SLC3A1

solute carrier family 3 member 1, the group of Solute carrier family 3

Basic information

Region (hg38): 2:44275458-44321494

Links

ENSG00000138079

∙ NCBI:6519 ∙ OMIM:104614 ∙ HGNC:11025 ∙ Uniprot:Q07837 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

cystinuria type A (Supportive), mode of inheritance: AR
cystinuria (Strong), mode of inheritance: AR
cystinuria (Definitive), mode of inheritance: AR
cystinuria (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cystinuria	AD/AR	Biochemical; Renal	Measures to maintain high fluid intake, as well as medical therapy (eg, urine alkalinization, and, in some, penicillamine) can be beneficial	Biochemical; Renal	5925065; 2502678; 8054986; 7573036; 12239244; 12820697; 15635077; 19782624; 20052367; 20399395; 21255007; 21677404; 21863055

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC3A1 gene.

Cystinuria (448 variants)
not_provided (61 variants)
Inborn_genetic_diseases (45 variants)
SLC3A1-related_disorder (24 variants)
Cystine_urolithiasis (13 variants)
not_specified (12 variants)
Kidney_disorder (3 variants)
See_cases (2 variants)
Nephrocalcinosis (1 variants)
Autism_spectrum_disorder (1 variants)
Nephrolithiasis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC3A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000341.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	2 clinvar		12 clinvar	57 clinvar	3 clinvar	74
missense	9 clinvar	40 clinvar	265 clinvar	12 clinvar		326
nonsense	19 clinvar	13 clinvar				32
start loss			1			1
frameshift	22 clinvar	12 clinvar				34
splice donor/acceptor (+/-2bp)	4 clinvar	13 clinvar				17
Total	56	78	278	69	3

Highest pathogenic variant AF is 0.0031612667

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC3A1	protein_coding	protein_coding	ENST00000260649	10	46035

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.22e-27	0.0000138	104942	1336	19470	125748	0.0865

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-3.14	559	385	1.45	0.0000223	4580
Missense in Polyphen		164	123.69	1.3259		1455
Synonymous	-2.34	183	147	1.25	0.00000940	1249
Loss of Function	-1.16	36	29.3	1.23	0.00000134	353

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.303	0.303
Ashkenazi Jewish	0.0939	0.0888
East Asian	0.00120	0.00120
Finnish	0.101	0.101
European (Non-Finnish)	0.104	0.104
Middle Eastern	0.00120	0.00120
South Asian	0.0208	0.0207
Other	0.0906	0.0895

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in the high-affinity, sodium-independent transport of cystine and neutral and dibasic amino acids (system B(0,+)-like activity). May function as an activator of SLC7A9 and be involved in the high-affinity reabsorption of cystine in the kidney tubule. {ECO:0000269|PubMed:11318953, ECO:0000269|PubMed:7686906, ECO:0000269|PubMed:8486766, ECO:0000269|PubMed:8663184}.;
Disease: DISEASE: Hypotonia-cystinuria syndrome (HCS) [MIM:606407]: Characterized generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. {ECO:0000269|PubMed:16385448}. 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);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;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;Glycerophospholipid metabolism (Consensus)

Recessive Scores

pRec: 0.432

Intolerance Scores

loftool: 0.129
rvis_EVS: -1.59
rvis_percentile_EVS: 3.1

Haploinsufficiency Scores

pHI: 0.148
hipred: N
hipred_score: 0.216
ghis: 0.415

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.00420

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Slc3a1
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); skeleton phenotype; renal/urinary system phenotype; immune system phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: carbohydrate metabolic process;cellular amino acid metabolic process;amino acid transport;basic amino acid transport;L-cystine transport;basic amino acid transmembrane transport
Cellular component: vacuolar membrane;plasma membrane;integral component of plasma membrane;membrane;brush border membrane;extracellular exosome
Molecular function: catalytic activity;protein binding;amino acid transmembrane transporter activity;basic amino acid transmembrane transporter activity;L-cystine transmembrane transporter activity;protein heterodimerization activity