Sialidosis type 1

Summary

Sialidosis type 1 (MONDO:0019346) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 4
• Phenotypes (HPO): 42

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Validated
Prevalence at birth	<1 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

42 HPO clinical features (Orphanet curated; top 42 by frequency):

HPO ID	Term	Frequency
HP:0000179	Thick lower lip vermilion	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000407	Sensorineural hearing impairment	Very frequent (80-99%)
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000488	Retinopathy	Very frequent (80-99%)
HP:0000505	Visual impairment	Very frequent (80-99%)
HP:0000529	Progressive visual loss	Very frequent (80-99%)
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0000768	Pectus carinatum	Very frequent (80-99%)
HP:0000943	Dysostosis multiplex	Very frequent (80-99%)
HP:0000962	Hyperkeratosis	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0001336	Myoclonus	Very frequent (80-99%)
HP:0001350	Slurred speech	Very frequent (80-99%)
HP:0001744	Splenomegaly	Very frequent (80-99%)
HP:0002167	Abnormality of speech or vocalization	Very frequent (80-99%)
HP:0002650	Scoliosis	Very frequent (80-99%)
HP:0002652	Skeletal dysplasia	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0003355	Aminoaciduria	Very frequent (80-99%)
HP:0003461	Increased urinary O-linked sialopeptides	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0007957	Corneal opacity	Very frequent (80-99%)
HP:0010306	Short thorax	Very frequent (80-99%)
HP:0010729	Cherry red spot of the macula	Very frequent (80-99%)
HP:0011276	Vascular skin abnormality	Very frequent (80-99%)
HP:0012061	Urinary excretion of sialylated oligosaccharides	Very frequent (80-99%)
HP:0100022	Abnormality of movement	Very frequent (80-99%)
HP:0000762	Decreased nerve conduction velocity	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001337	Tremor	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002353	EEG abnormality	Frequent (30-79%)
HP:0003202	Skeletal muscle atrophy	Frequent (30-79%)
HP:0003312	Abnormal form of the vertebral bodies	Frequent (30-79%)
HP:0100790	Hernia	Frequent (30-79%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0002808	Kyphosis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	sialidosis type 1
Mondo ID	MONDO:0019346
Orphanet	812
ICD-11	1154773192
SNOMED CT	34960006, 723675006
UMLS	C0023806
MedGen	44174
GARD	0007639
Is cancer (heuristic)	no

Also known as: cherry red spot myoclonus syndrome · cherry-red spot-myoclonus syndrome · lipomucopolysaccharidosis · myoclonus cherry red spot syndrome · Normomorphic sialidosis · normosomatic sialidosis · sialidosis type I

Data availability: 4 ClinVar variants · 1 GenCC gene-disease record · 8 cell lines.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › oligosaccharidosis › sialidosis › sialidosis type 1

Related subtypes (1): sialidosis type 2

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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2443	NM_000434.4(NEU1):c.1129G>T (p.Glu377Ter)	NEU1	Pathogenic	no assertion criteria provided
2449	NM_000434.4(NEU1):c.649G>A (p.Val217Met)	NEU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2450	NM_000434.4(NEU1):c.727G>A (p.Gly243Arg)	NEU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2454	NM_000434.4(NEU1):c.946C>T (p.Pro316Ser)	NEU1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
NEU1	Definitive	Autosomal recessive	sialidosis type 2	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NEU1	Orphanet:812	Sialidosis type 1
NEU1	Orphanet:93399	Juvenile sialidosis type 2
NEU1	Orphanet:93400	Congenital sialidosis type 2

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
NEU1	HGNC:7758	ENSG00000204386	Q99519	Sialidase-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NEU1	Sialidase-1	Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NEU1	Enzyme (other)	yes	3.2.1.18	Sialidase, Sialidase_fam, Sialidase_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
islet of Langerhans	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NEU1	132	ubiquitous	marker	islet of Langerhans, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NEU1	794

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NEU1	Q99519	89.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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 NEU1 causes sialidosis	1	2855.0×	0.007	NEU1
Diseases associated with N-glycosylation of proteins	1	634.4×	0.011	NEU1
Sialic acid metabolism	1	326.3×	0.011	NEU1
Glycosphingolipid metabolism	1	300.5×	0.011	NEU1
Synthesis of substrates in N-glycan biosythesis	1	292.8×	0.011	NEU1
Glycosphingolipid catabolism	1	292.8×	0.011	NEU1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	207.6×	0.013	NEU1
Sphingolipid metabolism	1	167.9×	0.014	NEU1
Diseases of glycosylation	1	131.3×	0.016	NEU1
Diseases of metabolism	1	80.4×	0.024	NEU1
Asparagine N-linked glycosylation	1	60.1×	0.029	NEU1
Metabolism of lipids	1	31.6×	0.050	NEU1
Innate Immune System	1	25.5×	0.057	NEU1
Neutrophil degranulation	1	23.1×	0.059	NEU1
Post-translational protein modification	1	19.2×	0.066	NEU1
Disease	1	13.1×	0.085	NEU1
Immune System	1	13.0×	0.085	NEU1
Metabolism of proteins	1	12.4×	0.085	NEU1
Metabolism	1	11.6×	0.086	NEU1

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
ganglioside catabolic process	1	1872.4×	7e-04	NEU1
oligosaccharide catabolic process	1	1532.0×	7e-04	NEU1

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
NEU1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
NEU1	27	Binding:27

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NEU1	3.2.1.18	exo-alpha-sialidase

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	0
D	Druggable family + AlphaFold only, no drug	1	NEU1
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)
NEU1	27	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.