GNE

Chr 9ARAD

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

Also known as: DMRV, GLCNE, IBM2, NM, THC12, Uae1

This bifunctional enzyme initiates and regulates the biosynthesis of N-acetylneuraminic acid, serving as the rate-limiting enzyme in the sialic acid biosynthetic pathway that is crucial for cell surface molecule function in adhesion and signal transduction. Mutations cause autosomal recessive Nonaka myopathy and inclusion body myopathy, autosomal dominant sialuria, and thrombocytopenia with or without myopathy. The pathogenic mechanism involves disrupted sialylation of cell surface molecules due to impaired sialic acid biosynthesis.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
AR/ADLOEUF 1.163 OMIM phenotypes
Clinical SummaryGNE
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Gene-Disease Validity (ClinGen)
macrothrombocytopenia, isolated · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — GNE
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.16LOEUF
pLI 0.000
Z-score 0.83
OE 0.84 (0.621.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
2.59Z-score
OE missense 0.64 (0.580.71)
271 obs / 420.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.84 (0.621.16)
00.351.4
Missense OE0.64 (0.580.71)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 27 / 32.1Missense obs/exp: 271 / 420.5Syn Z: 1.59

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GNE · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

X-Linked Retinitis Pigmentosa

Follow-up Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene

ACTIVE NOT RECRUITING
NCT04794101Phase PHASE3Janssen Research & Development, LLCStarted 2020-12-04
Genetic: AAV5-hRKp.RPGR Intermediate DoseGenetic: AAV5-hRKp.RPGR Low Dose
Non-small Cell Lung Cancer

Study of Telisotuzumab Vedotin (ABBV-399) in Participants With Previously Treated c-Met+ Non-Small Cell Lung Cancer

ACTIVE NOT RECRUITING
NCT03539536Phase PHASE2AbbVieStarted 2018-10-10
Telisotuzumab vedotin
Neoplasms, Breast

Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease

ACTIVE NOT RECRUITING
NCT04915755Phase PHASE3GlaxoSmithKlineStarted 2021-06-28
NiraparibPlacebo
Leber Congenital Amaurosis 10BlindnessLeber Congenital Amaurosis

A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)

ACTIVE NOT RECRUITING
NCT03913143Phase PHASE2, PHASE3ProQR TherapeuticsStarted 2019-04-04
sepofarsenSham
Systemic SclerosisScleroderma

Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)

ACTIVE NOT RECRUITING
NCT05925803Phase PHASE3AstraZenecaStarted 2023-11-08
Anifrolumab (blinded)Placebo (blinded)Anifrolumab (unblinded, open label)
Leukemia, Myeloid, Acute

A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)

RECRUITING
NCT06852222Phase PHASE3Janssen Research & Development, LLCStarted 2025-06-04
BleximenibVenetoclax (VEN)Azacitidine (AZA)
Spinal Muscular AtrophySMASpinal Muscular Atrophy Type 2

A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy

RECRUITING
NCT07047144Phase PHASE2Scholar Rock, Inc.Started 2025-09-15
ApitegromabNusinersenRisdiplam
Neovascular Age-related Macular Degeneration

Study to Assess the Injection Burden, Adverse Events, Change in Disease Activity, and Long-Term Preservation of Visual Acuity of Surabgene Lomparvovec in Adult Participants With Neovascular Age-Related Macular Degeneration (nAMD)

RECRUITING
NCT07007065Phase PHASE3AbbVieStarted 2025-11-05
Surabgene Lomparvovec (ABBV-RGX-314)Ranibizumab Control
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
Neoplasms

Long-Term Follow-up Protocol for Participants Treated With Gene-Modified T Cells

RECRUITING
NCT03435796Phase PHASE2, PHASE3CelgeneStarted 2018-07-19
Gene-modified (GM) T cell therapy
Pregnancy Complications

Early PrEgnancy Complications Testing

RECRUITING
NCT04079361Phase NAUniversity Hospital, GhentStarted 2019-04-01
Blood samples
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
Clinical Literature
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Full-Text Mentions
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