Sialuria

Summary

Sialuria (MONDO:0010028) is a disease caused by GNE (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: GNE (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 916
• Phenotypes (HPO): 36

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

36 HPO clinical features (Orphanet curated; top 36 by frequency):

HPO ID	Term	Frequency
HP:0000219	Thin upper lip vermilion	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000286	Epicanthus	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000319	Smooth philtrum	Very frequent (80-99%)
HP:0000369	Low-set ears	Very frequent (80-99%)
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000629	Periorbital fullness	Very frequent (80-99%)
HP:0000943	Dysostosis multiplex	Very frequent (80-99%)
HP:0001081	Cholelithiasis	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001256	Intellectual disability, mild	Very frequent (80-99%)
HP:0001290	Generalized hypotonia	Very frequent (80-99%)
HP:0001382	Joint hypermobility	Very frequent (80-99%)
HP:0001433	Hepatosplenomegaly	Very frequent (80-99%)
HP:0001609	Hoarse voice	Very frequent (80-99%)
HP:0001847	Long hallux	Very frequent (80-99%)
HP:0001939	Abnormality of metabolism/homeostasis	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0002354	Memory impairment	Very frequent (80-99%)
HP:0002474	Expressive language delay	Very frequent (80-99%)
HP:0002487	Hyperkinetic movements	Very frequent (80-99%)
HP:0002574	Episodic abdominal pain	Very frequent (80-99%)
HP:0002705	High, narrow palate	Very frequent (80-99%)
HP:0002781	Upper airway obstruction	Very frequent (80-99%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Very frequent (80-99%)
HP:0003645	Prolonged partial thromboplastin time	Very frequent (80-99%)
HP:0004691	2-3 toe syndactyly	Very frequent (80-99%)
HP:0007018	Attention deficit hyperactivity disorder	Very frequent (80-99%)
HP:0008151	Prolonged prothrombin time	Very frequent (80-99%)
HP:0008443	Spinal deformities	Very frequent (80-99%)
HP:0010535	Sleep apnea	Very frequent (80-99%)
HP:0011220	Prominent forehead	Very frequent (80-99%)
HP:0012103	Abnormality of the mitochondrion	Very frequent (80-99%)
HP:0001263	Global developmental delay	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	sialuria
Mondo ID	MONDO:0010028
OMIM	269921
Orphanet	3166
DOID	DOID:3659
ICD-11	154329034
SNOMED CT	238051008
UMLS	C0342853
MedGen	137980
GARD	0004865
MedDRA	10067529
Is cancer (heuristic)	no

Also known as: sialuria · sialuria, French type

Data availability: 916 ClinVar variants · 5 GenCC gene-disease records.

Disease family

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

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

600 retrieved; paginated sample, class counts are floors:

305 likely benign, 179 uncertain significance, 40 pathogenic, 36 conflicting classifications of pathogenicity, 17 likely pathogenic, 16 pathogenic/likely pathogenic, 4 benign, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068026	NM_005476.7(GNE):c.2005_2011del (p.Gly669fs)	GNE	Pathogenic	criteria provided, single submitter
1069453	NM_001128227.3(GNE):c.55_62del (p.Glu18_Leu19insTer)	GNE	Pathogenic	criteria provided, single submitter
1070560	NM_005476.7(GNE):c.1690del (p.Ala564fs)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072426	NM_005476.7(GNE):c.1816+5G>A	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
1075047	NM_005476.7(GNE):c.221_222del (p.Thr74fs)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
1323024	NM_005476.7(GNE):c.1220dup (p.Ser408fs)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
1323025	NM_005476.7(GNE):c.723_727del (p.Ile241_Ser242insTer)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
1371995	NM_005476.7(GNE):c.454_616+70delinsTAG	GNE	Pathogenic	criteria provided, single submitter
1377078	NM_005476.7(GNE):c.1789C>T (p.Gln597Ter)	GNE	Pathogenic	criteria provided, single submitter
1388859	NM_005476.7(GNE):c.1018C>T (p.Gln340Ter)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1412885	NM_005476.7(GNE):c.1112del (p.Ile370_Leu371insTer)	GNE	Pathogenic	criteria provided, single submitter
1413067	NM_005476.7(GNE):c.997dup (p.His333fs)	GNE	Pathogenic	criteria provided, single submitter
1428290	NM_005476.7(GNE):c.952_953del (p.Leu318fs)	GNE	Pathogenic	criteria provided, single submitter
1448509	NM_005476.7(GNE):c.174_177dup (p.Met60fs)	GNE	Pathogenic	criteria provided, single submitter
1451866	NM_005476.7(GNE):c.1643del (p.Gly548fs)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452395	NM_005476.7(GNE):c.1501_1529del (p.Arg501fs)	GNE	Pathogenic	criteria provided, single submitter
1453995	NM_005476.7(GNE):c.1048C>T (p.Gln350Ter)	GNE	Pathogenic	criteria provided, single submitter
1458582	NC_000009.11:g.(?36227235)(36227465_?)del	GNE	Pathogenic	criteria provided, single submitter
162151	NM_005476.7(GNE):c.711G>A (p.Leu237=)	GNE	Pathogenic	criteria provided, single submitter
188796	NM_005476.7(GNE):c.612G>A (p.Trp204Ter)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188847	NM_005476.7(GNE):c.829C>T (p.Arg277Cys)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188882	NM_005476.7(GNE):c.1760T>C (p.Ile587Thr)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
188916	NM_005476.7(GNE):c.1306C>T (p.Gln436Ter)	GNE	Pathogenic	criteria provided, multiple submitters, no conflicts
189156	NM_005476.7(GNE):c.386G>A (p.Arg129Gln)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
197184	NM_005476.7(GNE):c.736C>T (p.Arg246Trp)	GNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2014927	NM_005476.7(GNE):c.798del (p.Lys267fs)	GNE	Pathogenic	criteria provided, single submitter
2018618	NM_005476.7(GNE):c.1139_1140insTAGCCTATAATTTAACTTTGACAAAGTTATGAAATGGTTTTTCTAATACCTTTTTGAAAAAGTCATGGAGGCCATGGGGTTGGCTTGAAACCAGCTTTGGGGGGTTCGATTCCTTCCTTTTTTGTCTAGATTTTATGTATACGGGTTCTTCGAATGTGTGGTTCA (p.Gln380delinsHisSerLeuTer)	GNE	Pathogenic	criteria provided, single submitter
2021712	NM_005476.7(GNE):c.1926_1927insCGGCCCAGAGCATCCTA (p.Arg643_Thr644insProArgAlaSerTer)	GNE	Pathogenic	criteria provided, single submitter
2108109	NM_005476.7(GNE):c.2135del (p.Met712fs)	GNE	Pathogenic	criteria provided, single submitter
2121685	NM_001128227.3(GNE):c.22C>T (p.Gln8Ter)	GNE	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · 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
GNE	Strong	Autosomal dominant	sialuria	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNE	Orphanet:3166	Sialuria
GNE	Orphanet:438207	Severe autosomal recessive macrothrombocytopenia
GNE	Orphanet:602	GNE myopathy

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
GNE	HGNC:23657	ENSG00000159921	Q9Y223	Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNE	Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase	Bifunctional enzyme that possesses both UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities, and serves as the initiator of the biosynthetic pathway leading to the production of N-acetylneuraminic acid (NeuAc), a…

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)
GNE	Enzyme (other)	yes	2.7.1.60	ROK, UDP_GlcNAc_Epimerase_2_dom, UDP-GlcNAc_Epase

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
colonic mucosa	1
mucosa of sigmoid colon	1
nasal cavity epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNE	286	ubiquitous	marker	mucosa of sigmoid colon, colonic mucosa, nasal cavity epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNE	2,210

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNE	Q9Y223	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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 GNE causes sialuria, NK and IBM2	1	11420.0×	2e-04	GNE
Sialic acid metabolism	1	326.3×	0.003	GNE

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
N-acetylglucosamine biosynthetic process	1	8426.0×	4e-04	GNE
N-acetylneuraminate biosynthetic process	1	5617.3×	4e-04	GNE
UDP-N-acetylglucosamine metabolic process	1	2808.7×	4e-04	GNE
CMP-N-acetylneuraminate biosynthetic process	1	2808.7×	4e-04	GNE

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
GNE	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
GNE	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GNE	2.7.1.60, 3.2.1.183, 5.1.3.14	N-acylmannosamine kinase, UDP-N-acetylglucosamine 2-epimerase (hydrolysing), UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)

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	GNE
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)
GNE	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.