SLC6A20

solute carrier family 6 member 20, the group of Solute carrier family 6

Basic information

Region (hg38): 3:45755449-45796574

Links

ENSG00000163817 ∙ NCBI:54716 ∙ OMIM:605616 ∙ HGNC:30927 ∙ Uniprot:Q9NP91 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperglycinuria (No Known Disease Relationship), mode of inheritance: Unknown
• hyperglycinuria (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Iminoglycinuria, digenic; Hyperglycinuria/Iminoglycinuria, modifier of	AD/Digenic	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Renal	19033659

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC6A20 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC6A20 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			10	11	4	25
missense			63	6	3	72
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region			2		1	3
non coding			77	12	27	116
Total	0	0	153	29	34

Variants in SLC6A20

This is a list of pathogenic ClinVar variants found in the SLC6A20 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-45755457-C-A		Hyperglycinuria	Uncertain significance (Jan 12, 2018)
3-45755459-C-T		Hyperglycinuria	Benign (Jan 13, 2018)
3-45755492-T-C		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45755542-G-A		Hyperglycinuria	Likely benign (Jan 12, 2018)
3-45755542-G-C		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45755570-T-C		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45755574-G-A		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45755595-G-A		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45755636-T-A		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45755658-G-C		Hyperglycinuria	Uncertain significance (Jan 12, 2018)
3-45755860-T-C		Hyperglycinuria	Benign (Jan 12, 2018)
3-45755876-C-A		Hyperglycinuria	Uncertain significance (Jan 12, 2018)
3-45755877-G-A		Hyperglycinuria	Uncertain significance (Jan 12, 2018)
3-45755927-T-A		Hyperglycinuria	Uncertain significance (Jan 12, 2018)
3-45755963-A-G		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45756039-T-C		Hyperglycinuria	Uncertain significance (Mar 16, 2018)
3-45756080-A-T		Hyperglycinuria	Uncertain significance (Jan 12, 2018)
3-45756095-G-A		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45756145-G-A		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45756170-G-A		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45756216-T-A		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45756229-C-T		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45756293-A-G		Hyperglycinuria	Benign (Jan 13, 2018)
3-45756302-A-T		Hyperglycinuria	Uncertain significance (Jan 13, 2018)
3-45756303-G-C		Hyperglycinuria	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC6A20	protein_coding	protein_coding	ENST00000358525	11	41086

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.66e-17	0.0164	125349	4	395	125748	0.00159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.497	333	359	0.926	0.0000215	3843
Missense in Polyphen		139	151.59	0.91694		1663
Synonymous	-0.877	180	166	1.09	0.0000118	1191
Loss of Function	0.435	27	29.6	0.914	0.00000135	313

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00119	0.00118
Ashkenazi Jewish	0.0000998	0.0000992
East Asian	0.000384	0.000381
Finnish	0.00996	0.00979
European (Non-Finnish)	0.00118	0.00114
Middle Eastern	0.000384	0.000381
South Asian	0.000332	0.000327
Other	0.00115	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates the calcium-dependent uptake of imino acids such as L-proline, N-methyl-L-proline and pipecolate as well as N- methylated amino acids. Involved in the transport of glycine. {ECO:0000269|PubMed:15632147, ECO:0000269|PubMed:19033659}.
• Disease: DISEASE: Iminoglycinuria (IG) [MIM:242600]: A disorder of renal tubular reabsorption of glycine and imino acids (proline and hydroxyproline), marked by excessive levels of all three substances in the urine. {ECO:0000269|PubMed:19033659}. Note=The disease is caused by mutations affecting the gene represented in this entry. Haploinsufficiency of SLC6A20 combined with deficiency of the neutral amino acid transporter SLC6A19 or partially inactivating mutations in SLC36A2, is responsible for iminoglycinuria. Additional polymorphisms and mutations in SLC6A18 can contribute to the IG phenotype in some families.
• Pathway: 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;Nuclear Receptors Meta-Pathway;NRF2 pathway;Amine compound SLC transporters;Amino acid transport across the plasma membrane;Amino acid and oligopeptide SLC transporters;Transport of inorganic cations/anions and amino acids/oligopeptides;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Na+/Cl- dependent neurotransmitter transporters (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.906
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.89

Haploinsufficiency Scores

• pHI: 0.107
• hipred: N
• hipred_score: 0.167
• ghis: 0.456

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.335

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc6a20b

Gene ontology

• Biological process: amino acid transport;glycine transport;proline transport;proline transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;apical plasma membrane
• Molecular function: neurotransmitter:sodium symporter activity;protein binding;amino acid transmembrane transporter activity;L-proline transmembrane transporter activity