Juvenile sialidosis type 2

Summary

Juvenile sialidosis type 2 (MONDO:0019681) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• Phenotypes (HPO): 38

Clinical features

Signs & symptoms

Clinical features (HPO)

38 HPO clinical features (Orphanet curated; top 38 by frequency):

HPO ID	Term	Frequency
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000943	Dysostosis multiplex	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0003271	Visceromegaly	Very frequent (80-99%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0008947	Floppy infant	Frequent (30-79%)
HP:0010729	Cherry red spot of the macula	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000077	Abnormality of the kidney	Occasional (5-29%)
HP:0000212	Gingival overgrowth	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000572	Visual loss	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)
HP:0001270	Motor delay	Occasional (5-29%)
HP:0001310	Dysmetria	Occasional (5-29%)
HP:0001336	Myoclonus	Occasional (5-29%)
HP:0001433	Hepatosplenomegaly	Occasional (5-29%)
HP:0001537	Umbilical hernia	Occasional (5-29%)
HP:0001618	Dysphonia	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002061	Lower limb spasticity	Occasional (5-29%)
HP:0002086	Abnormality of the respiratory system	Occasional (5-29%)
HP:0002123	Generalized myoclonic seizure	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0002505	Loss of ambulation	Occasional (5-29%)
HP:0003312	Abnormal form of the vertebral bodies	Occasional (5-29%)
HP:0004554	Generalized hypertrichosis	Occasional (5-29%)
HP:0007957	Corneal opacity	Occasional (5-29%)
HP:0009891	Underdeveloped supraorbital ridges	Occasional (5-29%)
HP:0010808	Protruding tongue	Occasional (5-29%)
HP:0010864	Intellectual disability, severe	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile sialidosis type 2
Mondo ID	MONDO:0019681
Orphanet	93399
ICD-11	1730484030
SNOMED CT	111383007
UMLS	C5681598
MedGen	1825999
GARD	0019183
Is cancer (heuristic)	no

Also known as: dysmorphic sialidosis, juvenile form

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › oligosaccharidosis › sialidosis › sialidosis type 2 › juvenile sialidosis type 2

Related subtypes (1): congenital 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

No tiered GWAS variants or ClinVar records for this disease.

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

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.