SLC7A7

Summary

SLC7A7 (solute carrier family 7 member 7, HGNC:11065) is a protein-coding gene on chromosome 14q11.2, encoding Y+L amino acid transporter 1 (Q9UM01). Heterodimer with SLC3A2, that functions as an antiporter which operates as an efflux route by exporting cationic amino acids from inside the cells in exchange with neutral amino acids plus sodium ions and may participate in nitric oxide synthesis via the transport of L-arginine.

The protein encoded by this gene is the light subunit of a cationic amino acid transporter. This sodium-independent transporter is formed when the light subunit encoded by this gene dimerizes with the heavy subunit transporter protein SLC3A2. This transporter is found in epithelial cell membranes where it transfers cationic and large neutral amino acids from the cell to the extracellular space. Defects in this gene are a cause of lysinuric protein intolerance (LPI). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9056 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lysinuric protein intolerance (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 881 total — 68 pathogenic, 65 likely-pathogenic
• Phenotypes (HPO): 100
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_003982

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11065
Approved symbol	SLC7A7
Name	solute carrier family 7 member 7
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	y+LAT-1, Y+LAT1
Ensembl gene	ENSG00000155465
Ensembl biotype	protein_coding
OMIM	603593
Entrez	9056

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 18 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000285850, ENST00000397528, ENST00000397529, ENST00000397532, ENST00000488800, ENST00000553351, ENST00000553632, ENST00000553874, ENST00000554061, ENST00000554517, ENST00000554741, ENST00000554758, ENST00000555251, ENST00000555678, ENST00000555702, ENST00000555911, ENST00000555959, ENST00000556287, ENST00000556350, ENST00000557129, ENST00000557629, ENST00000674313, ENST00000698939, ENST00000698940, ENST00000894387, ENST00000941692

RefSeq mRNA: 3 — MANE Select: NM_003982 NM_001126105, NM_001126106, NM_003982

CCDS: CCDS9574

Canonical transcript exons

ENST00000674313 — 10 exons

Exon	Start	End
ENSE00001594789	22812900	22813440
ENSE00002524474	22773222	22773716
ENSE00003459756	22778793	22778937
ENSE00003583654	22776195	22776318
ENSE00003591353	22779926	22780051
ENSE00003620639	22775833	22775936
ENSE00003641875	22773933	22774116
ENSE00003648850	22774354	22774503
ENSE00003693139	22775444	22775540
ENSE00003898025	22815320	22815435

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6096 / max 388.7812, expressed in 1129 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142242	7.2178	639
142240	3.0470	474
142248	1.6924	669
142241	0.8796	279
142247	0.8782	275
142245	0.8028	206
142246	0.6866	208
142252	0.3688	108
142251	0.3365	90
142244	0.2565	72

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.17	gold quality
monocyte	CL:0000576	99.11	gold quality
mononuclear cell	CL:0000842	99.05	gold quality
leukocyte	CL:0000738	99.02	gold quality
granulocyte	CL:0000094	98.40	gold quality
jejunal mucosa	UBERON:0000399	98.03	gold quality
oocyte	CL:0000023	97.97	gold quality
ileal mucosa	UBERON:0000331	97.34	gold quality
nephron tubule	UBERON:0001231	96.85	gold quality
blood	UBERON:0000178	96.34	gold quality
spleen	UBERON:0002106	96.33	gold quality
kidney epithelium	UBERON:0004819	96.24	gold quality
duodenum	UBERON:0002114	95.83	gold quality
adult organism	UBERON:0007023	95.56	gold quality
renal glomerulus	UBERON:0000074	95.48	gold quality
metanephric glomerulus	UBERON:0004736	95.24	gold quality
adult mammalian kidney	UBERON:0000082	95.10	gold quality
right lung	UBERON:0002167	94.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.97	gold quality
small intestine	UBERON:0002108	93.24	gold quality
right testis	UBERON:0004534	93.07	gold quality
left testis	UBERON:0004533	92.99	gold quality
kidney	UBERON:0002113	92.61	gold quality
upper lobe of left lung	UBERON:0008952	92.58	gold quality
upper lobe of lung	UBERON:0008948	92.00	gold quality
bone marrow cell	CL:0002092	90.92	gold quality
cortex of kidney	UBERON:0001225	90.69	gold quality
testis	UBERON:0000473	90.63	gold quality
vermiform appendix	UBERON:0001154	90.58	gold quality
visceral pleura	UBERON:0002401	90.00	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	36.06
E-CURD-112	yes	28.85
E-MTAB-6701	yes	26.94
E-MTAB-9221	yes	26.55
E-HCAD-9	yes	17.54
E-MTAB-8498	yes	9.93
E-MTAB-9801	yes	7.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1H4

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 24)

• novel SLC7A7 mutations in patients with lysinuric protein intolerance (PMID:12402335)
• expression levels and putative 5’ promoter elements of the SLC7A7 gene (PMID:12589791)
• putative multiheteromeric structure of both [4F2hc/y(+)LAT-1] and [4F2hc/y(+)LAT-2], and the interference between y(+)LAT-1 and y(+)LAT-2 proteins may have a role in the pathogenesis of lysinuric protein intolerance (PMID:15756301)
• mutations of the SLC7A7 gene may have a role in lysinuric protein intolerance (PMID:15776427)
• identified a novel alternative, TATA-box-containing promoter that plays a role in the tissue-specific regulation of SLC7A7 gene expression (PMID:17196863)
• Mutation in the SLC7A7 gene is associated with lysinuric protein intolerance (PMID:17666782)
• A review of the current knowledge of SLC7A7 mutations and their role in LPI pathogenesis. (PMID:17764084)
• results suggest genomic rearrangement of SLC7A7 play more important role in lysinuric protein intolerance than has been reported; 3’ region AluY repeat could be a recombination hot spot as it is involved in 38% of SLC7A7 rearranged chromosomes described (PMID:18716612)
• during differentiation of human monocytes from peripheral blood, SLC7A7 mRNA and system y(+)L activity are increased (PMID:21586674)
• SLC7A7/y+LAT1 mutations lead to a defective phenotype of macrophages resulting in lysinuric Protein Intolerance. (PMID:22325938)
• SLC7A7 plays a critical role in glioblastoma carcinogenesis and overexpression of SLC7A7 is correlated with worse outcomes in patients (PMID:23408368)
• heteromerization of y+LAT1 and 4F2hc within the cell is not disrupted by any of the tested LPI mutations (PMID:23940088)
• SLC7A7 genetic variants are associated with increase risk for glioma in a Chinese population. (PMID:23975734)
• the 1471 delTTCT mutation was identified in exon 9 in the homozygous state for all Tunisian patients with lysinuric protein Intolerance; The 1471 deITTCT mutation seems to be a common mutation of Tunisian population (PMID:26882824)
• The study reports a significant association between SLC7A7 rs12436190 and the risk of glioma in a Chinese population. (PMID:28510245)
• At present, 51 kinds of SLC7A7 gene mutations causing lysinuric protein intolerance have been found worldwide, including insert (C.1384-1385 ins ACTA), delete (C.1185-1188 del TTCT) and point mutations (P.R410X, P.Y457X, P.R 468X, P.L124p, etc).3, 4 In our cases, there were two heterozygous mutations in the SLC7A7 gene of the two sisters: C.1387 del C and IVS4+1C>T, which has never been reported worldwide. (PMID:29058386)
• Confirmed by mRNA and protein expression, the amino acid transporters SLC7A7 and SLC38A5 showed marked differences between controls and intrauterine growth restriction/pre-eclampsia and were regulated by both diseases. In contrast, ABCA1 may play an exclusive role in the development of pre-eclempsia. (PMID:29499643)
• this study shows that downregulation of SLC7A7 triggers an inflammatory phenotype in human macrophages and airway epithelial cells (PMID:29616026)
• SLC7A7 overexpression decreased the apoptosis rate, increased the proportion of cells in the G1 phase, decreased the proportion of G2 cells, and significantly increased cell migration and invasion and increased intracellular arginine would activate mTOR, and induce apoptosis in SLC7A7 knockdown Jurkat cells. (PMID:30025393)
• The three mutations studied of y+LAT1 transporter result in a defective arginine transport both in ex vivo (monocytes) and in vitro (CHO transfected cells) models, likely caused by the retention of the mutated proteins in the cytosol (PMID:30832686)
• SLC7A7 gene detection showed three pathogenic mutations in these children, namely c.1387delG(p.V463CfsX56), c.1215G>A(p.W405X) and homozygous c.625+1G>A (PMID:31014432)
• y+LAT1 and y+LAT2 contribution to arginine uptake in different human cell models: Implications in the pathophysiology of Lysinuric Protein Intolerance. (PMID:31705628)
• A global Slc7a7 knockout mouse model demonstrates characteristic phenotypes of human lysinuric protein intolerance. (PMID:32504080)
• L-type amino acid transporter 1 is associated with chemoresistance in breast cancer via the promotion of amino acid metabolism. (PMID:33436954)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc7a7	ENSDARG00000055226
mus_musculus	Slc7a7	ENSMUSG00000000958
rattus_norvegicus	Slc7a7	ENSRNOG00000010296
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), SLC7A5 (ENSG00000103257), SLC7A10 (ENSG00000130876), SLC7A1 (ENSG00000139514), SLC7A11 (ENSG00000151012), SLC7A13 (ENSG00000164893), SLC7A3 (ENSG00000165349)

Protein

Protein identifiers

Y+L amino acid transporter 1 — Q9UM01 (reviewed: Q9UM01)

Alternative names: Monocyte amino acid permease 2, Solute carrier family 7 member 7, y(+)L-type amino acid transporter 1

All UniProt accessions (14): Q9UM01, A0A0S2Z502, A0A8V8TP95, D6RFE5, G3V273, G3V2H8, G3V2K0, G3V2L0, G3V362, G3V4U1, G3V4Z6, G3V5A1, G3V5W2, H0YJ95

UniProt curated annotations — full annotation on UniProt →

Function. Heterodimer with SLC3A2, that functions as an antiporter which operates as an efflux route by exporting cationic amino acids from inside the cells in exchange with neutral amino acids plus sodium ions and may participate in nitric oxide synthesis via the transport of L-arginine. Also mediates arginine transport in non-polarized cells, such as monocytes, and is essential for the correct function of these cells. The transport mechanism is electroneutral and operates with a stoichiometry of 1:1. In vitro, Na(+) and Li(+), but also H(+), are cotransported with the neutral amino acids.

Subunit / interactions. Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.

Subcellular location. Basolateral cell membrane.

Tissue specificity. Highest expression in kidney and peripheral blood leukocytes. Weaker expression is observed in lung, heart, placenta, spleen, testis and small intestine. Expressed in normal fibroblasts and those from LPI patients. Also expressed in HUVECs, monocytes, retinal pigment epithelial cells, and various carcinoma cell lines, with highest expression in a colon-carcinoma cell line.

Disease relevance. Lysinuric protein intolerance (LPI) [MIM:222700] A metabolic disorder characterized by increased renal excretion of cationic amino acid (CAA), reduced CAA absorption from intestine, and orotic aciduria. On a normal diet, LPI patients present poor feeding, vomiting, diarrhea, episodes of hyperammoniaemic coma and growth retardation. Hepatosplenomegaly, osteoporosis and a life-threatening pulmonary involvement (alveolar proteinosis) are also seen. Biochemically LPI is characterized by defective transport of dibasic amino acids at the basolateral membrane of epithelial cells in kidney and intestine. The disease is caused by variants affecting the gene represented in this entry.

Induction. Expression is stimulated and enhanced by IFNG/IFN-gamma.

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

RefSeq proteins (3): NP_001119577, NP_001119578, NP_003973* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002293	AA/rel_permease1	Family
IPR050598	AminoAcid_Transporter	Family

Pfam: PF13520

Catalyzed reactions (Rhea), 3 shown:

• L-leucine(out) + L-arginine(in) + Na(+)(out) = L-leucine(in) + L-arginine(out) + Na(+)(in) (RHEA:70831)
• L-leucine(out) + L-ornithine(in) + Na(+)(out) = L-leucine(in) + L-ornithine(out) + Na(+)(in) (RHEA:74963)
• L-leucine(out) + L-lysine(in) + Na(+)(out) = L-leucine(in) + L-lysine(out) + Na(+)(in) (RHEA:74971)

UniProt features (72 total): helix 23, sequence variant 22, transmembrane region 12, strand 6, turn 4, modified residue 2, chain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9KJU	ELECTRON MICROSCOPY	2.7
8YLP	ELECTRON MICROSCOPY	2.9
8XXI	ELECTRON MICROSCOPY	3.04
8XYJ	ELECTRON MICROSCOPY	3.33
9KH5	ELECTRON MICROSCOPY	3.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UM01-F1	83.89	0.58

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 (2): 18, 25

Glycosylation sites (1): 325

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-210991	Basigin interactions
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-5660862	Defective amino acid transport by SLC7A7 causes lysinuric protein intolerance (LPI)

MSigDB gene sets: 511 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, ZHAN_MULTIPLE_MYELOMA_PR_DN, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, WIELAND_UP_BY_HBV_INFECTION, GOBP_ORGANIC_ACID_TRANSPORT, COUP_01, BROWNE_HCMV_INFECTION_48HR_DN, BORLAK_LIVER_CANCER_EGF_UP, GNF2_CD1D, MODULE_171, GOBP_AMINO_ACID_TRANSPORT

GO Biological Process (8): obsolete regulation of arginine metabolic process (GO:0000821), amino acid transmembrane transport (GO:0003333), L-leucine transport (GO:0015820), L-arginine transmembrane transport (GO:1903826), basic amino acid transmembrane transport (GO:1990822), amino acid transport (GO:0006865), transmembrane transport (GO:0055085), L-alpha-amino acid transmembrane transport (GO:1902475)

GO Molecular Function (5): basic amino acid transmembrane transporter activity (GO:0015174), L-amino acid transmembrane transporter activity (GO:0015179), L-arginine transmembrane transporter activity (GO:0061459), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (3): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1
SLC-mediated transport of amino acids	1
SLC transporter disorders	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transport	2
L-amino acid transport	2
L-alpha-amino acid transmembrane transport	2
basic amino acid transmembrane transport	2
amino acid transmembrane transport	2
transport	2
amino acid transmembrane transporter activity	2
amino acid transport	1
branched-chain amino acid transport	1
neutral amino acid transport	1
basic amino acid transport	1
cellular process	1
carboxylic acid transmembrane transport	1
carboxylic acid transmembrane transporter activity	1
basic amino acid transmembrane transporter activity	1
L-amino acid transmembrane transporter activity	1
L-arginine transmembrane transport	1
binding	1
transporter activity	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC7A7	SLC3A2	P08195	999
SLC7A7	SLC3A1	Q07837	819
SLC7A7	SLC6A19	Q695T7	668
SLC7A7	SLC6A14	Q9UN76	655
SLC7A7	SLC43A2	Q8N370	645
SLC7A7	SLC1A1	P43005	633
SLC7A7	SLC15A1	P46059	617
SLC7A7	SLC38A2	Q96QD8	605
SLC7A7	SLC1A4	P43007	577
SLC7A7	SLC38A1	Q9H2H9	543
SLC7A7	OTC	P00480	534
SLC7A7	SLC1A5	Q15758	522
SLC7A7	SLC16A10	Q8TF71	485
SLC7A7	SLC38A7	Q9NVC3	466
SLC7A7	SLC38A3	Q99624	462

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SLC7A7	SLC3A2	psi-mi:“MI:0915”(physical association)	0.560
SLC7A6	FAAH	psi-mi:“MI:0914”(association)	0.350
SLC7A7	KLRG2	psi-mi:“MI:0914”(association)	0.350
prmC	SLC7A7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): SLC7A7 (Affinity Capture-MS), SLC7A7 (Positive Genetic), SLC7A7 (Reconstituted Complex), SLC3A2 (Reconstituted Complex), SLC7A7 (Proximity Label-MS), SLC7A7 (Affinity Capture-MS), ADCY9 (Affinity Capture-MS), ANKRD13C (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP7B (Affinity Capture-MS), ATRN (Affinity Capture-MS), CANT1 (Affinity Capture-MS), CSPG5 (Affinity Capture-MS), CYP4X1 (Affinity Capture-MS), GOLPH3 (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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	68
Likely pathogenic	65
Uncertain significance	283
Likely benign	353
Benign	43

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069542	NM_003982.4(SLC7A7):c.293dup (p.Lys99fs)	Pathogenic
1071672	NC_000014.9:g.22774114_22774118del	Pathogenic
1075788	NM_003982.4(SLC7A7):c.889dup (p.Ala297fs)	Pathogenic
1076198	NM_003982.4(SLC7A7):c.701del (p.Tyr233_Ser234insTer)	Pathogenic
1076350	NC_000014.8:g.(?23241431)(23290020_?)del	Pathogenic
1076351	NC_000014.8:g.(?23282099)(23285111_?)del	Pathogenic
1355862	NM_003982.4(SLC7A7):c.949del (p.Ala317fs)	Pathogenic
1376330	NM_003982.4(SLC7A7):c.126_129del (p.Val43fs)	Pathogenic
1397899	NC_000014.8:g.(?23242819)(23282607_?)del	Pathogenic
1430248	NM_003982.4(SLC7A7):c.608_609del (p.Ile203fs)	Pathogenic
1452476	NM_003982.4(SLC7A7):c.371del (p.Leu124fs)	Pathogenic
1459477	NM_003982.4(SLC7A7):c.1400del (p.Lys467fs)	Pathogenic
1459832	NM_003982.4(SLC7A7):c.465T>G (p.Tyr155Ter)	Pathogenic
1460241	NM_003982.4(SLC7A7):c.635_638dup (p.Phe214fs)	Pathogenic
1999250	NM_003982.4(SLC7A7):c.1429+2T>C	Pathogenic
2009233	NM_003982.4(SLC7A7):c.1028_1031dup (p.Pro345fs)	Pathogenic
2025262	NM_003982.4(SLC7A7):c.501T>A (p.Cys167Ter)	Pathogenic
2029046	NM_003982.4(SLC7A7):c.1215del (p.Arg404_Trp405insTer)	Pathogenic
2035963	NM_003982.4(SLC7A7):c.1281C>A (p.Cys427Ter)	Pathogenic
2126833	NM_003982.4(SLC7A7):c.894+1G>C	Pathogenic
2137552	NM_003982.4(SLC7A7):c.1098dup (p.Ile367fs)	Pathogenic
2423735	NC_000014.8:g.(?23242421)(23285111_?)del	Pathogenic
2501105	NC_000014.8:g.(?23242430)(23245528_23248001)del	Pathogenic
2754357	NM_003982.4(SLC7A7):c.158_159delinsGA (p.Ser53Ter)	Pathogenic
2810304	NM_003982.4(SLC7A7):c.816_822del (p.Ile273fs)	Pathogenic
2838829	NM_003982.4(SLC7A7):c.285del (p.Thr96fs)	Pathogenic
2846912	NM_003982.4(SLC7A7):c.970_989del (p.Leu324fs)	Pathogenic
2860078	NM_003982.4(SLC7A7):c.616del (p.Gly207fs)	Pathogenic
2886233	NM_003982.4(SLC7A7):c.1429+1G>C	Pathogenic
3014738	NM_003982.4(SLC7A7):c.537G>A (p.Trp179Ter)	Pathogenic

SpliceAI

2570 predictions. Top by Δscore:

Variant	Effect	Δscore
14:22774088:C:CT	acceptor_gain	1.0000
14:22774112:CTGAG:C	acceptor_gain	1.0000
14:22774117:C:CC	acceptor_gain	1.0000
14:22774348:CCTTA:C	donor_loss	1.0000
14:22774349:CTTA:C	donor_loss	1.0000
14:22774350:TTAC:T	donor_loss	1.0000
14:22774351:TA:T	donor_loss	1.0000
14:22774353:C:CG	donor_loss	1.0000
14:22774500:TACC:T	acceptor_gain	1.0000
14:22774502:CC:C	acceptor_gain	1.0000
14:22774503:CC:C	acceptor_gain	1.0000
14:22774504:C:CC	acceptor_gain	1.0000
14:22775442:A:AC	donor_gain	1.0000
14:22775443:C:CC	donor_gain	1.0000
14:22775528:C:CT	acceptor_gain	1.0000
14:22775528:C:T	acceptor_gain	1.0000
14:22775933:AAGT:A	acceptor_gain	1.0000
14:22776187:T:TA	donor_gain	1.0000
14:22779920:TCTTA:T	donor_loss	1.0000
14:22779921:CTTA:C	donor_loss	1.0000
14:22779922:TTAC:T	donor_loss	1.0000
14:22779923:TAC:T	donor_loss	1.0000
14:22779924:AC:A	donor_gain	1.0000
14:22779924:ACCC:A	donor_loss	1.0000
14:22779925:CC:C	donor_gain	1.0000
14:22812898:A:AC	donor_gain	1.0000
14:22812899:C:CC	donor_gain	1.0000
14:22813439:CC:C	acceptor_gain	1.0000
14:22813440:CCTT:C	acceptor_gain	1.0000
14:22813441:C:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000044987 (14:22781127 C>T), RS1000087617 (14:22775098 C>CAA), RS1000088527 (14:22816828 CTT>C), RS1000133867 (14:22808357 C>A,T), RS1000152434 (14:22790924 G>C), RS1000266041 (14:22797691 G>T), RS1000280760 (14:22809678 C>A,T), RS1000455047 (14:22792101 C>G), RS1000490643 (14:22817139 T>A), RS1000505455 (14:22792399 CA>C,CAA), RS1000648132 (14:22810741 G>A), RS1000715798 (14:22809433 C>T), RS1000773842 (14:22804852 A>G), RS1000783991 (14:22797515 G>A), RS1000790505 (14:22805122 C>T)

Disease associations

OMIM: gene MIM:603593 | disease phenotypes: MIM:222700, MIM:612653

GenCC curated gene-disease

Disease	Classification	Inheritance
lysinuric protein intolerance	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
lysinuric protein intolerance	Definitive	AR

Mondo (3): lysinuric protein intolerance (MONDO:0009109), autoinflammatory syndrome (MONDO:0019751), hereditary spherocytosis type 4 (MONDO:0012981)

Orphanet (3): Lysinuric protein intolerance (Orphanet:470), Autoinflammatory syndrome (Orphanet:93665), Hereditary spherocytosis (Orphanet:822)

HPO phenotypes

100 total (30 of 100 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000091	Abnormal renal tubule morphology
HP:0000093	Proteinuria
HP:0000099	Glomerulonephritis
HP:0000121	Nephrocalcinosis
HP:0000124	Renal tubular dysfunction
HP:0000725	Psychotic episodes
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000973	Cutis laxa
HP:0000974	Hyperextensible skin
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001394	Cirrhosis
HP:0001399	Hepatic failure
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001627	Abnormal heart morphology
HP:0001733	Pancreatitis
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001882	Decreased total leukocyte count

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006138_27	Resting-state electroencephalogram vigilance	1.000000e-06
GCST007741_8	Iris color (b* coordinate)	5.000000e-06
GCST007945_2	Psychological resilience (outcome-based) in high deployment stress exposure	8.000000e-07
GCST007998_17	Intraocular pressure	6.000000e-17
GCST009379_191	Type 2 diabetes	2.000000e-08
GCST010483_2	Cardiovascular death, myocardial infarction or stroke in response to clopidogrel treatment	5.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement
EFO:0009764	eye colour measurement
EFO:0009945	psychological resilience measurement
EFO:0004695	intraocular pressure measurement
EFO:0006919	cardiovascular event measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C562687	Lysinuric Protein Intolerance (supp.)
C567208	Spherocytosis, Type 4 (supp.)

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 — SLC7 family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance	4
Valproic Acid	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance	3
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Arsenic	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	2
Smoke	decreases expression, increases expression	2
Zidovudine	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
potassium perchlorate	decreases expression	1
beta-lapachone	increases expression	1
sodium bichromate	decreases expression	1
benzo(e)pyrene	increases methylation	1
4-nonylphenol	affects cotreatment, decreases expression	1
mercuric bromide	increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-tert-octylphenol	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
ormosil	affects binding, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1536	NCI-H2171	Cancer cell line	Male
CVCL_D4UL	HuH7-SLC7A7-KO-c6	Cancer cell line	Male
CVCL_D4UM	HuH7-SLC7A7-KO-c9	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT05706714	Not specified	COMPLETED	Th1, Th2, Th17 Phenotype in Urea Cycle Disorders
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION