GNE

Chr 9ARAD

glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase

ENSG00000159921UniProt: Q9Y223

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 critical precursor in the synthesis of sialic acids. By catalyzing this pivotal and rate-limiting step in sialic acid biosynthesis, this enzyme assumes a pivotal role in governing the regulation of cell surface sialylation, playing a role in embryonic angiogenesis (PubMed:10334995, PubMed:11326336, PubMed:14707127, PubMed:16503651, PubMed:2808337, PubMed:38237079). Sialic acids represent a category of negatively charged sugars that reside on the surface of cells as terminal components of glycoconjugates and mediate important functions in various cellular processes, including cell adhesion, signal transduction, and cellular recognition (PubMed:10334995, PubMed:14707127)

Primary Disease Associations & Inheritance

Nonaka myopathyMIM #605820
AR
SialuriaMIM #269921
AD
Thrombocytopenia 12 with or without myopathyMIM #620757
AR
1312
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical Summary— GNE
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
1312 total variants — no pathogenic classifications of 1312 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.16LOEUF
pLI 0.000
Z-score 0.83
OE 0.84 (0.62–1.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.59Z-score
OE missense 0.64 (0.58–0.71)
271 obs / 420.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.84 (0.62–1.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.58–0.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.84
0≤1.21.6
LoF obs/exp: 27 / 32.1Missense obs/exp: 271 / 420.5Syn Z: 1.59

ClinVar Variant Classifications

1312 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

GNE · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GNE-related sialuria

limited
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗

GNE-related congenital myopathy

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Nonaka myopathy

MIM #605820

Molecular basis of disorder known

Autosomal recessive

Sialuria

MIM #269921

Molecular basis of disorder known

Autosomal dominant

Thrombocytopenia 12 with or without myopathy

MIM #620757

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Panorama of the distal myopathies.
Savarese M et al.·Acta Myol
2020Review
[Remudy].
Kimura E et al.·Brain Nerve
2014Review
[GNE myopathy].
Urtizberea JA et al.·Med Sci (Paris)
2015Review
Hereditary inclusion-body myopathies.
Broccolini A et al.·Biochim Biophys Acta
2015Review
Estimating the Prevalence of GNE Myopathy Using Population Genetic Databases.
Derksen A et al.·Hum Mutat
2024
Novel variants and genotype-phenotype correlation in a multicentre cohort of GNE myopathy in China.
Jiao K et al.·J Med Genet
2024Cohort
Clinical, Histopathologic, and Genetic Features of Patients With Myofibrillary and Distal Myopathies: Experience From the Italian Network.
Bortolani S et al.·Neurology
2024Cohort
Recent advances in establishing a cure for GNE myopathy.
Yoshioka W et al.·Curr Opin Neurol
2022Review
Beyond sialylation: Exploring the multifaceted role of GNE in GNE myopathy.
Pereira BL et al.·Mol Genet Metab
2025Review
What is in the Myopathy Literature?
Isfort M et al.·J Clin Neuromuscul Dis
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Aortic AneurysmAortic DissectionAortic Diseases

Montalcino Aortic Consortium: Precision Medicine for Heritable Thoracic Aortic Disease

RECRUITING
NCT04005976The University of Texas Health Science Center, HoustonStarted 2016-06-15
Solid TumorMetastatic Cancer

A Study to Examine the Clinical Value of Comprehensive Genomic Profiling Performed by Belgian NGS Laboratories: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Centre

RECRUITING
NCT05058937Phase NAThe Belgian Society of Medical OncologyStarted 2021-06-01
Comprehensive genomic profiling
Platinum SensitiveBRCA MutatedRelapsed Ovarian Cancer

Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

ACTIVE NOT RECRUITING
NCT01874353Phase PHASE3AstraZenecaStarted 2013-09-03
Olaparib 300mg tabletsPlacebo to match olaparib 300mg
Inherited Non-Duchenne Myopathies

Clinical and Functional Assessment of Patients With Inherited Non-Duchenne Myopathies in Sohag University Hospital

RECRUITING
NCT06574919Sohag UniversityStarted 2024-08-01
Prostate Cancer

Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC

ACTIVE NOT RECRUITING
NCT04821622Phase PHASE3PfizerStarted 2021-05-12
talazoparib plus enzalutamidePlacebo plus enzalutamide
GNE Myopathy

Multi-Center Study of ManNAc for GNE Myopathy

ACTIVE NOT RECRUITING
NCT04231266Phase PHASE2Leadiant Biosciences, Inc.Started 2022-04-05
ManNAcPlacebo
Acute Myeloid LeukemiaMyelodysplastic Syndrome With Excess Blasts-2

A Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy

ACTIVE NOT RECRUITING
NCT04027309Phase PHASE3Stichting Hemato-Oncologie voor Volwassenen NederlandStarted 2019-12-20
GilteritinibMidostaurin
Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen

Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen

RECRUITING
NCT06127407Phase PHASE3Servier Bio-Innovation LLCStarted 2024-07-09
Ivosidenib 500mgPlacebo
Meningococcal Meningitis, Serogroup BTransgender PersonsSex Differences in Immune Response

Investigating Gender and Sex Differences in Immune Responses Through Vaccination of Transgender and Cisgender Persons

RECRUITING
NCT06832514Phase PHASE4University GhentStarted 2025-01-31
Serogroup B meningococal vaccine
Metastatic Castration-Sensitive Prostate Cancer

Saruparib (AZD5305) vs Placebo in Men With Metastatic Castration-Sensitive Prostate Cancer Receiving Physician's Choice New Hormonal Agents

RECRUITING
NCT06120491Phase PHASE3AstraZenecaStarted 2023-11-21
SaruparibPlaceboAbiraterone Acetate
Locally Advanced or Metastatic Non-Small Cell Lung Cancer

A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations

ACTIVE NOT RECRUITING
NCT05048797Phase PHASE3AstraZenecaStarted 2021-10-28
Trastuzumab DeruxtecanCisplatinCarboplatin
Advanced Solid Tumor

A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations

ACTIVE NOT RECRUITING
NCT04083976Phase PHASE2Janssen Research & Development, LLCStarted 2019-11-20
Erdafitinib

External Resources

Links to major genomics databases and tools