SLC17A5

Chr 6

solute carrier family 17 member 5

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

NCBI Gene: 26503ENSG00000119899UniProt: Q9NRA2

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]

Primary Disease Associations & Inheritance

UniProtSalla disease
UniProtInfantile sialic acid storage disorder
575
ClinVar variants
141
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— SLC17A5
🧬
Gene-Disease Validity (ClinGen)
free sialic acid storage disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
141 Pathogenic / Likely Pathogenic· 195 VUS of 575 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.71Z-score
OE missense 0.88 (0.79–0.98)
230 obs / 262.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.70 (0.48–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.79–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 18 / 25.6Missense obs/exp: 230 / 262.5Syn Z: 0.57

ClinVar Variant Classifications

575 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic87
VUS195
Likely Benign220
Benign12
Conflicting7
54
Pathogenic
87
Likely Pathogenic
195
VUS
220
Likely Benign
12
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
3
30
0
54
Likely Pathogenic
49
9
28
1
87
VUS
1
157
33
4
195
Likely Benign
0
18
96
106
220
Benign
0
0
10
2
12
Conflicting
—7
Total71187197113575

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC17A5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLC17A5-related Salla disease

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — SLC17A5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease.
Robak LA et al.·Brain
2017
SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population.
Mir A et al.·Hum Genet
2022
Atypical free sialic acid storage disorder associated with tissue specific mosaicism of SLC17A5.
Shinawi M et al.·Mol Genet Metab
2025Case report
Free sialic acid storage disorder: Progress and promise.
Huizing M et al.·Neurosci Lett
2021Review
Identification of a large intronic transposal insertion in SLC17A5 causing sialic acid storage disease.
Tarailo-Graovac M et al.·Orphanet J Rare Dis
2017
Molecular autopsy in maternal-fetal medicine.
Shamseldin HE et al.·Genet Med
2018
Longitudinal Characterization of the Clinical Course of Intermediate-Severe Salla Disease.
Chapleau A et al.·Pediatr Neurol
2023Natural history
Implementation of fetal clinical exome sequencing: Comparing prospective and retrospective cohorts.
Marangoni M et al.·Genet Med
2022Cohort
Hypogammaglobulinemia and imaging features in a patient with infantile free sialic acid storage disease (ISSD) and a novel mutation in the SLC17A5 gene.
Žigman T et al.·J Pediatr Endocrinol Metab
2018Case report
Comprehensive analysis of SLC17A5 variants in large European cohorts reveals no association with Parkinson's disease risk.
Sabir MS et al.·Parkinsonism Relat Disord
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
LeukodystrophyWhite Matter DiseaseLeukoencephalopathies

The Myelin Disorders Biorepository Project

RECRUITING
NCT03047369Children's Hospital of PhiladelphiaStarted 2016-12-08

External Resources

Links to major genomics databases and tools