Free sialic acid storage disease

Summary

Free sialic acid storage disease (MONDO:0019366) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 30

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		130	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

30 HPO clinical features (Orphanet curated; top 30 by frequency):

HPO ID	Term	Frequency
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001257	Spasticity	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0001760	Abnormal foot morphology	Very frequent (80-99%)
HP:0007256	Abnormal pyramidal sign	Very frequent (80-99%)
HP:0010318	Aplasia/Hypoplasia of the abdominal wall musculature	Very frequent (80-99%)
HP:0000657	Oculomotor apraxia	Frequent (30-79%)
HP:0001000	Abnormality of skin pigmentation	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001531	Failure to thrive in infancy	Frequent (30-79%)
HP:0001541	Ascites	Frequent (30-79%)
HP:0001789	Hydrops fetalis	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002167	Abnormality of speech or vocalization	Frequent (30-79%)
HP:0002205	Recurrent respiratory infections	Frequent (30-79%)
HP:0002305	Athetosis	Frequent (30-79%)
HP:0002652	Skeletal dysplasia	Frequent (30-79%)
HP:0002817	Abnormality of the upper limb	Frequent (30-79%)
HP:0004349	Reduced bone mineral density	Frequent (30-79%)
HP:0007730	Iris hypopigmentation	Frequent (30-79%)
HP:0200042	Skin ulcer	Frequent (30-79%)
HP:0000093	Proteinuria	Occasional (5-29%)
HP:0000100	Nephrotic syndrome	Occasional (5-29%)
HP:0001744	Splenomegaly	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	free sialic acid storage disease
Mondo ID	MONDO:0019366
MeSH	C538523
Orphanet	834
ICD-11	1817428569
SNOMED CT	278991002
UMLS	C2931872
MedGen	419512
GARD	0010870
MedDRA	10067529, 10067531
Is cancer (heuristic)	no

Also known as: free sialic acid storage disease

Data availability: 1 ClinVar variant · 12 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › lysosomal storage disease › inborn disorder of lysosomal amino acid transport › free sialic acid storage disease

Related subtypes (1): cystinosis

Subtypes (4): free sialic acid storage disease, infantile form, sialuria, Salla disease, intermediate severe Salla disease

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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3780610	NM_012434.5(SLC17A5):c.1238del (p.Asn413fs)	SLC17A5	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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	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.