SLC3A2

solute carrier family 3 member 2, the group of Solute carrier family 3

Basic information

Region (hg38): 11:62856003-62888880

Previous symbols: [ "MDU1" ]

Links

ENSG00000168003 ∙ NCBI:6520 ∙ OMIM:158070 ∙ HGNC:11026 ∙ Uniprot:P08195 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC3A2 gene.

• Inborn genetic diseases (23 variants)
• not provided (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC3A2 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				4	3	7
missense			18	4	2	24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			2	1	1	4
Total	0	0	20	9	6

Variants in SLC3A2

This is a list of pathogenic ClinVar variants found in the SLC3A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-62856275-G-A		not specified	Likely benign (Sep 25, 2023)
11-62856286-C-T		not specified	Uncertain significance (Aug 22, 2022)
11-62856292-C-T		not specified	Uncertain significance (Mar 06, 2023)
11-62856303-G-T		not specified	Uncertain significance (Nov 06, 2023)
11-62856389-A-T			Benign (Jun 08, 2018)
11-62876814-C-A		not specified	Uncertain significance (Jun 21, 2022)
11-62876837-A-G		not specified	Uncertain significance (Oct 26, 2022)
11-62876882-G-A			Benign (Dec 31, 2019)
11-62881102-G-T		not specified	Uncertain significance (Jan 27, 2022)
11-62881135-G-C		not specified	Uncertain significance (Mar 17, 2023)
11-62881160-A-G		not specified	Uncertain significance (Mar 02, 2023)
11-62881164-G-A			Likely benign (Dec 31, 2019)
11-62881250-G-T		not specified	Uncertain significance (Aug 20, 2023)
11-62881276-C-T			Benign (Dec 31, 2019)
11-62881314-T-G			Benign (May 30, 2018)
11-62881316-G-T		not specified	Uncertain significance (Jan 05, 2022)
11-62881456-A-G			Likely benign (Aug 06, 2018)
11-62881893-G-T		not specified	Uncertain significance (Oct 25, 2023)
11-62881949-G-T		not specified	Uncertain significance (Oct 05, 2021)
11-62881955-A-G		not specified	Uncertain significance (Jan 30, 2024)
11-62881973-G-A		not specified	Uncertain significance (May 27, 2022)
11-62882963-C-G		not specified	Uncertain significance (May 27, 2022)
11-62882993-G-A			Likely benign (Aug 16, 2018)
11-62884506-G-A		not specified	Uncertain significance (Feb 05, 2024)
11-62884644-T-G		not specified	Uncertain significance (Sep 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC3A2	protein_coding	protein_coding	ENST00000377891	12	32835

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.22e-8	0.949	125725	0	21	125746	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	290	350	0.828	0.0000187	4044
Missense in Polyphen		97	137.24	0.7068		1573
Synonymous	0.890	140	154	0.909	0.00000851	1328
Loss of Function	1.94	16	26.8	0.596	0.00000123	302

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000264	0.000264
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.0000478	0.0000462
European (Non-Finnish)	0.0000813	0.0000703
Middle Eastern	0.000110	0.000109
South Asian	0.0000341	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the function of light chain amino-acid transporters. Involved in sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan. Involved in guiding and targeting of LAT1 and LAT2 to the plasma membrane. When associated with SLC7A6 or SLC7A7 acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Required for normal and neoplastic cell growth. When associated with SLC7A5/LAT1, is also involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. When associated with SLC7A5 or SLC7A8, involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L- nitrosocysteine (L-CNSO) across the transmembrane. Together with ICAM1, regulates the transport activity LAT2 in polarized intestinal cells, by generating and delivering intracellular signals. When associated with SLC7A5, plays an important role in transporting L-leucine from the circulating blood to the retina across the inner blood-retinal barrier. When associated with LAPTM4B, recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (PubMed:25998567). {ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:14603368, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Ferroptosis - 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;mRNA, protein, and metabolite inducation pathway by cyclosporin A;Tryptophan catabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;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;Methionine and cysteine metabolism;Valine, leucine and isoleucine degradation;Aminosugars metabolism;Glycerophospholipid metabolism;Cell surface interactions at the vascular wall;Hemostasis;Basigin interactions;Glycine, serine, alanine and threonine metabolism;Calcineurin-regulated NFAT-dependent transcription in lymphocytes (Consensus)

Recessive Scores

• pRec: 0.418

Intolerance Scores

• loftool: 0.0424
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.15

Haploinsufficiency Scores

• pHI: 0.274
• hipred: N
• hipred_score: 0.455
• ghis: 0.432

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc3a2
• 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; neoplasm; immune system phenotype; digestive/alimentary phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: slc3a2a
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved ventral

Gene ontology

• Biological process: carbohydrate metabolic process;calcium ion transport;amino acid transport;tryptophan transport;sodium ion transmembrane transport;response to exogenous dsRNA;leukocyte migration;L-leucine import across plasma membrane
• Cellular component: nucleus;cytosol;plasma membrane;cell surface;membrane;integral component of membrane;apical plasma membrane;melanosome;extracellular exosome
• Molecular function: RNA binding;double-stranded RNA binding;catalytic activity;calcium:sodium antiporter activity;protein binding;neutral amino acid transmembrane transporter activity;cadherin binding