Sialidosis

Summary

Sialidosis (MONDO:0017734) is a disease with 2 cohort genes and 2 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 17
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

6 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Validated
Prevalence at birth	<1 / 1 000 000	0.05	Europe	Validated
Prevalence at birth	<1 / 1 000 000	0.05	Netherlands	Validated
Prevalence at birth	<1 / 1 000 000	0.02	Australia	Validated
Prevalence at birth	<1 / 1 000 000	0.07	Czech Republic	Validated
Prevalence at birth	1-9 / 1 000 000	0.1	Sweden	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	sialidosis
Mondo ID	MONDO:0017734
Orphanet	309294
ICD-11	1180347697
SNOMED CT	38795005
UMLS	C0268226
MedGen	120621
GARD	0021331
MedDRA	10058800
NORD	1713
Is cancer (heuristic)	no

Data availability: 17 ClinVar variants.

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

Related subtypes (6): aspartylglucosaminuria, fucosidosis, alpha-mannosidosis, beta-mannosidosis, galactosialidosis, alpha-N-acetylgalactosaminidase deficiency

Subtypes (2): sialidosis type 2, sialidosis type 1

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

17 retrieved; paginated sample, class counts are floors:

8 pathogenic/likely pathogenic, 6 pathogenic, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1331449	NM_000434.4(NEU1):c.982G>A (p.Gly328Ser)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
1804680	NM_000434.4(NEU1):c.163C>T (p.Gln55Ter)	NEU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2445712	NM_000434.4(NEU1):c.1004C>A (p.Pro335Gln)	NEU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2449	NM_000434.4(NEU1):c.649G>A (p.Val217Met)	NEU1	Pathogenic/Likely 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
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
631977	NM_000434.4(NEU1):c.45G>A (p.Trp15Ter)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
918138	NM_000434.4(NEU1):c.838C>T (p.Arg280Ter)	NEU1	Pathogenic	criteria provided, multiple submitters, no conflicts
946976	NM_000434.4(NEU1):c.160G>A (p.Val54Met)	NEU1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
948536	NM_000434.4(NEU1):c.692T>A (p.Leu231His)	NEU1	Pathogenic/Likely 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
2203542	NM_000232.5(SGCB):c.544A>G (p.Thr182Ala)	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2457	NM_000434.4(NEU1):c.893C>T (p.Ala298Val)	NEU1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2691715	NM_000434.4(NEU1):c.1021C>G (p.Arg341Gly)	NEU1	Likely pathogenic	criteria provided, single submitter
3251791	NM_000434.4(NEU1):c.839G>A (p.Arg280Gln)	NEU1	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SGCB	Orphanet:119	Beta-sarcoglycan-related limb-girdle muscular dystrophy R4
NEU1	Orphanet:812	Sialidosis type 1
NEU1	Orphanet:93399	Juvenile sialidosis type 2
NEU1	Orphanet:93400	Congenital sialidosis type 2

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SGCB	HGNC:10806	ENSG00000163069	Q16585	Beta-sarcoglycan	clinvar
NEU1	HGNC:7758	ENSG00000204386	Q99519	Sialidase-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SGCB	Beta-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
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: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SGCB	Other/Unknown	no		Sarcoglycan, Sgcb
NEU1	Enzyme (other)	yes	3.2.1.18	Sialidase, Sialidase_fam, Sialidase_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
tendon of biceps brachii	1
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
SGCB	288	ubiquitous	marker	tendon of biceps brachii, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii
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
SGCB	781

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NEU1	Q99519	89.12
SGCB	Q16585	76.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 2 evidence-associated genes (2 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 2 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	1427.5×	0.015	NEU1
Diseases associated with N-glycosylation of proteins	1	317.2×	0.021	NEU1
Sialic acid metabolism	1	163.1×	0.021	NEU1
Formation of the dystrophin-glycoprotein complex (DGC)	1	154.3×	0.021	SGCB
Glycosphingolipid metabolism	1	150.3×	0.021	NEU1
Synthesis of substrates in N-glycan biosythesis	1	146.4×	0.021	NEU1
Glycosphingolipid catabolism	1	146.4×	0.021	NEU1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	103.8×	0.026	NEU1
Sphingolipid metabolism	1	84.0×	0.028	NEU1
Non-integrin membrane-ECM interactions	1	77.2×	0.028	SGCB
Diseases of glycosylation	1	65.6×	0.030	NEU1
Diseases of metabolism	1	40.2×	0.045	NEU1
Extracellular matrix organization	1	31.6×	0.052	SGCB
Asparagine N-linked glycosylation	1	30.1×	0.052	NEU1
Metabolism of lipids	1	15.8×	0.092	NEU1
Innate Immune System	1	12.8×	0.106	NEU1
Neutrophil degranulation	1	11.5×	0.110	NEU1
Post-translational protein modification	1	9.6×	0.124	NEU1
Disease	1	6.5×	0.163	NEU1
Immune System	1	6.5×	0.163	NEU1
Metabolism of proteins	1	6.2×	0.163	NEU1
Metabolism	1	5.8×	0.165	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glucose import in response to insulin stimulus	1	1404.3×	0.003	SGCB
ganglioside catabolic process	1	936.2×	0.003	NEU1
vascular associated smooth muscle cell development	1	842.6×	0.003	SGCB
oligosaccharide catabolic process	1	766.0×	0.003	NEU1
cardiac muscle cell development	1	312.1×	0.006	SGCB
response to glucose	1	127.7×	0.012	SGCB
muscle organ development	1	83.4×	0.015	SGCB
glucose homeostasis	1	65.3×	0.017	SGCB
gene expression	1	39.9×	0.025	SGCB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SGCB	0	0
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: 2; 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	1	SGCB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SGCB	0	—
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