Free sialic acid storage disease, infantile form

Summary

Free sialic acid storage disease, infantile form (MONDO:0010027) is a disease caused by SLC17A5 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC17A5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 177

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Prevalence at birth	1-9 / 1 000 000	0.14	Sweden	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	free sialic acid storage disease, infantile form
Mondo ID	MONDO:0010027
OMIM	269920
Orphanet	309324
SNOMED CT	34566007
UMLS	C1096902
MedGen	203367
GARD	0000175
MedDRA	10067532
Is cancer (heuristic)	no

Also known as: infantile free sialic acid storage disease · infantile sialic acid storage disease · infantile sialic acid storage disorder · ISSD · sialic acid storage disorder, infantile · sialuria, infantile form

Data availability: 177 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorder of carbohydrate transmembrane transport and absorption › free sialic acid storage disease, infantile form

Related subtypes (13): congenital sucrase-isomaltase deficiency, congenital lactase deficiency, dystonia 9, Salla disease, hereditary cryohydrocytosis with reduced stomatin, exercise-induced hyperinsulinism, juvenile cataract-microcornea-renal glucosuria syndrome, diarrhea-vomiting due to trehalase deficiency, childhood onset GLUT1 deficiency syndrome 2, chronic diarrhea due to glucoamylase deficiency, intermediate severe Salla disease, glucose transport disorder, autosomal recessive non-syndromic intellectual disability

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

177 retrieved; paginated sample, class counts are floors:

76 uncertain significance, 32 likely pathogenic, 24 pathogenic/likely pathogenic, 18 benign, 10 conflicting classifications of pathogenicity, 7 pathogenic, 6 likely benign, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1355900	NM_012434.5(SLC17A5):c.1A>T (p.Met1Leu)	LOC129996727	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
167694	NM_012434.5(SLC17A5):c.43G>T (p.Glu15Ter)	LOC129996727	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2891846	NM_012434.5(SLC17A5):c.1del (p.Met1*)	LOC129996727	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2678779	NM_012434.5(SLC17A5):c.294_310del	LOC132089454	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072471	NM_012434.5(SLC17A5):c.144dup (p.Gly49fs)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1252083	NM_012434.5(SLC17A5):c.744_747del (p.Ser249fs)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1252085	NM_012434.5(SLC17A5):c.1111+1G>A	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1285238	NG_008272.1:g.(37212_43567)_(48616_58573)del	SLC17A5	Pathogenic	no assertion criteria provided
1454733	NM_012434.5(SLC17A5):c.738G>A (p.Trp246Ter)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457044	NM_012434.5(SLC17A5):c.829C>T (p.Gln277Ter)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
167693	NM_012434.5(SLC17A5):c.533del (p.Thr178fs)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
203395	NM_012434.5(SLC17A5):c.409del (p.Met137fs)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21493	NM_012434.5(SLC17A5):c.406A>G (p.Lys136Glu)	SLC17A5	Pathogenic	criteria provided, multiple submitters, no conflicts
2678771	NM_012434.5(SLC17A5):c.1260-2A>C	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2678776	NM_012434.5(SLC17A5):c.979-1G>T	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370393	NM_012434.5(SLC17A5):c.1259+1G>A	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370901	NM_012434.5(SLC17A5):c.905del (p.Asn302fs)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370976	NM_012434.5(SLC17A5):c.1016G>A (p.Trp339Ter)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371127	NM_012434.5(SLC17A5):c.819+1G>A	SLC17A5	Pathogenic	criteria provided, multiple submitters, no conflicts
431079	NM_012434.5(SLC17A5):c.116G>A (p.Arg39His)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
440272	NM_012434.5(SLC17A5):c.918T>G (p.Tyr306Ter)	SLC17A5	Pathogenic	criteria provided, multiple submitters, no conflicts
558121	NM_012434.5(SLC17A5):c.667dup (p.Tyr223fs)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
558174	NM_012434.5(SLC17A5):c.1355_1356insAA (p.Val453fs)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5615	NM_012434.5(SLC17A5):c.115C>T (p.Arg39Cys)	SLC17A5	Pathogenic	criteria provided, multiple submitters, no conflicts
5619	NM_012434.5(SLC17A5):c.1001C>G (p.Pro334Arg)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5620	SLC17A5, 500-BP INS, NT978	SLC17A5	Pathogenic	no assertion criteria provided
56554	NM_012434.5(SLC17A5):c.291G>A (p.Thr97=)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56556	NM_012434.5(SLC17A5):c.507del (p.Ala169_Leu170insTer)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56558	NM_012434.5(SLC17A5):c.802_816del (p.Ser268_Asn272del)	SLC17A5	Pathogenic	criteria provided, multiple submitters, no conflicts
960642	NM_012434.5(SLC17A5):c.619C>T (p.Gln207Ter)	SLC17A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SLC17A5	Strong	Autosomal recessive	free sialic acid storage disease, infantile form	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC17A5	Orphanet:309324	Free sialic acid storage disease, infantile form
SLC17A5	Orphanet:309331	Intermediate severe Salla disease
SLC17A5	Orphanet:309334	Salla disease

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC17A5	HGNC:10933	ENSG00000119899	Q9NRA2	Sialin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC17A5	Sialin	Multifunctional anion transporter that operates via two distinct transport mechanisms, namely proton-coupled anion cotransport and membrane potential-dependent anion transport.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC17A5	Transporter	yes		MFS, MFS_dom, MFS_trans_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	1
mucosa of sigmoid colon	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC17A5	264	ubiquitous	marker	corpus epididymis, stromal cell of endometrium, mucosa of sigmoid colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC17A5	1,170

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC17A5	Q9NRA2	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC17A5 causes Salla disease (SD) and ISSD	1	11420.0×	0.001	SLC17A5
Organic anion transport by SLC5/17/25 transporters	1	1427.5×	0.005	SLC17A5
Hyaluronan degradation	1	713.8×	0.007	SLC17A5
Sialic acid metabolism	1	326.3×	0.010	SLC17A5
Synthesis of substrates in N-glycan biosythesis	1	292.8×	0.010	SLC17A5
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	207.6×	0.011	SLC17A5
SLC transporter disorders	1	203.9×	0.011	SLC17A5
Disorders of transmembrane transporters	1	139.3×	0.013	SLC17A5
R-HSA-425393	1	129.8×	0.013	SLC17A5
Asparagine N-linked glycosylation	1	60.1×	0.023	SLC17A5
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC17A5
Transport of small molecules	1	25.1×	0.050	SLC17A5
Post-translational protein modification	1	19.2×	0.060	SLC17A5
Disease	1	13.1×	0.081	SLC17A5
Metabolism of proteins	1	12.4×	0.081	SLC17A5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sialic acid transport	1	16852.0×	4e-04	SLC17A5
carbohydrate derivative transport	1	8426.0×	4e-04	SLC17A5
neurotransmitter loading into synaptic vesicle	1	2808.7×	8e-04	SLC17A5
monoatomic anion transport	1	1404.3×	0.001	SLC17A5
amino acid transport	1	312.1×	0.004	SLC17A5
response to bacterium	1	193.7×	0.006	SLC17A5
monoatomic ion transport	1	156.0×	0.006	SLC17A5

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC17A5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SLC17A5	14	Binding:14

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	SLC17A5
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC17A5	14	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.