Lysinuric Protein Intolerance malady

NIH Rare Diseases: Lysinuric protein intolerance is a metabolic disorder caused by the body's inability to digest and use the amino acids lysine, arginine, and ornithine. Because the body cannot effectively break down these amino acids, which are found in many protein-rich foods, individuals experience nausea and vomiting after ingesting protein. Other features associated with protein intolerance may also occur, including short stature, muscle weakness, impaired immune function, and osteoporosis. A lung disorder called pulmonary alveolar proteinosis may develop in some individuals, as can end-stage renal disease, coma and intellectual disability. Symptoms usually develop after infants are weaned and begin to eat solid foods. Lysinuric protein intolerance is caused by mutations in the SLC7A7 gene. It is inherited in an autosomal recessive manner.³⁰

MalaCards: Lysinuric Protein Intolerance, also known as LPI, is related to aminoaciduria and growth hormone deficiency. An important gene associated with Lysinuric Protein Intolerance is SLC7A7 (solute carrier family 7 (amino acid transporter light chain, y+L system), member 7), and among its related pathways are Urea cycle and Sodium-coupled transporters and pumps. The compounds argininosuccinic acid and n-acetylglutamate have been mentioned in the context of this disorder. Affiliated tissues include lung and endothelial, and related mouse phenotypes are hematopoietic system and mortality/aging.

Genetics Home Reference: Lysinuric protein intolerance is a disorder caused by the body's inability to digest and use certain protein building blocks (amino acids), namely lysine, arginine, and ornithine. Because the body cannot effectively break down these amino acids, which are found in many protein-rich foods, nausea and vomiting are typically experienced after ingesting protein.¹⁷

Wikipedia: Lysinuric protein intolerance (LPI), also called hyperdibasic aminoaciduria type 2,cationic...⁴⁴ more...

OMIM: 222700

GeneReviews summary for lpi

lysinuric protein intolerance 7 15 30 16 17 33 32 43 lpi 30 16 17 cationic aminoaciduria 15 16 hyperdibasic aminoaciduria 17

dibasicamino aciduria ii 30 congenital lysinuria 17 aminoaciduria 43

Diseases related to lysinuric protein intolerance by text searches and GeneDecks gene sharing:

(show top 50)    (show all 59)

id	Related Disease	Score	Top Affiliating Genes
1	aminoaciduria	33.1	SLC3A2, SLC3A1, SLC7A7
2	growth hormone deficiency	29.9	SLC7A7, SLC3A1, EPO
3	cystinuria	29.3	SLC3A2, SLC7A8, SLC7A5, SLC3A1, SLC7A7, OTC
4	argininosuccinic aciduria	13.3	OTC, ASL
5	hyperlysinemia	13.3	ASS1, OTC
6	short-chain acyl-coa dehydrogenase deficiency	13.3	OTC, ASS1
7	reye syndrome	13.1	ASS1, OTC
8	oroticaciduria	13.1	OTC, ASS1, ASL
9	urea cycle disorder	13.1	OTC, ASS1, ASL
10	ornithine carbamoyltransferase deficiency	13.1	ASL, ASS1, OTC
11	hyperargininemia	13.1	OTC, ASS1, ASL
12	citrullinemia	13.1	OTC, ASS1, ASL
13	propionic acidemia	13.1	OTC, ASS1, ASL
14	nonspecific interstitial pneumonia	12.9	SLC7A2, SLC7A6
15	hyperammonemia with hypoornithinemia	12.9	ASL, ASS1, OTC, SLC7A7
16	phenylketonuria	12.8	SLC7A5, G6PD, OTC
17	chronic granulomatous disease	12.8	G6PD, OTC
18	galactosemia	12.8	OTC, G6PD
19	fetal erythroblastosis	12.7	G6PD, EPO
20	congenital hemolytic anemia	12.6	G6PD, EPO
21	pyruvate kinase deficiency	12.6	EPO, G6PD
22	hemoglobinopathy	12.6	EPO, G6PD
23	microcytic anemia	12.6	G6PD, EPO
24	bilirubin metabolic disorder	12.6	ASS1, OTC, G6PD, SLC3A1
25	essential thrombocythemia	12.5	EPO, G6PD
26	orthostatic hypotension	12.4	EPO, G6PD
27	colon carcinoma	12.4	SLC3A2, SLC7A6, SLC7A7, OTC, ASS1
28	beta thalassemia	12.4	EPO, G6PD
29	oculomotor apraxia cogan type	12.2	ASS1, OTC, SLC7A7, EPO
30	iron metabolism disease	12.2	G6PD, EPO
31	pulmonary hypertension	12.1	EPO, G6PD, ASS1, ASL
32	carnitine deficiency	12.1	OTC, EPO
33	leiomyoma	11.9	EPO, SLC3A2, SLC7A8, SLC7A5
34	rheumatic pulmonary valve disease	11.8	EPO, SLC3A2, G6PD, TRA@
35	hypertension	11.4	EPO, SLC3A1, G6PD, OTC, ASS1, ASL
36	pneumonia	11.2	SLC3A2, SLC3A1, SLC7A2, G6PD, OTC, ASS1
37	lymphoblastic leukemia	11.0	EPO, NEU2, G6PD, TRA@, SFTPD
38	lung carcinoma	10.9	SFTPD, G6PD, SLC7A2, SLC7A5, EPO
39	retinitis	10.8	EPO, SLC3A2, SLC7A8, SLC7A6, SLC7A5, SLC7A7
40	cerebritis	10.8	EPO, SLC3A2, SLC7A8, SLC7A5, G6PD, OTC
41	thyroiditis	10.4	EPO, SLC3A2, SLC7A8, SLC7A5, G6PD, TRA@
42	tuberculosis	10.1	EPO, SLC3A2, SLC3A1, SLC7A2, G6PD, OTC
43	leukemia	9.9	EPO, NEU2, SLC3A2, SLC7A7, G6PD, OTC
44	carcinoma	8.3	EPO, NEU2, SLC3A2, SLC7A8, SLC7A6, SLC7A5
45	nephropathy	7.5
46	dibasic aminoaciduria 2	7.5
47	fanconi syndrome	7.5
48	dibasic aminoaciduria 1	6.8
49	dicarboxylicaminoaciduria	6.8
50	gracile syndrome	6.8

Clinical features from OMIM: 222700

Approved drugs:

Drug clinical trials:

Genetic tests related to lysinuric protein intolerance:

id	Genetic test	Affiliating Genes
1	Lysinuric Protein Intolerance clinical/research	SLC7A7

MalaCards organs/tissues related to lysinuric protein intolerance:

²²

MGI Mouse Phenotypes related to lysinuric protein intolerance:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	hematopoietic system phenotype	MP:0005397	7.3	SFTPD, EPO, SLC3A2, SLC7A7, G6PD, OTC
2	mortality/aging	MP:0010768	7.0	SLC3A2, SLC7A5, SLC7A7, G6PD, OTC, ASS1

Articles related to lysinuric protein intolerance:

(show all 35)

id	Title	Authors	Year	Affiliating Genes
1	Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat. (18716612)	Font-LlitjA^s M.... Nunes V.	2009	SLC7A7
2	SP-D counteracts GM-CSF-mediated increase of granulom a formation by alveolar macrophages in lysinuric protein intolerance. (20030831)	Douda D.N.... Palaniyar N.	2009	SFTPD
3	Gene symbol: SLC7A7. Disease: Lysinuric protein intolerance. (18846670)	Font-Llitjos M.	2008	SLC7A7
4	Gene symbol: SLC7A7. Disease: Lysinuric protein intolerance. (18846668)	Font-Llitjos M.... Nunes V.	2008	SLC7A7
5	Gene symbol: SLC7A7. Disease: Lysinuric protein intolerance. (18846669)	Font-Llitjos M.	2008	SLC7A7
6	Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene. (17764084)	Sperandeo M.P.... Sebastio G.	2008	SLC7A7
7	Gene symbol: SLC7A7. Disease: Lysinuric protein intolerance. (18846671)	Font-Llitjos M.	2008	SLC7A7
8	Gene symbol: SLC7A7. Disease: Lysinuric protein intolerance. (18846672)	Font-Llitjos M.... Nunes V.	2008	SLC7A7
9	Gene symbol: SLC7A7. Disease: Lysinuric protein intolerance. (18846673)	Font-Llitjos M.... Nunes V.	2008	SLC7A7
10	Nephropathy advancing to end-stage renal disease: a novel complication of lysinuric protein intolerance. (17517249)	Tanner L.M.... Simell O.	2007	EPO
11	Two alternative promoters regulate the expression of lysinuric protein intolerance gene SLC7A7. (17196863)	Puomila K.... Mykkanen J.	2007	SLC7A7
12	Slc7a7 disruption causes fetal growth retardation by downregulating Igf1 in the mouse model of lysinuric protein intolerance. (17376816)	Sperandeo M.P.... Sebastio G.	2007	SLC7A7
13	Renal Fanconi syndrome with ultrastructural defects in lysinuric protein intolerance. (17530437)	Benninga M.A.... Poll-The B.T.	2007	SLC7A7
14	First reported case of lysinuric protein intolerance (LPI) in Lithuania, confirmed biochemically and by DNA analysis. (17666782)	Cimbalistiene L.... Kucinskas V.	2007	SLC7A7
15	Growth hormone deficiency in a patient with lysinuric protein intolerance. (16775724)	Esposito V.... Salerno M.	2006	SLC7A7
16	Lysinuric protein intolerance: identification and functional analysis of mutations of the SLC7A7 gene. (15776427)	Sperandeo M.P.... Sebastio G.	2005	SLC7A7
17	A y(+)LAT-1 mutant protein interferes with y(+)LAT-2 activity: implications for the molecular pathogenesis of lysinuric protein intolerance. (15756301)	Sperandeo M.P.... Sebastio G.	2005	SLC7A7, SLC7A6
18	Increased NO production in lysinuric protein intolerance. (15877200)	Mannucci L.... Dionisi-Vici C.	2005	SLC7A7
19	Five novel SLC7A7 variants and y+L gene-expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance. (12402335)	Shoji Y.... Takada G.	2002	SLC7A7, SLC7A6
20	The molecular bases of cystinuria and lysinuric protein intolerance. (11377971)	Palacin M.... Sebastio G.	2001	SLC7A7, SLC3A2
21	Vascular endothelial dysfunction resulting from L-arginine deficiency in a patient with lysinuric protein intolerance. (11544277)	Kamada Y.... Matsuzawa Y.	2001	SLC7A7
22	SLC7A7 genomic structure and novel variants in three Japanese lysinuric protein intolerance families. (10737982)	Noguchi A.... Takada G.	2000	SLC7A7
23	Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance. (10631139)	Sperandeo M.P.... Borsani G.	2000	SLC7A7
24	Functional analysis of novel mutations in y+LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI). (10655553)	Mykkaenen J.... Aula P.	2000	SLC7A7
25	SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. (10080183)	Borsani G.... Sebastio G.	1999	SLC7A7, SLC7A8
26	SLC7A8, a gene mapping within the lysinuric protein intolerance critical region, encodes a new member of the glycoprotein-associated amino acid transporter family. (10610726)	Bassi M.T.... Sebastio G.	1999	SLC7A8, NEU2
27	Feasibility of prenatal diagnosis of lysinuric protein intolerance by linkage analysis: a case report. (10451527)	Sperandeo M.P.... Sebastio G.	1999	TRA@
28	Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene. (10080182)	Torrents D.... Palacin M.	1999	SLC7A7, SLC3A2
29	Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance. (9829974)	Torrents D.... Palacin M.	1998	SLC7A7, SLC7A5, SLC3A2
30	Genetic homogeneity of lysinuric protein intolerance. (9887380)	Lauteala T.... Aula P.	1998	SLC7A7
31	Lysinuric protein intolerance (LPI) gene maps to the long arm of chromosome 14. (9199570)	Lauteala T.... Aula P.	1997	SLC7A7
32	Human cationic amino acid transporter gene hCAT-2 is assigned to 8p22 but is not the causative gene in lysinuric protein intolerance . (9225973)	Lauteala T.... Aula P.	1997	SLC7A2
33	Lysinuric Protein Intolerance (20301535)	Sebastio G.... Sperandeo M.P.	1993	SLC7A7
34	Lysinuric protein intolerance presenting deficiency of argininosuccinate synthetase. (1568044)	Ono N.... Fujii M.	1992	ASS1
35	A difficult diagnosis of lysinuric protein intolerance: association with glucose-6-phosphate dehydrogenase deficiency. (1779632)	Parini R.... Piceni Sereni L.	1991	G6PD

Genes related to lysinuric protein intolerance according to GeneCards:

(show all 15)

id	Symbol	Description	Score	GeneCards Section Context
1	SLC7A7	solute carrier family 7 (amino acid transporter light chain, y+L system), member 7	11.1	Summaries, Publications
2	SLC7A6	solute carrier family 7 (amino acid transporter light chain, y+L system), member 6	11.0	Publications
3	ASL	argininosuccinate lyase	11.0
4	SLC3A2	solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2	11.0	Publications
5	SLC7A5	solute carrier family 7 (amino acid transporter light chain, L system), member 5	11.0	Publications
6	OTC	ornithine carbamoyltransferase	11.0
7	ASS1	argininosuccinate synthase 1	11.0	Publications
8	SLC3A1	solute carrier family 3 (cystine, dibasic and neutral amino acid transporters, activator of cystine, dibasic and neutral amino acid transport), member 1	11.0
9	G6PD	glucose-6-phosphate dehydrogenase	11.0	Publications
10	NEU2	sialidase 2 (cytosolic sialidase)	11.0	Publications
11	SLC7A8	solute carrier family 7 (amino acid transporter light chain, L system), member 8	11.0	Functions, Publications
12	SLC7A2	solute carrier family 7 (cationic amino acid transporter, y+ system), member 2	11.0	Publications
13	SFTPD	surfactant protein D	11.0	Publications
14	EPO	erythropoietin	11.0	Publications
15	TRA@	T cell receptor alpha locus	11.0	Publications

Pathways related to lysinuric protein intolerance according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Urea cycle38	9.7	OTC, ASS1, ASL
2	Sodium-coupled transporters and pumps10	9.7	SLC7A6, SLC3A2
3	Arginine and proline metabolism20	9.6	OTC, ASS1, ASL
4	Glucose / Energy Metabolism3	9.6	SLC3A2, SLC7A5, G6PD
5	Amino acid transport across the plasma membrane38	9.5	SLC7A2, SLC3A1
6	Protein digestion and absorption20	9.2	SLC7A7, SLC3A1, SLC7A8, SLC3A2
7	Cell surface interactions at the vascular wall38	9.1	SLC7A7, SLC7A5, SLC7A6, SLC7A8, SLC3A2

Compounds related to lysinuric protein intolerance according to GeneDecks:

(show all 36)

id	Compound	Score	Top Affiliating Genes
1	argininosuccinic acid32 18	11.3	ASS1, ASL
2	n-acetylglutamate32	10.3	ASL, OTC
3	guanidinoacetate32	10.2	ASS1, ASL
4	delta(1)pyrroline-5-carboxylate32	10.1	ASS1, OTC
5	2-aminobicyclo(2,2,1)heptane-2-carboxylic acid32	10.1	SLC7A5, SLC7A8
6	L-Citrulline9 9	11.1	ASS1, OTC
7	L-Leucine9 18 9	12.0	SLC3A2, SLC7A8
8	sodium benzoate34	10.0	ASL, ASS1, OTC
9	carbamoyl phosphate32	10.0	OTC, ASL, ASS1
10	ammonium32	10.0	OTC, ASS1, ASL
11	citrulline32 18	11.0	ASL, ASS1, OTC
12	malate32	9.9	G6PD, ASL, OTC
13	L-Ornithine9 9	10.8	OTC, SLC7A2
14	bamhi32	9.8	OTC, TRA@
15	cystine32	9.8	SLC3A1, SLC3A2, SLC7A8
16	sodium32 18	10.8	SLC7A6, SLC7A7, OTC, SLC3A1
17	L-Arginine9 18 9	11.6	ASL, ASS1, SLC7A7, SLC7A6, SLC3A2
18	23-diphosphoglycerate32	9.5	EPO, G6PD
19	L-Cysteine9 18 9	11.5	SLC7A8, SLC3A2
20	zinc protoporphyrin32	9.4	EPO, G6PD
21	phenylalanine32	9.4	SLC7A5, SLC3A2, SLC3A1, SLC7A8
22	fumarate32 9 9	11.4	ASL, EPO, G6PD
23	phenylbutyrate32	9.3	EPO, OTC
24	melphalan32 9 9	11.2	SLC7A5, SLC7A8, EPO
25	carnitine32	9.2	EPO, OTC, G6PD
26	urea32 9 18 9	12.1	EPO, ASL, ASS1, OTC
27	glutamate32	9.1	SLC3A1, OTC, ASL, SLC3A2, ASS1
28	glutamine32	9.0	ASL, OTC, G6PD, SLC7A5, SFTPD
29	ornithine32 18	9.9	ASS1, ASL, OTC, SLC7A7, SLC3A1, SLC7A5
30	alanine32	8.8	SLC3A1, SLC7A5, SLC7A8, ASS1, SLC3A2
31	aspartate32	8.7	ASS1, OTC, ASL, G6PD, EPO
32	creatinine32	8.4	ASS1, G6PD, OTC, SLC3A1, EPO, ASL
33	nitric oxide32 9 18 9	11.4	SFTPD, ASL, ASS1, OTC, SLC3A1, SLC7A2
34	lactate32	8.4	G6PD, SFTPD, EPO, OTC
35	arginine32	8.1	SLC7A7, SLC7A2, SLC3A1, OTC, ASS1, SLC7A6
36	leucine32	8.0	SFTPD, ASS1, OTC, SLC3A1, SLC7A5, SLC7A8

Cellular components related to lysinuric protein intolerance according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	basolateral plasma membrane	GO:016323	9.5	SLC7A7, SLC7A6, SLC7A8

Biological processes related to lysinuric protein intolerance according to GeneDecks:

(show all 13)

id	Name	GO ID	Score	Top Affiliating Genes
1	arginine biosynthetic process	GO:006526	10.0	ASS1, OTC
2	response to zinc ion	GO:010043	9.9	OTC, ASS1
3	urea cycle	GO:000050	9.8	ASL, OTC, ASS1
4	neutral amino acid transport	GO:015804	9.7	SLC7A8, SLC7A5
5	midgut development	GO:007494	9.6	OTC, ASS1
6	leukocyte migration	GO:050900	9.2	SLC7A6, SLC3A2, SLC7A8, SLC7A7, SLC7A5
7	erythrocyte maturation	GO:043249	9.2	G6PD, EPO
8	blood coagulation	GO:007596	9.1	SLC7A8, SLC3A2, SLC7A5, SLC7A7, SLC7A6
9	transport	GO:006810	8.9	SLC7A2, SLC7A7, SLC7A8, SLC7A6, SLC7A5
10	cellular amino acid metabolic process	GO:006520	8.7	SLC7A6, SLC7A7, SLC7A2, SLC7A5, SLC3A1, SLC7A8
11	amino acid transport	GO:006865	8.4	SLC7A5, SLC3A1, SLC7A2, SLC7A7, SLC7A6, SLC7A8
12	ion transport	GO:006811	8.4	SLC7A2, SLC3A2, SLC7A6, SLC7A5, SLC3A1, SLC7A7
13	transmembrane transport	GO:055085	8.4	SLC3A1, SLC7A7, SLC7A5, SLC7A2, SLC7A6, SLC7A8

Molecular functions related to lysinuric protein intolerance according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	peptide antigen binding	GO:042605	9.7	SLC7A5, SLC7A8
2	L-amino acid transmembrane transporter activity	GO:015179	9.6	SLC7A5, SLC7A8
3	basic amino acid transmembrane transporter activity	GO:015174	9.6	SLC3A1, SLC7A2
4	neutral amino acid transmembrane transporter activity	GO:015175	9.5	SLC7A5, SLC3A2, SLC7A8
5	catalytic activity	GO:003824	9.2	SLC3A1, NEU2, SLC3A2
6	amino acid transmembrane transporter activity	GO:015171	9.0	SLC7A6, SLC7A7, SLC3A1, SLC7A5, SLC7A8