 25.8% of screened cell lines
• MANE Select transcript: NM_003486

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11063
Approved symbol	SLC7A5
Name	solute carrier family 7 member 5
Location	16q24.2
Locus type	gene with protein product
Status	Approved
Aliases	LAT1, E16, D16S469E, MPE16, CD98
Ensembl gene	ENSG00000103257
Ensembl biotype	protein_coding
OMIM	600182
Entrez	8140

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000261622, ENST00000563489, ENST00000565644, ENST00000850914

RefSeq mRNA: 1 — MANE Select: NM_003486 NM_003486

CCDS: CCDS10964

Canonical transcript exons

ENST00000261622 — 10 exons

Exon	Start	End
ENSE00000695886	87839702	87839825
ENSE00000695887	87838714	87838817
ENSE00000695889	87837845	87837941
ENSE00000695890	87836498	87836647
ENSE00001113644	87868885	87869507
ENSE00003469652	87834414	87834591
ENSE00003501556	87841050	87841155
ENSE00003512706	87851724	87851849
ENSE00003551045	87840429	87840473
ENSE00004282255	87830023	87833025

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 103.5546 / max 3160.0366, expressed in 1810 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158527	98.6714	1809
158526	1.5897	852
158499	0.8467	480
158493	0.5438	302
158495	0.4672	256
158491	0.3686	190
158525	0.3588	182
158497	0.1727	77
158494	0.1702	69
158496	0.1686	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	98.74	gold quality
retina	UBERON:0000966	98.71	gold quality
type B pancreatic cell	CL:0000169	98.27	gold quality
tongue squamous epithelium	UBERON:0006919	97.82	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.64	gold quality
pharyngeal mucosa	UBERON:0000355	97.27	gold quality
endometrium epithelium	UBERON:0004811	96.56	gold quality
inferior olivary complex	UBERON:0002127	95.87	gold quality
esophagus mucosa	UBERON:0002469	95.32	gold quality
body of tongue	UBERON:0011876	95.12	gold quality
corpus epididymis	UBERON:0004359	94.82	gold quality
medulla oblongata	UBERON:0001896	94.75	gold quality
left testis	UBERON:0004533	94.68	gold quality
right testis	UBERON:0004534	94.61	gold quality
ventral tegmental area	UBERON:0002691	94.52	gold quality
right frontal lobe	UBERON:0002810	94.52	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.36	gold quality
superior vestibular nucleus	UBERON:0007227	94.36	gold quality
subthalamic nucleus	UBERON:0001906	94.30	gold quality
substantia nigra pars compacta	UBERON:0001965	94.18	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.02	gold quality
hypothalamus	UBERON:0001898	93.89	gold quality
inferior vagus X ganglion	UBERON:0005363	93.85	gold quality
cartilage tissue	UBERON:0002418	93.83	gold quality
testis	UBERON:0000473	93.77	gold quality
midbrain	UBERON:0001891	93.72	gold quality
substantia nigra	UBERON:0002038	93.61	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.59	gold quality
tongue	UBERON:0001723	93.49	gold quality
lower esophagus mucosa	UBERON:0035834	93.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8559	yes	579.32
E-CURD-11	yes	85.24
E-HCAD-35	yes	20.74
E-CURD-122	yes	13.93
E-MTAB-9067	yes	12.87
E-ANND-3	yes	10.30
E-GEOD-135922	yes	9.55

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
DDIT3	Repression

Upstream regulators (CollecTRI, top): AHR, SP1

miRNA regulators (miRDB)

80 targeting SLC7A5, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-486-3P	99.51	66.82	1901

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• study indicates the functional interaction between CD98 and CD147 in the regulation of cell fusion (PMID:12925876)
• Increased LAT1 expression can be induced by lipid oxidation products relevant to inflammatory responses in atherogenesis. LAT1 mediates lysophosphatidylcholine-enhanced cytokine production by endothelial cells. (PMID:15178563)
• Differences in L-DOPA handling between SHR and WKY cells may result from over-expression of LAT1 and LAT2 transporters in the former. (PMID:15200428)
• studies demonstrate that the only known SNP in the open reading frame of human LAT1 has no effect on the kinetics of large neutral amino acid transport via this carrier (PMID:15589117)
• identify LAT1 and LAT2 as members of system L that mediate transmembrane movement of l-CSNO (PMID:15769744)
• In vivo efforts focusing on LAT1/CD98 as a potential therapeutic target in liver cells. (PMID:15900591)
• LAT1 expression may increase with the upregulation of metabolic activity and cell proliferation in high-grade atypical adenomatous hyperplasia and bronchioloalveolar carcinoma. (PMID:16175382)
• Findings suggest that LAT1 could be one of the molecular targets in glioma therapy. (PMID:16496379)
• Genetic variation in LAT1 and LAT2 does not appear to be a major cause of inter-individual variability in pharmacokinetics and of adverse reactions to melphalan. (PMID:17558306)
• expression of LAT1 protein and mRNA in 124 cases of transitional cell carcinoma of the upper urinary tract was examined; detection of the active form LAT1 protein appears to be of value in informing the risk of progression (PMID:17622555)
• The expression of LAT1 was always higher in infiltrating glioma cells than in cells located in the center of the tumor. (PMID:18095110)
• Overexpression of L-type amino acid transporter 1 is associated with nonsmall cell lung cancer (PMID:18253116)
• This study demonstrated that LAT1 is involved in 90% of total uptake of tyrosine and also around 51% of alanine. Not more than 10% can be accounted for by LAT2, LAT3 and LAT4 isoforms. (PMID:18262359)
• Comparative immunohistochemical analyses of normal human tissues with anti-CD98 hc and anti-LAT1 revealed LAT1 to be an excellent molecular target for antibody therapy, possibly even superior to CD98 hc. (PMID:18294274)
• LAT1 may play an important role in enhancing the rates of tumor cell proliferation and growth in vivo. (PMID:18382329)
• Expression of LAT1 tended to increase from low-grade to high-grade neuroendocrine tumors. (PMID:18440724)
• Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast cancer cells. (PMID:18813831)
• LAT1 expression in primary and metastatic neoplasms is reported. (PMID:19018776)
• Elevated expression of CD98 is associated with squamous cell carcinoma of the lung. (PMID:19068093)
• elevated LAT1 expression in prostate cancers is a novel independent biomarker of high-grade malignancy (PMID:19121087)
• over expression of Lat1 is a pathological factor to predict the prognosis in patients with resectable stage I pulmonary adenocarcinoma (PMID:19171406)
• LAT1 is frequently expressed in thymic carcinomas but is absent in thymomas (PMID:19347882)
• the percentage of lung carcinoma patients remaining unclassifiable by TTF-1/TP63 was twice that of the five-antibody (TRIM29, CEACAM5, SLC7A5, MUC1, and CK5/6) test (PMID:19430419)
• higher mRNA levels in non-small-cell lung carcinomas compared to normal lung tissues (PMID:19559497)
• Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis in surgically resected stage I non-small cell lung cancer. (PMID:19635099)
• High LAT1 expression is associated with non-small-cell lung cancer with lymph node metastases. (PMID:19777189)
• High expression of LAT1 and increased L-methyl-11C-methionine uptake is associated with high-grade gliomas. (PMID:20091333)
• Host protein CD98 contributes to protection against enteropathogenic Escherichia coli-mediated cytotoxicity by interacion with bacterial sepZ protein. (PMID:20374249)
• upregulation of LAT1 is associated with ovarian cancer. (PMID:20375792)
• LAT1 increased expression in human ovarian cancer cell lines makes it a possible target for combination therapy with anti-proliferative aminopeptidase inhibitors. (PMID:20510678)
• LAT1 may have a critical and complex role in regulating human leiomyoma cell growth. (PMID:20601542)
• LAT1 mRNA was detectable only in fresh-frozen tissues of TSC, and it was upregulated in the cortical tuber lesion (PMID:20680301)
• LAT1 expression is a stronger prognostic factor than (18)F-FAMT uptake in surgically resected non-small cell lung cancer (PMID:21055621)
• All these results indicate essential roles of LAT1 in the cell proliferation and occurrence of malignant phenotypes. (PMID:21371427)
• Data shwo that SLC7A5 is a direct target of miR-126. (PMID:21439283)
• Compared with the adult cerebral cortex, mRNAs encoding OATP1A2, OATP1C1, OATP3A1 variant 2, OATP4A1, LAT2 and CD98 were reduced in fetal cortex at different gestational ages, whilst mRNAs encoding MCT8, MCT10, OATP3A1 variant 1 and LAT1 were similar. (PMID:21486766)
• LAT 1 expression may be linked with cell proliferation and prognosis of gastric carcinomas. (PMID:21501294)
• LAT1 expression decreases because of human papillomavirus infection as reflected by p16 overexpression in cervical intraepithelial neoplasia, whereas LAT1 expression in invasive carcinoma is associated with acquired malignant potential (PMID:21530999)
• Variations in the ability of LAT1/DMT1/MTF1/MT1a to process and transport Hg may not play a significant role in the etiology of autism. (PMID:21798283)
• Data show that signaling via the androgen receptor and ATF4 pathways regulates expression of the amino acid transporters LAT1 and LAT3, thereby coordinating their increased expression in prostate cancer cells. (PMID:22007000)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc7a5	ENSDARG00000099265
mus_musculus	Slc7a5	ENSMUSG00000040010
rattus_norvegicus	Slc7a5	ENSRNOG00000018824
drosophila_melanogaster	mnd	FBGN0002778
drosophila_melanogaster	CG7255	FBGN0036493
drosophila_melanogaster	CG5535	FBGN0036764
drosophila_melanogaster	slif	FBGN0037203
drosophila_melanogaster	CG1607	FBGN0039844
caenorhabditis_elegans		WBGENE00000002
caenorhabditis_elegans		WBGENE00000003
caenorhabditis_elegans		WBGENE00000005
caenorhabditis_elegans	aat-9	WBGENE00000010
caenorhabditis_elegans		WBGENE00015197
caenorhabditis_elegans		WBGENE00017747

Paralogs (12): SLC7A2 (ENSG00000003989), SLC7A14 (ENSG00000013293), SLC7A9 (ENSG00000021488), SLC7A8 (ENSG00000092068), SLC7A4 (ENSG00000099960), SLC7A6 (ENSG00000103064), SLC7A10 (ENSG00000130876), SLC7A1 (ENSG00000139514), SLC7A11 (ENSG00000151012), SLC7A7 (ENSG00000155465), SLC7A13 (ENSG00000164893), SLC7A3 (ENSG00000165349)

Protein

Protein identifiers

Large neutral amino acids transporter small subunit 1 — Q01650 (reviewed: Q01650)

Alternative names: 4F2 light chain, CD98 light chain, Integral membrane protein E16, L-type amino acid transporter 1, Solute carrier family 7 member 5, y+ system cationic amino acid transporter

All UniProt accessions (2): Q01650, A0A0C4DGL4

UniProt curated annotations — full annotation on UniProt →

Function. The heterodimer with SLC3A2 functions as a sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, leucine, histidine, methionine, tryptophan, valine, isoleucine and alanine. The heterodimer with SLC3A2 mediates the uptake of L-DOPA. Functions as an amino acid exchanger. May play a role in the transport of L-DOPA across the blood-brain barrier. May act as the major transporter of tyrosine in fibroblasts. May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier. Can mediate the transport of thyroid hormones diiodothyronine (T2), triiodothyronine (T3) and thyroxine (T4) across the cell membrane. When associated with LAPTM4B, the heterodimer formed by SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation. Involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the membrane. (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis.

Subunit / interactions. Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc. Interacts with LAPTM4B; this recruits the heterodimer formed by SLC3A2/4F2hc and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation.

Subcellular location. Apical cell membrane. Cell membrane. Lysosome membrane.

Tissue specificity. Detected in placenta, in the syncytiotrophoblast layer (at protein level). Expressed abundantly in adult lung, liver, brain, skeletal muscle, placenta, bone marrow, testis, resting lymphocytes and monocytes, and in fetal liver. Weaker expression in thymus, cornea, retina, peripheral leukocytes, spleen, kidney, colon and lymph node. During gestation, expression in the placenta was significantly stronger at full-term than at the mid-trimester stage. Also expressed in all human tumor cell lines tested and in the astrocytic process of primary astrocytic gliomas. Expressed in retinal endothelial cells and in the intestinal epithelial cell line Caco-2.

Activity regulation. The uptake of leucine, tyrosine and tryptophan is inhibited by the different iodothyronines, in particular T3. The uptake of T3 is almost completely blocked by coincubation with leucine, tryptophan, tyrosine, and phenylalanine, or 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH). Methionine uptake was inhibited by the L-system substrates L-leucine, BCH, L-cysteine and by the MeHg-L-cysteine complex and structurally related S-ethyl-L-cysteine. MeHg-L-cysteine uptake is inhibited by L-methionine, L-leucine, BCH and S-ethyl-L-cysteine. L-leucine transport is inhibited by phenylalanine, tyrosine, L-dopa, 3-O-methyldopa, a-methyltyrosine, a-methyldopa, gabapentin, triiodothyronine, thyroxine, melphalan and BCH. L-leucine uptake was inhibited by L-CNSO. Tyrosine uptake in fibroblasts was inhibited by D-methionine, and methyl-aminoisobutyric acid (MeAIB).

Induction. (Microbial infection) Up-regulation of the complex formed by SLC3A2 and SLC7A5/LAT1 upon hepatitis C virus/HCV infection. Expression induced in quiescent peripheral blood lymphocytes after treatment with phorbol myristate acetate (PMA) and phytohemagglutinin (PHA). Expression and the uptake of leucine is stimulated in mononuclear, cytotrophoblast-like choriocarcinoma cells by combined treatment with PMA and calcium ionophore.

Similarity. Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.

RefSeq proteins (1): NP_003477* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002293	AA/rel_permease1	Family
IPR004760	L_AA_transporter	Family
IPR050598	AminoAcid_Transporter	Family

Pfam: PF13520

Catalyzed reactions (Rhea), 12 shown:

• L-phenylalanine(in) = L-phenylalanine(out) (RHEA:27950)
• L-valine(in) = L-valine(out) (RHEA:29703)
• L-tyrosine(in) = L-tyrosine(out) (RHEA:68572)
• L-alanine(in) = L-alanine(out) (RHEA:70719)
• L-methionine(in) = L-methionine(out) (RHEA:70939)
• L-isoleucine(in) = L-isoleucine(out) (RHEA:70943)
• L-tryptophan(in) = L-tryptophan(out) (RHEA:70947)
• 3,3’,5-triiodo-L-thyronine(out) = 3,3’,5-triiodo-L-thyronine(in) (RHEA:71811)
• L-thyroxine(out) = L-thyroxine(in) (RHEA:71819)
• 3,3’-diiodo-L-thyronine(out) = 3,3’-diiodo-L-thyronine(in) (RHEA:71823)
• L-histidine(out) = L-histidine(in) (RHEA:72807)
• L-leucine(in) = L-leucine(out) (RHEA:73011)

UniProt features (91 total): helix 24, topological domain 13, transmembrane region 12, mutagenesis site 10, turn 8, sequence conflict 6, strand 6, modified residue 3, compositionally biased region 2, cross-link 2, sequence variant 2, chain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
7DSK	ELECTRON MICROSCOPY	2.9
7DSL	ELECTRON MICROSCOPY	2.9
7DSN	ELECTRON MICROSCOPY	3.1
8X0W	ELECTRON MICROSCOPY	3.1
8IDA	ELECTRON MICROSCOPY	3.2
6IRS	ELECTRON MICROSCOPY	3.3
8XPU	ELECTRON MICROSCOPY	3.3
6JMQ	ELECTRON MICROSCOPY	3.31
7DSQ	ELECTRON MICROSCOPY	3.4
6IRT	ELECTRON MICROSCOPY	3.5
8J8L	ELECTRON MICROSCOPY	3.56
8J8M	ELECTRON MICROSCOPY	3.58
8KDI	ELECTRON MICROSCOPY	3.58
8KDG	ELECTRON MICROSCOPY	3.68
8KDJ	ELECTRON MICROSCOPY	3.73
8KDH	ELECTRON MICROSCOPY	3.78
8KDD	ELECTRON MICROSCOPY	3.83
8KDF	ELECTRON MICROSCOPY	3.89
8KDN	ELECTRON MICROSCOPY	4.12
8KDO	ELECTRON MICROSCOPY	4.12
8KDP	ELECTRON MICROSCOPY	4.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01650-F1	86.44	0.57

Antibody-complex structures (SAbDab): 3 — 8KDD, 8KDG, 8KDI

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 (5): 31, 35, 45, 19, 30

Disulfide bonds (1): 164

Mutagenesis-validated functional residues (10):

Position	Phenotype
117	strongly decreased leucine transport activity.
246	nearly abolishes leucine transport activity.
252	nearly abolishes leucine transport activity.
257	nearly abolishes leucine transport activity.
258	decreased leucine transport activity.
258	nearly abolishes leucine transport activity.
259	strongly decreased leucine transport activity.
303	decreased leucine transport activity.
375	nearly abolishes leucine transport activity.
483–507	nearly abolishes leucine transport activity.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-210991	Basigin interactions
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-71240	Tryptophan catabolism
R-HSA-109582	Hemostasis
R-HSA-1430728	Metabolism
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 515 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_RESPONSE_TO_ACID_CHEMICAL, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_VACUOLAR_MEMBRANE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (38): positive regulation of cytokine production involved in immune response (GO:0002720), amino acid transmembrane transport (GO:0003333), negative regulation of autophagy (GO:0010507), negative regulation of gene expression (GO:0010629), response to muscle activity (GO:0014850), neutral amino acid transport (GO:0015804), isoleucine transport (GO:0015818), L-leucine transport (GO:0015820), methionine transport (GO:0015821), phenylalanine transport (GO:0015823), proline transport (GO:0015824), tryptophan transport (GO:0015827), tyrosine transport (GO:0015828), valine transport (GO:0015829), alanine transport (GO:0032328), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-17 production (GO:0032740), positive regulation of interleukin-4 production (GO:0032753), cellular response to glucose starvation (GO:0042149), xenobiotic transport (GO:0042908), response to hyperoxia (GO:0055093), positive regulation of glial cell proliferation (GO:0060252), thyroid hormone transport (GO:0070327), cellular response to lipopolysaccharide (GO:0071222), amino acid import across plasma membrane (GO:0089718), liver regeneration (GO:0097421), transport across blood-brain barrier (GO:0150104), L-histidine transport (GO:1902024), cellular response to L-arginine (GO:1903577), L-leucine import across plasma membrane (GO:1903801), L-tryptophan transmembrane transport (GO:1904556), negative regulation of vascular associated smooth muscle cell apoptotic process (GO:1905460), positive regulation of L-leucine import across plasma membrane (GO:1905534), amino acid transport (GO:0006865), L-amino acid transport (GO:0015807), transmembrane transport (GO:0055085), cellular response to amino acid stimulus (GO:0071230), L-alpha-amino acid transmembrane transport (GO:1902475)

GO Molecular Function (11): amino acid transmembrane transporter activity (GO:0015171), aromatic amino acid transmembrane transporter activity (GO:0015173), neutral L-amino acid transmembrane transporter activity (GO:0015175), L-amino acid transmembrane transporter activity (GO:0015179), L-leucine transmembrane transporter activity (GO:0015190), L-tryptophan transmembrane transporter activity (GO:0015196), antiporter activity (GO:0015297), thyroid hormone transmembrane transporter activity (GO:0015349), peptide antigen binding (GO:0042605), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (12): lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), microvillus membrane (GO:0031528), extracellular exosome (GO:0070062), external side of apical plasma membrane (GO:0098591), amino acid transport complex (GO:1990184), lysosome (GO:0005764)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1
SLC-mediated transport of amino acids	1
Metabolism of amino acids and derivatives	1
Hemostasis	1
Transport of small molecules	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neutral amino acid transport	6
positive regulation of cytokine production	4
amino acid transport	4
branched-chain amino acid transport	3
L-amino acid transport	3
aromatic amino acid transport	3
plasma membrane region	3
transmembrane transport	2
carboxylic acid transport	2
nitrogen compound transport	2
carboxylic acid transmembrane transporter activity	2
amino acid transmembrane transporter activity	2
L-amino acid transmembrane transporter activity	2
secondary active transmembrane transporter activity	2
cellular anatomical structure	2
cytokine production involved in immune response	1
positive regulation of production of molecular mediator of immune response	1
regulation of cytokine production involved in immune response	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
response to activity	1
sulfur amino acid transport	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-17 production	1
regulation of interleukin-17 production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
cellular response to starvation	1
transport	1
amino acid transmembrane transport	1
transmembrane transporter activity	1
L-alpha-amino acid transmembrane transport	1
neutral L-amino acid transmembrane transporter activity	1
branched-chain amino acid transmembrane transporter activity	1
aromatic amino acid transmembrane transporter activity	1

Protein interactions and networks

STRING

2270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC7A5	SLC3A2	P08195	999
SLC7A5	SLC43A1	O75387	913
SLC7A5	LLGL2	Q6P1M3	883
SLC7A5	SLC3A1	Q07837	876
SLC7A5	SLC1A5	Q15758	834
SLC7A5	ASNS	P08184	806
SLC7A5	SLC43A2	Q8N370	794
SLC7A5	SLC38A2	Q96QD8	768
SLC7A5	FGD6	Q6ZV73	713
SLC7A5	SLC7A8	Q9UHI5	712
SLC7A5	SLC38A1	Q9H2H9	707
SLC7A5	TRIB3	Q96RU7	685
SLC7A5	USP16	Q9Y5T5	648
SLC7A5	SLC1A1	P43005	645
SLC7A5	TRMT2A	Q8IZ69	643

IntAct

113 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
SLC3A2	SLC7A5	psi-mi:“MI:0407”(direct interaction)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
SLC7A5	SLC3A2	psi-mi:“MI:0195”(covalent binding)	0.600
SLC7A5	SLC3A2	psi-mi:“MI:0407”(direct interaction)	0.600
SLC3A2	SLC7A5	psi-mi:“MI:0195”(covalent binding)	0.600
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
	DENR	psi-mi:“MI:0915”(physical association)	0.400
NCSTN	ESYT2	psi-mi:“MI:0914”(association)	0.350
Smn1	CLNS1A	psi-mi:“MI:0914”(association)	0.350
Tmed2		psi-mi:“MI:0914”(association)	0.350
MBOAT1	DERL1	psi-mi:“MI:0914”(association)	0.350
TUBA1C	TCP11L2	psi-mi:“MI:0914”(association)	0.350
TMEM63B	CAV1	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
OCRL	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (302): SLC7A5 (Affinity Capture-MS), SLC7A5 (Proximity Label-MS), SLC7A5 (Proximity Label-MS), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-RNA), SLC7A5 (Affinity Capture-MS), SLC7A5 (Affinity Capture-MS)

ESM2 similar proteins: A1L3M3, A7MBD8, B3TP03, B5D5N9, D3ZMM8, O08812, O61369, P11170, P13866, P18581, P30823, P30825, P52569, P70423, P83740, Q01650, Q09143, Q1EHB4, Q22397, Q28I80, Q3ZMH1, Q49B93, Q59I64, Q5BL81, Q5PR34, Q5RAE3, Q5RAG7, Q5RKI7, Q63016, Q6DCE8, Q7SYH5, Q7T384, Q7YQK4, Q8BGK6, Q8BYF6, Q8N695, Q8TCU3, Q8WY07, Q91WN3, Q92536

Diamond homologs: A1L3M3, D3ZMM8, O34739, P63115, P63116, P82251, P82252, Q01650, Q22397, Q28I80, Q59I64, Q5RAE3, Q5RAG7, Q5RKI7, Q63016, Q7YQK4, Q8BGK6, Q8MH63, Q8TCU3, Q91WN3, Q92536, Q9GIP4, Q9N1Q4, Q9N1R6, Q9NS82, Q9QXA6, Q9QXW9, Q9R0S5, Q9UHI5, Q9UM01, Q9UPY5, Q9WTR6, Q9WVR6, Q9Z127, Q9Z1K8, Q8VIE6, A0JNI9, A8I499, B0UYF2, B3TP03

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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
Basigin interactions	5	27.8×	1e-04
Signaling by BRAF and RAF1 fusions	5	10.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
MAPK cascade	7	11.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	11
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

1658 predictions. Top by Δscore:

Variant	Effect	Δscore
16:87833024:GA:G	acceptor_gain	1.0000
16:87833024:GAC:G	acceptor_loss	1.0000
16:87833025:ACT:A	acceptor_loss	1.0000
16:87833026:C:A	acceptor_loss	1.0000
16:87833026:C:CC	acceptor_gain	1.0000
16:87833027:T:C	acceptor_loss	1.0000
16:87834405:GATAC:G	donor_loss	1.0000
16:87834406:ATACT:A	donor_loss	1.0000
16:87834407:TACT:T	donor_loss	1.0000
16:87834410:TCACA:T	donor_loss	1.0000
16:87834411:CACA:C	donor_loss	1.0000
16:87834412:A:AC	donor_gain	1.0000
16:87834413:C:CT	donor_gain	1.0000
16:87834413:CAG:C	donor_gain	1.0000
16:87834587:TTCAC:T	acceptor_gain	1.0000
16:87834588:TCAC:T	acceptor_gain	1.0000
16:87834588:TCACC:T	acceptor_loss	1.0000
16:87834589:CAC:C	acceptor_gain	1.0000
16:87834589:CACC:C	acceptor_gain	1.0000
16:87834590:ACC:A	acceptor_loss	1.0000
16:87834592:C:CC	acceptor_gain	1.0000
16:87834592:CTGG:C	acceptor_loss	1.0000
16:87834593:T:G	acceptor_loss	1.0000
16:87834598:C:CT	acceptor_gain	1.0000
16:87836493:CTCA:C	donor_loss	1.0000
16:87836494:TCAC:T	donor_loss	1.0000
16:87836495:CA:C	donor_loss	1.0000
16:87836496:A:AT	donor_loss	1.0000
16:87836643:ACACA:A	acceptor_gain	1.0000
16:87836644:CACA:C	acceptor_gain	1.0000

AlphaMissense

3248 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:87841051:A:G	W257R	1.000
16:87841051:A:T	W257R	1.000
16:87869158:A:G	W89R	1.000
16:87869158:A:T	W89R	1.000
16:87869216:G:C	F69L	1.000
16:87869216:G:T	F69L	1.000
16:87869218:A:G	F69L	1.000
16:87837921:C:G	R355P	0.999
16:87838714:C:A	R348M	0.999
16:87838714:C:G	R348T	0.999
16:87838735:C:T	G341E	0.999
16:87838736:C:A	G341W	0.999
16:87838736:C:G	G341R	0.999
16:87838736:C:T	G341R	0.999
16:87838737:A:C	N340K	0.999
16:87838737:A:T	N340K	0.999
16:87838752:G:C	C335W	0.999
16:87838753:C:T	C335Y	0.999
16:87839706:G:T	A312D	0.999
16:87840461:A:C	N261K	0.999
16:87840461:A:T	N261K	0.999
16:87840473:C:A	W257C	0.999
16:87840473:C:G	W257C	0.999
16:87841064:A:C	F252L	0.999
16:87841064:A:T	F252L	0.999
16:87841066:A:G	F252L	0.999
16:87841071:C:T	G250D	0.999
16:87841072:C:G	G250R	0.999
16:87851830:G:C	N186K	0.999
16:87851830:G:T	N186K	0.999

dbSNP variants (sampled 300 via entrez): RS1000165615 (16:87846237 T>A), RS1000218071 (16:87855183 C>T), RS1000275601 (16:87842478 C>T), RS1000360406 (16:87863739 C>A), RS1000478920 (16:87841743 G>A), RS1000508504 (16:87838448 C>A,T), RS1000519993 (16:87852116 C>A,T), RS1000592255 (16:87837010 T>A), RS1000608372 (16:87859423 C>T), RS1000613394 (16:87829865 G>A), RS1000619279 (16:87870450 C>G), RS1000753603 (16:87870608 T>C), RS1000772617 (16:87837253 T>C), RS1000802445 (16:87852738 C>A,T), RS1000839715 (16:87848995 G>A)

Disease associations

OMIM: gene MIM:600182 | disease phenotypes: MIM:261600

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	AR

Mondo (3): autism spectrum disorder (MONDO:0005258), phenylketonuria (MONDO:0009861), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (2): Phenylketonuria (Orphanet:716), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004602_282	Mean corpuscular volume	4.000000e-20
GCST004630_206	Mean corpuscular hemoglobin	8.000000e-17
GCST012020_517	Serum metabolite levels	5.000000e-22
GCST90002383_51	Hematocrit	2.000000e-11
GCST90002384_394	Hemoglobin	4.000000e-12
GCST90002390_96	Mean corpuscular hemoglobin	9.000000e-52
GCST90002392_512	Mean corpuscular volume	4.000000e-60
GCST90002396_597	Mean reticulocyte volume	2.000000e-71
GCST90002397_716	Mean spheric corpuscular volume	5.000000e-63
GCST90002399_274	Neutrophil percentage of white cells	3.000000e-09
GCST90002400_188	Plateletcrit	2.000000e-16
GCST90002402_472	Platelet count	4.000000e-19

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0010701	mean reticulocyte volume
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010661	Phenylketonurias	C10.228.140.163.100.687; C16.320.565.100.766; C16.320.565.189.687; C18.452.132.100.687; C18.452.648.100.766; C18.452.648.189.687

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4459 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,730,763 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1009	LEVODOPA	4	103,854
CHEMBL925	TYROSINE	4	703,519
CHEMBL291962	LEUCINE	3	617,878
CHEMBL301523	PHENYLALANINE	3	530,828
CHEMBL17962	HISTIDINE	2	1,294,563
CHEMBL43068	VALINE	2	480,121

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4240803	Toxicity	3	melphalan	Multiple Myeloma
rs4240803	Toxicity	3	pregabalin	adverse events;Neuropathic pain
rs4240803	Toxicity	3	gabapentin	adverse events;Neuropathic pain
rs4240803	Efficacy	3	gabapentin	Neuropathic pain
rs4240803	Dosage	3	gabapentin	Neuropathic pain
rs4240803	Efficacy	3	pregabalin	Neuropathic pain

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4240803	SLC7A5	3	3.25	6	gabapentin;pregabalin;melphalan

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC7 family

Binding affinities (BindingDB)

36 measured of 36 human assays (36 total across all organisms); most potent 36 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-2-Amino-3-(5-(N-(3-bromophenyl)sulfamoyl)-2-methylphenyl)propanoic Acid	IC50	9 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-(N-(4-methoxyphenyl)sulfamoyl)-2-methylphenyl)propanoic Acid	IC50	10 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-(N-(4-chlorophenyl)sulfamoyl)-2-isopropylphenyl)propanoic Acid	IC50	10 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-(N-(4-bromophenyl)sulfamoyl)-2-methylphenyl)propanoic Acid	IC50	12 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-(N-(4-chlorophenyl)sulfamoyl)-2-methylphenyl)propanoic Acid	IC50	12 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-(N-benzylsulfamoyl)-2-methylphenyl)propanoic Acid	IC50	20 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(2-methyl-5-(N-(naphthalen-1-yl)sulfamoyl)phenyl)propanoic Acid	IC50	24 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-3-(5-(N-([1,1’-Biphenyl]-4-yl)sulfamoyl)-2-methylphenyl)-2-aminopropanoic Acid	IC50	25 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(2-methyl-5-(N-phenylsulfamoyl)phenyl)propanoic Acid Hydrochloride	IC50	30 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-((3-bromophenyl)sulfonamido)-2-methylphenyl)propanoic Acid	IC50	40 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-3-(5-([1,1’-Biphenyl]-3-sulfonamido)-2-methylphenyl)-2-aminopropanoic Acid	IC50	40 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-((5-(dimethylamino)naphthalene)-1-sulfonamido)-2-isopropylphenyl)propanoic Acid	IC50	50 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-(N-butylsulfamoyl)-2-methylphenyl)propanoic Acid	IC50	56 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-(N-cyclohexylsulfamoyl)-2-methylphenyl)propanoic Acid	IC50	60 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(3-(N-(4-chlorophenyl)sulfamoyl)phenyl)propanoic Acid	IC50	80 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-(N-(5-(dimethylamino)naphthalen-1-yl)sulfamoyl)-2-methylphenyl)propanoic Acid	IC50	80 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(2-methyl-5-(phenylsulfonamido)phenyl)propanoic Acid	IC50	100 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(S)-2-Amino-3-(5-((4-(tert-butyl)phenyl)sulfonamido)-2-methylphenyl)propanoic Acid	IC50	100 nM	US-20250319046: PHENYLALANINE-BASED LAT1 INHIBITORS AND USES THEREOF
(5R)-5-phenyl-5-[4-(trifluoromethoxy)phenoxy]pentan-1-amine	IC50	10400 nM	US-9771316: Phenoxyalkylamine compound
(5R)-5-[3-fluoro-4-(trifluoromethoxy)phenoxy]-5-phenylpentan-1-amine	IC50	36400 nM	US-9771316: Phenoxyalkylamine compound
5-phenyl-5-[4-(trifluoromethoxy)phenoxy]pentan-1-amine	IC50	39400 nM	US-9771316: Phenoxyalkylamine compound
5-thiophen-2-yl-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	56600 nM	US-9771316: Phenoxyalkylamine compound
5-(4-butan-2-ylphenoxy)-5-phenylpentan-1-amine	IC50	57000 nM	US-9771316: Phenoxyalkylamine compound
5-phenyl-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	57500 nM	US-9771316: Phenoxyalkylamine compound
(5R)-5-phenyl-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	62800 nM	US-9771316: Phenoxyalkylamine compound
5-(3-fluorophenyl)-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	63000 nM	US-9771316: Phenoxyalkylamine compound
(5S)-5-[3-fluoro-4-(trifluoromethyl)phenoxy]-5-phenylpentan-1-amine	IC50	69000 nM	US-9771316: Phenoxyalkylamine compound
5-[3-fluoro-4-(trifluoromethyl)phenoxy]-5-phenylpentan-1-amine	IC50	76000 nM	US-9771316: Phenoxyalkylamine compound
6-phenyl-6-[4-(trifluoromethyl)phenoxy]hexan-1-amine	IC50	89100 nM	US-9771316: Phenoxyalkylamine compound
(5S)-5-phenyl-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	96200 nM	US-9771316: Phenoxyalkylamine compound
CHEMBL2074957	IC50	112000 nM
5-thiophen-2-yl-5-[4-(trifluoromethoxy)phenoxy]pentan-1-amine	IC50	123000 nM	US-9771316: Phenoxyalkylamine compound
5-[3-fluoro-4-(trifluoromethoxy)phenoxy]-5-thiophen-2-ylpentan-1-amine	IC50	146000 nM	US-9771316: Phenoxyalkylamine compound
5-[3-fluoro-4-(trifluoromethyl)phenoxy]-5-thiophen-2-ylpentan-1-amine	IC50	177000 nM	US-9771316: Phenoxyalkylamine compound
(5S)-5-phenyl-5-[4-(trifluoromethoxy)phenoxy]pentan-1-amine	IC50	244000 nM	US-9771316: Phenoxyalkylamine compound
5-(4-butan-2-ylphenoxy)-5-thiophen-2-ylpentan-1-amine	IC50	261000 nM	US-9771316: Phenoxyalkylamine compound

ChEMBL bioactivities

13 potent at pChembl≥5 of 51 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	IC50	60	nM	CHEMBL4538666
6.10	IC50	790	nM	CHEMBL4538666
6.01	IC50	980	nM	CHEMBL4526588
5.92	Kd	1189	nM	CHEMBL5653589
5.92	ED50	1189	nM	CHEMBL5653589
5.65	Kd	2219	nM	CHEMBL3752910
5.65	ED50	2219	nM	CHEMBL3752910
5.46	IC50	3480	nM	CHEMBL4642431
5.18	IC50	6600	nM	CHEMBL58129
5.14	IC50	7300	nM	CHEMBL3809112
5.04	IC50	9100	nM	CHEMBL3809645

PubChem BioAssay actives

11 with measured affinity, of 400 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-amino-3-[4-[(5-amino-2-phenyl-1,3-benzoxazol-7-yl)methoxy]-3,5-dichlorophenyl]propanoic acid	1626036: Inhibition of [14C]-L-leucine uptake at LAT1 in human HT-29 cells after 1 hr by liquid scintillation counting	ic50	0.0600	uM
4-chloro-N-[5-(trifluoromethoxy)-2-pyridinyl]dithiazol-5-imine	1608434: Inhibition of recombinant human LAT1	ic50	0.9800	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149434: Binding affinity to human SLC7A5 incubated for 45 mins by Kinobead based pull down assay	kd	1.1894	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149434: Binding affinity to human SLC7A5 incubated for 45 mins by Kinobead based pull down assay	kd	2.2190	uM
(2R)-N-benzyl-3-cyclohexyl-2-[(3S)-4-(3-methylbutyl)-3-(2-methylpropyl)piperazin-1-yl]propan-1-amine	1654351: Induction of LAT1-mediated polyamine efflux in human L3.6PL cells assessed as reduction in cell viability after 48 hrs by MTS assay	ic50	3.4800	uM
(2S)-2-amino-3-(3-phenylphenyl)propanoic acid	1303220: Inhibition of human LAT1 expressed in HEK cells assessed as reduction in uptake of [3H]-gabapentin after 3 mins by scintillation counting based cis-inhibition assay	ic50	6.6000	uM
(2S)-2-amino-3-(3-benzylphenyl)propanoic acid	1303220: Inhibition of human LAT1 expressed in HEK cells assessed as reduction in uptake of [3H]-gabapentin after 3 mins by scintillation counting based cis-inhibition assay	ic50	7.3000	uM
(2S)-2-amino-3-(3-benzyl-4-hydroxyphenyl)propanoic acid	1303220: Inhibition of human LAT1 expressed in HEK cells assessed as reduction in uptake of [3H]-gabapentin after 3 mins by scintillation counting based cis-inhibition assay	ic50	9.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, affects cotreatment, increases expression	14
Estradiol	affects cotreatment, decreases expression, increases expression	11
bisphenol A	affects expression, increases expression, decreases expression	9
Valproic Acid	affects cotreatment, increases expression, increases methylation	8
Cyclosporine	decreases expression, increases expression	6
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
Benzo(a)pyrene	affects methylation, increases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
Acetaminophen	increases expression, decreases expression	4
Tretinoin	decreases expression, increases expression	4
Genistein	increases reaction, increases expression	4
Particulate Matter	increases expression, affects cotreatment, increases abundance	4
trichostatin A	affects cotreatment, increases expression	3
nickel sulfate	increases expression	3
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	3
Cisplatin	affects expression, decreases expression, increases expression	3
Methylmercury Compounds	increases expression, affects transport, increases uptake	3
Tobacco Smoke Pollution	increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	increases expression	2
entinostat	increases expression, affects cotreatment	2
bisphenol S	increases expression, affects expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Zoledronic Acid	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Diethylstilbestrol	increases expression	2
Ethinyl Estradiol	affects expression, increases expression	2
Nickel	increases expression	2

ChEMBL screening assays

80 unique, capped per target: 71 binding, 9 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1119374	Binding	Activity at LAT1 by Michaelis-Menten constant	Regiospecific and conformationally restrained analogs of melphalan and DL-2-NAM-7 and their affinities for the large neutral amino acid transporter (system LAT1) of the blood-brain barrier. — Bioorg Med Chem Lett
CHEMBL4235005	ADMET	Drug uptake in human MCF7 cells assessed as LAT1-mediated drug transportation rate at 3.125 to 100 uM after 10 mins by LC-MS analysis	Secondary carbamate linker can facilitate the sustained release of dopamine from brain-targeted prodrug. — Bioorg Med Chem Lett

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4QH	HCT116-SLC7A5-KO-c12	Cancer cell line	Male
CVCL_D4QI	HCT116-SLC7A5-KO-c21	Cancer cell line	Male
CVCL_D8VF	Ubigene HCT 116 SLC7A5 KO	Cancer cell line	Male
CVCL_D9S4	Ubigene HEK293 SLC7A5 KO	Transformed cell line	Female
CVCL_DX59	HAP1 SLC7A5 (-) SLC7A8 (-) 1	Cancer cell line	Male
CVCL_DX60	HAP1 SLC7A5 (-) SLC7A8 (-) 2	Cancer cell line	Male
CVCL_E0P4	Ubigene HeLa SLC7A5 KO	Cancer cell line	Female
CVCL_TP14	HAP1 SLC7A5 (-) 1	Cancer cell line	Male
CVCL_XT35	HAP1 SLC7A5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder