Affinage

SLC7A7

Y+L amino acid transporter 1 · UniProt Q9UM01

Length
511 aa
Mass
56.0 kDa
Annotated
2026-06-10
85 papers in source corpus 25 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC7A7 encodes y+LAT1, the catalytic light subunit of the heterodimeric system y+L amino acid transporter, which mediates cationic amino acid transport in epithelial and myeloid cells and whose loss causes lysinuric protein intolerance (LPI) (PMID:10080182, PMID:10080183). y+LAT1 has no transport activity on its own: it must heterodimerize with the heavy chain 4F2hc (CD98), an interaction that begins in the endoplasmic reticulum and Golgi and is required to chaperone the transporter to the plasma membrane (PMID:10080182, PMID:10080183, PMID:17560897). Cryo-EM structures of the human y+LAT1–4F2hc complex captured inward-open and outward-open states and identified Asp243 as critical for Na+ coordination and substrate selectivity, providing an alternating-access framework for cationic versus neutral amino acid handling and for the molecular impact of LPI mutations (PMID:40106545). In epithelial cells y+LAT1 is the dominant arginine transporter and mediates basolateral arginine efflux in exchange for leucine plus sodium, explaining defective intestinal and renal handling of cationic amino acids in LPI (PMID:31705628); paralog SLC7A6 (y+LAT2) compensates in fibroblasts but not in epithelia, partly because mutant y+LAT1 can exert a dominant-negative effect on y+LAT2 (PMID:11078698, PMID:15756301). LPI-causing mutations either disrupt catalytic function while still reaching the membrane (e.g. L334R, G54V) or are retained intracellularly, with mutant proteins showing reduced expression and increased cytotoxicity (PMID:10655553, PMID:30832686). Conditional and whole-body knockout mice recapitulate LPI — cationic aminoaciduria, hypoargininemia, hyperammonemia, pulmonary alveolar proteinosis, proximal tubular dysfunction, impaired skeletal development, and perinatal lethality — with citrulline rescuing the metabolic derangement (PMID:31653080, PMID:32504080), and intrauterine growth restriction linked to downregulation of hepatic IGF-1 (PMID:17376816). Beyond transport, y+LAT1 supports macrophage biology: it is required for macrophage survival during efferocytosis (PMID:32973110) and for glutamine uptake feeding GLS1-dependent glutaminolysis and metabolic reprogramming in atherosclerosis (PMID:40983679), while defective erythropoiesis in knockout mice is cell-non-autonomous, arising from impaired renal erythropoietin production rather than loss within the erythroid or myeloid lineage (PMID:39881295). Independently of transport, y+LAT1 restrains NFκB-driven inflammatory cytokine output in macrophages and airway epithelial cells (PMID:29616026). SLC7A7 transcription is directly activated by the intestinal factor CDX2 (PMID:27121315) and by ATF3, the latter coupling it to suppression of mTORC1 signaling and lipogenesis (PMID:39996726).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Establishing the gene-disease link and the obligate co-subunit requirement defined SLC7A7 as a transporter whose function depends on 4F2hc.

    Evidence Mutation identification in LPI patients plus transport reconstitution of mutant y+LAT1 with 4F2hc in Xenopus oocytes

    PMID:10080182 PMID:10080183

    Open questions at the time
    • Did not resolve which cell types depend on SLC7A7 versus paralogs
    • No structural basis for transport or for mutation effects
  2. 2000 High

    Mutational dissection separated catalytic defects from trafficking defects, showing some LPI residues are essential for transport itself rather than membrane targeting.

    Evidence Functional and localization analysis of multiple LPI mutants in Xenopus oocytes; genomic characterization of gene structure and additional mutations

    PMID:10631139 PMID:10655553

    Open questions at the time
    • Mechanism linking individual residues to catalysis not defined
    • Tissue specificity of the defect not yet explained
  3. 2000 Medium

    Discovery of paralog compensation explained why fibroblasts are spared in LPI while epithelia are not.

    Evidence Bidirectional flux and inhibitor-profiling transport assays plus mRNA analysis in LPI and control fibroblasts

    PMID:11078698

    Open questions at the time
    • Why compensation fails in epithelia not yet mechanistically established
    • Single-lab functional characterization
  4. 2005 Medium

    A dominant-negative interaction between mutant y+LAT1 and y+LAT2 offered a mechanism for incomplete paralog rescue in LPI.

    Evidence Co-expression of E36del mutant with y+LAT2 in oocytes and mammalian cells with transport assays

    PMID:15756301

    Open questions at the time
    • Structural basis of the proposed multiheteromeric interference unknown
    • Single-lab observation
  5. 2007 High

    Direct visualization of the y+LAT1–4F2hc interaction within the ER/Golgi established 4F2hc as a trafficking chaperone, not merely a surface partner.

    Evidence Acceptor-photobleaching FRET microscopy of tagged y+LAT1 and 4F2hc in HEK293 cells

    PMID:17560897

    Open questions at the time
    • Did not define the assembly determinants or stoichiometry
    • Inference of chaperone function from interaction localization
  6. 2007 High

    A knockout mouse provided the first in vivo demonstration that Slc7a7 loss drives growth restriction via IGF-1 downregulation and reproduces human LPI metabolic features.

    Evidence Gene-trap knockout mouse with qRT-PCR, immunostaining, Western blot, and microarray profiling

    PMID:17376816

    Open questions at the time
    • Neonatal lethality limited adult phenotyping
    • Mechanism linking transporter loss to hepatic IGF-1 not resolved
  7. 2013 Medium

    FRET across many LPI mutants showed heterodimer assembly is preserved, redirecting the pathogenic mechanism toward reduced expression and cytotoxicity rather than failed 4F2hc binding.

    Evidence FACS-FRET in cells co-expressing tagged y+LAT1 mutants and 4F2hc

    PMID:23940088

    Open questions at the time
    • Cause of increased mutant-induced mortality unknown
    • Did not quantify residual transport for each mutant
  8. 2018 Medium

    Identification of an NFκB-restraining role independent of arginine levels revealed a non-transport immunomodulatory function for y+LAT1.

    Evidence siRNA knockdown with ELISA, qRT-PCR, and NFκB pathway analysis in THP-1 macrophages and A549 cells

    PMID:29616026

    Open questions at the time
    • Molecular mechanism linking y+LAT1 to NFκB not defined
    • Single-lab loss-of-function
  9. 2019 Medium

    Quantitative transport profiling and patient-cell analysis localized the y+L defect to epithelia and myeloid cells, defining basolateral arginine efflux as the physiologically relevant activity.

    Evidence Kinetic transport assays and siRNA across MDM, Caco-2, renal and fibroblast cells; mutant localization in CHO cells and ex vivo monocytes/lymphoblasts

    PMID:30832686 PMID:31705628

    Open questions at the time
    • Cell-type-specific expression control not fully mapped
    • Single-lab studies
  10. 2019 High

    An inducible knockout linked y+LAT1 deficiency to cationic amino acid depletion and hyperammonemia and demonstrated therapeutic rescue.

    Evidence Tamoxifen-inducible conditional knockout mouse with metabolic and histopathological analysis and citrulline rescue

    PMID:31653080

    Open questions at the time
    • Did not dissect organ-specific contributions to hyperammonemia
    • Mechanism of pulmonary alveolar proteinosis not resolved
  11. 2020 High

    Genetic studies established y+LAT1 as essential for macrophage survival under high efferocytic load.

    Evidence Zebrafish genetic mutants with live imaging, lineage tracing, in vivo efferocytosis assays, and induction-kinetics measurement

    PMID:32973110

    Open questions at the time
    • Metabolic substrate driving the survival requirement not identified in this model
    • Mammalian relevance not addressed here
  12. 2020 High

    CRISPR knockout mice consolidated the multi-organ LPI phenotype including renal tubular and skeletal defects.

    Evidence CRISPR/Cas9 knockout mouse lines with plasma/urine amino acid quantification, histopathology, and micro-CT

    PMID:32504080

    Open questions at the time
    • Cell-autonomy of each organ phenotype not yet dissected
    • Background-dependent lethality mechanism unexplained
  13. 2025 High

    Cryo-EM structures and MD simulations delivered an atomic alternating-access mechanism, pinpointing Asp243 in Na+ coordination and rationalizing LPI mutations.

    Evidence Cryo-EM of the human y+LAT1–4F2hc complex in two conformations, molecular dynamics, and transport assays

    PMID:40106545

    Open questions at the time
    • Conformational transition intermediates not captured
    • Structural basis of non-transport functions not addressed
  14. 2025 High

    Cell-type-specific and transplant epistasis experiments separated the transporter's metabolic roles from cell-non-autonomous phenotypes, defining glutamine-fueled glutaminolysis in macrophages and renal-EPO-dependent erythropoiesis.

    Evidence Macrophage-specific KO in atherosclerosis with glutamine flux/glutaminolysis assays; whole-body and lineage-specific KOs with bone marrow transplants for erythropoiesis

    PMID:39881295 PMID:40983679

    Open questions at the time
    • Link between glutaminolysis and specific restorative macrophage programs incompletely mapped
    • How renal EPO production depends on the transporter not mechanistically resolved
  15. 2022 Medium

    Transcriptional regulators were placed upstream of SLC7A7, connecting it to mTORC1/lipogenesis control in cancer and to glucocorticoid-driven muscle metabolism.

    Evidence ATF3 gain/loss-of-function with enhancer-binding and mTORC1/lipogenesis assays in HCC; dexamethasone treatment with m6A and mTOR/protein synthesis readouts in porcine muscle cells

    PMID:35054897 PMID:39996726

    Open questions at the time
    • Whether mTORC1 effects depend on transport activity not established
    • Porcine m6A finding is low-confidence and indirect

Open questions

Synthesis pass · forward-looking unresolved questions
  • How y+LAT1 restrains NFκB and supports macrophage survival/EPO production at a molecular level — and whether these depend on its transport activity — remains unresolved.
  • No molecular intermediary linking y+LAT1 to NFκB identified
  • Transport-dependent versus transport-independent contributions not disentangled across functions

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140104 molecular carrier activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-382551 Transport of small molecules 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1430728 Metabolism 2
Partners
SLC3A2SLC7A6
Complex memberships
y+L transporter (y+LAT1–4F2hc heterodimer)

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 SLC7A7 (encoding y+LAT-1) was identified as the gene mutated in lysinuric protein intolerance (LPI); a missense mutation in y+LAT-1 abolishes dibasic amino acid (cationic amino acid) transport activity when co-expressed with the heavy chain of 4F2hc (CD98) in Xenopus laevis oocytes, establishing that y+LAT-1 requires 4F2hc as a co-subunit for transport function. Mutation identification in patients + functional expression assay in Xenopus oocytes + transport activity measurement Nature genetics High 10080182 10080183
2000 Five LPI-causing mutations (L334R, G54V, 1291delCTTT, 1548delC, and LPIFin) were functionally characterized: all abolished y+L amino acid transport when co-expressed with 4F2hc in Xenopus oocytes. Frameshift mutants (1291delCTTT, 1548delC, LPIFin) were retained intracellularly, while missense mutants L334R and G54V reached the plasma membrane, demonstrating that residues L334 and G54 are critical for transport catalytic function rather than membrane targeting. Expression in Xenopus oocytes, transport activity assays, immunostaining/subcellular localization Human molecular genetics High 10655553
2000 SLC7A7 (y+LAT-1) gene comprises 10 exons; novel LPI mutations include missense M1L (start codon change), missense S386R, nonsense W242X, splice mutations IVS3+1G>A and IVS6+1G>T, insertion 786insT, and deletions 455delCTCT and 1425delTTCT, all causing loss of functional cationic amino acid transport. Genomic sequencing, mutational analysis American journal of human genetics Medium 10631139
2000 In LPI fibroblasts, arginine transport through system y+L is normal (not defective), attributable to SLC7A6 (y+LAT2) activity rather than SLC7A7 (y+LAT1), demonstrating cell-type-specific compensation between paralogs. Both SLC7A7 and SLC7A6 are expressed in fibroblasts, and the LPI transport defect is limited to epithelial cells where SLC7A7 predominates. Amino acid transport characterization (bidirectional flux assays, inhibitor profiling with NEM, membrane potential, Na+ dependence) in patient-derived and control fibroblasts; mRNA expression analysis American journal of physiology. Cell physiology Medium 11078698
2005 The LPI-causing y+LAT-1 mutant E36del displays a partial dominant-negative effect on y+LAT-2 activity when co-expressed in Xenopus oocytes and mammalian cells, suggesting a multiheteromeric structure for both [4F2hc/y+LAT-1] and [4F2hc/y+LAT-2] complexes and interference between y+LAT-1 and y+LAT-2 proteins that can explain why upregulation of SLC7A6 does not fully compensate for SLC7A7 loss in LPI. Expression in Xenopus laevis oocytes and mammalian cells, transport activity assays, dominant-negative functional analysis European journal of human genetics Medium 15756301
2005 Functional analysis of eight SLC7A7 mutations by expression in Xenopus oocytes or patient renal tubular cells revealed loss of y+L transport activity. The R333M mutation disrupts a functional splicing motif (last nucleotide of exon 7), generating misspliced transcripts in addition to protein dysfunction. Expression in Xenopus oocytes, transport activity assay, analysis of patient renal tubular cells, splicing analysis Human mutation Medium 15776427
2006 y+LAT-1 (SLC7A7) is the transporter responsible for uptake of the iNOS inhibitor GW274150 in murine macrophage J774 cells, operating via system y+L (Na+-independent, trans-stimulated, inhibited by cationic amino acids and neutral amino acids in a Na+-dependent manner). Northern blot confirmed expression of y+LAT-1 but not y+LAT-2 transcripts in these cells. Saturable transport assay with pharmacological profiling (inhibitors, ion substitution, trans-stimulation), Northern blot Amino acids Medium 16699825
2006 Two alternative promoters regulate SLC7A7 expression: a novel TATA-box-containing downstream promoter upstream of exon 2 is active in tissues with strong cationic amino acid transport defects in LPI patients, revealing tissue-specific transcriptional regulation of the gene. Promoter identification and analysis, tissue-specific expression studies Molecular genetics and metabolism Medium 17196863
2007 y+LAT-1 and 4F2hc form a heterodimer that assembles prior to reaching the plasma membrane; FRET (acceptor photobleaching) microscopy in HEK293 cells showed the interaction occurring in the endoplasmic reticulum and Golgi complex as well as at the plasma membrane, providing direct evidence that 4F2hc acts as a chaperone to assist trafficking of y+LAT-1 to the plasma membrane. Acceptor photobleaching FRET microscopy in HEK293 cells expressing fluorescently-tagged y+LAT-1 (ECFP) and 4F2hc (EYFP) Biochimica et biophysica acta High 17560897
2007 Slc7a7 knockout mice (gene-trap retroviral insertion) exhibit intrauterine growth restriction (IUGR) and neonatal lethality. IUGR is mechanistically linked to marked downregulation of insulin-like growth factor 1 (IGF-1) in fetal liver, demonstrated by quantitative real-time RT-PCR, immunostaining, and Western blot. Adult surviving Slc7a7-/- mice show metabolic derangement consistent with human LPI after protein ingestion. Mouse knockout (retroviral gene-trap), quantitative RT-PCR, immunostaining, Western blot, DNA microarray gene expression profiling American journal of physiology. Cell physiology High 17376816
2013 FACS-FRET analysis confirmed that heteromerization of y+LAT1 with 4F2hc is not disrupted by any tested LPI mutations (including missense and frameshift mutants), but LPI mutant y+LAT1 proteins are expressed at significantly lower levels and cause markedly increased cellular mortality compared to wild-type y+LAT1. FACS-FRET (flow cytometry-based FRET) in cells expressing CFP-tagged y+LAT1 and YFP-tagged 4F2hc General physiology and biophysics Medium 23940088
2016 CDX2, an intestine-specific transcription factor, directly binds the SLC7A7 promoter (demonstrated by luciferase reporter and chromatin immunoprecipitation assays) and activates SLC7A7 transcription, establishing SLC7A7 as a direct CDX2 target gene in intestinal epithelial cells. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), overexpression in IPEC-1 cells Oncotarget Medium 27121315
2018 Silencing of SLC7A7/y+LAT1 in human THP-1 macrophages and A549 airway epithelial cells via siRNA induces expression and release of IL-1β and TNFα independent of intracellular arginine levels, via activation of the NFκB signaling pathway at the transcriptional level. Furthermore, SLC7A7 silencing potentiates IL-1β-stimulated CCL5/RANTES expression without affecting CXCL8/IL-8, revealing a non-transport immunomodulatory function of y+LAT1. siRNA knockdown, ELISA, qRT-PCR, NFκB pathway analysis in THP-1 macrophages and A549 cells Frontiers in immunology Medium 29616026
2019 y+LAT1 (SLC7A7) is the dominant arginine transporter in monocyte-derived macrophages and intestinal Caco-2 cells, while y+LAT2 (SLC7A6) dominates in fibroblasts. At the basolateral side of Caco-2 cells, system y+L mediates arginine efflux in exchange with leucine plus sodium, explaining defective intestinal absorption/reabsorption of arginine in LPI. Kinetic transport assays, mRNA expression analysis across multiple human cell types (MDM, Caco-2, HRPTEpC, fibroblasts), siRNA knockdown Journal of cellular and molecular medicine Medium 31705628
2019 Three LPI-causing y+LAT1 mutations reproduced as eGFP-tagged proteins in CHO cells result in defective arginine transport and retention of the mutant proteins in the cytosol (confirmed by confocal microscopy), with heterogeneous subcellular distribution patterns among mutants. System y+L activity is impaired in monocytes from LPI patients but not in lymphoblasts carrying the same mutations, attributed to differential SLC7A7 mRNA expression between cell types. eGFP-tagged mutant expression in CHO cells, confocal microscopy, transport assays in transfected CHO cells and ex vivo patient monocytes/lymphoblasts Orphanet journal of rare diseases Medium 30832686
2019 A tamoxifen-inducible Slc7a7 knockout mouse recapitulates human LPI phenotype including malabsorption and impaired reabsorption of cationic amino acids, hypoargininemia, hyperammonemia, pulmonary alveolar proteinosis, and neurological impairment. Citrulline treatment improves metabolic derangement and survival, confirming the mechanistic link between y+LAT1 deficiency, cationic amino acid depletion, and hyperammonemia. Tamoxifen-inducible conditional knockout mouse, metabolic analysis (plasma/urine amino acids), histopathology, citrulline rescue experiment International journal of molecular sciences High 31653080
2020 In zebrafish, Slc7a7 is the main cationic amino acid transporter expressed in macrophages; its expression is induced within 1–2 hours upon efferocytosis (phagocytosis of apoptotic cells). Slc7a7-deficient macrophages that engage in sustained efferocytic work die, demonstrating that Slc7a7 is required for macrophage survival during intense phagocytic activity, likely to cope with catabolism of dead cell material. Zebrafish genetic mutant screen, live imaging, macrophage lineage tracing, in vivo efferocytosis assay, gene expression analysis Journal of cell science High 32973110
2020 Global Slc7a7 knockout mice (CRISPR/Cas9, exons 3–4 deletion) on mixed background display reduced plasma and increased urinary cationic amino acids, proximal tubular dysfunction (loss of brush border, lipid vacuolation in renal cortex), delayed skeletal development with decreased mineralization, and perinatal lethality on inbred backgrounds, recapitulating human LPI. CRISPR/Cas9 knockout mouse generation, amino acid quantification in plasma/urine, histopathology, micro-computed tomography Human molecular genetics High 32504080
2022 ATF3 transcriptionally activates SLC7A7 by binding to its enhancer region, and through this axis suppresses mTORC1 signaling to inhibit lipogenesis in hepatocellular carcinoma (HCC). Functional assays in ATF3-overexpressing and knockdown HCC cell lines confirmed that SLC7A7 acts downstream of ATF3 to restrain mTORC1 activity. Transcriptomic analysis, ATF3 overexpression/knockdown in HCC cell lines, chromatin/enhancer binding assay, mTORC1 activity assay, lipogenesis assay Cells Medium 39996726
2025 Cryo-EM structures of the human y+LAT1–4F2hc complex were determined in two conformations: apo inward-open and substrate-bound outward-open states. Structural analysis identified Asp243 in y+LAT1 as critical for sodium ion coordination and substrate selectivity. Molecular dynamics simulations revealed different transport mechanisms for cationic versus neutral amino acids, and the structural framework explained the molecular basis of LPI-causing mutations. Cryo-EM structure determination (two conformations), molecular dynamics simulation, functional transport assay in mammalian cells Science advances High 40106545
2025 Macrophage-specific deletion of Slc7a7 in atherosclerotic mice accelerates disease with more complex necrotic core composition. Slc7a7-silenced macrophages have reduced glutamine influx and reduced GLS1-dependent glutaminolysis, impairing downstream signaling for restorative macrophage functions. This establishes SLC7A7-dependent glutamine uptake as upstream of glutaminolysis and macrophage metabolic reprogramming in atherosclerosis. Macrophage-specific conditional Slc7a7 knockout in atherosclerosis mouse model, in vitro Slc7a7 silencing, glutamine flux measurement, glutaminolysis assay, histopathology Nature metabolism High 40983679
2025 Defective erythropoiesis in Slc7a7 whole-body knockout mice is not caused by intrinsic loss of Slc7a7 in erythroblasts or myeloid cells (erythroblast- and myeloid-specific KOs do not recapitulate the phenotype; bone marrow transplants do not rescue), but is linked to impaired erythropoietin production in the kidney and subsequent iron overload. Whole-body and cell-type-specific conditional Slc7a7 knockouts (erythroblast- and myeloid-specific), bone marrow transplantation experiments, erythropoiesis analysis, erythropoietin measurement Molecular medicine High 39881295
2022 Glucocorticoid (dexamethasone) reduces SLC7A7 expression in porcine skeletal muscle cells via changes in m6A mRNA modification, and reduced SLC7A7 expression in turn reduces mTOR signaling pathway activity and protein synthesis. Dexamethasone treatment of porcine skeletal muscle cells, m6A modification analysis, mTOR pathway readouts, protein synthesis assay International journal of molecular sciences Low 35054897
2003 The SLC7A7 promoter region (upstream of exon 1) lacks classical TATA-box and Inr elements but contains E-box and AP-2 elements that bind proteins in HEK293 cells and adult kidney extracts (but not fibroblasts). The first two introns (in the untranslated region) contain transcriptional enhancer elements, demonstrated by transient transfection luciferase reporter assays. Electrophoretic mobility shift assay (EMSA), transient transfection with luciferase reporter, Northern blot Biochemical and biophysical research communications Medium 12589791

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene. Nature genetics 240 10080182
1999 SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nature genetics 187 10080183
2004 Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator. Blood 108 15155464
2018 SFPEL-LPI: Sequence-based feature projection ensemble learning for predicting LncRNA-protein interactions. PLoS computational biology 103 30533006
2013 Dietary arginine supplementation enhances intestinal expression of SLC7A7 and SLC7A1 and ameliorates growth depression in mycotoxin-challenged pigs. Amino acids 102 24368521
2012 Lysinuric protein intolerance (LPI): a multi organ disease by far more complex than a classic urea cycle disorder. Molecular genetics and metabolism 72 22402328
2008 Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene. Human mutation 70 17764084
2000 Functional analysis of novel mutations in y(+)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI). Human molecular genetics 62 10655553
2000 Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance. American journal of human genetics 59 10631139
2019 y+LAT1 and y+LAT2 contribution to arginine uptake in different human cell models: Implications in the pathophysiology of Lysinuric Protein Intolerance. Journal of cellular and molecular medicine 45 31705628
2017 LPI-ETSLP: lncRNA-protein interaction prediction using eigenvalue transformation-based semi-supervised link prediction. Molecular bioSystems 45 28702594
2000 Arginine transport through system y(+)L in cultured human fibroblasts: normal phenotype of cells from LPI subjects. American journal of physiology. Cell physiology 43 11078698
2018 Downregulation of SLC7A7 Triggers an Inflammatory Phenotype in Human Macrophages and Airway Epithelial Cells. Frontiers in immunology 41 29616026
2007 Slc7a7 disruption causes fetal growth retardation by downregulating Igf1 in the mouse model of lysinuric protein intolerance. American journal of physiology. Cell physiology 40 17376816
2021 LPI-deepGBDT: a multiple-layer deep framework based on gradient boosting decision trees for lncRNA-protein interaction identification. BMC bioinformatics 39 34607567
1997 Lysinuric protein intolerance (LPI) gene maps to the long arm of chromosome 14. American journal of human genetics 35 9199570
2021 Capsule-LPI: a LncRNA-protein interaction predicting tool based on a capsule network. BMC bioinformatics 32 33985444
2017 The LPI/GPR55 axis enhances human breast cancer cell migration via HBXIP and p-MLC signaling. Acta pharmacologica Sinica 32 29188802
2023 Saturated fatty acids increase LPI to reduce FUNDC1 dimerization and stability and mitochondrial function. EMBO reports 31 36847607
2020 LPI-CNNCP: Prediction of lncRNA-protein interactions by using convolutional neural network with the copy-padding trick. Analytical biochemistry 31 32454029
2017 LPI-NRLMF: lncRNA-protein interaction prediction by neighborhood regularized logistic matrix factorization. Oncotarget 28 29262614
2020 LPI-SKF: Predicting lncRNA-Protein Interactions Using Similarity Kernel Fusions. Frontiers in genetics 25 33362868
2019 l-α-Lysophosphatidylinositol (LPI) aggravates myocardial ischemia/reperfusion injury via a GPR55/ROCK-dependent pathway. Pharmacology research & perspectives 25 31149342
2008 Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat. European journal of human genetics : EJHG 25 18716612
2002 Five novel SLC7A7 variants and y+L gene-expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance. Human mutation 25 12402335
2022 The oncogenic lysophosphatidylinositol (LPI)/GPR55 signaling. Life sciences 24 35500681
2019 LPI-IBNRA: Long Non-coding RNA-Protein Interaction Prediction Based on Improved Bipartite Network Recommender Algorithm. Frontiers in genetics 24 31057602
2000 SLC7A7 genomic structure and novel variants in three Japanese lysinuric protein intolerance families. Human mutation 24 10737982
2000 A cluster of lysinuric protein intolerance (LPI) patients in a northern part of Iwate, Japan due to a founder effect. The Mass Screening Group. Human mutation 24 10980538
2019 Inducible Slc7a7 Knockout Mouse Model Recapitulates Lysinuric Protein Intolerance Disease. International journal of molecular sciences 23 31653080
2017 New mutations in the SLC7A7 gene of two chinese sisters with lysinuric protein intolerance. Pediatric pulmonology 23 29058386
2013 Regulation of GPR55 in rat white adipose tissue and serum LPI by nutritional status, gestation, gender and pituitary factors. Molecular and cellular endocrinology 23 24378736
2005 Lysinuric protein intolerance: identification and functional analysis of mutations of the SLC7A7 gene. Human mutation 20 15776427
2021 LPI-EnEDT: an ensemble framework with extra tree and decision tree classifiers for imbalanced lncRNA-protein interaction data classification. BioData mining 19 34861891
2005 A y(+)LAT-1 mutant protein interferes with y(+)LAT-2 activity: implications for the molecular pathogenesis of lysinuric protein intolerance. European journal of human genetics : EJHG 19 15756301
2021 LPI-HyADBS: a hybrid framework for lncRNA-protein interaction prediction integrating feature selection and classification. BMC bioinformatics 18 34836494
2020 A global Slc7a7 knockout mouse model demonstrates characteristic phenotypes of human lysinuric protein intolerance. Human molecular genetics 15 32504080
2020 The effect of intra-striatal administration of GPR55 agonist (LPI) and antagonist (ML193) on sensorimotor and motor functions in a Parkinson's disease rat model. Acta neuropsychiatrica 15 32967746
2018 Function of SLC7A7 in T-Cell Acute Lymphoblastic Leukemia. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 15 30025393
2016 Imbalance of plasma amino acids, metabolites and lipids in patients with lysinuric protein intolerance (LPI). Metabolism: clinical and experimental 15 27506743
2011 Exploring the transcriptomic variation caused by the Finnish founder mutation of lysinuric protein intolerance (LPI). Molecular genetics and metabolism 15 22221392
2006 Two alternative promoters regulate the expression of lysinuric protein intolerance gene SLC7A7. Molecular genetics and metabolism 13 17196863
2020 The cationic amino acid exporter Slc7a7 is induced and vital in zebrafish tissue macrophages with sustained efferocytic activity. Journal of cell science 12 32973110
2015 Lysinuric protein intolerance in a family of Mexican ancestry with a novel SLC7A7 gene deletion. Case report and review of the literature. Molecular genetics and metabolism reports 12 28649527
2007 First reported case of lysinuric protein intolerance (LPI) in Lithuania, confirmed biochemically and by DNA analysis. Journal of applied genetics 12 17666782
2015 Urine Beta2-Microglobulin Is an Early Marker of Renal Involvement in LPI. JIMD reports 11 26122628
2019 Prioritization of SNPs in y+LAT-1 culpable of Lysinuric protein intolerance and their mutational impacts using protein-protein docking and molecular dynamics simulation studies. Journal of cellular biochemistry 10 31211457
2019 SLC transporters ASCT2, B0 AT1-like, y+ LAT1, and LAT4-like associate with methionine electrogenic and radio-isotope flux kinetics in rainbow trout intestine. Physiological reports 9 31705630
2022 RLF-LPI: An ensemble learning framework using sequence information for predicting lncRNA-protein interaction based on AE-ResLSTM and fuzzy decision. Mathematical biosciences and engineering : MBE 8 35430839
2022 LPI-CSFFR: Combining serial fusion with feature reuse for predicting LncRNA-protein interactions. Computational biology and chemistry 8 35785626
2019 Analysis of LPI-causing mutations on y+LAT1 function and localization. Orphanet journal of rare diseases 8 30832686
2016 CDX2 increases SLC7A7 expression and proliferation of pig intestinal epithelial cells. Oncotarget 8 27121315
2025 The Relationship Between Non-Transferrin-Bound Iron (NTBI), Labile Plasma Iron (LPI), and Iron Toxicity. International journal of molecular sciences 7 40650208
2020 Quantitative Proteomics Reveals the Development of HBV-Associated Glomerulonephritis Triggered by the Downregulation of SLC7A7. Journal of proteome research 7 32155069
2003 Promoter analysis of the human SLC7A7 gene encoding y+L amino acid transporter-1 (y+LAT-1). Biochemical and biophysical research communications 7 12589791
2025 Absorption, transport, blood-brain barrier penetration, and neuroprotection of walnut peptides LR and LPI. Food research international (Ottawa, Ont.) 6 40253149
2024 LPI-GPR55 promotes endothelial cell activation and inhibits autophagy through inducing LINC01235 expression. Annals of medicine 6 39316662
2022 Familial hemophagocytic lymphohistiocytosis syndrome due to lysinuric protein intolerance: a patient with a novel compound heterozygous pathogenic variant in SLC7A7. International journal of hematology 6 35532875
2013 Interactions of y+LAT1 and 4F2hc in the y+l amino acid transporter complex: consequences of lysinuric protein intolerance-causing mutations. General physiology and biophysics 6 23940088
2007 Heterodimerization of y(+)LAT-1 and 4F2hc visualized by acceptor photobleaching FRET microscopy. Biochimica et biophysica acta 6 17560897
2006 y+ LAT-1 mediates transport of the potent and selective iNOS inhibitor, GW274150, in control J774 macrophages. Amino acids 6 16699825
2025 ATF3-SLC7A7 Axis Regulates mTORC1 Signaling to Suppress Lipogenesis and Tumorigenesis in Hepatocellular Carcinoma. Cells 5 39996726
2025 Single-cell to pre-clinical evaluation of Trem2, Folr2, and Slc7a7 as macrophage-associated biomarkers for atherosclerosis. Cardiovascular research 5 41206594
2019 [Clinical features of children with lysinuric protein intolerance and SLC7A7 gene mutation: an analysis of 3 cases]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 5 31014432
2019 Lysinuric protein intolerance with homozygous SLC7A7 mutation caused by maternal uniparental isodisomy of chromosome 14. Journal of human genetics 5 31427715
2025 Defective Slc7a7 transport reduces erythropoietin compromising erythropoiesis. Molecular medicine (Cambridge, Mass.) 4 39881295
2025 Exosomes containing miR-152-3p targeting FGFR3 mediate SLC7A7-induced angiogenesis in bladder cancer. NPJ precision oncology 4 40075158
2025 Slc7a7 licenses macrophage glutaminolysis for restorative functions in atherosclerosis. Nature metabolism 4 40983679
2022 The Interactional Characterization of Lentil Protein Isolate (LPI) with Cyanidin-3-O-Glucoside (C3G) and Their Effect on the Stability and Antioxidant Activity of C3G. Foods (Basel, Switzerland) 4 36613320
2013 Cloning and molecular characterization of cationic amino acid transporter y⁺LAT1 in grass carp (Ctenopharyngodon idellus). Fish physiology and biochemistry 4 23817987
2025 Structural basis for the substrate recognition and transport mechanism of the human y+LAT1-4F2hc transporter complex. Science advances 3 40106545
2025 Empagliflozin alleviates type 2 diabetic renal fibrosis by inhibiting SLC7A7-mediated ferroptosis. Diabetology & metabolic syndrome 3 40804641
2023 Elucidation of GPR55-Associated Signaling behind THC and LPI Reducing Effects on Ki67-Immunoreactive Nuclei in Patient-Derived Glioblastoma Cells. Cells 3 37998380
2022 Glucocorticoid Regulates the Synthesis of Porcine Muscle Protein through m6A Modified Amino Acid Transporter SLC7A7. International journal of molecular sciences 3 35054897
2023 Lysinuric protein intolerance caused by a homozygous SLC7A7 deletion and presented with hyperferritinemia and osteoporosis in two siblings. Molecular genetics and metabolism reports 2 38053936
2024 LPI-SKMSC: Predicting LncRNA-Protein Interactions with Segmented k-mer Frequencies and Multi-space Clustering. Interdisciplinary sciences, computational life sciences 1 38206558
2023 LPI-IBWA: Predicting lncRNA-protein interactions based on an improved Bi-Random walk algorithm. Methods (San Diego, Calif.) 1 37972912
2011 Membrane protein digestion - comparison of LPI HexaLane with traditional techniques. Methods in molecular biology (Clifton, N.J.) 1 21604120
1999 Characterization of the lysinuric protein intolerance (LPI) region within T-cell receptor alpha/delta gene cluster on chromosome site 14q11. Hereditas 1 10364825
2026 A Protective Super-Enhancer Variant Regulating SLC7A7 Modulates Autism Spectrum Disorder Risk: A Cross-Population Study. Autism research : official journal of the International Society for Autism Research 0 41693594
2026 Monogenic lupus with SLC7A7 mutations: a retrospective study from a Chinese center. Orphanet journal of rare diseases 0 41821046
2026 Targeting the LPI/GPR55 Axis in MAFLD and MASH: Novel Insights, Therapeutic Strategies and Future Directions. Liver international : official journal of the International Association for the Study of the Liver 0 41823054
2026 SLC7A7 Downregulation in Monocytes Drives Immunosuppression and Osteosarcoma Progression. International journal of genomics 0 42099775
2025 MFH-LPI: based on multi-view similarity networks fusion and hypergraph learning for long non-coding RNA-protein interactions prediction. BMC genomics 0 40596835
2025 Single-Cell Transcriptomic Analysis Identifies a Novel OLR1+ SLC7A7+ Liver-Enriched Metastatic Subset With Immunometabolic Rewiring in Pancreatic Cancer. Cancer medicine 0 41176774

Missed literature

Know a paper Affinage missed for SLC7A7? Flag it for the maintainers and the community.

No submissions yet.