SLC7A7

solute carrier family 7 member 7, the group of Solute carrier family 7

Basic information

Region (hg38): 14:22773221-22829820

Previous symbols: [ "LPI" ]

Links

ENSG00000155465 ∙ NCBI:9056 ∙ OMIM:603593 ∙ HGNC:11065 ∙ Uniprot:Q9UM01 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lysinuric protein intolerance (Strong), mode of inheritance: AR
• lysinuric protein intolerance (Strong), mode of inheritance: AR
• lysinuric protein intolerance (Supportive), mode of inheritance: AR
• lysinuric protein intolerance (Definitive), mode of inheritance: AR
• lysinuric protein intolerance (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lysinuric protein intolerance	AR	Biochemical	Individuals may manifest with a range of manifestations (eg, developmental delay, failure to thrive with malabsorption, anemia/thrombocytopenia, immunodeficiency, osteoporosis, hemophagocytic lymphohistiocytosis, and pulmonary and renal complications), and dietary/medical therapy (eg, protein restriction, citrulline substitution with use of nitrogen scavengers, lysine supplementation, and carnitine supplementation when necessary) may be beneficial	Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Pulmonary; Renal	4158034; 6076999; 5666624; 5431208; 5553484; 7204568; 3917550; 2732736; 8163273; 8655715; 8892019; 10080183; 9931537; 10080182; 10655553; 10737982; 10451527; 17764084; 18328359; 18716612; 20301535; 21308987; 21716135; 22402328; 22876067; 23358709; 23430827; 23542076; 23772603

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC7A7 gene.

• Lysinuric protein intolerance (584 variants)
• not provided (79 variants)
• not specified (38 variants)
• Inborn genetic diseases (22 variants)
• Autoinflammatory syndrome (17 variants)
• SLC7A7-related condition (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC7A7 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	184	5	192
missense	1	3	180	1	1	186
nonsense	12	12				24
start loss	2	1				3
frameshift	21	27	1			49
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)	10	12				22
splice region			7	25	1	33
non coding			15	69	35	119
Total	46	56	201	254	41

Highest pathogenic variant AF is 0.000341

Variants in SLC7A7

This is a list of pathogenic ClinVar variants found in the SLC7A7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-22773283-G-GAGAC		Lysinuric protein intolerance	Uncertain significance (Jun 14, 2016)
14-22773338-G-A		Lysinuric protein intolerance • Autoinflammatory syndrome	Conflicting classifications of pathogenicity (Mar 06, 2019)
14-22773364-C-G		Lysinuric protein intolerance	Uncertain significance (Jan 13, 2018)
14-22773375-C-G		Lysinuric protein intolerance	Uncertain significance (Jan 13, 2018)
14-22773383-C-T		Lysinuric protein intolerance	Uncertain significance (Jan 13, 2018)
14-22773385-C-T		Lysinuric protein intolerance	Uncertain significance (Jan 12, 2018)
14-22773405-T-G		Lysinuric protein intolerance	Uncertain significance (Jan 13, 2018)
14-22773464-CA-C			Likely benign (Sep 16, 2021)
14-22773469-A-C		Lysinuric protein intolerance	Likely benign (Jan 13, 2018)
14-22773476-T-C			Likely benign (Sep 16, 2021)
14-22773496-G-A		Lysinuric protein intolerance	Uncertain significance (Jan 13, 2018)
14-22773594-G-A		Lysinuric protein intolerance	Uncertain significance (Jan 12, 2018)
14-22773602-G-C		not specified	Likely benign (Dec 08, 2016)
14-22773609-TTTAG-T		not specified	Uncertain significance (Aug 10, 2022)
14-22773611-T-C		Lysinuric protein intolerance	Likely benign (Apr 28, 2023)
14-22773613-G-A		Lysinuric protein intolerance	Likely benign (Nov 17, 2023)
14-22773619-T-C		not specified • Lysinuric protein intolerance	Benign (Feb 01, 2024)
14-22773622-G-C		Lysinuric protein intolerance	Likely benign (Aug 06, 2021)
14-22773625-A-G		Lysinuric protein intolerance	Likely benign (Aug 16, 2023)
14-22773626-T-C		Lysinuric protein intolerance	Uncertain significance (Sep 15, 2021)
14-22773628-CCGTTGCTTGGG-C		Lysinuric protein intolerance	Uncertain significance (Mar 27, 2022)
14-22773630-G-A		Lysinuric protein intolerance • Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
14-22773630-G-T		Lysinuric protein intolerance	Likely benign (Oct 09, 2023)
14-22773631-T-C		Lysinuric protein intolerance	Likely benign (Dec 03, 2019)
14-22773635-T-A		Inborn genetic diseases	Uncertain significance (Jun 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC7A7	protein_coding	protein_coding	ENST00000397532	9	56599

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.95e-7	0.916	125576	0	171	125747	0.000680

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.485	254	277	0.918	0.0000149	3298
Missense in Polyphen		106	106.77	0.99275		1315
Synonymous	-0.316	114	110	1.04	0.00000619	1067
Loss of Function	1.71	13	21.6	0.603	0.00000117	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000633	0.000633
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000598	0.000598
Finnish	0.00462	0.00463
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.000598	0.000598
South Asian	0.000294	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the sodium-independent uptake of dibasic amino acids and sodium-dependent uptake of some neutral amino acids. Requires coexpression with SLC3A2/4F2hc to mediate the uptake of arginine, leucine and glutamine. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Involved in the transport of L- arginine in monocytes. {ECO:0000269|PubMed:14603368, ECO:0000269|PubMed:15280038, ECO:0000269|PubMed:17329401, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:10080182, ECO:0000269|PubMed:10631139, ECO:0000269|PubMed:10655553, ECO:0000269|PubMed:12402335, ECO:0000269|PubMed:15756301, ECO:0000269|PubMed:15776427, ECO:0000269|PubMed:17764084, ECO:0000269|PubMed:9829974}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Polythiazide Action Pathway;Methyclothiazide Action Pathway;Bumetanide Action Pathway;Spironolactone Action Pathway;Eplerenone Action Pathway;Triamterene Action Pathway;Amiloride Action Pathway;Ethacrynic Acid Action Pathway;Quinethazone Action Pathway;Bendroflumethiazide Action Pathway;Chlorthalidone Action Pathway;Trichlormethiazide Action Pathway;Iminoglycinuria;Lysinuric Protein Intolerance;Blue diaper syndrome;Lysinuric protein intolerance (LPI);Glutaminolysis and Cancer;Cystinuria;Indapamide Action Pathway;Furosemide Action Pathway;Torsemide Action Pathway;Hartnup Disorder;Glucose Transporter Defect (SGLT2);Kidney Function;Glucose Transporter Defect (SGLT2);Metolazone Action Pathway;Hydrochlorothiazide Action Pathway;Cyclothiazide Action Pathway;Hydroflumethiazide Action Pathway;Chlorothiazide Action Pathway;TYROBP Causal Network;Amino acid transport across the plasma membrane;Amino acid and oligopeptide SLC transporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Cell surface interactions at the vascular wall;Hemostasis;Basigin interactions (Consensus)

Recessive Scores

• pRec: 0.163

Intolerance Scores

• loftool: 0.114
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.57

Haploinsufficiency Scores

• pHI: 0.350
• hipred: N
• hipred_score: 0.199
• ghis: 0.582

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.879

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Slc7a7
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; embryo phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: slc7a7
• Affected structure: macrophage
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of arginine metabolic process;amino acid transmembrane transport;cellular amino acid metabolic process;leukocyte migration;protein-containing complex assembly;L-alpha-amino acid transmembrane transport;basic amino acid transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;basolateral plasma membrane
• Molecular function: basic amino acid transmembrane transporter activity;L-amino acid transmembrane transporter activity