Sialidosis type 2

Summary

Sialidosis type 2 (MONDO:0009738) is a disease caused by NEU1 (GenCC Definitive), with 1 cohort gene and 2 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: NEU1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 67
• Phenotypes (HPO): 31
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	<1 / 1 000 000		Europe	Validated
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0000023	Inguinal hernia	Very frequent (80-99%)
HP:0000112	Nephropathy	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000365	Hearing impairment	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0000943	Dysostosis multiplex	Very frequent (80-99%)
HP:0001103	Abnormal macular morphology	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001537	Umbilical hernia	Very frequent (80-99%)
HP:0001541	Ascites	Very frequent (80-99%)
HP:0001744	Splenomegaly	Very frequent (80-99%)
HP:0001789	Hydrops fetalis	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0002808	Kyphosis	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:0010741	Pedal edema	Very frequent (80-99%)
HP:0100022	Abnormality of movement	Very frequent (80-99%)
HP:0000768	Pectus carinatum	Frequent (30-79%)
HP:0000939	Osteoporosis	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001337	Tremor	Frequent (30-79%)
HP:0003202	Skeletal muscle atrophy	Frequent (30-79%)
HP:0001324	Muscle weakness	Occasional (5-29%)
HP:0001371	Flexion contracture	Occasional (5-29%)
HP:0001618	Dysphonia	Occasional (5-29%)
HP:0002094	Dyspnea	Occasional (5-29%)
HP:0005561	Abnormality of bone marrow cell morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	sialidosis type 2
Mondo ID	MONDO:0009738
MeSH	C562606
OMIM	256150, 256550
Orphanet	87876
DOID	DOID:3343
ICD-11	1855856697
NCIT	C125596
SNOMED CT	52186006, 81896006
UMLS	C4282398
MedGen	924303
GARD	0007183
Is cancer (heuristic)	no

Also known as: dysmorphic sialidosis · dysmorphic sialidosis with renal involvement · infantile dysmorphic sialidosis · ML1 · mucolipidosis I · mucolipidosis type 1 · nephrosialidosis · NEU 1 deficiency · NEU1 sialidosis · sialidosis · sialidosis caused by mutation in NEU1 · sialidosis type II · sialidosis, type 2 · sialidosis, type I · sialidosis, type II

Data availability: 67 ClinVar variants · 4 GenCC gene-disease records · 3 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (1): sialidosis type 1

Subtypes (2): juvenile sialidosis type 2, 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

ClinVar germline variants

67 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 16 pathogenic, 11 conflicting classifications of pathogenicity, 6 likely pathogenic, 4 pathogenic/likely pathogenic, 4 benign, 2 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
218331	NM_000434.4(NEU1):c.353-2A>G	NEU1	Pathogenic	no assertion criteria provided
218332	NM_000434.4(NEU1):c.1170C>G (p.Tyr390Ter)	NEU1	Pathogenic	no assertion criteria provided
2444	NM_000434.4(NEU1):c.272T>G (p.Leu91Arg)	NEU1	Pathogenic	no assertion criteria provided
2445	NM_000434.4(NEU1):c.1208del (p.Ser403fs)	NEU1	Pathogenic	no assertion criteria provided
2446	NM_000434.4(NEU1):c.779T>A (p.Phe260Tyr)	NEU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2448	NM_000434.4(NEU1):c.625del (p.Glu209fs)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
2451	NM_000434.4(NEU1):c.87G>A (p.Trp29Ter)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
2452	NM_000434.4(NEU1):c.239C>T (p.Pro80Leu)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
2453	NM_000434.4(NEU1):c.718T>C (p.Trp240Arg)	NEU1	Pathogenic	no assertion criteria provided
2455	NM_000434.4(NEU1):c.1021+1G>C	NEU1	Pathogenic	criteria provided, single submitter
2456	NM_000434.4(NEU1):c.674G>C (p.Arg225Pro)	NEU1	Pathogenic	no assertion criteria provided
2458	NM_000434.4(NEU1):c.69G>A (p.Trp23Ter)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
2708625	NM_000434.4(NEU1):c.880C>T (p.Arg294Cys)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
2734833	NM_000434.4(NEU1):c.913C>T (p.Arg305Cys)	NEU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430337	NM_000434.4(NEU1):c.544A>G (p.Ser182Gly)	NEU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430342	NM_000434.4(NEU1):c.679G>A (p.Gly227Arg)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
435974	NM_000434.4(NEU1):c.114_115del (p.Leu40fs)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
870391	GRCh37/hg19 6p21.33(chr6:31824828-31834398)	NEU1	Pathogenic	criteria provided, single submitter
986732	NM_000434.4(NEU1):c.1109A>G (p.Tyr370Cys)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
997915	NM_000434.4(NEU1):c.1021C>T (p.Arg341Ter)	NEU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802170	NM_000434.4(NEU1):c.[353-11A>G];[541T>C]		Likely pathogenic	criteria provided, single submitter
1324798	NM_000434.4(NEU1):c.947del (p.Pro316fs)	NEU1	Likely pathogenic	criteria provided, single submitter
1332806	NM_000434.4(NEU1):c.887A>G (p.Tyr296Cys)	NEU1	Likely pathogenic	criteria provided, single submitter
2447	NM_000434.4(NEU1):c.1088T>C (p.Leu363Pro)	NEU1	Likely pathogenic	criteria provided, single submitter
2457	NM_000434.4(NEU1):c.893C>T (p.Ala298Val)	NEU1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3341344	NM_000434.4(NEU1):c.352+1G>T	NEU1	Likely pathogenic	criteria provided, single submitter
1324799	NM_000434.4(NEU1):c.238C>A (p.Pro80Thr)	NEU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356230	NM_000434.4(NEU1):c.1107C>A (p.Gly369=)	NEU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356231	NM_000434.4(NEU1):c.888T>C (p.Tyr296=)	NEU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356232	NM_000434.4(NEU1):c.799-4T>C	NEU1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01891422	Not specified	COMPLETED	Longitudinal Studies of the Glycoproteinoses
NCT04624789	Not specified	UNKNOWN	Registry Gangliosidoses