SLC6A19

solute carrier family 6 member 19, the group of Solute carrier family 6

Basic information

Region (hg38): 5:1201594-1225111

Links

ENSG00000174358 ∙ NCBI:340024 ∙ OMIM:608893 ∙ HGNC:27960 ∙ Uniprot:Q695T7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hartnup disease (Strong), mode of inheritance: AR
• Hartnup disease (Supportive), mode of inheritance: AR
• Hartnup disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hartnup disease	AR	Biochemical; Dermatologic	Medical therapy (nicotinamide) and sun avoidance can be beneficial for pellagra-like findings; Optimal protein-related treatment is unclear	Biochemical; Dermatologic; Neurologic; Renal	13358233; 5647741; 5813128; 5041315; 2582682; 11394870; 15286787; 15286788; 19033659; 19185582; 19335424; 20399395

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC6A19 gene.

• not provided (7 variants)
• Neutral 1 amino acid transport defect (3 variants)
• SLC6A19-related disorder (2 variants)
• Iminoglycinuria;Hyperglycinuria;Neutral 1 amino acid transport defect (1 variants)
• Neutral 1 amino acid transport defect;Hyperglycinuria;Iminoglycinuria (1 variants)
• Hyperglycinuria;Iminoglycinuria;Neutral 1 amino acid transport defect (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC6A19 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			2	106	8	116
missense	1	5	145	10	1	162
nonsense	3	4				7
start loss						0
frameshift	3					3
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region			4	19	3	26
non coding			2	45	29	76
Total	8	12	152	161	38

Highest pathogenic variant AF is 0.000283

Variants in SLC6A19

This is a list of pathogenic ClinVar variants found in the SLC6A19 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-1201643-C-T		SLC6A19-related disorder	Benign (May 23, 2021)
5-1201654-G-T			Likely benign (Aug 10, 2023)
5-1201662-C-T			Likely benign (Jul 18, 2023)
5-1201663-G-A			Uncertain significance (May 22, 2023)
5-1201663-G-C		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
5-1201674-C-A			Uncertain significance (Jun 11, 2022)
5-1201675-C-A		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
5-1201676-C-T		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
5-1201677-C-T			Likely benign (Nov 29, 2023)
5-1201678-G-A		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
5-1201679-G-A			Uncertain significance (Aug 06, 2022)
5-1201686-C-T			Likely benign (Oct 23, 2023)
5-1201687-G-A		Inborn genetic diseases	Uncertain significance (Sep 01, 2022)
5-1201690-C-T			Uncertain significance (Sep 27, 2022)
5-1201691-G-A			Benign/Likely benign (Jan 20, 2024)
5-1201695-C-G		Iminoglycinuria;Neutral 1 amino acid transport defect;Hyperglycinuria	Benign/Likely benign (Dec 28, 2023)
5-1201697-C-T			Likely benign (Aug 04, 2023)
5-1201698-G-A		Hyperglycinuria;Neutral 1 amino acid transport defect;Iminoglycinuria	Benign/Likely benign (Oct 25, 2023)
5-1201706-C-T			Uncertain significance (Nov 01, 2023)
5-1201717-A-G		Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
5-1201720-A-G			Uncertain significance (Jul 01, 2022)
5-1201721-T-C			Uncertain significance (Feb 25, 2022)
5-1201722-C-T			Likely benign (Apr 24, 2023)
5-1201723-G-A			Uncertain significance (Jun 28, 2022)
5-1201729-G-C		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC6A19	protein_coding	protein_coding	ENST00000304460	12	23523

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.77e-24	0.000184	125542	0	205	125747	0.000815

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0401	388	386	1.01	0.0000271	4134
Missense in Polyphen		163	171.82	0.94868		1852
Synonymous	-1.67	210	181	1.16	0.0000155	1291
Loss of Function	-0.383	35	32.6	1.07	0.00000194	302

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00118	0.00118
Ashkenazi Jewish	0.00	0.00
East Asian	0.000816	0.000816
Finnish	0.00120	0.00116
European (Non-Finnish)	0.00101	0.00100
Middle Eastern	0.000816	0.000816
South Asian	0.000654	0.000653
Other	0.000817	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transporter that mediates resorption of neutral amino acids across the apical membrane of renal and intestinal epithelial cells. This uptake is sodium-dependent and chloride- independent. {ECO:0000269|PubMed:15286788}.
• Disease: DISEASE: Hyperglycinuria (HG) [MIM:138500]: A condition characterized by excess of glycine in the urine. In some cases it is associated with renal colic and renal oxalate stones. {ECO:0000269|PubMed:19033659}. Note=The disease may be caused by mutations affecting the gene represented in this entry. SLC6A19 deficiency combined with haploinsufficiency of SLC6A20 or partially inactivating mutations in SLC36A2, can be responsible for hyperglycinuria.; 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 may be caused by mutations affecting the gene represented in this entry. SLC6A19 deficiency combined with haploinsufficiency of SLC6A20 or partially inactivating mutations in SLC36A2, can be responsible for iminoglycinuria. Additional polymorphisms and mutations in SLC6A18 can contribute to the IG phenotype in some families.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Mineral absorption - Homo sapiens (human);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: 0.165

Intolerance Scores

• loftool: 0.687
• rvis_EVS: -1.92
• rvis_percentile_EVS: 1.92

Haploinsufficiency Scores

• pHI: 0.200
• hipred: N
• hipred_score: 0.170
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.202

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc6a19
• 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; 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); homeostasis/metabolism phenotype; pigmentation phenotype; digestive/alimentary phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: amino acid transmembrane transport;neurotransmitter transport;amino acid transport;response to nutrient;neutral amino acid transport
• Cellular component: plasma membrane;integral component of plasma membrane;apical plasma membrane;brush border membrane;extracellular exosome
• Molecular function: neurotransmitter:sodium symporter activity;protein binding;amino acid transmembrane transporter activity;neutral amino acid transmembrane transporter activity