SLC17A5

solute carrier family 17 member 5, the group of Solute carrier family 17

Basic information

Region (hg38): 6:73593378-73653992

Previous symbols: [ "SIASD" ]

Links

ENSG00000119899 ∙ NCBI:26503 ∙ OMIM:604322 ∙ HGNC:10933 ∙ Uniprot:Q9NRA2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Salla disease (Definitive), mode of inheritance: AR
• Salla disease (Definitive), mode of inheritance: AR
• Salla disease (Strong), mode of inheritance: AR
• free sialic acid storage disease, infantile form (Strong), mode of inheritance: AR
• free sialic acid storage disease, infantile form (Supportive), mode of inheritance: AR
• intermediate severe Salla disease (Supportive), mode of inheritance: AR
• Salla disease (Supportive), mode of inheritance: AR
• free sialic acid storage disease, infantile form (Strong), mode of inheritance: AR
• free sialic acid storage disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Infantile sialic acid storage disorder; Sialuria, Finnish type (Salla disease)	AR	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; Cardiovascular; Gastrointestinal; Neurologic	4043964; 10546100; 10069709; 10581036; 10947946; 12121352; 12794687; 12794688; 15172005; 16170568; 19557856; 20101035; 20301643; 20637281

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC17A5 gene.

• Salla disease (438 variants)
• not provided (86 variants)
• Sialic acid storage disease, severe infantile type (83 variants)
• Inborn genetic diseases (32 variants)
• Sialic acid storage disease, severe infantile type;Salla disease (19 variants)
• not specified (12 variants)
• Salla disease;Sialic acid storage disease, severe infantile type (5 variants)
• SLC17A5-related condition (2 variants)
• Focal segmental glomerulosclerosis (1 variants)
• SLC17A5-Related Disorders (1 variants)
• Familial hypokalemia-hypomagnesemia (1 variants)
• Intermediate severe Salla disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC17A5 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				126	2	128
missense	1	9	92	1		103
nonsense	12	17	3			32
start loss	2	1				3
frameshift	17	33	4			54
inframe indel	1		3			4
splice donor/acceptor (+/-2bp)	4	18	1			23
splice region		1	4	27		32
non coding			28	39	53	120
Total	37	78	131	166	55

Highest pathogenic variant AF is 0.000453

Variants in SLC17A5

This is a list of pathogenic ClinVar variants found in the SLC17A5 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-73593381-A-G		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 13, 2018)
6-73593385-C-T		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 12, 2018)
6-73593447-C-A		Salla disease • Sialic acid storage disease, severe infantile type	Conflicting classifications of pathogenicity (Jan 13, 2018)
6-73593489-TA-T		Salla disease	Uncertain significance (Jun 14, 2016)
6-73593511-C-T		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 12, 2018)
6-73593512-G-A		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 13, 2018)
6-73593544-T-C		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 12, 2018)
6-73593585-G-C		Salla disease • Sialic acid storage disease, severe infantile type	Conflicting classifications of pathogenicity (Jan 13, 2018)
6-73593627-C-T		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 12, 2018)
6-73593744-TA-T		Salla disease	Uncertain significance (Jun 14, 2016)
6-73593745-A-T		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 13, 2018)
6-73593871-C-T		Sialic acid storage disease, severe infantile type • Salla disease	Uncertain significance (Jan 13, 2018)
6-73593922-A-T		Sialic acid storage disease, severe infantile type • Salla disease	Uncertain significance (Jan 13, 2018)
6-73594021-T-C		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 12, 2018)
6-73594106-C-T		Salla disease • Sialic acid storage disease, severe infantile type	Benign (Jan 13, 2018)
6-73594168-G-A		Sialic acid storage disease, severe infantile type • Salla disease	Benign (Jan 12, 2018)
6-73594176-G-A		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 12, 2018)
6-73594240-G-A		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 12, 2018)
6-73594260-C-T		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 12, 2018)
6-73594278-A-G		Salla disease • Sialic acid storage disease, severe infantile type	Likely benign (Jan 13, 2018)
6-73594313-C-T		Sialic acid storage disease, severe infantile type • Salla disease	Benign (Jan 12, 2018)
6-73594315-G-A		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 12, 2018)
6-73594411-G-A		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 13, 2018)
6-73594482-G-C		Salla disease • Sialic acid storage disease, severe infantile type	Uncertain significance (Jan 13, 2018)
6-73594489-C-T		Salla disease • Sialic acid storage disease, severe infantile type	Likely benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC17A5	protein_coding	protein_coding	ENST00000355773	11	60777

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.85e-10	0.668	125648	0	100	125748	0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.714	230	263	0.876	0.0000128	3179
Missense in Polyphen		78	101.01	0.77217		1167
Synonymous	0.565	88	95.0	0.926	0.00000478	1000
Loss of Function	1.39	18	25.6	0.704	0.00000118	309

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000796	0.000796
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000218	0.000217
Finnish	0.000141	0.000139
European (Non-Finnish)	0.000551	0.000545
Middle Eastern	0.000218	0.000217
South Asian	0.0000980	0.0000980
Other	0.000676	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transports glucuronic acid and free sialic acid out of the lysosome after it is cleaved from sialoglycoconjugates undergoing degradation, this is required for normal CNS myelination. Mediates aspartate and glutamate membrane potential- dependent uptake into synaptic vesicles and synaptic-like microvesicles. Also functions as an electrogenic 2NO(3)(-)/H(+) cotransporter in the plasma membrane of salivary gland acinar cells, mediating the physiological nitrate efflux, 25% of the circulating nitrate ions is typically removed and secreted in saliva. {ECO:0000269|PubMed:10581036, ECO:0000269|PubMed:11751519, ECO:0000269|PubMed:15510212, ECO:0000269|PubMed:21781115, ECO:0000269|PubMed:22778404}.
• Disease: DISEASE: Infantile sialic acid storage disorder (ISSD) [MIM:269920]: Severe form of sialic acid storage disease. Affected newborns exhibit visceromegaly, coarse features and failure to thrive immediately after birth. These patients have a shortened life span, usually less than 2 years. {ECO:0000269|PubMed:10581036, ECO:0000269|PubMed:10947946}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Sialuria or French Type Sialuria;Sialuria or French Type Sialuria;Amino Sugar Metabolism;G(M2)-Gangliosidosis: Variant B, Tay-sachs disease;Tay-Sachs Disease;Salla Disease/Infantile Sialic Acid Storage Disease;Post-translational protein modification;Metabolism of proteins;Organic anion transporters;Amino acid and oligopeptide SLC transporters;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Phosphatidylinositol phosphate metabolism;Aminosugars metabolism;Sialic acid metabolism;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.256

Intolerance Scores

• loftool: 0.882
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.85

Haploinsufficiency Scores

• pHI: 0.187
• hipred: Y
• hipred_score: 0.704
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.514

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Slc17a5
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; vision/eye 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Gene ontology

• Biological process: ion transport;anion transport;amino acid transport;response to bacterium;sialic acid transport;carbohydrate transmembrane transport;proton transmembrane transport
• Cellular component: lysosome;lysosomal membrane;cytosol;plasma membrane;integral component of plasma membrane;membrane;integral component of membrane;cell junction;synaptic vesicle membrane
• Molecular function: carbohydrate:proton symporter activity;sialic acid transmembrane transporter activity;sialic acid:proton symporter activity