SLC17A5

Chr 6AR

solute carrier family 17 member 5

Also known as: AST, ISSD, NSD, SD, SIALIN, SIASD, SLD, VEAT

NCBI Gene: 26503 ENSG00000119899 UniProt: Q9NRA2 OMIM: 604322

This gene encodes a lysosomal membrane transporter that exports free sialic acid from lysosomes after it has been cleaved from cell surface glycoproteins and glycolipids. Biallelic loss-of-function mutations cause autosomal recessive sialic acid storage diseases, including the severe infantile form (infantile sialic acid storage disorder) and the milder adult-onset Salla disease. The pathogenic mechanism involves defective sialic acid transport leading to lysosomal accumulation of free sialic acid.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a membrane transporter that exports free sialic acids that have been cleaved off of cell surface lipids and proteins from lysosomes. Mutations in this gene cause sialic acid storage diseases, including infantile sialic acid storage disorder and and Salla disease, an adult form. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.042 OMIM phenotypes

Clinical Summary— SLC17A5

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Gene-Disease Validity (ClinGen)

free sialic acid storage disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

175 unique Pathogenic / Likely Pathogenic· 229 VUS of 775 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLC17A5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.39

OE 0.70 (0.48–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.71Z-score

OE missense 0.88 (0.79–0.98)

230 obs / 262.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.48–1.04)

0≤0.351.4

Missense OE?0.88 (0.79–0.98)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 18 / 25.6Missense obs/exp: 230 / 262.5Syn Z: 0.57

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLC17A5-related Salla diseaseLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.80top 25%

GOF

0.7125th %ile

LOF

0.2191th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

775 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54

Likely Pathogenic121

VUS229

Likely Benign291

Benign60

Conflicting12

Pathogenic

121

Likely Pathogenic

229

VUS

291

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	34	4	16	0	54
Likely Pathogenic	101	13	6	1	121
VUS	8	179	39	3	229
Likely Benign	0	31	116	144	291
Benign	0	0	58	2	60
Conflicting	—				12
Total	143	227	235	150	767

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap SLC17A5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →